Foot health in diabetes mellitus: Epidemiological and

Foot health in diabetes mellitus:

Epidemiological and educational aspects

Mendel Murasaki Baba

BPHE W.Aust (UWA), GradCertHlthProm(Curtin), B.Pod(Hons)(La Trobe)

This thesis is presented in partial fulfilment of the requirements for the

Doctor of Podiatry

May 2015

School of Surgery and School of Medicine & Pharmacology

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ABSTRACT

Diabetes mellitus (DM) is a global health problem that can lead to a multitude of

complications. DM contributes to the development of diabetic peripheral neuropathy

(DPN) and peripheral arterial disease (PAD) in the lower extremities, which in turn

increases the risk of foot complications such as ulceration, infection and lower extremity

amputation (LEA). These complications are particularly debilitating for the patient as they

have a significant impact on mobility and quality of life, while also contributing

disproportionately to the costs of diabetes care. Reducing the burden of foot

complications for both the individual and health care providers is thus a fundamental goal

of government and health care organisations worldwide. Achieving this goal is a complex

and multifaceted task, however three practical approaches to addressing this issue involve

supporting the patient to care for their feet, improving diabetes management and

education, and expanding the evidence base to assist clinical decision making.

Early detection of foot problems, and their timely management, plays an important role in

reducing the incidence of complications. To this end, improving patient awareness of their

foot health is a critical component of diabetes management. A lack of patient awareness

increases the risk of a greater number of complications, and potentially leads to more

severe outcomes. Determining awareness of foot health, and patient perceptions of their

feet, will provide a better understanding of possible barriers to optimal foot care. In this

thesis, a cross sectional investigation of awareness of foot health in a cohort of patients

with type 2 diabetes is first presented. The characteristics of patients who believed their

feet were normal and abnormal, and gaps in patient knowledge, were assessed. The results

demonstrate that a large majority of patients who considered their feet normal had features

on inspection such as deformity, dry skin, callouses and skin fissures that could promote

more serious complications. Most patients with self-reported normal feet had objective

evidence of peripheral sensory neuropathy, and smaller proportions had peripheral arterial

disease and a combination of neuropathy and arteriopathy.

A second important aspect relevant to reducing foot complications in diabetes is the

utilisation of foot care education. Such education is routinely provided in the clinical

setting as part of the diabetes management plan, but whether this education translates to a

meaningful uptake of positive foot care behaviours and reductions in identifiable foot

problems is not well understood. It is also currently unclear what type of education is most

beneficial to patients with diabetes. Therefore, a comparison of two methods of diabetic

foot care education on outcomes related to improving knowledge, behaviour and attitudes

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regarding foot health was undertaken. Written information proved more effective at

improving foot health, while interactive education improved participant‟s confidence in

undertaking preventive measures. These results suggest that the most effective foot care

education should include both written information and interaction with a qualified health

care professional, and these findings may have implications on future foot care education

planning and delivery.

Finally, improving our understanding of the epidemiology of foot ulceration in type 2

diabetes, and ascertaining the significant factors contributing to the development of foot

ulcers, provides critical information that can reduce diabetes related morbidity, mortality

and costs. Risk factors for foot ulceration have been incompletely characterised, and few

studies provide a full range of predictive variables that would assist in identifying these at-

risk patients. A study of the natural history of foot ulceration over time provides an

opportunity to define these characteristics in a representative cohort. To this end, the

prevalence and associates of foot ulceration in patients with type 2 diabetes from the

Fremantle Diabetes Study (FDS) were determined, and the incidence and predictors of foot

ulceration severe enough to require hospitalisation during 17 years follow up were

identified. The baseline prevalence of foot ulceration in Phase I of the FDS was 1.2%, and

the strongest independent associates of an active ulcer at baseline were intermittent

claudication, DPN, diabetes duration and antihypertensive therapy. Furthermore, the

incidence of first ever hospitalisation for a foot ulcer was 5.21 per 1,000 patient years.

Investigation of FDS data relating to temporal changes in foot ulceration between Phase I

(recruitment between 1993-1996) and Phase II (recruitment between 2008-2011) were also

examined, and the relationship between changes in established risk factors for ulceration

and its prevalence over the same period was assessed. There was no difference in baseline

foot ulcer prevalence between Phase I and Phase II (1.2% and 1.5%, respectively, P=0.62).

Consistent with Phase I, the unchanged independent associates of ulceration identified in

Phase II were diabetes duration and peripheral sensory neuropathy, but Aboriginality and

prior hospitalisations for foot ulcer also became significant risk factors.

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CONTENTS

Abstract………………………………………………………………………..3

List of figures…………………………………………………………………11

List of tables…………………………………………………………………..13

Acknowledgements……………………………………………………………15

Author contributions……….………………………………………………….17

Publications……………………………………………………………………21

Structure of thesis…….………………………………………………………..23

List of acronyms………………………………………………………………25

Chapter 1: Introduction…………………………………………………….29

1.1 Prevalence of diabetes…………………………………………………….32

1.2 Costs……………………………………………………………………...32

1.3 Diabetes complications……………………………………………………32

1.3.1 Macrovascular complications……………………………………32

1.3.1.1 Peripheral Arterial Disease…………………………….33

1.3.2 Microvascular complications…………………………………….34

1.3.2.1 Nephropathy…………………………………………..34

1.3.2.2 Retinopathy……………………………………………35

1.3.2.3 Neuropathy……………………………………………35

1.4 The Diabetic Foot………………………………………………………….36

1.4.1 Foot deformity and the intrinsic minus foot………………………37

1.4.2 Foot ulceration……………………………………………………39

1.4.3 Infection………………………………………………………….43

1.4.4 Lower Extremity Amputation…………………………………….44

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1.4.5 Charcot foot……………………………………………………………45

1.5 Assessment of the diabetic foot…………………………………………………..46

1.5.1 Neurological examination………………………………………………47

1.5.1.1 Pressure……………………………………………………….47

1.5.1.2 Vibration Perception Threshold……………………………….48

1.5.1.3 Deep tendon reflexes………………………………………….50

1.5.1.4 Pain and temperature………………………………………….51

1.5.1.5 Light touch and joint position…………………………………51

1.5.1.6 Other tests…………………………………………………….52

1.5.1.7 Evaluation of neuropathy……………………………………...52

1.5.2 Vascular examination……………………………………………………53

1.5.2.1 Palpation of peripheral pulses………………………………….53

1.5.2.2 Hand-held Doppler ultrasound………………………………...53

1.5.2.3 Ankle Brachial Index…………………………………………..54

1.5.2.4 Toe pressures and Toe Brachial Index………………………....55

1.5.2.5 Other…………………………………………………………..55

1.5.3 Dermatologic examination……………………………………………….56

1.5.4 Musculoskeletal examination…………………………………………….56

1.5.5 Footwear…………………………………………………………………..57

1.6 Assessing risk………………………………………………………………………57

1.7 Management of the diabetic foot…………………………………………………...58

1.8 The burden of diabetic foot complications…………………………………………59

1.9 Reducing the burden of diabetic foot complications………………………………..60

1.10 Predictors of foot ulceration………………………………………………………60

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1.11 Foot care education………………………………………………………………..64

1.12 Awareness of foot health in diabetes…………………………………....68

1.13 Summary………………………………………………………………..69

1.14 Research objectives……………………………………………………..71

Chapter 2: Methods and materials………………………………………...75

2.1 Fremantle Diabetes Study (FDS) study design overview……………………77

2.2 FDS approval and ethical considerations…………………………………77

2.3 FDS personnel…………………………………………………………..78

2.4 FDS patients…………………………………………………………….78

2.5 FDS survey methods…………………………………………………….78

2.5.1 Questionnaire…………………………………………………78

2.5.2 FDS clinical examination……………………………………...79

2.5.3 FDS laboratory tests……………………………………….......80

2.6 FDS annual assessment………………………………………………….81

2.7 Awareness of foot health………………………………………………..81

2.8 Diabetic foot care education…………………………………………….81

2.8.1 Baseline assessment……………………………………………82

2.8.2 Interventions………………………………………………….82

2.8.3 Follow-up assessment…………………………………………83

2.9 Epidemiology of foot ulceration………………………………………...83

2.9.1 Data linkage…………………………………………………...83

2.9.2 Hospitalisation for foot ulcer………………………………….83

Chapter 3: Self-awareness of foot health status in patients with type 2 diabetes: The

Fremantle Diabetes Study (Phase II)…………………………………....85

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3.1 Introduction………………….……….……………………..………………………87

3.2 Patients and Methods………………………………………………………………..88

3.3 Statistical analysis…………………………………………………………………….88

3.4 Results……………………………………………………………………………....88

3.4.1 Prevalence and associates of self-perceived abnormal foot health………….88

3.5 Discussion………………………………………………………………………..….95

Chapter 4: A comparison of two methods of foot care education: the Fremantle

Diabetes Study (Phase II)……………………………………………………………..99

4.1 Introduction………………………………………………………………………101

4.2 Patients and Methods…………………………………………………………….102

4.2.1 Interventions……………………………………………………………103

4.2.2 Follow-up assessment……………………………………………………103

4.3 Statistical analysis…………………………………………………………………103

4.4 Results……………………………………………………………………………..104

4.4.1 Intervention effects………………………………………………………105

4.5 Discussion…………………………………………………………………………111

Chapter 5: A longitudinal study of foot ulceration and its risk factors in community

based patients with type 2 diabetes: The Fremantle Diabetes Study……………115

5.1 Introduction……………………………………………………………………….117

5.2 Patients and Methods………………………………………………………………118

5.2.1 Data linkage………………………………………………………………119

5.2.2 Hospitalisation for foot ulcer…………………………………………….119

5.3 Statistical analysis………………………………………………………………….120

5.4 Results……………………………………………………………………………..120

5.5 Discussion…………………………………………………………………………124

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Chapter 6: Temporal changes in prevalence and associates of foot ulceration in type

2 diabetes: The Fremantle Diabetes Study...…………………………...129

6.1 Introduction…………………………………………………………...131

6.2 Patients and Methods…………………………………………………..132

6.3 Statistical analysis……………….……………………………………...133

6.4 Results…………………………………………………………………134

6.4.1 Patient characteristics………………………………………...134

6.4.2 Baseline foot ulcer prevalence and associates…………………136

6.5 Discussion……………………………………………………………...139

Chapter 7: Overview and recommendations for future research..............143

7.1 Overview…………………………………………………………….145

7.2 Recommendations for future research……………………………….147

7.2.1 Awareness of foot health…………………………………...147

7.2.2 Diabetic foot care education……………………………….148

7.2.3 Foot ulcer prevalence, incidence and predictors……………148

7.3 Conclusion…………………………………………………………..149

7.4 Concluding remarks………………………………………………....150

References……………………………………………………………..151

Appendices…………………………………………………………….173

Appendix A - FDS foot clinical assessment……………………………..175

Appendix B – Awareness questionnaire…………………………………179

Appendix C – Flow diagram…………………………………………….181

Appendix D – Foot score……………………………………………….183

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Appendix E – Modified Nottingham Assessment of Functional Footcare

(NAFFC)………………………………………………………………………………185

Appendix F – Attitudes survey………………………………………………………..187

Appendix G – “My feet and diabetes” foot care booklet………………………………189

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LIST OF FIGURES

Figure 1-1 The intrinsic minus foot ……………………………………………………39

Figure 1-2 Plantar foot ulcer……………………………………………………………40

Figure 1-3 Pathways to development of a diabetic foot ulcer ………………………….40

Figure 1-4 A Charcot foot……………………………………………………………..48

Figure 1-5 Monofilament assessment…………………………………………………..48

Figure 1-6 Biothesiometer assessment…………………………………………………49

Figure 1-7 Vibration sensation assessment using a tuning fork………………………...50

Figure 1-8 Testing the Achilles tendon reflex………………………………………….51

Figure 1-9 Palpation of the dorsalis pedis (DP) and posterior tibial (PT) pulses……….53

Figure 1-10 Performing the Ankle Brachial Index (ABI)………………………………54

Figure 1-11 Target areas to reduce the risk of diabetes related foot complications…….61

Figure 1-12 The diabetic foot paradigm….……………………………………………72

Figure 3-1 Pie graphs showing findings on standardised foot examination classified by self-

perceived foot health status…………………………………………………………….92

Figure 4-1 Responses to open-ended question regarding worries about diabetes foot

complications before education…………………………………………………….….110

Figure 4-2 Responses to open-ended question regarding worries about diabetes foot

complications after education……………………………………………………….…110

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LIST OF TABLES

Table 1-1 Prevalence and incidence of diabetic foot ulceration………………………....42

Table 1-2 Medical and foot history…………………………………………………….47

Table 1-3 ABI ratios and interpretation………………………………………………..55

Table 1-4 Diabetic foot risk stratification, indicators and recommendations for

review………………………………………………………………………………….58

Table 1-5 Summary of research of predictors of foot ulceration……………………….62

Table 3-1 Sociodemographic and diabetes related associates of self-perceived foot

status……………………………………………………………………………….…89

Table 3-2 Foot related associates of self-perceived foot status………………………...91

Table 3-3 Associates of foot complications in patients who believe their feet to be

normal………………………………………………………………………………..94

Table 4-1 Patient characteristics at trial entry by allocated intervention………………105

Table 4-2 Baseline, and absolute and percentage change in foot score and Nottingham

Assessment of Functional Foot Care (NAFFC) survey score by allocated

intervention……………………………………………………………………….…107

Table 4-3 Attitudes survey responses at baseline and at 3 months by intervention

group…………………………………………………………………………………109

Table 5-1 Baseline characteristics of FDS patients with type 2 diabetes by foot ulcer

status…………………………………………………………………………………121

Table 5-2 Significant independent associates of foot ulcer at study entry……………..122

Table 5-3 Baseline characteristics of FDS participants with type 2 diabetes by incident foot

ulcer status during follow up…………………………………………………………123

Table 5-4 Cox proportional hazards model of baseline predictors of time to first-ever

diabetes related foot ulceration during follow up……………………………………..124

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Table 6-1 Baseline characteristics of Fremantle Diabetes Study Phase 1 (FDSI) compared

with Fremantle Diabetes Study Phase 2 (FDSII) participants with type 2

diabetes……………………………………………………………………………….135

Table 6-2 Independent associates of foot ulcer at baseline in FDSI and FDSII……….136

Table 6-3 Baseline characteristics of pooled FDSI and FDSII participants with or without a

foot ulcer……………………………………………………………………………..138

Table 6-4 Independent associates of foot ulcer at baseline in pooled FDSI and FDSII

samples……………………………………………………………………………….139

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ACKNOWLEDGEMENTS

There are many people I would like to thank, who have been a crucial part of this journey.

To my supervisors - Winthrop Professor Tim Davis, Research Associate Professor Wendy

Davis and Associate Professor Laurie Foley - thank you for your guidance and support

throughout this process. This project would not have been possible without your ongoing

encouragement, advice and expertise.

To all the FDS and UWA staff – Kerry Somers, Chris Underwood, Violetta Cetrullo, Erin

Latkovic, Dr Kirsten Peters, Michelle England, Jocelyn Drinkwater, Dr Ashley Makepeace,

Brenda Riley and Caroline Martin – thank you for your assistance with data collection, as

well as your friendship and moral support.

To all the participants of the FDS – thank you for giving your time to the FDS, and for

being part of my research.

Thank you to Jenny Duff for presenting Footsmart, as well as Catherine Carland, Cassie

Gleadhill and Jamal Tatarinoff for your time and assistance with data collection.

To my colleagues on Level 6 – Dr Rina Fu, Kristine Fu, Dr Angela Chew, Dr Yoke Leng

Ng, Dr Desiree Ho – thank you for your incredible support and encouragement, and for

being so helpful with lots of the little things! Thanks also to Assistant Professor Jane

Allen, Dr Laurens Manning and Dr Brioni Moore for all your helpful comments and

suggestions.

I undertook a Postgraduate Teaching Internship at UWA in 2013, and I thank the

university and the Podiatric Medicine Unit for the opportunity to enhance my teaching

skills during my candidature.

To Professor Alan Bryant (Head of Podiatric Medicine) – thank you for your support, and

for the opportunity to present my work at the UWA Podiatric Medicine Conference

(2013/2014).

To all my friends and podiatry colleagues who have been there encouraging me along the

way, your moral support is very much appreciated. Thanks to Dr Loretta Scolaro and Dr

Ben Atcliffe for all your helpful advice, and for providing feedback on some of my work.

A special thank you goes to Jamal Tatarinoff for your unwavering support.

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Finally, I would like to thank my family. To my mum, Rae, and dad, Kenji, step-father Dr

Rob Docters van Leeuwen, my brothers Ramon and Anton, and my grandparents Manuel

and Jean Starke, I am so grateful for your tremendous love, support and encouragement

throughout this journey.

I dedicate this thesis to my late grandfather, Dr Manuel Starke OBE. Thank you for your

steadfast belief in me – this is for you.

Financial support

I would like to thank the following funding bodies and other organisations that supported

me throughout my candidature:

The FDS was funded by the Raine Foundation and an NHMRC grant. I would also

like to acknowledge the Western Australian Data Linkage (WADLS) system for

providing access to outcome data.

I was supported by an Australian Postgraduate Award, a UWA Top-Up

Scholarship, and a UWA Student Travel Award. I also thank the School of

Medicine and Pharmacology for assistance in covering the costs of conference

registration and posters.

A Research Travel Grant provided by the International Diabetes Federation, which

enabled me to present my work at the World Diabetes Congress in Melbourne in

2013.

Roche Diagnostics Pty Ltd (Australia) and SciGen Ltd (Australia), who provided

funding to cover refreshments for patients participating in the educational

intervention study.

Diabetes WA for permission to use the Footsmart program and providing

information booklets for the educational intervention study.

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AUTHOR CONTRIBUTIONS

This thesis is an account of the research that I, Mendel Baba, have undertaken during my

candidature at Fremantle Hospital, within the School of Medicine and Pharmacology, and

supported by the School of Surgery, at the University of Western Australia. Except as

otherwise indicated here and by due acknowledgement throughout this thesis, the work

described is my own.

Self-awareness of foot health status in patients with type 2 diabetes: The Fremantle

Diabetes Study Phase II (Chapter 3):

Author Percentage Contributions

Mendel Baba 55% Drafted the protocol

Developed questionnaire

Coordinated data collection

Assisted with statistical analysis

Prepared draft manuscript

Laurie Foley 5% Reviewed draft manuscript

Wendy Davis 20% Researched data

Performed all statistical analyses

Reviewed/edited the manuscript

Timothy Davis 20% Principal investigator of the FDS

Assisted with study design, development of

questionnaire, data analysis and interpretation

Prepared final version of manuscript

A comparison of two methods of foot care education: The Fremantle Diabetes

Study Phase II (Chapter 4):



Developed questionnaire



Prepared draft manuscript

Jenny Duff 10% Presented all interactive sessions

Assisted with development of study protocol

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Reviewed draft manuscript

Laurie Foley 5% Reviewed draft manuscript

Wendy Davis 15% Performed all statistical analyses



Assisted with study design, development of

questionnaire, data analysis and interpretation


A longitudinal study of foot ulceration and its risk factors in community-based

patients with type 2 diabetes: The Fremantle Diabetes Study (Chapter 5):





Assisted with drafting of the manuscript


Performed statistical analyses



Assisted with study design, data analysis and

interpretation


Temporal changes in prevalence and associates of foot ulceration in patients with

type 2 diabetes: The Fremantle Diabetes Study (Chapter 6):





Assisted with drafting of the manuscript


Performed statistical analyses


Paul Norman 10% Chief investigator of the FDS Phase II

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Reviewed manuscript


Assisted with study design, data analysis and

interpretation

Produced the final version of the manuscript

Candidate signature: Date:

Coordinating supervisor signature: Date:

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PUBLICATIONS

The following is a list of publications arising from this thesis.

Fully refereed journal articles:

M. Baba, L. Foley, W.A. Davis, T.M.E. Davis. “Self- awareness of foot health status

in patients with type 2 diabetes: The Fremantle Diabetes Study Phase II”. Diabetic

Medicine, 2014 July. DOI: 10.1111/dme.12521

M. Baba, J. Duff, L. Foley, W.A. Davis, T.M.E. Davis. “A comparison of two

methods of foot health education: The Fremantle Diabetes Study Phase II. Primary

Care Diabetes, 2014 June. DOI: 10.1016/j.pcd.2014.05.004

M. Baba, W.A. Davis, T.M.E. Davis. “A longitudinal study of foot ulceration and

its risk factors in community-based patients with type 2 diabetes: The Fremantle

Diabetes Study. Diabetes Research and Clinical Practice, 2014 July. DOI:

10.1016/j.diabres.2014.07.021

M. Baba, W.A. Davis, P. Norman, T.M.E. Davis. “Temporal changes in prevalence

and associates of foot ulceration in type 2 diabetes: The Fremantle Diabetes Study.

The Journal of Diabetes and Its Complications, 2015 January. In press.

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STRUCTURE OF THIS THESIS

Chapter 1 – Introduction

Chapter 1 provides a global view of diabetes and its complications. The diabetic foot is

described in more detail, and a brief overview of the assessment and management of the

diabetic foot is provided. A summary of the current available literature relating to the

prevalence, incidence and predictors of diabetic foot ulceration is presented, as well as the

status of research with regard to the effectiveness of foot care education, and awareness of

foot health in diabetes. The objectives of this research are also outlined.

Chapter 2 – Methods and Materials

A summary of the research tools and methods for Chapters 3, 4, 5 and 6 are provided.

This chapter also provides information relating to the FDS protocol, including recruitment

and assessment of patients, and collection and analysis of data.

Chapter 3 – Self-awareness of foot health status in patients with type 2 diabetes:

The Fremantle Diabetes Study (Phase II)

This chapter, presented as a paper, investigates awareness and perceptions of foot health,

in patients with type 2 diabetes. A short summary of the importance of foot health

awareness in diabetes is set out, followed by the results and discussion. This section

concludes with a discussion on the implications of the findings.

Chapter 4 - A comparison of two methods of foot care education: The Fremantle

Diabetes Study

This chapter, presented as a paper, details the findings of a comparative study of two

methods of diabetic foot care education, written and oral, provided to two groups of

patients with type 2 diabetes. The written information was provided in booklet form, while

the oral education was presented as a 90 minute interactive seminar. Although there are

many foot care education modalities, we compared these two methods, as they are widely

available through the community organisation Diabetes WA, and are currently accessible

throughout Australia. This section provides an introduction to the topic, followed by

results and discussion of the findings.

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Chapter 5 – A longitudinal study of foot ulceration and its risk factors in community

based patients with type 2 diabetes: The Fremantle Diabetes Study (Phase I)

In Chapter 5, presented as a paper, we investigate the prevalence, incidence and associates

of foot ulceration in 1,296 patients enrolled in Phase I of the FDS, recruited from 1993-

1996. We present data pertaining to hospitalisation for incident ulceration, and the

independent predictors of time to first-ever diabetes related foot ulcer, using a Cox

proportional hazards model.

Chapter 6 – Temporal changes in prevalence and associates of foot ulceration in

patients with type 2 diabetes: The Fremantle Diabetes Study

Chapter six, presented as a paper, describes temporal changes in prevalence and associates

of foot ulceration from data relating to Phase I (1993-1996) and Phase II (2008-2011) of

the FDS. This chapter presents the predictors of ulceration as they relate to the two phases

separately, followed by the pooled results, to give an overview of the most significant

factors predicting foot ulceration in the FDS cohort. This chapter concludes with a

discussion of the findings, and how they expand our understanding of foot ulcer

epidemiology and risk factors in type 2 diabetes.

Chapter 7 – Conclusions and recommendations for future research

The final chapter summarises the main findings. First, a large majority of patients who

considered their feet normal had abnormal features on inspection, and that most patients

with self-reported normal feet also had objective evidence of peripheral sensory

neuropathy, peripheral arterial disease and a combination of neuropathy and arteriopathy.

In addition, self-assessment of diabetes related foot problems was unreliable, and intensive

education and monitoring may be necessary in those who consider their feet normal but

who have neurovascular, structural and/or other precursors of serious foot pathology.

Secondly, a comparison of two types of foot care education demonstrated improved

outcomes for foot health using written information, but greater improvements in

participants‟ confidence in undertaking preventative measures was associated with

interactive education, suggesting that the most effective method of foot care education

should include both modalities. Finally, the investigation of foot ulceration in the Phase I

and II cohort of the FDS identified the significant predictors of ulceration, and showed

that the prevalence and major risk determinants of foot ulceration have not changed in

community based cohorts assessed 15 years apart. A discussion of future research that

could expand upon the findings is also presented.

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LIST OF ACRONYMS

ABI Ankle brachial index

AC Anglo-Celt

ADA American Diabetes Association

ADDQoL Audit of Diabetes Dependent Quality of Life

AIDS Acquired Immunodeficiency Syndrome

AIHW Australian Institute of Health and Welfare

ANS Autonomic nervous system

APodC Australasian Podiatry Council

ATSI Aboriginal and Torres Strait Islander

AusDiab Australian Diabetes, Obesity and Lifestyle Study

BMI Body mass index

BP Blood pressure

CAD Coronary Artery Disease

CDC Centres for Disease Control and Prevention

CHD Coronary heart disease

CI Confidence interval

CVD Cerebrovascular disease

DAN Diabetic autonomic neuropathy

DBP Diastolic blood pressure

DCCT Diabetes Control and Complications Trial

DFU Diabetic foot ulcer

DM Diabetes mellitus

DN Diabetic nephropathy

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DOB Date of birth

DP Dorsalis pedis (pulse)

DPN Diabetic peripheral neuropathy

DR Diabetic retinopathy

ECG Electrocardiogram

FDS Fremantle Diabetes Study

FDSI Fremantle Diabetes Study Phase I

FDSII Fremantle Diabetes Study Phase II

FPG Fasting plasma glucose

FH Fremantle Hospital

FHHS Fremantle Hospital and Health Service

GP General Practitioner

HAV Hallux Abducto Valgus

HbA1c Glycosylated haemoglobin

HREC Human Research Ethics Committee

IDDM Insulin dependent diabetes mellitus

HRQOL Health related quality of life

IC Intermittent claudication

IFG Impaired fasting glucose

IGT Impaired glucose tolerance

IHD Ischaemic heart disease

IQR Interquartile range

IWGDF International Working Group on the Diabetic Foot

LEA(s) Lower extremity amputation(s)

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LDL Low density lipoproteins

MI Myocardial infarction

MNSI Michigan Neuropathy Screening Instrument

MPJ Metatarsophalangeal joint

MPP Mean plantar pressure

MRI Magnetic resonance imaging

NAFFC Nottingham Assessment of Functional Footcare

NDS Neuropathy disability score

NIDDM Non-insulin dependent diabetes mellitus

NSAID Non-steroidal anti-inflammatory drugs

OGTT Oral glucose tolerance test

OHA Oral hypoglycaemic agent

OR Odds ratio

PAD Peripheral arterial disease

PPG Photoplethysmography

PT Posterior tibial (pulse)

PVD Peripheral vascular disease

QoL Quality of life

RCT Randomised controlled trial

SBP Systolic blood pressure

sd Standard deviation

SF-12 Short form-12

SMAHS South Metropolitan Area Health Service

SMBG Self-monitoring of blood glucose

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SSEPs Somatosensory evoked potentials

STJ Subtalar joint

SWM Semmes-Weinstein monofilament

TBI Toe Brachial Index

TcPO2 Transcutaneous oxygen tension

UK United Kingdom

UKPDS United Kingdom Prospective Diabetes Study

US United States

USA United States of America

VPT(s) Vibration perception threshold (s)

WA Western Australia

WHO World Health Organisation

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Chapter One

INTRODUCTION

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INTRODUCTION

Diabetes mellitus (DM) is a major health problem affecting an estimated 285 to 347 million

people worldwide (Danaei et al., 2011; Zhang et al., 2010), with numbers expected to

double by 2030 (World Health Organization & International Diabetes Federation, 2004).

On a global scale, more than 3 million deaths are attributable to diabetes each year and as

the world population continues to grow, developing nations in particular can expect a

significant rise in the number of people with diabetes (World Health Organization &

International Diabetes Federation, 2004). This places a heavy burden on individuals, the

community, and government agencies in the management of diabetes-related health

complications.

DM is defined by the World Health Organisation (WHO) as “a metabolic disorder of

multiple aetiology characterized by chronic hyperglycaemia with disturbances of

carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin

action, or both.” (Alberti & Zimmet, 1998, p.540). The two major types of DM are type 1

and type 2, formally known as Insulin Dependent Diabetes Mellitus (IDDM) and Non-

Insulin Dependent Diabetes Mellitus (NIDDM), respectively (Alberti & Zimmet, 1998).

Type 1 accounts for approximately 5-10% of cases (Association, 2011) and is primarily due

to pancreatic islet beta cell destruction, by an autoimmune process (Alberti & Zimmet,

1998). Type 2, the most common form of diabetes, results from insulin resistance, defects

in insulin secretion, or both (Alberti & Zimmet, 1998). Although the specific reasons for

its manifestation are unknown, genetic predisposition and environmental influences

(including obesity, sedentary lifestyles and poor diet) are thought to be contributing factors

(Hoogwerf, Sferra, & Donley, 2006). According to a 2009 report by the Australian

Institute of Health and Welfare (AIHW), risk factors for the development of type 2 DM

include being overweight or obese, physical inactivity, poor diet, tobacco smoking, high

serum cholesterol, impaired glucose regulation, and low birth weight (Australian Institute

of Health and Welfare, 2009). Other types of DM include gestational diabetes, genetic

defects of beta cell function, genetic defects in insulin action, diseases of the pancreas,

endocrinopathies, and drug or chemical induced diabetes (Alberti & Zimmet, 1998).

32

1.1 Prevalence of diabetes

From global prevalence estimates in 2004, it has been estimated that 4.4% of the world‟s

population will be affected by diabetes by 2030 (Wild, Roglic, Green, Sicree, & King, 2004).

According to 2010 estimates, the prevalence of diabetes among adults globally is expected

to increase from 6.4% in 2010, to 7.7% by 2030, with an annual growth rate of 2.2% and a

total predicted increase of 54% worldwide (Shaw, Sicree, & Zimmet, 2010). The greatest

proportional increases are expected in people over 65 years of age and those from

developing nations (Shaw et al., 2010). By 2025, it is expected that the prevalence of

diabetes in Australia will increase to 11.4% of the population, approximately an additional 1

million cases (Magliano et al., 2008).

1.2 Costs

Around 2-3% of the total health care budget in every country can be attributed to diabetes

(Jonsson, 1998). This can include direct care costs such as hospital admission, medical and

specialist services, transport and home care, while other less tangible costs include impact

on quality of life and lost productivity (Australian Institute for Health and Welfare, 2008).

According to the AIHW Disease Expenditure Database, the most recent estimate of

expenditure for diabetes in Australia was calculated to be almost AU$1 billion (2004-2005),

which included hospital and medical services, diabetes related pharmaceuticals and diabetes

research (Australian Institute for Health and Welfare, 2008). The costs of managing

diabetes related complications, such as renal disease, foot ulcers and amputations are an

additional and significant health care burden.

1.3 Diabetes complications

Over the long term, DM results in macrovascular and microvascular complications,

including damage, dysfunction and failure of various organs (Alberti & Zimmet, 1998).

1.3.1 Macrovascular complications

Major macrovascular complications of diabetes include coronary artery disease (CAD),

ischaemic heart disease (IHD), cerebrovascular disease, and peripheral vascular disease

(PVD) (Aronson & Johnstone, 2001; Lopes-Virella, 2001). Cardiovascular disease risk is

two- to four-fold higher in people with diabetes (Skyler et al., 2009) and CAD mortality

rates are up to three times higher than in non-diabetic individuals (Aronson & Johnstone,

2001). The United Kingdom Prospective Diabetes Study (UKPDS) found that

hyperglycaemia was linked to an increased risk of developing chronic complications

33

(Stratton et al., 2000) emphasising the need for good metabolic control. The UKPDS also

identified a relationship between tight blood pressure control and clinically important

reductions in both microvascular and macrovascular complications (UK Prospective

Diabetes Study Group, 1998) while optimal lipid management and lifestyle modifications

have also been identified as important for reducing diabetes complications (Januszewski,

Alderson, Metz, Thorpe, & Baynes, 2003; Klein et al., 2004; Sone et al., 2002; Turner et al.,

1998).

1.3.1.1 Peripheral Arterial Disease

PAD is a fibroproliferative disease characterised by calcification of the tunica intima and

media, and atherosclerotic occlusion of the vessels of the lower extremity (American

Diabetes Association, 2003; Dinh & Veves, 2005; Knox, Dutch, Blume, & Sumpio, 2000).

This results in decreased arterial perfusion, and flow-on effects such as intermittent

claudication, poor wound healing and in advanced stages, gangrene (American Diabetes

Association, 2003; Knox et al., 2000).

PAD has been associated with increasing age and diabetes duration, CAD, CVD,

hypertension, hyperlipidaemia, and smoking (Bembi et al., 2006; Criqui, 2001; M. D.

Muller, Reed, Leuenberger, & Sinoway, 2013; Norman, Davis, Bruce, & Davis, 2006). It is

difficult to accurately ascertain the prevalence and incidence of PAD as patients may be

asymptomatic or they do not report symptoms (American Diabetes Association, 2003).

There are also currently inconsistencies with regard to internationally agreed methods of

screening and assessment of PAD. A clinic based study of patients with diabetes reported

a prevalence of 33% in asymptomatic patients >60 years (Elhadd T, Robb R, Jung R,

Stonebridge P, & Belch J, 1999), while the incidence rate of PAD has been calculated at

13.9 per 1000 person years in diabetic patients (Wattanakit et al., 2005), compared to 9.0

per 1000 person-years in the non-diabetic population (Hooi et al., 2001).

PAD in diabetes also has a tendency to affect the distal segments of the lower limb

(American Diabetes Association, 2003; Haltmayer et al., 2001; He et al., 2014; van der Feen

et al., 2002). Compared to non-diabetic patients, atherosclerotic lesions appear to be more

prevalent in the distal or lower leg arteries (popliteal artery, anterior and posterior tibial

artery, peroneal artery, dorsalis pedis artery) in patients with diabetes (Jude, Oyibo,

Chalmers, & Boulton, 2001; van der Feen et al., 2002). Consequently, PAD in diabetes is

one of the major complications contributing to foot problems such as impaired wound

healing. Although it is currently unclear why the distal arterial segments are more often

affected in patients with diabetes, it is speculated that diabetes alters the process of arterial

34

remodelling leading to diffusely narrowed distal arteries, and these narrowed vessels lack

the mechanisms for compensatory enlargement of the vessel circumference (van der Feen

et al., 2002). In addition, the histology of large/proximal vessels differs from that of

small/distal vessels (Aboyans, Lacroix, & Criqui, 2007). For example, there is a greater

amount of elastic fibre in large vessels, while the media and adventitia in small vessels is

thinner, therefore the pathogenesis of atherosclerosis in the upper and lower arterial

segments is unique and manifests differently (Aboyans et al., 2007). Research suggests that

diabetic patients with PAD have a greater likelihood of worse angiographic findings

(occlusion of below knee arterial segments), more amputations and higher mortality than

non-diabetic patients with PAD (Jude et al., 2001). In fact, PAD is present in almost 50%

of patients with a foot ulcer (Prompers et al., 2007) and has been identified as an

independent predictor of both foot ulceration (Prompers, Schaper, et al., 2008) and LEA in

diabetes (W. A. Davis, Norman, Bruce, & Davis, 2006).

1.3.2 Microvascular complications

Microvascular complications of diabetes can affect the kidneys (nephropathy, renal failure),

eyes (retinopathy), and nervous system (sensory, autonomic, motor neuropathy).

1.3.2.1 Nephropathy

Diabetic nephropathy (DN) affects up to 40% of patients with Type 1 or 2 DM, and is the

leading cause of end stage renal disease worldwide (Marshall, 2004). Structural changes in

the kidneys such as glomerular basement membrane thickening and glomerulosclerosis,

induced by diabetes-related altered metabolic and haemodynamic pathways, result in

progressive proteinuria and reduced glomerular filtration rate (GFR) (Giunti, Barit, &

Cooper, 2006; Marshall, 2004). An Australian based cross-sectional study of more than

11,000 people identified that independent predictors of the presence of kidney damage

(proteinuria) include older age, presence of DM and hypertension (Chadban et al., 2003).

Furthermore, proteinuria and reduced GFR were found to be four and three times higher

respectively, in patients with DM compared to those without DM. Risk factors

representing both early and advanced kidney disease have been linked with foot

complications. For example microalbuminuria and dialysis treatment have both been

identified as independent risk factors for foot ulceration in type 2 diabetes (Guerrero-

Romero & Rodriguez-Moran, 1998; Ndip, Rutter, et al., 2010). Indeed, recent reports

suggest a „risk continuum‟, linking progressive renal impairment and increasing risk of

35

diabetic foot complications (Margolis, Hofstad, & Feldman, 2008; Ndip, Lavery, &

Boulton, 2010).

Screening for DN should begin at diagnosis of DM and occur annually (Gross et al., 2005).

Optimising metabolic control, utilisation of pharmacotherapy to control the renin-

angiotensin-aldosterone system, and treating comorbidities such as hypertension and

dyslipidaemia are recommended for preventing or delaying the development of proteinuria

(Chadban S et al., 2009; Giunti et al., 2006; Gross et al., 2005; Marshall, 2004).

1.3.2.2 Retinopathy

Diabetic retinopathy (DR) is the result of microvascular retinal changes, and is a major

cause of new cases of blindness in adults aged 20-74 (Fong et al., 2004). According to the

Australian Diabetes, Obesity and Lifestyle Study (AusDiab), more than 15% of people with

diabetes have retinopathy at diagnosis (Tapp, Shaw, Harper, et al., 2003).

1.3.2.2 Neuropathy

Neuropathy, otherwise known as diabetic peripheral neuropathy (DPN) is defined as “the

presence of symptoms and/or signs of peripheral nerve dysfunction in people with

diabetes after the exclusion of other causes” (A. J. Boulton, Gries, & Jervell, 1998; A. J.

Boulton, Vinik, et al., 2005; R. Malik, Tesfaye, & Ward, 2001). DPN is the most common

microvascular complication of diabetes (Perkins & Bril, 2002) affecting approximately a

third or more of patients, and increasing in prevalence with age and duration of diabetes

(R. Malik et al., 2001; Said, 1996; Young, Boulton, MacLeod, Williams, & Sonksen, 1993).

The pathogenesis of DPN is considered multifactorial but hyperglycaemia is believed to be

the major precipitating factor (Albers et al., 1995; Cameron, Eaton, Cotter, & Tesfaye,

2001; Johnson, Doll, & Cromey, 1986; Vinik, 1999). It is thought that hyperglycaemia

leads to oxidative stress and nerve conduction velocity abnormalities which may be

complicated by structural changes in nerve microvasculature (Cameron et al., 2001;

Johnson et al., 1986). As such, either absolute or relative vascular insufficiency exists in

diabetic patients due to thickening or occlusion of epineural and endoneural blood vessels,

as well as degenerative changes (Giannini & Dyck, 1994; Vinik, 1999). Multifocal

ischaemia may also be evident, due to large vessel complications (Johnson et al., 1986).

Other suggested factors include inflammation, autoimmune activity against motor and

sensory nerve structures and neuronal growth factor deficiency (Edwards, Vincent, Cheng,

& Feldman, 2008; Vinik, 1999).

36

According to the CDC, the age adjusted incidence rate (based on hospital discharge figures)

for diabetes related peripheral neuropathy was 6.8 per 1000 person-years in the US in 2007

(Centre for Disease Control and Prevention, 2013). In 2003, the health care costs of DPN

were estimated in the range of US$4.6-13.7 billion (including both Type 1 and 2), with

more than a quarter of the direct medical costs of diabetes management attributable to

DPN (Gordois, Scuffham, Shearer, Oglesby, & Tobian, 2003).

DPN can be divided into three components: sensory, motor and autonomic. Sensory

neuropathy refers to the development of acute painful symptoms in the extremities, while

motor neuropathy refers to abnormalities in muscle innervation leading to atypical muscle

sensory function (A.J. Boulton, 2005). Autonomic neuropathy (or Diabetic Autonomic

Neuropathy, DAN) refers to a disorder of the autonomic nervous system (ANS), and can

involve the entire ANS (Ewing, Burt, Williams, Campbell, & Clarke, 1976; Vinik, Maser,

Mitchell, & Freeman, 2003). Body systems commonly affected by autonomic neuropathy

include the cardiovascular, gastrointestinal, urogenital and thermoregulatory systems

(Clarke, Ewing, & Campbell, 1979; Vinik et al., 2003).

Patients often present with the symptoms of sensory and motor neuropathy together, and

this is known as chronic sensorimotor neuropathy. Its symptoms are most often

experienced in the feet or limbs (A. J. Boulton, Vinik, et al., 2005) but the hands can also

be affected, in a manner colloquially termed a “stocking and glove” distribution (R. Malik

et al., 2001). Patients may be asymptomatic, or experience a range of symptoms including

burning, aching, numbness, stabbing sensations, paraesthesia, and hyperaesthesia (A. J.

Boulton, Vinik, et al., 2005; Greene, Stevens, & Feldman, 1999) however, symptom

development is not directly proportionate to the severity of neurological damage (Britland,

Young, Sharma, & Clarke, 1990). Examination usually reveals sensory loss of vibration,

pressure, pain and temperature perception, while motor neuropathy results in depressed or

absent ankle reflexes, atrophy of both intrinsic and extrinsic musculature and muscle

weakness (A. J. Boulton, Vinik, et al., 2005; R. Malik et al., 2001; Reiber, Lipsky, &

Gibbons, 1998).

1.4 THE DIABETIC FOOT

The “diabetic foot” is a broad term used to cover a range of heterogeneous conditions

affecting the foot in diabetes. It is defined by the International Consensus on the Diabetic

Foot as “infection, ulceration and/or destruction of deep tissues associated with

37

neurological abnormalities and various degrees of peripheral vascular disease in the lower

limb” (International Working Group on the Diabetic Foot, 2014). The major diabetes

related complications contributing to foot disorders are DPN and PAD, and this interplay

of vascular and neurological impairment can result in damage to many components of the

lower extremity, including the skin, subcutaneous tissue, muscles, bones, and joints (Leung,

2007) giving rise to foot ulceration, infection and LEA.

1.4.1 Foot deformity and the intrinsic minus foot

Motor neuropathy has direct implications for the structure and dynamic movement of the

foot. Muscular atrophy of both the long flexors and extensors of the leg, as well as the

intrinsic muscles of the foot such as the interossei and lumbricals, characterise diabetes

related motor neuropathy in the lower limb. Andersen and colleagues found that,

compared to non-neuropathic diabetic patients, there was a 41% reduction in the strength

of the ankle dorsal and plantar flexors in neuropathic patients, and a 32% reduction in

muscle volume (Andersen, Gadeberg, Brock, & Jakobsen, 1997). These findings were

supported by Bus and colleagues, who identified up to 73% atrophy of the distal foot

musculature in diabetic patients with neuropathy, suggesting a profound loss of muscle and

motor function (Bus et al., 2002). This loss of muscle strength and volume underpins

other structural deformities of the foot, such as clawing of digits, prominent metatarsal

heads, anterior displacement of plantar fat pads and a high arch, and is often referred to as

an “intrinsic minus foot” (Figure 1-1) (Bernstein, 2003; Knox et al., 2000; Lippmann H,

Perotto A, & Farrar R, 1976). These changes may occur in addition to alterations or

limitations of joint range of motion via thickening of periarticular structures, considered to

be a consequence of diabetes related collagen abnormalities (Delbridge et al., 1988; Dinh &

Veves, 2005; Fernando, Masson, Veves, & Boulton, 1991; Goh & Cooper, 2008; Zimny,

Schatz, & Pfohl, 2004).

It is hypothesised that these combined effects, weakness of the intrinsic foot muscles,

imbalances between flexor and extensor tendons and limited joint mobility, results in a

permanently altered and rigid foot shape, increasing the risk of foot ulceration (Delbridge

et al., 1988; Fernando et al., 1991; Laing, 1998; Lippmann H et al., 1976; van Schie,

Vermigli, Carrington, & Boulton, 2004; Zimny et al., 2004). In addition, a range of

functional deficits are seen in gait, including loss of stability (Knox et al., 2000), poor

proprioceptive acuity (Courtemanche et al., 1996; Van den Bosch, Gilsing, Lee,

Richardson, & Ashton-Miller, 1995) and impaired balance (Resnick et al., 2002), which

increase the risk of falls (Tinetti, Speechley, & Ginter, 1988). The loss of intrinsic muscle

38

strength and/or unopposed functioning of the dorsal extrinsic muscles was thought to

initiate contracture of the digits (Knox et al., 2000; Reiber et al., 1998), however research

suggests that intrinsic muscle atrophy is not a primary cause of toe deformity in

neuropathic patients (Bus et al., 2002). Retracted digits can however, contribute to the

anterior displacement of the fibro-fatty padding across the forefoot, increasing pressure

over the metatarsal heads (Laing, 1998; Lippmann H et al., 1976). This is in addition to

atrophy of plantar fat pads at the heel and metatarsal heads that normally function to

absorb shock and cushion underlying bone and joints (Gooding et al., 1986). These

changes increase the risk of foot ulceration via abnormal pressure points, increased

shearing of the skin, and development of hyperkeratosis (Knox et al., 2000). Abouaesha et

al reported a strong inverse relationship between plantar tissue thickness and foot pressures

in diabetic patients (Abouaesha, van Schie, Griffths, Young, & Boulton, 2001). Thus, in

combination with sensory deprivation, motor neuropathy contributes to a foot vulnerable

to the effects of deformity, poor functional capacity, mechanical instability and elevated

pressures (Knox et al., 2000; Lippmann H et al., 1976).

The clinical manifestations of diabetic peripheral neuropathy such as sudomotor

dysfunction and impaired neurovascular function directly affect the functioning of the

lower limb and foot (R. Malik et al., 2001; Said, 1996; Vinik et al., 2003). For example,

DAN can lead to alterations in microvascular blood flow to the skin, inability of arterioles

to respond to variable temperature stimuli, atrophy of sweat glands leading to diminished

or absent sweating, loss of skin integrity, and anhydrosis (Clarke et al., 1979; Knox et al.,

2000; Reiber et al., 1998). In the context of diabetes related foot complications, anhydrosis

and skin fissuring render the foot vulnerable to infection, while impaired vascular

responses might predispose to skin ischaemia (Deanfield, Daggett, & Harrison, 1980),

increasing the risk of foot ulceration. In fact, Deanfield and colleagues found that diabetic

patients with foot ulcers had a greater degree of abnormality of autonomic function

compared to those without foot ulceration, highlighting the significant role of peripheral

neuropathy in the development of foot pathology (Deanfield et al., 1980).

39

Figure 1-1. The intrinsic minus foot. (Frykberg, Bevilacqua, & Habershaw, 2010)

1.4.2 Foot Ulceration

Foot ulcers are a significant complication of diabetes due to the heavy personal and

financial burden associated with their management. The lifetime risk of developing a

diabetes related foot ulcer is estimated to be as high as 25% (Singh, Armstrong, & Lipsky,

2005). Foot ulcers typically arise as the sequelae of neuropathy, pressure and trauma,

causing an erosion of cutaneous tissue that extends from the epithelium through to deeper

tissues (Figure 1-2) (Reiber et al., 1998; Reiber et al., 1999). They can be ischaemic,

neuropathic or jointly neuro-ischaemic in origin. Neuropathic or neuro-ischaemic ulcers

result due to a lack of perception of excessive pressure or trauma, which often leads to the

development of ulcers over bony prominences in the foot (Laing, 1998), while tissue

ischaemia due to PAD results in ulcers occurring at any affected part of the foot. Foot

deformities associated with the intrinsic minus foot, such as prominent metatarsal heads

and atrophy of the plantar fat pad, are associated with elevated pressures and an increased

risk of ulcer occurrence in patients with diabetes, particularly in those with neuropathy

(Bus, Maas, de Lange, Michels, & Levi, 2005; Ledoux et al., 2005). As a consequence of

this foot deformity, research suggests that almost 78% of ulcers are found at the forefoot,

followed by almost 12% at the midfoot and approximately 10% at the hindfoot (Oyibo et

al., 2001). Foot ulceration as a complication of diabetes is known to be an independent

predictor of LEA (W. A. Davis et al., 2006) and the prognosis for patients with foot

ulceration is poor. More than 50% of diabetic patients who develop a foot ulcer will

develop another ulcer within 2 years (J. Apelqvist, Larsson, & Agardh, 1993) and mortality

40

rates are higher among ulcerated compared to non-ulcerated patients (Boyko, Ahroni,

Smith, & Davignon, 1996; Pham et al., 2000; Ramsey et al., 1999). A flowchart of the

pathological processes leading to foot ulceration is presented in Figure 1-3.

Figure 1-2. A plantar foot ulcer at the first metatarsal head, displaying hyperkeratosis at the

ulcer margins and a moist granulating base (Laborde M, 2014).

Figure 1-3. Pathways to the development of a diabetic foot ulcer. (Milwaukee Advanced

Foot and Ankle Clinic)

41

Available data from largely primary care studies suggest that the point prevalence of an

active ulcer is up to 1.8% (de Sonnaville, Colly, Wijkel, & Heine, 1997; Kumar et al., 1994).

The annual incidence ranges from 1.0% to 4.1% (Singh et al., 2005), with an average of

approximately 2% (C. A. Abbott et al., 2002; Crawford et al., 2011; I. S. Muller et al., 2002;

Ramsey et al., 1999). Such estimates can, however, be influenced by how foot ulcers are

defined and ascertained, by racial/ethnic differences in propensity to foot ulceration (C.A.

Abbott et al., 2005; Lavery, Armstrong, Wunderlich, Tredwell, & Boulton, 2003) and

between-sample differences in the management of diabetes and associated foot disease that

are strongly influenced by socio-economic and behavioural factors (Margolis & Jeffcoate,

2013). The average annual incidence of foot ulceration varies considerably, and has been

reported to range from 1.9% in a community based prospective study in the UK, to 6.8%

in a clinic based study of patients with abnormally high plantar pressures (C. A. Abbott et

al., 2002; C. A. Abbott, Vileikyte, Williamson, Carrington, & Boulton, 1998; Crawford et

al., 2011; Ramsey et al., 1999; Veves, Murray, Young, & Boulton, 1992). As such, this

broad incidence range reflects differing methods of sampling, recruitment and varying

levels of risk of ulceration. Therefore, available data from community based prospective

and retrospective studies suggest an average annual incidence around 2% (C. A. Abbott et

al., 2002; Crawford et al., 2011; Ramsey et al., 1999) while clinic based studies are generally

higher (C. A. Abbott et al., 1998; Veves et al., 1992) (see Table 1-1). Some data are now

more than twenty years old, and highlights the need for contemporary prospective

observational studies investigating the prevalence and incidence of foot ulceration.

The costs of managing a foot ulcer are significant due to the need for expensive dressings

and consumable items, and approximately 1 in 4 patients with a lower extremity ulcer will

require inpatient care (Harrington, Zagari, Corea, & Klitenic, 2000). Data from a US based

study conducted between 2000 and 2001 suggested that the total inpatient costs of lower

extremity ulcer were US$13,179 per episode, with costs ranging from US$1892 to

US$27,721, depending on severity (Stockl, Vanderplas, Tafesse, & Chang, 2004). In

addition, mean length of hospital stay associated with ulceration was 87.3±82.8 days (Stockl

et al., 2004). Non-healing chronic ulcers are associated with a significantly increased cost

of care (Harrington et al., 2000).

42

Table 1-1 Prevalence and incidence of diabetic foot ulceration.

Author Year Evidence level†

Summary Prevalence of foot ulceration

Incidence of foot ulceration

Critique/comment

Abbott et al UK

2002 II Community based prospective cohort study N=9710 (6613 patients screened at baseline and completed 2 year follow up questionnaire)

2.2% annual average

-Mixed type 1 and 2 -Screening conducted 1994-1996, data now 20 years old -70% response rate at follow up (2300 lost to follow up)

Crawford et al UK

2011 II Community based prospective cohort study -Mean follow up 11.43 months (±1.8) N=1192

1.93% annual average

-Patients who developed a foot ulcer identified from podiatry records -Lack of data relating to non-participants (n=78) -Only 1 year follow up -103 lost to follow up

Boyko et al USA

1999 II Prospective cohort study Mean follow up 3.7 years N=749 (1483 limbs)

3.0 per 100 person-years

-Based in a Veterans Affairs clinic (mean age 63 years) -98% male -Mixed type 1 and 2

Abbott et al UK

1998 II Multi-centre clinic based prospective cohort study of patients with neuropathy N=1035 subjects from 44 centres in the UK, US and Canada

7.2% annual average

-Clinic based -Mixed type 1 and 2, plus overrepresentation of type 1 patients (24.6%) -20% (n=206) lost to follow up -Subjects had neuropathy, increasing the risk of ulceration

Pham et al USA

2000 II Multi-centre clinic based prospective cohort study N=248 Followed for mean period of 30 months

7.6% annual average

-Clinic based -Higher risk population -Mixed type 1 and 2

Muller et al Netherlands

2002 II Multi-centre clinic based prospective cohort study (Only type 2s) N=511, increasing to 665 over 6 years

2.1% annual average (1.2 - 3.0%)

-Primary health care setting (10 GP clinics)

Veves et al UK

1992 II Clinic based prospective cohort study N=86 14 non-diabetic controls Followed for a mean 30 months

*6.8% annual average

-Clinic based -Small sample size -Mixed type 1 and 2 -71% male

43

Ramsey et al USA

1999 III Retrospective cohort study of patients in a large health maintenance organisation N=8905

1.93% annual average (5.8% over 3 years)

-Clinic based -Mixed type 1 and 2 -Foot ulcers identified though automated claims data

Kumar et al UK

1994 IV Community based cross-sectional study of type 2 patients in 37 GP practices in the UK N=811

1.4% prevalent ulceration 5.3% current or past ulcers

-Cross sectional -Primary health care setting

de Sonnaville et al

Netherlands

1997 IV Community based cross-sectional study of type 2 patients in 22 GP practices in the Netherlands N=609

1.8% prevalent ulceration

-Cross sectional -Primary health care setting

*Average annual incidence calculated from figures provided in paper (17% / 2.5 years (=30 months) = 6.8%

per year)

†(NHMRC, 2009)

1.4.3 Infection

Infection in a diabetic foot is a major cause of hospitalisation. It is considered a limb

threatening condition, preceding minor amputation in up to 60% of cases and major

amputation in up to 40% of cases (International Working Group on the Diabetic Foot,

2014). The major predisposing factor for foot infection in diabetes is a foot ulcer, which

exposes tissues to colonisation due to loss of the protective dermal tissue (Lipsky et al.,

2006). Staphylococcus aureus and other aerobic gram positive cocci are the predominant

infective organism in uncomplicated foot ulcer infections (non-limb threatening) (Dang,

Prasad, Boulton, & Jude, 2003; Gerding, 1995; Lipsky et al., 2006). Polymicrobial

infections are often found in complicated (limb/life threatening) or chronic wounds, with

an increasing prevalence of anaerobic bacteria in more severe infections (Gerding, 1995).

Antibiotic treatment is only recommended for clinically infected wounds (Lipsky et al.,

2012). Osteomyelitis is a potential complication of a deep wound, and increases the

likelihood of surgical intervention and longer duration of antibiotic therapy (Lipsky, 1997;

Lipsky et al., 2006). Bone biopsies are indicated to confirm a diagnosis of osteomyelitis

(Lavery, Peters, Armstrong, & Lipsky, 2007) however imaging may also be employed, such

as plain radiography, magnetic resonance imaging (MRI) or Technetium-99m methylene

diphosphonate bone scanning (Bader, 2008; Lipsky et al., 2012).

44

1.4.4 Lower Extremity Amputation (LEA)

LEA is a devastating and costly consequence of diabetes, significantly impacting on

mobility and quality of life. LEAs are approximately 15 times more common in diabetic

patients compared to individuals without diabetes (Bild et al., 1989; Most & Sinnock, 1983;

The Global Lower Extremity Amputation Study Group, 2000). Patients requiring LEA are

at increased risk of death from cardiovascular disease (Faglia, Favales, & Morabito, 2001).

Diabetes-related LEAs usually occur as a consequence of neuropathy and PAD, but other

risk factors for diabetes-related LEA include macro and micro-circulatory changes,

presence of a foot ulcer, previous amputation, poor glycaemic control, DPN, infection,

type and duration of diabetes and older age (Bild et al., 1989; W. A. Davis et al., 2006;

Reiber, Pecoraro, & Koepsell, 1992). Research suggests that men have a higher risk of

LEA than women (Lazzarini, O'Rourke, Russell, Clark, & Kuys, 2012; Moss, Klein, &

Klein, 1999; van Houtum, Lavery, & Harkless, 1996), and there is conflicting evidence for

the impact of ethnicity on LEA risk (Lavery et al., 1996; Lavery, van Houtum, Ashry,

Armstrong, & Pugh, 1999; Leggetter, Chaturvedi, Fuller, & Edmonds, 2002).

Aside from the physical implications of a minor or major amputation of the lower limb,

LEAs contribute significantly to inpatient health care costs. In 2000, the median inpatient

costs of LEA per admission in an Australian hospital setting were calculated to be

A$12,485 (A$6037-A$24,415), with an associated hospital stay of 24 days (10-43 days), not

including ongoing medical management required post-amputation (W. A. Davis et al.,

2006).

There is wide variation in the reported incidence of first LEA which may be due to

differences in study design (prospective vs retrospective), sample characteristics, and the

impact of improved surgical planning and practice over time (Rayman, Krishnan, Baker,

Wareham, & Rayman, 2004). Incidence rates reported in the UK range from 5.1 to 176 per

100,000 population (Moxey et al., 2011), while rates in the US are reportedly 38 per 100,000

population (Moxey et al., 2011). According to the US-based Centres for Disease Control

and Prevention (CDC), age-adjusted hospital discharge rates for lower extremity

amputation were 3.3 per 1000 person-years (Centre for Disease Control and Prevention,

2013). In Australia, a LEA incidence rate of 3.8 per 1000 person-years was identified in a

community based cohort of type 2 diabetic patients (W. A. Davis et al., 2006) a figure

comparable to the CDC figures. Other Australian based research investigating LEA

incidence using a National Hospital Morbidity Database from 2000 to 2010 found that

there was a marked decline in major above ankle amputations (trans-tibial, trans-femoral)

45

and a shift towards greater numbers of partial foot amputations, or below ankle

amputations (Dillon, Kohler, & Peeva, 2014). However the overall age-standardised

incidence of LEA procedures remained unchanged over the 10 year period, at 37.41±1.01

per 100,000 head of population per annum (Dillon et al., 2014).

1.4.5 Charcot foot

A rare consequence of neurological impairment is the development of neuropathic

osteoarthropathy of the foot, also known as a Charcot foot, named after French physician

Jean-Martin Charcot (Hartemann-Heurtier, Van, & Grimaldi, 2002; L. J. Sanders, 2004). It

is considered a rare foot complication, estimated to affect less than 1% of the diabetic

population (Fabrin, Larsen, & Holstein, 2000; Sinha, Munichoodappa, & Kozak, 1972) but

it is more common in patients with severe distal symmetrical neuropathy (Cofield,

Morrison, & Beabout, 1983; Frykberg & Belczyk, 2008) and a diabetes duration of at least

10 years (Hartemann-Heurtier et al., 2002; W. Jeffcoate, Lima, & Nobrega, 2000). It is

defined as a condition affecting the bones, joints and soft tissues of the foot and ankle,

characterised by inflammation in the earliest phase, leading to varying degrees of

destruction, subluxation, dislocation and deformity (Rogers et al., 2011).

Anatomical classifications of Charcot foot vary, and multiple classification systems have

been developed over time. For example, Sanders and Frykberg (Sanders L & Frykberg R,

1991) divide the foot into five patterns of destruction; Pattern I – Forefoot; Pattern II –

Tarsometatarsal joints; Pattern III – Naviculocuneiform, Talonavicular and

Calcaneocuboid; Pattern IV – Ankle and subtalar joint; Pattern V – Calcaneus. Any of

these anatomical aspects may be involved in a presentation of Charcot foot but

involvement of the midfoot and subtalar/ankle joint regions are considered to be the most

functionally disabling (Wukich & Sung, 2009).

In the acute phase, patients present with a red, hot, swollen foot, which may be painful

(Hartemann-Heurtier et al., 2002; W. Jeffcoate et al., 2000; Shaw J & Boulton A, 1995;

Wukich & Sung, 2009). These changes may occur insidiously, spontaneously or following

minor trauma (W. Jeffcoate et al., 2000). Diagnosis of Charcot foot can be delayed at this

stage because signs and symptoms can resemble traumatic fracture, gout, local infection or

osteomyelitis (Baker IDI Heart and Diabetes Institute, 2011; W. Jeffcoate et al., 2000;

Sommer & Lee, 2001). On examination, there may be bounding pedal pulses, and a

temperature difference of a few degrees between an affected and unaffected foot (Baker

46

IDI Heart and Diabetes Institute, 2011; Hartemann-Heurtier et al., 2002; Rogers et al.,

2011). The exact causes of Charcot foot are unknown, and there are many proposed

pathways to its development. Neuropathy of any origin is considered the key aetiological

factor (Rogers et al., 2011; Sommer & Lee, 2001) and the syndrome may be observed in

other neuropathy-inducing conditions. Trauma and metabolic abnormalities of bone, or a

combination of these factors, are considered part of the pathological process (Rogers et al.,

2011). Over time, the integrity of the medial longitudinal arch is lost, leading to midfoot

collapse and a “rocker-bottom foot” (Figure 1-4), the hallmark deformity associated with

the condition (Rogers et al., 2011). A Charcot foot is therefore a major impediment to

normal ambulation, and can lead to plantar midfoot neuropathic ulceration from continued

weight bearing (W. Jeffcoate et al., 2000; W. J. Jeffcoate, 2005). In the chronic state there is

increased bone formation, osteosclerosis, arthrodesis and ankylosis, resulting in significant

foot deformity (W. Jeffcoate et al., 2000).

Figure 1-4. A Charcot foot, showing midfoot collapse and resulting “rockerbottom” foot

(Rogers et al., 2011).

1.5 Assessment of the diabetic foot

Assessment of the diabetic patient begins with a thorough medical and foot history (Table

1-2). Thereafter, the presence and severity of complications such as DPN and PAD are

assessed using a number of clinical tests.

47

Table 1-2. Components of the medical and foot history.

Medical history Foot inspection Wound/ulcer history

-diabetes duration -glycaemic control -cardiovascular, renal and ophthalmic assessment -nutritional status -alcohol, tobacco use -current medications -allergies -previous hospitalisations -past history diabetic foot complications -symptoms of neuropathy -symptoms of PAD - claudication, rest pain -work, social activities

-footwear -orthotic inserts -callous formation -foot deformities -previous foot infections and/or surgery -pedal pulses -neurological assessment

-location -duration -recurrence -infection -hospitalisation -wound care and response -patient compliance -offloading -interference with wound care -previous foot trauma and/or surgery -oedema -Charcot foot and related treatment

Adapted from (Frykberg et al., 2006) and (A. J. Boulton et al., 2008).

1.5.1 Neurological examination

1.5.1.1 Pressure

The 5.07/10 gram (g) nylon Semmes Weinstein Monofilament (SWM) is widely used as a

tool to assess pressure perception. A force is applied via the filament perpendicular to the

foot over prominent joints, and the patient reports whether they can feel this (Figure 1-5).

An inability to feel the application of the SWM, which is designed to buckle at 10 grams of

force, is considered a loss of large fibre nerve function (A. J. Boulton et al., 2008). There is

still wide variation in the ideal number of applications and sites tested using the SWM

(Mayfield & Sugarman, 2000). A recent systematic review suggested the highest SWM

sensitivity (≥90%) is found when testing the plantar hallux and 3rd and 5th plantar

metatarsal heads (Feng, Schlosser, & Sumpio, 2009; S. Lee et al., 2003). Other sites can

also be incorporated including the dorsal and plantar midfoot, and plantar heel. False-

positive responses may occur in patients presenting with pedal oedema or significant

plantar hyperkeratosis (Mayfield & Sugarman, 2000). If there is established neuropathy of

the foot, the assessment sites can be extended proximally to incorporate the anterior ankle

and leg in order to determine the extent of the neuropathy. The 10g SWM has been

demonstrated to be reliable for assessment of DPN, and it is a simple to use and relatively

inexpensive tool (Kumar et al., 1991).

48

Figure 1-5. Performing the monofilament assessment (The University of Sydney & The

Diabetes Centre Royal Prince Alfred Hospital).

1.5.1.2 Vibration Perception Threshold (VPT)

A biothesiometer is a useful, non-invasive method of assessing vibratory perception

thresholds in patients with diabetes. A biothesiometer is an electronic tool used to measure

vibration threshold, using increasing amplitude of vibrations between 0 and 50 volts. The

device is applied to the foot over a bony prominence and vibrations are set initially at low

amplitude (Figure 1-6). Mechanoreceptors in the skin respond to this oscillation,

developing action potentials that are transmitted through afferent nerve fibres to the spinal

cord (Ford, 2011a). The patient will then report whether they can feel the vibration,

depending on the level of impairment of nerve conduction velocity. Vibration amplitude

can be manually increased by the clinician until the patient reports feeling the sensation.

Less than or equal to 20-25V is considered to be in a normal range, while 25V or greater is

strongly associated with the risk of foot ulceration in diabetes (Young, Breddy, Veves, &

Boulton, 1994).

49

Figure 1-6. Performing the biothesiometer assessment.

A 128Hz tuning fork may be used as a substitute if a biothesiometer is not available. A

graduated tuning fork offers a simple quantitative assessment of vibration sensation, by

providing a scale of vibration intensity from 0 to 8 (Thivolet, el Farkh, Petiot, Simonet, &

Tourniaire, 1990). A value of ≤4 out of 8 is regarded as a threshold value for increased risk

of ulceration (Liniger, Albeanu, Bloise, & Assal, 1990). The tuning fork is tapped to start

the vibration, and then applied perpendicular to the patient‟s foot over a bony prominence

(Figure1-7) (J. Apelqvist, Bakker, van Houtum, Nabuurs-Franssen, & Schaper, 2000). In

comparison to a biothesiometer, a graduated tuning fork has been demonstrated to have a

very high positive predictive value for diagnosis of peripheral neuropathy, and is

considered to be a reliable and useful tool to quantify vibration sensations (Kastenbauer,

Sauseng, Brath, Abrahamian, & Irsigler, 2004).

50

Figure 1-7. Assessing vibration sensation using a tuning fork (The University of

Manchester).

1.5.1.3 Deep tendon reflexes

The ankle (Achilles) reflex is assessed by placing the ankle joint in a neutral position and

tapping the Achilles tendon proximal to the calcaneal insertion with a reflex hammer

(Figure 1-8). If there is no response, the patient can be asked to perform the Jendrassik

Manoeuvre, which is thought to enhance the reflex action (Gregory, Wood, & Proske,

2001). The Jendrassik Manoeuvre is performed by attempting to pull clenched hands apart

while tapping the tendon with the reflex hammer (Gregory et al., 2001). An absent or

abnormal Achilles reflex response, indicating sensory nerve damage (Bromberg, 2010), has

been identified as an independent predictor of foot ulceration (C. A. Abbott et al., 2002;

McNeely et al., 1995).

51

Figure 1-8. Testing the Achilles tendon reflex.

1.5.1.4 Pain and temperature

Small fibre neuropathy is evaluated through assessment of pain and temperature

perception. Pain sensation is commonly assessed using a pinprick test. Using enough

pressure to deform, but not pierce the skin, the patient is asked to distinguish between a

sharp and blunt touch using a sterile pin (Baker IDI Heart and Diabetes Institute, 2011; A.

J. Boulton et al., 2008). There are various tools available to assess temperature when

screening for DPN, ranging from warm and cool rods (C. A. Abbott et al., 2002) to

computer-driven thermodes (Chong P & Cros D, no date). Choice of assessment tool may

depend on cost and availability.

1.5.1.5 Light touch and joint position

In addition to vibration sensation, light touch and joint position assess neuropathy of large

myelinated fibres (LaFontaine, 2005). Light touch is usually assessed over the same sites as

the pinprick test, using a cotton wool ball or the index finger (Cornblath, 2004). Position

sense is assessed by grasping the hallux between the thumb and first finger on the medial

and lateral aspects and slowly moving the hallux to either a dorsiflexed or plantarflexed

position (Gilman, 2002). With the eyes closed, the patient is asked to indicate the position

of the toe, and if position sense appears to be impaired, joints proximal to the hallux, such

as the ankle, can also be assessed (Gilman, 2002).

52

1.5.1.6 Other tests

Additional neurological tests can also be incorporated such as the Babinski test and

Romberg test (Frykberg et al., 2006), as well as the heel-shin test and the heel-toe (tandem

walking) test. Patients with abnormal or impaired position sense may demonstrate a

positive Romberg test (Gilman, 2002). Referral for nerve conduction studies is rarely

required to diagnose DPN (Frykberg et al., 2006).

1.5.1.7 Evaluation of neuropathy

A number of composite scoring systems have been developed for screening and evaluation

of the severity of neuropathy in diabetes (Cornblath, 2004). According to Australian

diabetic foot care guidelines, a modified version of the Neuropathy Disability Score (NDS)

(Dyck, 1988; Dyck, Karnes, Daube, O'Brien, & Service, 1985) is recommended for the

evaluation of neuropathy disability (Baker IDI Heart and Diabetes Institute, 2011). The

NDS comprises the assessment of VPT, temperature perception and pin-prick (pain)

sensation as normal (0 points) or abnormal (1 point per assessment), while the Achilles

tendon reflex is assessed as present (0 points), present with reinforcement (1 point) or

absent (2 points). A NDS score is calculated per foot (maximum of 5 per foot) and added

together, for a total score out of 10 (both feet). Normal responses would result in a score

of 0 out of 10. Guidelines developed by The International Working Group on the

Diabetic Foot also advocate for use of these screening tools for assessment of sensory

neuropathy, including the Semmes-Weinstein monofilament for pressure perception, the

128Hz tuning fork for vibration sensation, a sterile pin to assess pin-point discrimination,

cotton wool to check tactile sensation and the Achilles tendon reflex to assess reflexes (J.

Apelqvist et al., 2000).

The Michigan Neuropathy Screening Instrument (MNSI) is another widely used

neurological assessment tool, which encompasses a 15-item questionnaire and clinical

assessment. The questionnaire component requires patients to answer “yes” or “no” to

questions relating to foot sensation (symptoms of pain, numbness and sensitivity to

temperature), while the clinical component includes foot inspection for deformities, dry

skin, callous, infection or ulceration, as well as assessment of vibration sensation at the

hallux and grading of the ankle reflexes (Feldman et al., 1994). The MNSI has been

validated and is considered an accurate screening tool for the assessment of neuropathy in

patients with diabetes (Moghtaderi, Bakhshipour, & Rashidi, 2006).

53

1.5.2 Vascular examination

1.5.2.1 Palpation of peripheral pulses

Palpation of dorsalis pedis (DP), posterior tibial (PT) (Figure 1-9), popliteal and femoral

pulses is a useful clinical tool to assess the presence of PAD (American Diabetes

Association, 2003; Christensen, Freundlich, Jacobsen, & Falstie-Jensen, 1989; Khan,

Rahim, Anand, Simel, & Panju, 2006; McGee & Boyko, 1998). Auscultation of bruits,

indicating turbulent blood flow and occlusion of the vessel, is also considered a useful

assessment tool, and the presence of at least one bruit (iliac, femoral, popliteal) increases

the likelihood of PAD (Khan et al., 2006). Reliability of the assessment is improved with

clinical experience (Meade, Gardner, Cannon, & Richardson, 1968) although a small

proportion of patients will not have a DP or PT pulse due to normal anatomical variation

(American Diabetes Association, 2003). Pulses are recorded as present or absent (A. J.

Boulton et al., 2008), but clinicians may wish to record additional information such as

strength and regularity of pulse. Reduced or absent pulses indicate that an Ankle Brachial

Index (ABI) should be performed (A. J. Boulton et al., 2008; Orchard & Strandness, 1993).

Figure 1-9. Palpation of the DP (left) and PT (right) pulses.

1.5.2.2 Hand-held Doppler Ultrasound

Doppler ultrasound is used to locate the pulse, and characterise arterial sounds (Khan et al.,

2006). Normal pulsatile sounds of the artery are triphasic following the cardiac cycle, but

54

in the presence of arterial disease may be biphasic or monophasic, or there may be no

audible sounds in severe occlusive disease (Khan et al., 2006).

1.5.2.3 Ankle Brachial Index (ABI)

The ABI calculates the ratio of systolic pressures in the upper and lower limb. The ABI is

a simple, non-invasive tool to assess the presence and severity of PAD (American Diabetes

Association, 2003). A low ABI (<0.9) has also been identified as an independent risk

factor for increased CV mortality (Norman et al., 2006). A pneumatic cuff is placed

around the ankle, and using a Doppler ultrasound to listen for arterial flow in either the DP

or PT pulses, the cuff is inflated until there is loss of audible flow (Figure 1-10). The cuff

is then slowly deflated, and the systolic pressure is recorded when the first arterial sounds

are heard, indicating return of flow. The same procedure is repeated for the upper limb

using the brachial artery, and the ratio is calculated by dividing the highest ankle pressure

by the highest brachial pressure (American Diabetes Association, 2003; Norgren et al.,

2007). Diagnostic criteria for severity of PAD are based on the ratios presented in Table 1-

3 (American Diabetes Association, 2003; Potier, Khalil, Mohammedi, & Roussel, 2011).

Figure 1-10. Performing the ABI.

55

Table 1-3. ABI ratios and interpretation.

Ratio Interpretation

0.91-1.30 Normal/no PAD 0.70-0.90 Mild obstruction/PAD 0.40-0.69 Moderate obstruction/PAD <0.40 Severe obstruction/PAD >1.30 Poorly compressible arteries, medial calcification of

vessel wall

1.5.2.4 Toe pressures and Toe Brachial Index (TBI)

In patients presenting with overt vessel calcification (ABI >1.3), evaluation of toe pressures

and calculation of a TBI can be a useful clinical assessment tool (Brooks B et al., 2001).

Measurement of blood pressure of the hallux and calculation of the TBI are considered

reliable adjuncts for assessing PAD in the lower limb, particularly where compressibility of

the tibial arteries is compromised due to calcification of the tunica media (Norgren et al.,

2007; Scanlon, Park, Mapletoft, Begg, & Burns, 2012). Normal toe pressure thresholds to

indicate healing potential are ≤50mmHg, and TBI values ≤0.7 (Norgren et al., 2007).

Traditionally, toe pressures/TBIs are performed in a vascular laboratory with standardised

equipment. Assessment of toe pressures/TBIs can also be conducted in the clinical setting

using a portable Doppler unit, a digital cuff applied to the hallux, and an infrared

photoplethysmography (PPG) sensor. There are limitations to using portable equipment

however, including discrepancies in assessor training and skill in performing toe

pressures/TBIs, non-standardised placement of cuffs and probes, and possible equipment

inaccuracies, resulting in clinically significant measurement errors (Romanos, Raspovic, &

Perrin, 2010).

1.5.2.5 Other tests

Other vascular assessment procedures include duplex ultrasound, magnetic resonance

angiogram and contrast angiography (American Diabetes Association, 2003; Norgren et al.,

2007).

The vascular examination also includes questioning the patient regarding a history of

ischaemic symptoms, such as intermittent claudication (IC) and rest pain. IC is considered

a cardinal symptom of PAD, and is associated with an increased risk of cardiovascular

morbidity and mortality (Meru, Mittra, Thyagarajan, & Chugh, 2006). In patients with

56

diabetes, symptoms of IC and rest pain may be reduced or absent due to the presence of

PSN, and may instead present with more severe arterial complications such as an ischaemic

ulcer or gangrene (American Diabetes Association, 2003).

1.5.3 Dermatological examination

DM induces a number of alterations to the skin, and histologically changes include

thickening of the dermal collagen, increased cross-linking from non-enzymatic

glycosylation (Brik, Berant, & Vardi, 1991; Buckingham et al., 1984; Ferringer & Miller,

2002), vascular wall thickening and disruption and/or loss of elastic fibres, changes

analogous to accelerated aging (Braverman & Kehyen, 1984). Asymptomatic thickening of

the skin is also seen, which along with joint stiffening, can result in fixed flexion of the

joints in the hands (Ferringer & Miller, 2002; Goodfield & Millard, 1988).

Clinically there may be evidence of diabetic dermopathy, which may present as bilateral

pigmented pretibial papules (Ferringer & Miller, 2002). Other skin manifestations seen in

diabetes include necrobiosis lipoidica diabeticorum, bullosum diabeticorum, granuloma

annulare, and acanthosis nigricans (Ferringer & Miller, 2002; Frykberg et al., 2006; Goyal,

Raina, Kaushal, Mahajan, & Sharma, 2010).

The feet and between the toes should be inspected for mechanically induced skin lesions

such as callouses and corns, as well as fungal infections (eg. tinea pedis), areas of erythema,

ulcers, or gangrene (J. Apelqvist et al., 2000; A. J. Boulton et al., 2008). Trophic changes

associated with arterial disease should also be assessed. This includes evaluation of

skin/limb colour changes such as dependent rubor and pallor on elevation, hyperaemia, a

cool or cold limb, or other temperature variations (ipsilateral and contralateral limb),

integumentary changes (xerosis, fissures, absence of hair growth), and nail dystrophies

(American Diabetes Association, 2003; Ikem, Ikem, Adebayo, & Soyoye, 2010; Khan et al.,

2006).

1.5.4 Musculoskeletal examination

The feet should be assessed for any structural deformities including hammertoes, bunions,

Tailor‟s bunions, hallux limitus/rigidus, pes planus/pes cavus, Charcot deformity, and

post-surgical deformity. A 6-point Foot Deformity Score is used to ascertain the degree of

foot deformity, and a score of 3 or more indicates deformity (Baker IDI Heart and

57

Diabetes Institute, 2011). The score includes assessment of small muscle wasting, bony

prominence, prominent metatarsal heads, hammer or claw toes, limited joint mobility and

Charcot foot deformity. In concert with ill-fitting footwear, foot deformities such as

contracture of the metatarsophalangeal joints and/or interphalangeal joints increases the

potential for skin breakdown (J. Apelqvist et al., 2000; Frykberg et al., 2006; Lavery,

Armstrong, Vela, Quebedeaux, & Fleischli, 1998). Foot abnormalities such as limited joint

mobility, equinus and amputation sites may contribute to biomechanical and gait anomalies

and also increase the potential for elevated pressures (Frykberg et al., 2006; Lavery et al.,

1998). Patients with diabetes-related neuropathy may have muscle weakness associated

with the ankle and knee (Andersen, Nielsen, Mogensen, & Jakobsen, 2004) so muscle

strength assessment is important to determine the extent of intrinsic and extrinsic muscle

involvement or atrophy, and other complications such as foot drop (Frykberg et al., 2006).

1.5.5 Footwear

Poorly fitting footwear is considered to play an important role in the development of foot

ulceration (M. E. Edmonds et al., 1986). Research suggests that external factors, such as

ill-fitting footwear and acute mechanical trauma, are the most common precipitants in the

development of a diabetes related foot ulcer (Jan Apelqvist, Larsson, & Agardh, 1990;

Macfarlane & Jeffcoate, 1997). Tight footwear in combination with intrinsic factors such

as foot deformity or oedema may result in high pressure areas over bony prominences,

which over time can lead to ulceration in patients with PSN (M. E. Edmonds et al., 1986).

As such, footwear should be reviewed at regular intervals in at-risk patients, and those with

foot deformity may need footwear modification or customisation. Therapeutic customised

footwear has been demonstrated to significantly lower plantar foot pressures and reduce

the risk of re-ulceration in patients with diabetes (Uccioli et al., 1995; Viswanathan et al.,

2004), highlighting the beneficial pressure redistribution and offloading effects of

individualised footwear.

1.6 Assessing risk

Australian diabetic foot care guidelines recommend that all patients with diabetes should be

categorised into a level of risk for developing diabetic foot complications (Table 1-4)

(Baker IDI Heart and Diabetes Institute, 2011). Based on the assessments previously

described, the level of risk is determined using the following risk factors: history of

58

ulceration and amputation, DPN (SWM, vibration, NDS), PAD (peripheral pulses,

ABI/TBI), and foot deformity (Foot deformity score ≥3).

Table 1-4. Diabetic foot risk stratification, indicators and recommendations for review.

Category of risk Indicators Recommendation

Low risk No risk factors No previous history of foot ulcer or amputation

Annual foot assessment

Intermediate risk One risk factor (DPN, PAD, foot deformity) No history of ulcer or amputation

At least every 3-6 months

High risk Two or more risk factors (DPN, PAD, foot deformity) And/or a previous history of ulcer or amputation *All ATSI patients are considered high risk until assessed

At least every 3-6 months

Adapted from National Evidence-Based Guideline: Prevention, Identification and Management of Diabetic Foot Complications in Diabetes (Baker IDI Heart and Diabetes Institute, 2011).

1.7 Management of the diabetic foot

Management of diabetes related foot complications begins with preventive measures such

as ascertaining an understanding of the patient‟s level of awareness of foot problems,

followed by the provision of some form of patient education, especially in those with “at-

risk” feet (Campbell et al., 2000). Footwear should also be examined to determine fit and

wear patterns, as ill-fitting footwear and acute mechanical trauma has been shown to

precipitate a large proportion of foot ulcers in diabetes (Jan Apelqvist et al., 1990). Any

orthotic devices worn in the shoes should also be evaluated to ensure they are in the

correct position and supporting the foot effectively.

Treatment of conditions that may lead to ulceration is essential. Patients should be seen by

a podiatrist for any mechanical debridement or callouses and corns, and management of

elongated or chauxic nails, tinea pedis, blisters, verrucae or other skin abnormalities. If the

skin breaks down, the patient should be appropriately managed in a multi-disciplinary team

with pressure reduction/offloading, debridement of the wound, application of wound

dressings, and suitable footwear (Bergin et al., 2012; Frykberg et al., 2006). A

multidisciplinary foot care team, providing rapid access to a variety of specialist clinicians

and services, has been demonstrated to improve ulcer healing and reduce amputation rates

59

(M. Edmonds, 2008; M. E. Edmonds et al., 1986; Holstein, Ellitsgaard, Olsen, &

Ellitsgaard, 2000; Larsson, Apelqvist, Agardh, & Stenstrom, 1995) and should include

medical, surgical, podiatry, nursing and allied health care professionals (Baker IDI Heart

and Diabetes Institute, 2011; Scottish Intercollegiate Guidelines Network, 2010). Where

indicated, the patient may require peripheral revascularisation, or antibiotic therapy in the

case of infection, and attention should also be given to metabolic control, treatment of any

co-morbidities and appropriate patient education (J. Apelqvist et al., 2000; Bergin et al.,

2012).

1.8 The burden of diabetic foot complications

The impact of diabetes related foot complications affects patients on many levels. First,

they are costly and time consuming conditions to manage, often requiring resource-

intensive care. For example, it is estimated that the cost of care in patients with diabetic

foot ulcers is more than five times the cost in those without foot ulcers (Driver, Fabbi,

Lavery, & Gibbons, 2010). According to the Eurodiale Study, managing a foot ulcer starts

at approximately €4,500, in patients with no infection or arterial disease, and rises to more

than €11,000 in patients with these complicating factors (figures from 2005) (Prompers,

Huijberts, Schaper, et al., 2008), excluding the costs of amputation. Given a third of

patients presenting with diabetic foot ulcers have concomitant ischemia and infection

(Prompers et al., 2007), as well as ulcer recurrence rates of up to 70% (J. Apelqvist et al.,

1993), it is likely that these figures are a conservative estimate of the total cost associated

with management of a diabetes-related foot ulcer.

Secondly, foot disease has been demonstrated to negatively affect a patient‟s quality of life

(QoL) (Hogg, Peach, Price, Thompson, & Hinchliffe, 2012; Price, 2004). By virtue of the

fact that the foot is a weight bearing structure, foot complications are particularly

debilitating because of the significant impact on mobility, which may prevent patients from

carrying out simple activities of daily living, such as walking, climbing stairs, working or

participating in leisure activities (Vileikyte, 2001). In a comparison of patients with diabetic

foot ulcers compared to diabetic patients with no foot ulcers and non-diabetic controls, it

was found that patients with foot ulcers had much worse health-related QoL (HRQoL),

particularly with regard to physical functioning and general health (Ribu, Hanestad, Moum,

Birkeland, & Rustoen, 2007). The HRQoL of caregivers and family members are also

impacted by this process (Nabuurs-Franssen, Huijberts, Kruseman, Willems, & Schaper,

60

2005), with implications on social activities, increased family tensions and lost time at work

(Carrington, Mawdsley, Morley, Kincey, & Boulton, 1996).

Mental health may also be affected as patients can become frustrated due to the loss of

mobility and independence, or develop feelings of guilt due to their perceived burden on

others (Brod, 1998). The negative psychosocial impact of chronic ulceration was evident in

a study by Carrington et al, where diabetic amputees were age and sex matched with

diabetic patients with chronic ulceration and diabetic controls with no history of foot

ulceration. Poorer psychosocial adjustments were found in the ulcer and amputation group

compared to controls, while those with ulcers were significantly more depressed, had

poorer quality of life and a more negative attitude towards the feet than controls and

amputees (Carrington et al., 1996). Indeed, other research has also demonstrated that

active foot ulcers have a greater negative impact on HRQoL than healed ulcers (Nabuurs-

Franssen et al., 2005; Tennvall & Apelqvist, 2000). In patients who require a major

amputation, the prospect of living with a permanent disability, and the need for significant

lifestyle and behavioural changes, can be a considerable emotional burden (Price, 2004).

This can be accompanied by feelings of grief at losing a limb or part of a limb, in addition

to fears regarding pain and future functional capabilities, and uncertainty about the future

(Bradway, Malone, Racy, Leal, & Poole, 1984).

Thirdly, there is an increased risk of mortality associated with foot complications. A

prospective study by Moulik et al (Moulik, Mtonga, & Gill, 2003), found that of 185

diabetic patients followed following the development of a foot ulcer, the 5 year mortality

rate was 44%, with worse outcomes and a higher mortality rate of 56% in those with PVD

and ischaemic ulcers. Boyko and colleagues reported that the relative risk of death was

almost 2.4 times greater in patients who developed a diabetes related foot ulcer, compared

to those without foot ulcer (Boyko et al., 1996). Mortality rates after amputation are

particularly high. Apelqvist et al reported that the long term survival for diabetic patients

with a previous amputation was only 27% at 5 years post-amputation, compared to 58%

for patients who had not had a prior amputation (J. Apelqvist et al., 1993). This

association is supported by other research (J. Apelqvist et al., 1993; Faglia et al., 2001; J. S.

Lee et al., 1993), although some studies suggest no impact on mortality (Moulik et al., 2003;

Ramsey et al., 1999).

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1.9 Reducing the burden of diabetes related foot complications

It is clear that diabetes related foot complications are a significant burden on the patient,

their families and health care providers. In addition to addressing broader goals of

reducing diabetes prevalence and maximising glycaemic control in patients with diabetes,

reducing the burden of foot complications can be achieved through targeting three key

areas: characterising patient awareness of diabetic foot complications and working to

improve this standard, providing effective diabetic foot care education, and prompt

identification of those at risk (Figure 1-11) (American Diabetes Association, 2004, 2013;

Baker IDI Heart and Diabetes Institute, 2011; Frykberg et al., 2006; Singh et al., 2005).

Identifying the predictors of foot ulceration, and how might they have changed over time

can assist clinicians in rapidly identifying patients at high risk of future foot complications.

Determining foot health awareness in patients with diabetes will enable a better

understanding of how patients view their feet in a background of diabetes and whether

they are able to recognise potential precursors to ulceration and amputation. Finally,

evaluation of current foot care education programs will provide more detailed information

regarding the effectiveness of this education, and potential areas for improvement.

Figure 1-11. Target areas to reduce diabetes-related foot complications.

1.10 Predictors of foot ulceration

There are many potential physiological predictors of foot health outcomes in a background

of diabetes, and a number of conceivable pathways to foot ulceration. Given the serious

Reducing diabetes-

related foot complications

Identify clinical indicators of risk

Evaluate and enhance foot

care education

Characterise and improve

patient awareness

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potential consequences of ulceration, it is clearly a priority to identify the predictors of

ulceration and high risk patients as early as possible. To date, DPN has been established as

a key predictor of ulceration (C. A. Abbott et al., 2002; A. J. Boulton et al., 1986; Boyko,

Ahroni, Cohen, Nelson, & Heagerty, 2006; Crawford, Inkster, Kleijnen, & Fahey, 2007;

McNeely et al., 1995; Monteiro-Soares, Boyko, Ribeiro, Ribeiro, & Dinis-Ribeiro, 2012;

Pham et al., 2000; Sriussadaporn et al., 1997; Young et al., 1994). Many other factors have

been implicated in the development of foot ulcers, such as macrovascular and

microvascular disease, abnormal biochemical markers and metabolic control,

dermatological abnormalities and foot deformities. A summary of the significant relevant

research, and their findings and limitations, are summarised in Table 1-5.

Table 1-5. Summary of research of predictors of foot ulceration.

Author Year Summary Predictors of ulceration

Critique/comment

Crawford et al UK

2007 Systematic review and meta-analysis -Quantify the predictive value of diagnostic tests and physical signs and elements from the patients history in relation to diabetic foot ulcers -16 studies identified: 5 case control, 11 cohort design

-Diagnostic tests that detect DPN (VPTs using biothesiometer or tuning fork, high plantar pressures, 10g monofilament, absent ankle reflex) -Physical signs (limited joint motion at 1st MPJ and STJ) -Vascular disease (previous amputation, ulceration or lower limb bypass procedure)

-Studies included were conducted in the 90s and early 2000s, the most recent study included was 2004 (10 years ago) -Mixed type 1 and 2 -Majority conducted in the USA -Different cut points for diagnostic tests, different definitions for some predictive factors, different lengths of follow up -Lack of detail regarding characteristics of patients lost to follow up -Included some weaker evidence - case control studies -None of the published studies reported on the predictive value of signs associated with foot trauma -Unclear the role of variables that could predispose to ulceration: HbA1c, ABI/ABPI, presence or absence of pedal pulses, diabetes duration, presence of callous, exercise levels, foot deformity

Monteiro-Soares et al Portugal

2012 Systematic review -To identify all studies of factors associated with DFU and assess whether DFU risk stratification systems incorporate those factors -71 studies included -100 independent variables

-Neuropathy -Vascular disease -Foot deformity -Previous diabetic foot ulceration or LEA

-Included papers only in English, French, Italian, Spanish or Portugese -Different outcome measures of included studies (DFU development, DFU recurrence/re-ulceration, active or recently healed DFU, active or past history of DFU, DFU history only -Lack of definition of foot ulcer in 41% of studies, remaining studies presented 20 different definitions of foot ulcer -Different cut off points for some variables -Mixed methodological quality -Mixed type 1 and 2 -Few studies investigated foot trauma, foot care habits, preventative measures such as diabetes education, level of

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education -Unclear association with age, gender, diabetes duration, nephropathy, metabolic components such as waist circumference, lipids, triglycerides -Quality assessment, data analysis and extraction performed by one reviewer -Lack of clear conclusions

Abbott et al UK

2002 Community based prospective cohort study -Determine which clinical foot screening methods are most effective for predicting the risk of diabetic foot ulceration and incidence of foot ulceration N=9710 (6613 patients screened at baseline and completed 2 year follow up questionnaire)

-History of foot ulcers (past or present at baseline) -Abnormal neuropathy disability score (NDS ≥6/10) -Any previous podiatry or foot care advice -Insensitivity to 10g monofilament -Reduced number of pedal pulses -Foot deformities -Increasing abnormal ankle reflex score -Decreasing age

-Mixed type 1 and 2 -Screening conducted 1994-1996, data now 20 years old -70% response rate at follow up (2300 lost to follow up) -Unclear impact of factors not measured at baseline such as extent of healthcare provision, patient behaviour, adherence to foot care advice, provision of or access to podiatry care

Crawford et al UK

2011 Community based prospective cohort study -To quantify the predictive value of clinical risk factors in relation to foot ulceration in a community population N=1192

-Previous amputation -Insulin use before 3 months * inability to distinguish between cool and cold temperatures (interaction) -Failure to obtain at least one blood pressure reading for the calculation of an ABI index * inability to feel monofilament (interaction)

-Patients who developed a foot ulcer identified from podiatry records -Lack of data relating to non-participants (n=78) -Only 1 year follow up -103 lost to follow up

Abbott et al UK

1998 Multi-centre clinic based prospective cohort study -Determine important prognostic factors for foot ulceration in patients with neuropathy and incidence of first foot ulceration over 1 year. Patients followed up at weeks 13, 26, 39, 52) N=1035 subjects from 44 centres in the UK, US and Canada

-VPT >25V at the hallux -Muscle and reflex components of the Michigan clinical DPN score* -Decreasing age (hazard of foot ulcer decreased with increasing age)

-Clinic based -Mixed type 1 and 2, plus overrepresentation of type 1 patients (24.6%) -20% (n=206) lost to follow up -Subjects had neuropathy, increasing the risk of ulceration -No assessment of foot deformities, calluses or neuroarthropathy, podiatry attendance -Clinical tests of muscle strength are subjective, and damage to muscular innervation likely to be a byproduct of neuropathic status -10g SWM only tested at the hallux

Pham et al USA

2000 Multi-centre clinic based prospective cohort study -To determine which risk factors in foot screening have a high association with the development of foot ulceration N=248 Followed for mean period of 30 months

-NDS ≥5/22 -elevated VPTs (>25V) -elevated SWFs (>10g pressure) -elevated foot pressures (>6kg/cm2)

-Clinic based population -Mixed type 1 and 2, majority Caucasian -35% of subjects had a history of foot ulceration -No data relating to non-recruited subjects

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Boyko et al USA

2006 Clinic-based prospective cohort study (Veterans Affairs Medical Centre) -To predict the occurrence of diabetic foot ulcer using commonly available clinical information N=1285 Annual clinical evaluations and quarterly mailed questionnaires to identify foot problems. Subjects re-evaluated at 12-18month intervals (mean 13 months) for a mean follow up of 3.38 years

-HbA1c -Vision poorer than 20/40 (Snellen chart) -History of foot ulcer -History of amputation -Monofilament insensitivity -Tinea pedis -Onychomycosis

-Single centre (clinic) population -487 died or lost to follow up (21.6%) -Majority male Caucasian participants (94.9%)

Kästenbauer et al Austria

2001 Clinic based prospective cohort study -To analyse risk factors for foot ulceration and determine incidence of ulceration N= 187

- elevated VPT -elevated mean plantar pressure (MMP) -daily alcohol intake

-Single centre (clinic) population -25 subjects (13%) lost to follow up -Lack of data regarding non-recruited subjects (n=49) -Small sample size

Sriussadaporn et al Thailand

1996 Case control study -To determine factors involved in foot ulceration in That non-insulin dependent (Type 2) diabetic patients 55 cases (with foot ulcers) 110 controls (without foot ulcers)

-Peripheral nerve status (determined by somatosensory evoked potentials, SSEPs) -visual acuity -fasting plasma glucose

-Small sample size -Unclear if cases were age and/or sex matched -A single plasma glucose measurement at the time of the study may not adequately reflect glycaemic control -Prevalence of macrovascular disease may be low in the Thai population -Use of SSEPs not typical in the assessment of neurological status

Lavery et al USA

1998 Case-control study -To evaluate risk factors for foot ulceration among persons with DM 76 cases (existing foot ulcer or recent history of a foot ulcer) 149 age matched controls (no history of foot ulceration)

-elevated plantar pressure -history of amputation -duration of diabetes (>10 years) -foot deformities (hallux rigidus or hammer toes) -male sex -poor diabetes control (HbA1c >9%) -1 or more subjective symptoms of neuropathy -elevated VPT (>25V)

-Clinic based -Small sample size -Mixed type 1 and 2 -No data regarding non-recruited subjects -Proportions of male and female subjects unclear -Peripheral sensory neuropathy assessed only using biothesiometer

McNeely et al USA

1995 Case control study -To describe the relative contributions of neurological and vascular abnormalities to the overall risk of diabetic foot ulceration 46 cases

-absent Achilles tendon reflexes -insensitivity to the 10g SWM -low transcutaneous oxygen tension (TcPO2)

-Single centre (clinic) population -Conducted between 1987 and 1992 (data more than 20 years old) -Unclear if cases were age and/or sex matched -Majority Caucasian males -Some significant differences between cases and controls (controls were more likely to be male, older,

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322 controls

heavier, living with a spouse, less likely to have had a LEA, higher serum creatinine levels, less likely to report diabetic nephropathy, or prior lower extremity bypass surgery) -Unclear whether TcPO2 measurements would provide additional useful clinical information beyond that obtained from use of a monofilament and reflex testing

While there are consistent findings with regard to the role of neuropathy (or diagnostic

tests for the detection of neuropathy) in the development of a foot ulcer, there are

methodological flaws in a number of studies that suggest further research is necessary. For

example, clinic-based studies have limited applicability compared to community-based

studies, and few studies offer a comparison of how predictors of foot ulceration might

change over time, in light of improved diabetes care. In addition, the role of a number of

possible precursors to foot ulceration, such as vascular disease, foot deformity,

dermatological changes, and metabolic control remain inconclusive, and suggest further

research is necessary.

1.11 Foot care education

Patient education has the potential to play a key role in the prevention of diabetic foot

complications (A. J. M. Boulton, 1995). Although foot care education programs are

recommended as part of the overall diabetes management plan (American Diabetes

Association, 2004, 2013; J. Apelqvist et al., 2000; Baker IDI Heart and Diabetes Institute,

2011) substantiation of their effectiveness is inconsistent (Dorresteijn Johannes, Kriegsman

Didi, Assendelft Willem, & Valk Gerlof, 2010; Valk, Kriegsman, & Assendelft, 2002). A

few large scale systematic reviews and RCTs have been conducted, but outcome measures

focus on the impact of education on foot ulcer development. There is some evidence to

suggest that diabetic foot care education improves foot care knowledge and behaviour

(Barth, Campbell, Allen, Jupp, & Chisholm, 1991; Corbett, 2003; Donohoe et al., 2000;

Ward, Metz, Oddone, & Edelman, 1999) however methodological limitations such as small

sample sizes and high attrition rates limit the generalisability of the findings. In addition,

there is often wide variability in the style, structure and content of diabetic foot care

educational programs, and uncertainty as to the most effective format (Brown, 1999;

Radford K, Chipchase S, & Jeffcoate W, 2006).

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Valk et al carried out a systematic review of prospective randomised controlled trials

(RCTs) to evaluate the effect of education to reduce the incidence of foot ulceration in

people with diabetes (Valk et al., 2002). Eight RCTs were evaluated, which covered a range

of settings, types of educational interventions and risk of patient ulceration. Interventions

included brief and intensive education, demonstration and hands on teaching, as well as

complex interventions involving patient and practitioner education (Valk et al., 2002).

Three of the RCTs demonstrated short term effects of education on patient‟s foot care

knowledge, but at long term follow up (7 years), one study demonstrated this positive

effect had been lost (Valk et al., 2002). Patient behavior improved in four of the RCTs, but

behavior change was not sustained over the longer term (Valk et al., 2002). One RCT

demonstrated a statistically significant threefold reduction in the incidence of ulceration

and amputation in the intervention group at 12 months follow up after receiving a 1 hour

group education session on the diabetic foot by a podiatrist, compared with the control

group who received no education (Malone et al., 1989). The intervention included a review

of slides depicting infected diabetic feet and amputated diabetic limbs, and a simple set of

patient instructions for the care of the diabetic foot. These results appear promising,

however participants in this study were recruited via referral pathways that identified those

at high risk of foot ulceration, including those with active foot ulcers and prior amputation

(Valk et al., 2002) thus increasing the likelihood of a positive effect. It is also difficult to

extrapolate the findings to low or moderate risk patients, or people with diabetes within the

wider community. Furthermore, there may have been an overestimation of the effect as

outcomes were reported per limb rather than per patient (Dorresteijn Johannes et al.,

2010). Although the methodological quality and internal validity of most RCTs reviewed

by Valk et al were considered poor, patient education appeared to have brief but positive

effects on foot care knowledge and behavior, and may reduce foot ulceration and

amputation (Valk et al., 2002).

A Cochrane Collaboration systematic review of patient education for preventing diabetic

foot ulceration was in agreement with findings by Valk et al, which reported short term

improvements in foot care knowledge and behaviour, but a high risk of bias in most RCTs,

such as inadequate randomisation and blinding, and selective follow up. This may result in

an overestimation of effect size, and so the authors concluded there is insufficient robust

evidence that patient education alone is effective in reducing ulcers and amputations

(Dorresteijn Johannes et al., 2010). Recommendations from this review suggested future

research should focus on evaluating the effect of more comprehensive or intensive patient

education programs (Dorresteijn Johannes et al., 2010).

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Lincoln and colleagues conducted a RCT of a 1 hour education session in 172 people with

newly healed foot ulcers, compared to controls who received written foot care information,

in three specialist foot clinics in the UK (N. B. Lincoln, Radford, Game, & Jeffcoate, 2008).

The primary outcome measure was foot ulceration at 12 months, with secondary outcome

measures assessing incidence of ulcer incidence at 6 months and incidence of amputation,

mood and quality of life at 6 and 12 months (N. B. Lincoln et al., 2008). At follow up,

there were no significant differences between groups in ulcer incidence, mood or quality of

life, although foot care behaviours at 12 months were better in the intervention group than

the control group (N. B. Lincoln et al., 2008). The authors concluded that there was

insufficient evidence that targeted education for people with newly healed foot ulcers

reduces the incidence of new ulceration, and that further research was necessary (N. B.

Lincoln et al., 2008).

Barth et al carried out a study comparing the effect of a conventional diabetes foot

education program (1 hour lecture/discussion by a podiatrist) with an intensive foot care

intervention (4 sessions of 1.5 - 2.5 hours duration, 3 sessions provided by a podiatrist, 1

session provided by a psychologist that included use of motivational techniques) (Barth et

al., 1991). 62 patients with type 2 DM were recruited to the study, and follow up visits

were conducted at 1, 3 and 6 months post intervention. The intensive group demonstrated

significantly greater improvements in foot care knowledge, compliance with the

recommended foot care routine and compliance with advice to consult a podiatrist (Barth

et al., 1991). The intensive group also showed a significantly greater reduction in the

number of foot problems requiring treatment at the first follow up visit than the

conventional group (Barth et al., 1991). Despite these positive findings, there were a

number of limitations in this study, particularly the lack of a control group. Second, the

two intervention programs differed in a number of ways (time span, total hours, teaching

method, motivational techniques), making it difficult to compare the two interventions

(Barth et al., 1991). Third, the authors were unable to determine whether the greater

improvements in knowledge, compliance and foot problems resulted in an eventual

reduction in amputations due to the short follow-up period (Barth et al., 1991). Finally, the

implementation of an intensive program as described in this study is more expensive and

time-consuming that the conventional approach (Barth et al., 1991) and it is unclear

whether it is feasible for such a program to be implemented into daily clinical practice.

A large study by Litzelman et al investigated three elements of a preventative foot care

program by including activities affecting the patient, health care providers and the health

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care system (Litzelman et al., 1993). Specifically, the authors were interested in the effect

of a comprehensive foot care intervention on knowledge and performance of appropriate

foot care, increased referrals to a podiatry clinic, increased frequency of foot examination

by health care providers and documentation of risk factors in the medical notes, and

improved patient outcomes such as skin and nail conditions, compared to usual care.

Twelve months later, they found self-foot care behaviours among the intervention group

were improved with regard to washing and inspecting the feet, drying between toes and

checking shoes before putting them on, but there was no difference between groups

regarding examining the nails and between the toes, going barefoot indoors or using

heating pads or hot water bottles on the feet, or seeing a podiatrist (Litzelman et al., 1993).

Although health care providers in the intervention team were more likely to inspect the feet

of the patient and ask about symptoms of neuropathy, the teams did not differ with regard

to recording information such as foot deformities, dry or cracked skin, or foot lesions

and/or infections (Litzelman et al., 1993). Therefore, despite some improvements in

patient and health care provider behaviour, these changes were not all-inclusive, and it is

unclear whether behaviour changes were sustained. Other limitations include a lack of

detail regarding the amount of prior foot care education received by subjects in both

groups. It is also difficult to generalise these findings to a community based, multi-ethnic

population however, as their study was conducted in an academic general practice, and the

majority of participants were female, black and poorly educated.

Kruger and Guthrie investigated foot care knowledge retention, self-care practices and foot

health status in a small study of diabetic patients attending a hospital in the US (Kruger &

Guthrie, 1992). Subjects in the control group were provided with usual diabetes foot care

education, consisting of a videotape and supplementary explanation from an instructor.

The experimental group received a hands-on teaching/learning sessions, where they

participated in actual foot washing, foot inspection and assessment, demonstration of

appropriate care of the nails and skin, and evaluation of footwear. The experimental group

also received a patient education kit, which included basic foot care products. At 6 months

follow up, the authors reported inconclusive findings regarding the impact of “hands on”

foot care education (Kruger & Guthrie, 1992). There was no difference in foot care

knowledge, and minimal changes to foot health status and foot care practices in the two

groups, but there were a number of limitations to this study. First, there was a 44%

attrition rate between baseline and follow up, resulting in only 15 patients in each group

completing the study. Second, the hospital based nature of the program suggests the

findings could only be reliably interpreted in that context. Third, it was unclear what type

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of foot care information was provided in the usual care group, and how this might have

differed from the information provided to the experimental group.

It is clear from these studies that the impact of education on foot health is currently

inconclusive, and that this is a major limitation with regard to improving the delivery and

outcomes of foot care programs. Critical review of the current literature is difficult due to

methodological differences, including the style, content and length of education provided.

In particular, there is a paucity of data pertaining to the impact of written versus oral

diabetic foot care education on foot care knowledge, attitudes and behaviours, and there is

a distinct need for further research in this area. A comparison of these two foot care

education methods may be a more useful measure of educational effectiveness, as it better

replicates what is available in the community, and also what often occurs in the clinical

setting.

1.12 Awareness of foot health in diabetes

Awareness of foot health in diabetes is the first step in empowering patients to prevent

foot problems. As such, self-awareness plays an important role in diabetes management

(Afridi & Khan, 2003; Wee, Ho, & Li, 2002), but available data suggest that relatively few

patients with established but asymptomatic complications are aware of their presence. A

longitudinal study of 2,992 adults from the National Health and Nutrition Examination

Survey who had chronic kidney disease found that although self-awareness was greatest

amongst those with more advanced stages and risk factors, the proportions of these

patients remained <10% (Plantinga et al., 2008). In the context of diabetic foot disease, a

recent German population-based study (Bongaerts et al., 2013) found that 91% of 154

elderly patients with pre-diabetes or diabetes and PSN had not been told by a physician

that they had nerve damage, but this was the only index of self-awareness determined by

the investigators. A Moroccan study of awareness of diabetes related foot problems found

that more than 50% of the cohort was poorly aware of foot problems as a complication of

diabetes, and furthermore, subjects were unaware of the severity of foot complications and

prevention methods (Lamchahab et al., 2011). Sub-optimal levels of awareness have also

been described in a small study conducted in two teaching hospitals in Ireland. The

authors found that of 258 diabetic patients surveyed, only 16% were aware of PAD as a

complication of diabetes, and only 12% were aware of the potential for amputation

(O'Sullivan et al., 2009). In comparison, 61% were aware of the potential for eye

complications (O'Sullivan et al., 2009) suggesting there is a significant lack of awareness

relating to lower limb and foot problems.

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Murugesan and colleagues investigated awareness about diabetes with regard to physical

activity, diet, causes, symptoms, prevention and complications in a sample of 3681 people

between 20 and 65 years of age, in the southern Indian city of Chennai (Murugesan,

Snehalatha, Shobhana, Roglic, & Ramachandran, 2007). The authors reported that

knowledge regarding causes of diabetes, its prevention and methods to improve health,

were low in the general population (Murugesan et al., 2007). Less than 30% of subjects

knew that the kidneys, eyes and nerves could be affected, and 41% were unaware that their

health could be affected by diabetes, however this might be explained by the fact that 94%

of participants considered other health problems, such as AIDS, cancer, heart disease and

tuberculosis more important than diabetes (Murugesan et al., 2007). In a cross-sectional

study of public awareness of diabetes in Singapore, Wee and colleagues administered a

survey to determine the general public‟s knowledge of diabetes, assessing questions

covering general knowledge, risk factors, symptoms and complications, treatment and

management, and monitoring (Wee et al., 2002). Although they found that overall the

public were well informed about diabetes, this may have been due to the relatively high

proportion of tertiary-educated respondents. In addition, it was found that only about half

of the respondents believed that people with diabetes should care for their feet (Wee et al.,

2002).

It is likely that there are other contributing factors to awareness of foot health, including

socioeconomic barriers to optimal self-care, and physical limitations such as age, mobility,

and poor vision. Nonetheless, the available literature suggests that there are inadequate

levels of awareness about diabetes and its complications, and that a proactive and

preventative approach is needed by health care professionals to educate the diabetic

population. Despite some research on general awareness of diabetes and its complications

there is still a paucity of data focusing on personal awareness of diabetes related foot

health, particularly in a community-based Australian cohort. Currently, it remains unclear

whether patients with diabetes are able to recognise foot problems and whether patients

perceive neuropathy, vasculopathy, and other morphological or dermatological foot

changes as abnormal. Determining these factors will provide information important to

diabetes educators and clinicians, and guide the provision of diabetic foot care education.

1.13 Summary

The diabetic foot and its sequelae are a major burden on patients, families and health care

providers (Figure 1-12). The studies in this thesis will support efforts to reduce this burden

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by providing novel insights into the prevalence, incidence and predictors of foot ulceration

in patients with type 2 diabetes, thereby improving the identification of “at-risk” patients,

and optimising foot screening. In the available literature, the prevalence and incidence of

foot ulceration vary widely depending on sampling and recruitment methods, and with

varying levels of risk for ulceration, and data from an Australian community based context

are lacking. A range of predictors for ulceration have been identified, however they relate

primarily to patients recruited from specialised diabetic foot clinics based in the United

States, the United Kingdom or Europe, and there is no equivalent robust evidence from an

Australian perspective. DPN and/or abnormalities in neuropathy assessment measures as

predictive variables have frequently been supported by the literature (see Table 1-5), but

the predictive value of other physiological and metabolic risk factors is still inconclusive.

In addition, there is a significant gap in the literature with regard to awareness of foot

health, and recognition of foot problems in diabetes. The research in this thesis will help

determine whether patients are able to recognise changes in the feet and lower limb that

might act as a precursor to ulceration or infection. Finally, the effectiveness of foot care

education programs using written and oral information require further evaluation with

regard to their role in improving foot health status, foot care behaviours and attitudes

towards diabetes related foot complications.

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Figure 1-12. The diabetic foot paradigm: burden of care, potential risk factors and

interventions. (Abdul-Ghani, Williams, DeFronzo, & Stern, 2007; Adler et al., 1997;

Crawford et al., 2007; W. A. Davis et al., 2006; McEwen et al., 2012; Monteiro-Soares et al.,

2012; Stratton et al., 2000; Tesfaye et al., 2005).

1.14 OBJECTIVES OF THIS RESEARCH

The objectives of this research outline in this thesis are as follows:

1) To investigate awareness of foot heath in patients with type 2 diabetes

2) To compare two methods of foot care education, and determine their role in

improving foot health, foot care behaviours and attitudes towards diabetic foot

complications in a community based sample of patients with type 2 diabetes

3) To determine the prevalence, incidence and predictors of foot ulceration in the

Phase I cohort of the Fremantle Diabetes Study (FDS) during 17 years follow up

until end 2010 (including hospitalisations for diabetes related foot ulceration)

4) To determine the baseline prevalence and associates of foot ulceration in the Phase

I (recruited between 1993-1996) and Phase II (recruited between 2008-2011) FDS

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cohort and to identify any differences in the independent associates of foot

ulceration between the two phases

Significance of this research

The findings of this research will contribute to the growing body of literature regarding the

epidemiology of diabetic foot ulceration, elucidate the level of awareness of foot problems

in patients with type 2 diabetes, and evaluate the relative benefits of written and oral

information in foot care education. In the light of increasing worldwide diabetes

prevalence, and the accompanying morbidity and mortality associated with diabetic foot

complications, this project will provide a valuable summary of diabetic foot ulceration in a

representative community based population, support improved diabetes-related foot care

education, and prevent foot related complications.

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Chapter Two

Methods and Materials

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METHODS AND MATERIALS

2.1 FDS study design overview

The Fremantle Diabetes Study (FDS) is a longitudinal observational study of patients with

diabetes from the catchment area of Fremantle Hospital (FH) in Perth, Western Australia.

From this postcode-defined community of 120,097 people, 2,258 diabetic patients were

identified between 1993-1996, from multiple sources (hospital lists, general practitioners,

specialists, allied health services, pharmacies, and advertisements). In Phase I of the study,

1426 people were recruited to the study for annual comprehensive assessments of their

diabetes. Of these, 1296 (91%) people had type 2 diabetes and attended baseline

assessment.

Phase II is the second part of the FDS and recruited patients between 2008 and 2011,

utilising the same protocol as Phase I. From 4,667 patients with diabetes identified from all

available sources, 1,668 (36%) were recruited for comprehensive biennial face-to-face

assessment with postal questionnaires in intervening years (T. M. Davis, Bruce, & Davis,

2013). An additional 64 surviving FDS Phase I participants who had moved out of the

study area were also recruited, resulting in a total sample size of 1,732 participants.

2.2 FDS approval and ethical considerations

The FDS protocol was approved by the South Metropolitan Area Health Service Human

Research Ethics Committee (SMAHS HREC) at FH, and all subjects gave informed

consent before participation. Participants were advised that all information would remain

strictly confidential, and that they were free to withdraw from the study at any time without

prejudice to their ongoing medical management. Patients had full access to their own

results, and could discuss them with the principal investigator (Winthrop Professor T.M.E.

Davis), and medical results were made available to the participant‟s general practitioner

(GP) and other relevant health professionals only with the participant‟s permission. Each

patient was assigned a unique code number, to ensure patient confidentiality throughout

data analysis, and all computer-based data were kept on a password protected computer,

accessible only by staff in the Diabetes Research team at FH.

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2.3 FDS personnel

Two full time research nurses carried out the majority of clinical examinations, along with

the principal investigator and other clinical staff, and they also managed the FDS database

and patient information on a daily basis. One full-time and one part-time administrative

staff assisted with organisation of appointments, patient interviews and data entry. Other

Diabetes Research Unit staff assisted with the provision of food and drinks to participants,

and other general tasks as required.

2.4 FDS patients

Patients were recruited to the study via hospital inpatient and outpatient lists, local general

practitioners or specialist physicians, internal and external allied health services (referral

from diabetes educators, podiatrists, dieticians, community health nurses and Aboriginal

Health Workers) advertisements in local shopping centres and pharmacies,

relatives/friends or other diabetic contacts of recruited patients, and through local media

and word of mouth. Criteria for recruitment to the study included:

1. Diagnosis of diabetes by a GP or hospital clinic

2. Residence in a postcode-defined catchment area of FH

2.5 FDS survey methods

2.5.1 Questionnaire

Patients completed a questionnaire which was specifically developed for the FDS, to obtain

epidemiological data. Patients were interviewed face-to-face, at baseline and updated every

second year, which consisted of the following sections:

1. Demographic data: Age/DOB, sex, place of residence (including nursing home

and hostel), occupation, marital status, country of birth/parents‟ birth, ethnic

background (self-described), language normally spoken at home, fluency in English,

education level, employment status, annual household income bracket, name of GP

and specialist (where applicable), health insurance status, health care card holder

status, home support (carer, community nurse, meals on wheels), contact details of

two friends or relatives not living with the patient to facilitate patient

communication, if required.

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2. Diabetes-related data: Date/method of diagnosis (including gestational diabetes

in females), symptoms at the time of diagnosis, family history of diabetes, full

dietary, treatment and medication history, method and frequency of blood glucose

monitoring including duration and frequency, hypoglycaemia frequency, severity

and unawareness, vascular complications, hospital admissions, frequency of

GP/outpatient/specialist/allied health (diabetes education, dietetics, podiatry,

optometry, dental) appointments, physical activity.

3. Availability of Care: Access/transport to GP or other clinics, need/provision of

interpreter, domiciliary support, financial constraints on consultations, treatment

and aids for glycaemic monitoring

4. Knowledge of diabetes: Sources of knowledge of diabetes and their relative

contributions (doctors, nurses, educators, dieticians, friends, others), 15-question

multiple choice test of current diabetes knowledge

5. General medical information: Past and current illness and medications, family

history of illness, smoking history, alcohol intake, drug allergies, sleep patterns

(Berlin sleep questionnaires)

6. Current health status: SF-12, Audit of Diabetes Dependent Quality of Life

(ADDQoL).

7. Cognitive function, mood and activities of daily living: Mini mental state

examination

8. Costs of diabetes: Self-reported health service usage and linkage to West

Australian Data Linkage System (WADLS) and other databases

2.5.2 Clinical Examination

Patients underwent a clinical examination and biochemical assessment after their interview

and at every subsequent visit (every second year). The full assessment included:

1. Anthropometric measures: Height, weight, BMI, waist circumference, waist-hip

ratio, body fat by bio-impedance

2. Cardiovascular status: Supine/erect pulse rate and blood pressure,

presence/absence of carotid bruits, heart sounds, resting 12-lead electrocardiogram

(ECG), peripheral oedema

3. Respiratory assessment: Pulse oximetry, auscultation of lung fields, spirometry

4. Bilateral foot assessment (Appendix A): Palpation of peripheral pulses (Doppler

was used to assist with identification of sites of pulses but not in determining their

80

presence/absence), Doppler ultrasound assessment to determine Ankle Brachial

Indices (ABI), dry skin, callous/corns, skin fissures, ulcer/s (at or below the level

of the malleoli), deformity, condition of nails. Foot deformity was defined as any

congenital or acquired mal-alignment of the foot, including toes including hammer

or claw toes, hallux valgus and midfoot collapse. Hallux valgus was recorded as

present if there was any medial deviation or abduction of the distal end of the first

metatarsal and lateral deviation of the hallux, and/or bony enlargement of the first

metatarsal head. PAD was defined as an ABI <0.90 on either side, or the presence

of a diabetes-related amputation

5. Neurological assessment: Sensory testing of feet was assessed using a

monofilament (5 sites tested on each foot), biothesiometry and ankle jerk

responses, to determine a Michigan Neuropathy Screening Instrument (MNSI)

clinical score. DPN was defined as a score of >2/8 on the clinical portion of the

MNSI.

6. Ophthalmic assessment: Visual acuity (corrected/uncorrected, with/without

pinhole), fundus photography through dilated or undilated pupils (depending on

quality of photographs).

7. Skin autoflourescence: Phase II only

8. Pulse wave velocity: In a randomly selected sample of 50% of Phase II patients

9. Overnight home-based sleep studies: In a subset of Phase II patients with

Berlin sleep scores that are low or high risk for obstructive sleep apnoea

The primary investigator and/or other specialist (eg. ophthalmologist) reviewed and

commented on the results of the initial assessment, and a summary sent to the patient, and

the patient‟s GP, if patient consent was obtained.

2.5.3 Laboratory Tests

Laboratory tests were carried out every second year. Patients are required to attend their

appointment after a >10 hour overnight fast in order to collect fasting plasma glucose and

HbA1c, serum lipid profile, serum urea, creatinine and electrolyte concentrations, serum

uric acid, urinary microalbumin and creatinine concentrations. Full blood counts were

recorded in Phase II. Extraction and storage of DNA was also carried out. All standard-

care assays were performed promptly in a single nationally accredited laboratory (PathWest

Laboratory Medicine, at FH). Aliquots of remaining serum, plasma and urine were stored

at -80°C for further specialised analyses as appropriate.

81

2.6 FDS annual assessment

Patients recruited during the first three years of the study were offered annual

reassessments, which included updating the FDS interview data along with physical

assessment and laboratory tests as previously described. In light of the relatively slow

changes in clinical and laboratory variables, it was decided that alternate year physical data

collection seemed more appropriate, and hence biennial postal/telephone assessments were

interspersed with these appointments.

2.7 Awareness of foot health

The sample for the cross sectional study of awareness of foot health comprised 358

unselected consecutive FDSII patients with type 2 diabetes who attended for face-to-face

assessment between April 2012 and January 2013. A foot assessment was conducted as

previously described, and participants completed a short questionnaire (Appendix B). The

questionnaire was developed by the primary investigator, and aimed to capture patient

awareness of their foot health using simple statements, and avoiding use of complex

medical terminology. The responses to the questionnaire were then compared with data

collected as part of the standard FDS protocol.

The FDS Phase II protocol and that for the present sub-study were approved by the

Human Research Ethics Committee of the Southern Metropolitan Area Health Service,

and all subjects gave informed consent before participation.

2.8 Diabetic Foot Care Education

A convenience sample of adults with type 2 diabetes participating in the FDSII was

recruited to the present study from August to October 2012 inclusive. When recruitment

to the intervention trial started, 1,017 of the surviving type 2 patients were eligible for the

study as they were still being assessed annually and were considered able to both provide

informed consent and complete all study procedures.

Both the FDS Phase II protocol and the intervention trial were approved by the Southern

Metropolitan Health Services Human Research Ethics Committee, and all subjects gave

informed consent before participation.

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2.8.1 Baseline assessment

Eligible FDSII participants who did not have active foot ulceration were invited to

participate in the intervention trial. Recruited patients were consecutively assigned to

Group A (written information) or Group B (interactive group education) (Appendix C). At

the initial visit, a standardized detailed bilateral foot assessment was performed and a foot

score out of 90 was generated based on presence and severity of 15 podiatric disorders.

The disorders included in the foot score assessment tool included complaints commonly

seen in clinical podiatric practice. The foot score was the primary variable of interest in the

present study. Patients also completed a modified Nottingham Assessment of Functional

Foot Care (NAFFC) survey (Appendix D). This is a validated assessment tool designed to

evaluate foot care behaviours in people with diabetes after exposure to an education

program (N. Lincoln, Jeffcoate, Ince, Smith, & Radford, 2007). They also completed a 6-

item attitudes survey, and were invited to comment on foot care-related worries in diabetes

(Appendix E). This attitudes survey was developed by the primary investigator, with input

from an experienced diabetes educator, and aimed to capture information thought to be

the most useful for evaluating changes pre and post intervention. Both the Foot Score and

the modified NAFFC and attitudes survey were pilot tested on a small convenience sample

of 25 patients attending for their FDS appointment.

2.8.2 Interventions

The interventions chosen for the study are available to patients with diabetes in the state of

Western Australia (WA) through the consumer organisation Diabetes WA. Patients in

Group A were provided with a detailed information booklet entitled My feet and diabetes: A

pictorial guide (Appendix F) to be read in their own time. This resource contains five

illustrated sections relating to foot care information, recommended foot care activities,

footwear problems and selection, and foot care tools with accompanying simple

explanatory text.

Patients allocated to Group B were asked to attend a single audio-visual education session

as part of a group of 10-15 people. These sessions were co-ordinated by a credentialed

diabetes educator (JD) and ran for approximately 90 minutes. They were based on the

interactive Footsmart education program developed by Diabetes WA which provides

information under the headings i) foot facts, ii) diabetes complications, iii) how diabetes

affects your feet, iv) how to care for your feet, v) how to choose a shoe, vi) how to check

your feet, and problems to look for. No written information was provided in this arm of

the study.

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2.8.3 Follow-up assessment

Patients were invited to a review three months after recruitment. At this follow-up

appointment, their feet were re-examined and a Foot Score was assigned. Patients also

completed the modified NAFFC survey and the 6-item attitudes survey.

2.9 Epidemiology of foot ulceration

Details of the FDS data collection process and clinical examination have been described

previously.

2.9.1 Data linkage

A government register records details of all deaths and hospital admissions in Western

Australia and is part of WADLS. The Confidentiality of Health Information Committee

approved WADLS linkage with the FDS database to ascertain outcome data. These

sources provided hospital admissions from the beginning of the study until 31st December

2011.

2.9.2 Hospitalisation for foot ulcer

All hospital admissions, whether public or private, for foot ulceration were identified using

relevant International Classification of Disease (ICD) procedure codes (ICD-9-CM and

ICD-10-AM). ICD-10-AM primary diagnosis codes E10.73 (Type 1 DM with foot ulcer

due to multiple causes), E11.73 (Type 2 DM with foot ulcer due to multiple causes),

E13.73 (other specified DM with foot ulcer due to multiple causes) and E14.73

(unspecified DM with foot ulcer due to multiple causes) were coded as a foot ulcer with

verification from the casenotes if required. Casenote review was also performed in all

patients with ICD-10-AM codes L97 (ulcer of lower limb not elsewhere classified) and

I70.23 (atherosclerosis of native arteries of leg with ulceration), and, since ICD-9-CM

codes did not include a specific diagnosis code for diabetes-related foot ulcer, those with

codes 707.1 (ulcer of lower limb, except decubitus) and 440.23 (atherosclerosis of the

extremities with ulceration).

84

85

Chapter Three

Self-awareness of foot health status in patients with

type 2 diabetes: The Fremantle Diabetes Study (Phase

II)

86

87

Self-awareness of foot health status in patients with

type 2 diabetes: The Fremantle Diabetes Study (Phase

II)

3.1 Introduction

Diabetes-related foot complications represent a major public health problem due to the

associated personal, economic and health care burden (A. J. Boulton, Vileikyte, Ragnarson-

Tennvall, & Apelqvist, 2005). DPN, PAD and foot ulceration are all common and readily

detectable, but many patients with these complications remain undiagnosed (Herman &

Kennedy, 2005; W. Wang, Balamurugan, Biddle, & Rollins, 2011). Self-awareness should

play an important role in the ascertainment of complications of diabetes, but available data

suggest that relatively few patients with established but asymptomatic complications are

cognisant of their presence. A longitudinal study of 2,992 adults from the National Health

and Nutrition Examination Survey who had chronic kidney disease found that, although

self-awareness was greatest amongst those with more advanced stages and risk factors, the

proportions of these patients remained <10% (Plantinga et al., 2008). A recent study

found that only 45% of US adults aged ≥40 years with diabetic macular oedema reported

being told by a physician that diabetes had affected their eyes or that they had retinopathy

(Bressler, Varma, Doan, & et al., 2014). In the context of diabetic foot disease, a recent

German population-based study (Bongaerts et al., 2013) found that 91% of 154 elderly

patients with pre-diabetes or diabetes and PSN had not been told by a physician that they

had nerve damage, but this was the only index of self-awareness determined by the

investigators. In a US primary care study, only about a half the patients with diabetes who

had PAD were aware of their condition (Jude et al., 2001).

In view of the paucity of detailed data relating to foot health self-awareness in diabetes, we

assessed patient perceptions of foot health and their clinical associates in a large sample of

patients drawn from a large, well-characterised, community-based cohort of patients with

type 2 diabetes.

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3.2 Patients and methods

Patient recruitment and methods is described in Chapter 2. Patients were asked to

complete a one page questionnaire designed to elicit information regarding perception and

awareness of their current foot health status (Appendix B). All were asked to answer yes or

no, with space for further written details, to the following questions: i) “Do you think that

your feet are normal (e.g. circulation, sensation, skin and nails)?”, ii) “Have you had any

problems with your feet in the last 12 months and, if yes, who noticed the problem and

what was the problem?”, iii) “Do you have numbness, tingling or pain in your feet?”, iv)

“Do you have poor circulation in your feet? ”, v) “Do you have a foot ulcer?”, vi) “Are

there any other problems you have noticed in your feet in the last 12 months?”

3.3 Statistical analysis

The computer package SPSS Statistics 20 (IBM Corporation, Somers, NY, USA) was used.

Data are presented as proportions and means (±SD), geometric mean (SD range), or for

data that do not conform to a normal or log-normal distribution, medians [interquartile

range (IQR)]. For independent samples, two-way comparisons for proportions were by

Fisher‟s exact test, Students t-test was used for normally distributed variables and the

Mann-Whitney U test for non-normally distributed variables. A two-sided P value of

<0.05 was considered significant without adjustment for multiple comparisons.

3.4 Results

The mean±SD age of the 358 participants was 67.4±10.8 years, 56.1% were males and

their median [IQR] diabetes duration was 9.0 [3.9-16.8] years. The majority (59%) were in

their second year of FDS follow-up (first biennial review), while the remainder were

attending their first (baseline assessment; 3%) or fourth year assessment (second biennial

review; 38%).

3.4.1 Prevalence and associates of self-perceived abnormal foot health

There were 213 patients (59.5%) who considered their feet to be normal and 145 (40.5%)

who felt that they had abnormal feet. The demographic and diabetes-related characteristics

of the sample categorised by self-perceived foot status are shown in Table 3-1. Compared

to those who considered their feet to be normal, the patients who felt their feet were

abnormal were older and had longer diabetes duration (P<0.001). They were less likely to

be married/in a de facto relationship, and more likely to be treated for hypertension and to

have a higher urinary albumin:creatinine ratio (P≤0.04).

89

Table 3-1. Sociodemographic and diabetes-related associates of self-perceived foot status.

Self-perception

of normal feet

Self-perception

of abnormal feet

P-value

Number 213 145

Age (years) 65.3±11.2 70.6±9.4 <0.001

Male (%) 55.9 56.6 0.91

Age at diagnosis (years) 55.7±11.4 57.7±10.8 0.09

Diabetes duration (years) 7.1 [3.0-15.4] 11.6 [5.3-19.0] <0.001

Diabetes treatment (diet/oral agents/

insulin/insulinoral agents %)

27.7/53.1/3.3/16.0 25.5/44.8/6.9/22.8

0.12

Education beyond primary level (%) 92.8 94.5 0.66

Married/de facto relationship (%) 70.9 60.0 0.040

Smoking status (never/ex-/current %) 50.5/42.4/7.1 44.8/50.3/4.8 0.29

Alcohol use (standard drinks/day) 0.1[0.0-1.2] 0.1 [0.0-1.2] 0.81

Body mass index (kg/m2) 30.9±5.6 31.3±5.7 0.53

Fasting plasma glucose (mmol/L) 7.5 [6.5-8.9] 7.5[6.5-9.2] 0.58

HbA1c (mmol/mol (%)) 49 [43-58] 51 [45-60] 0.26

(6.6 [6.1-7.5]) (6.8 [6.3-7.6])

Systolic blood pressure (mmHg) 142±21 146±22 0.13

Diastolic blood pressure (mmHg) 81±13 79±15 0.12

Antihypertensive treatment (%) 69.5 82.8 0.004

Total serum cholesterol (mmol/L) 4.4±1.0 4.3±1.1 0.11

Serum HDL-cholesterol (mmol/L) 1.20±0.33 1.17±029 0.37

Serum triglycerides (mmol/L) 1.5 (0.9-2.5) 1.5 (0.9-2.5) 0.85

Lipid-lowering treatment (%) 70.9 80.0 0.06

Aspirin use (%) 35.2 37.9 0.66

Urinary albumin:creatinine (mg/mmol)

2.2 (0.6-8.0) 3.3 (0.7-15.0) 0.015

Self-reported ischaemic heart disease (%)

12.2 19.3 0.07

Self-reported stroke (%) 1.9 3.4 0.49

There was a significantly greater proportion who reported any foot problems in the last 12

months in the group with self-reported abnormal foot health (see Table 3-2; P<0.001). Of

the 141 patients in both groups reporting foot-related problems in the past year, 68% were

noticed by the patient, 9% were identified by a health professional (general practitioner,

podiatrist or nurse educator), 16% were observed by both the patient and the health

professional, and no source of identification was reported in the remaining 6% of cases.

The patients who were aware of abnormal foot health were substantially more likely to

90

report a history of numbness/tingling/pain, poor circulation and foot problems in the

previous 12 months (P<0.001; see Table 3-2), but one in six patients who considered their

feet to be normal had symptoms of a peripheral sensory neuropathy and one in 20 was

aware of poor circulation. Out of the total 358 patients, there were 18 (5.0%) who

reported both numbness/tingling/pain and intermittent claudication, and of these, 4

(22.2%) thought their feet were normal.

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Table 3-2. Foot-related associates of self-perceived foot status. Data relate to findings in

one or both feet. Data are percentages.

Self-perception of normal feet

Self-perception of abnormal feet

P-value

Self-reported numbness/tingling/pain 17.8 70.3 <0.001

Self-reported poor circulation 5.6 53.1 <0.001

Self-reported any problem with feet in last year

19.2 69.0 <0.001

Podiatry appointments in past year (0-2/3-5/6-8/9+)

19.7/30.0/9.4/40.8 20.0/33.8/8.3/37.9 0.87

Foot examinations in past year (0-2/3-5/6-8/9+)

26.8/18.3/4.7/50.2 25.5/20.7/3.4/50.3 0.90

Any abnormality 86.9 93.1 0.08

Foot deformity 35.7 37.9 0.74

Dry skin or callus 76.1 75.2 0.90

Infection or fissure 2.8 4.1 0.56

Foot ulcer 0.0 2.1 0.07

Other foot problems 23.9 36.6 0.013

Absent ankle reflex 37.1 47.6 0.050

Biothesiometer response ≥20V 21.1 42.8 <0.001

Light touch not detected in toes 5.6 25.5 <0.001

Monofilament not detected in toes 1.9 17.2 <0.001

Neuropathy (MNSI score >2/8) 67.9 77.1 0.056

Dorsalis pedis pulse absent 2.8 14.5 <0.001

Posterior tibial pulse absent 6.1 15.9 0.004

Peripheral arterial disease (ABI <0.9 and/or diabetes related amputation)

9.9 22.2 0.002

Self-reported intermittent claudication 5.2 11.0 0.043

DPN and PAD 6.1 15.3 0.001

There was no association between a patient‟s perception of foot health and the number of

times a patient had been to a podiatrist or had their feet examined in the previous 12

months (P≥0.87). Exactly 50.0% of the total sample of patients reported that they had not

had their feet examined by a health care professional in the past 12 months.

The majority of the 358 patients (89.4%) had one or more abnormalities on foot

inspection. In those who considered their feet to be normal, 86.9% had at least one

abnormality compared with 93.1% in those who felt they had abnormal feet (P=0.08; see

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Figure 3-2). In relation to categories of abnormality, the most common clinically-relevant

finding was dry skin or callus which was present in at least three quarters of the patients in

both groups (see Table 3-2). However, the only significant between-group difference in

specific foot abnormality was for common problems other than deformity (most

commonly hallux valgus), dry skin/callus and infection/fissure. Patients who were aware of

abnormal foot health were more likely to have a fungal nail or skin infection, recent nail or

skin trauma, heloma dura (corns), rash, oedema, blistering or verrucae on either or both

feet. Three patients had a foot ulcer and three had amputations (one patient had both) and

all considered their feet abnormal.

Patients who were aware of abnormal foot health were significantly more likely to have

absent ankle reflexes, and abnormal responses to vibration, light touch and monofilament

assessment (see Table 3-2; P≤0.05). They were more likely to have an MNSI score >2/8

but this did not reach statistical significance (P=0.056). The majority of patients who

regarded their feet as normal had objective evidence of PSN (see Figure 3-1).

Figure 3-1. Pie graphs showing findings on standardised foot examination classified by self-

perceived foot health status.

86.9

13.1

93.1

6.9

67.9

32.1

77.1

22.9

9.9

90.1

22.2

77.8

93.9

6.1

84.7

15.3

Self-perception of normal feet (%)

Self-perception of abnormal feet (%)

Abnormal foot appearance (any abnormality) (P=0.08)

Peripheral sensory neuropathy (MNSI >2/8; P=0.56)

Peripheral arterial disease (ABI <0.9;

P=0.002)

Peripheral sensory neuropathy and peripheral arterial disease (P=0.001)

Present

Absent

93

The patients with self-reported abnormal foot health were more likely to have absent

dorsalis pedis and posterior tibial pulses (P≤0.004). The prevalence of PAD was also

significantly greater in this group (P=0.002) but almost 10% of patients who regarded their

feet as normal had objective evidence of PAD (see Figure 3-1).

Although more patients with abnormal foot health self-perception had both DPN and

PAD (P=0.001), there were still over 6% of patients who considered their feet healthy in

this category (see Figure 3-1). The characteristics of these patients in comparison with

those of others who felt their feet were normal are shown in Table 3-3. Those without

objective evidence of foot pathology who believed their feet were normal were younger

than those with foot-related complications in the other groups (61.8±11.3 years vs.

66.4±11.0, 67.1±11.6 and 68.9±8.9 years in those with DPN alone, PAD alone and both

DPN and PAD, respectively; P=0.031), and they had a lower urinary albumin creatinine

ratio and lower pulse pressure (P≤0.007), but there were no other significant differences in

a range of socio-demographic, diabetes-related and other variables.

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Table 3-3. Associates of foot complications in patients who perceived their feet to be

normal.

No neuropathy or PAD

Neuropathy only

PAD only PAD and neuropathy

P-value

Number (%) 61 (28.6) 131 (61.5) 8 (3.8) 13 (6.1)

Age (years) 61.8±11.3 66.4±11.0* 67.1±11.6 68.9±8.9 0.031

Male (%) 63.9 53.4 37.5 53.8 0.39

Ethnicity (% Anglo-Celt/Southern European/Other)

50.8/8.2/41.0 62.6/9.9/27.5 75.0/12.5/12.5 53.8/7.7/38.5 0.46

Fluent in English (%) 100.0 95.4 100.0 92.3 0.23

Education beyond primary level (%)

96.6 91.5 100.0 84.6 0.29

Married/de facto relationship (%)

82.0 67.2 50.0 69.2 0.08

Gross household income (≤$25,000)

9.4 24.0 25.0 20.0 0.11

Age at diagnosis (years) 52.6±11.3 56.6±11.7 58.6±11.3 59.2±6.5 0.06

Diabetes duration at time of study (years)

6.3 [2.7-15.0] 7.1 [3.3-15.9] 5.4 [3.2-16.9] 8.8 [4.3-15.0] 0.88

Body mass index (kg/m2) 30.0±5.4 31.5±5.7 32.1±5.7 29.4±5.7 0.24

Fasting serum glucose (mmol/L)

7.3 [6.5-8.6] 7.4 [6.5-8.9] 7.5 [6.0-12.2] 8.4 [7.3-9.5] 0.38

HbA1c (mmol/L (%)) 49 [43-58]

(6.6 [6.1-7.5])

50 [44-58]

(6.7 [6.2-7.5])

44 [42-66]

(6.2 [6.0-8.2])

56 [44-62]

(7.3 [6.2-7.8])

0.64

Diabetes treatment (% diet/oral agents/ insulin±oral agents)

34.4/49.2/16.4 25.2/54.2/20.6 37.5/50.0/12.5 15.4/61.5/23.1 0.77

Systolic blood pressure (mm Hg)

142±23 141±20 137±15 157±22 0.054

Diastolic blood pressure (mm Hg)

83±15 80±13 78±11 80±15 0.61

Pulse pressure (mm Hg) 59±14 61±18 60±16 78±25**,†† 0.007

Antihypertensive medications (%)

57.4 74.0 75.0 76.9 0.12

Total serum cholesterol (mmol/L)

4.6±1.0 4.4±0.9 4.4±1.7 4.6±0.9 0.52

Serum HDL cholesterol (mmol/L)

1.22±0.32 1.20±0.35 1.14±0.31 1.22±0.28 0.91

Serum triglycerides (mmol/L) 1.5 (0.9-2.7) 1.4 (0.9-2.2) 1.7 (0.9-3.0) 1.8 (0.8-4.1) 0.39

Lipid-modifying medications (%)

68.9 72.5 62.5 69.2 0.85

On aspirin (%) 24.6 39.7 62.5 23.1 0.053

Urinary albumin:creatinine ratio (mg/mmol)

1.7 (0.5-5.6) 2.2 (0.6-7.5) 4.0 (0.8-20.1) 6.2 (1.4-28.5)**,†

0.004

Estimated glomerular filtration rate <60 ml/min/1.73m2 (%)

70.5 75.6 87.5 76.9 0.77

Self-reported stroke (%) 1.6 1.5 0.0 7.7 0.41

Self-reported ischaemic heart disease (%)

4.9 15.3 12.5 15.4 0.15

Smoking status (%): never/ex-/current

50.0/45.0/5.0 52.3/41.5/6.2 62.5/25.0/12.5 25.0/50.0/25.0 0.18

Alcohol consumption (standard drinks/day)

0.3 [0-1.3] 0.1 [0-0.8] 0 [0-0.6] 0.1 [0-1.5] 0.26

Values are proportions, mean±SD, geometric mean (SD range), and median [IQR]. For those comparisons with significant trends: *P<0.05; ** P<0.01; *** P<0.001 versus no PAD and no neuropathy; † P<0.05; †† P<0.01; ††† P<0.001 versus neuropathy only

95

3.5 Discussion

Detailed cross-sectional data from a large community-based sample of patients with type 2

diabetes shows that clinically-relevant foot abnormalities are very common, including in

those who consider their feet to be normal. Over two-thirds of patients in this latter group

had DPN, nearly 10% had PAD, and most had one or more features on inspection such as

deformity, dry skin, callus and fissures that could facilitate the development of more

serious pathology including ulceration and infection (Ledoux et al., 2005; Murray, Young,

Hollis, & Boulton, 1996; Reiber et al., 1999). This unawareness was related to older age.

These data suggest that the foot health-related aspects of diabetes education programs

should be improved, especially those delivered to elderly patients.

Illness perception is usually a consequence of the detection of unusual bodily symptoms,

and experiencing physical symptoms such as pain leads the patient to recognise that

his/her health is abnormal (Lange & Piette, 2005; Mechanic D, 1972). Consistent with this

suggestion, over 70% of the patients who regarded their feet as abnormal reported

numbness, tingling and/or pain compared with only 17.8% in the group who thought their

feet were normal. In a German population-based study (Bongaerts et al., 2013), elderly

participants who were aware of diagnosed DPN were also more likely to report recent foot

pain, paresthesiae and numbness, while a study of 816 patients with type 2 diabetes living in

five rural communities in the US also found a significant association between neuropathy

diagnosis and symptoms of DPN (W. Wang et al., 2011). By contrast, and consistent with

past studies (A. J. M. Boulton, 2012), 46% of the patients with diagnosed DPN did not

report numbness, tingling and/or pain. Patients who are asymptomatic or whose

symptoms are not severe enough to suggest they are abnormal are still at increased risk of

foot ulceration.

The data also shows that the perception of poor circulation was significantly associated

with self-awareness of abnormal foot health. This may have reflected the incorrect but

apparently common belief that foot pain and sensory changes are both prominent

manifestations of PAD complicating diabetes (Gale, Vedhara, Searle, Kemple, & Campbell,

2008; Hirsch et al., 2001), especially since diagnosed PAD was much less prevalent than

self-reported poor circulation in the patients who thought they had abnormal feet (22.1 %

vs. 53.1%). We did not assess whether awareness of poor circulation extended to its health

consequences. In a study of patients attending diabetes specialist centres in Ireland, only

16.3% recognised that PAD is associated with adverse health outcomes (O'Sullivan et al.,

96

2009). Similarly, a Moroccan study showed that >50% of patients with diabetes were not

aware of the risks associated with the diabetic foot (Lamchahab et al., 2011).

Perhaps the most concerning observation in the present study was that common

observable foot problems such as deformity, dry skin, callus, fissures and infections were

not associated with perceived abnormal foot health status. In fact, almost 90% of patients

in the total sample had at least one of these features without a significant difference in

prevalence between the two awareness groups. This suggests that patients do not consider

these disorders to be abnormal or that they are overlooked, especially as they can remain

asymptomatic. Foot deformities, dry skin, and callus are recognised risk factors for foot

ulceration (Ledoux et al., 2005; Murray et al., 1996; Reiber et al., 1999), especially in concert

with ill-fitting footwear (Jan Apelqvist et al., 1990). Even mild xerosis cutis reduces skin

elasticity and hydration of the stratum corneum, and has the potential to increase the risk

of elevated shearing forces and the formation of skin fissures (Sakai, Kikuchi, Satoh,

Tagami, & Inoue, 2005), features that are likely to contribute to the ulcers which develop in

low risk patients without significant PSN (Calle-Pascual et al., 2002).

The present data suggest that an important first step in optimising foot care in a patient

with diabetes is to ask about self-perceived foot health, as recommended previously by the

American Diabetes Association (American Diabetes Association, 2004). The response

should be assessed in relation to the findings on foot examination. The patients at greatest

potential risk are those who feel that their feet are normal but who have objective evidence

of DPN and/or PAD, since they may underplay or ignore subsequent serious

complications such as ulcers and cellulitis. This group represented over a third of the

present 358 patients. Even in patients with both symptomatic DPN and intermittent

claudication, almost a quarter regarded their feet as normal.

In a developed country with a well-resourced health system such as Australia, this relatively

high percentage may reflect inadequate government funding for diabetic foot care despite

subsidised allied health consultations (Lazzarini, Gurr, Rogers, Schox, & Bergin, 2012),

with the likelihood that available resources are insufficient for optimal foot assessment and

education. Indeed, >80% of patients in both awareness groups had undergone foot

examination in the previous 12 months, consistent with national recommendations (Baker

IDI Heart and Diabetes Institute, 2011), but patient awareness remained suboptimal

suggesting that there may be insufficient time and personnel to conduct durable education.

The situation is likely to be worse in the US, since a study of 55 community health centres

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found that only 51% of patients received any foot education and care (Chin et al., 2000).

Even a hospitalisation with an acute diabetes-related foot problem may not prompt

adequate assessment since an audit of such patients in a major Australian metropolitan

hospital showed that the rates of inpatient neurological examination by monofilament,

measurement of ABI and review of footwear were all <20% (Jessup, Spring, & Grollo,

2007).

This study had limitations. The foot health questionnaire relied on each patient‟s

understanding of normality, which may reflect social, psychological and situational

contexts, including access to health resources and facilities, as well as personal theories or

beliefs (Lange & Piette, 2005; Sen, 2002). We cannot exclude recall bias, and no attempt

was made to adjust for individual differences in foot-related education prior to recruitment.

The study was cross-sectional and so analyses have been restricted largely to bivariate

comparisons. The prevalence of DPN (approximately two-thirds of patients) was high

compared to a figure of around 50% in other samples (Vinik, Nevoret, Casellini, & Parson,

2013), but we used multiple vs. single testing modalities, recruitment strategies included

targeting older individuals (such as those in nursing homes) to increase the representative

nature of the cohort (T. M. Davis et al., 2013), and the median diabetes duration was

relatively long. The foot health survey has not yet been validated, and so results should be

evaluated in that context. The strengths of the present study include its relatively large

sample from a community-based cohort and detailed data collection.

The present study has shown that patients with type 2 diabetes and asymptomatic but

definite DPN are relatively common. Most of these patients consider that their feet are

normal, and they may represent a group at high risk of complications such as foot

ulceration as a result. Approaching 50% of patients with PAD also consider that they have

normal feet. Although relatively small in number, they may also be at high risk of

complications, especially since more than half of them have co-incident DPN. Foot

abnormalities such as dry skin, callus and fissures were as frequent in patients who

perceived their feet to be normal as in those who considered they had abnormal feet,

suggesting that these features are often unnoticed, disregarded or downplayed. The gaps in

patient understanding of common precursors to future potential foot complications of

diabetes need to be addressed in diabetes education programs, which should emphasise the

value of ascertaining and reversing patient unawareness of neurovascular and other

clinically significant abnormalities.

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99

Chapter Four

A comparison of two methods of foot care education:

The Fremantle Diabetes Study

100

101

A comparison of two methods of foot care education:

The Fremantle Diabetes Study

4.1 Introduction

Patient education is an important element of diabetes care, with demonstrated benefits for

knowledge, skills and self-care behaviours (Brown, 1990, 1992; Mazzucca S et al., 1986).

Although foot care education programs are recommended as part of overall diabetes

management (American Diabetes Association, 2004, 2013; J. Apelqvist et al., 2000; Baker

IDI Heart and Diabetes Institute, 2011), data substantiating their effectiveness are

inconsistent (Dorresteijn Johannes et al., 2010; Valk et al., 2002). There is evidence to

suggest that targeted education improves foot care knowledge and behaviour (Barth et al.,

1991; Corbett, 2003; Donohoe et al., 2000; Ward et al., 1999) but methodological

limitations such as small sample sizes and high attrition rates limit the generalizability of the

findings. In addition, there is substantial variability in the style, structure and content of

diabetes foot care education programs, and uncertainty as to the most effective format

(Brown, 1999; Radford K et al., 2006).

Contemporary diabetes education focuses on general management which has been shown

to have some effect on anthropometric and/or metabolic variables. For example, a meta-

analysis of the effects of educational and behavioural interventions in type 2 diabetes

identified modest benefits for glycaemic control but non-significant reductions in body

weight (Gary, Genkinger, Guallar, Peyrot, & Brancati, 2003). Assessing the impact of

education on foot-related outcomes is more difficult, and few high quality randomized

trials have been performed as a result. Barth and colleagues investigated the effect of

intensive versus conventional education on foot care knowledge and compliance, and

attendance at a podiatrist over a six-month period (Barth et al., 1991). The intensive group

received a total of nine hours of education over four weeks including psychologist-directed

motivational techniques, while the conventional group received a single one-hour lecture.

Intensive intervention improved foot care knowledge, compliance with foot care advice

and podiatry attendance (Barth et al., 1991). The patients in this group had fewer foot-

related problems after one month of follow-up, but this was not maintained at three and

six months (Barth et al., 1991). Cost-effectiveness was not examined and there was no

analysis of which elements of the intensive program were the most beneficial (Barth et al.,

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1991).

Patients with diabetes in developed countries like Australia will typically either access

written information or participate in a group session that allows interaction with an

accredited diabetes healthcare professional. Given that more intensive and costly programs

such as assessed by Barth and colleagues are unlikely to be implemented widely, as well as

the overall paucity of data relating to the effectiveness of diabetic foot care education in the

community, there is a need for a comparative trial of the impact of written diabetes-related

foot care information vs. that after an interactive group session on foot health, foot care

behaviours and attitudes towards diabetes related foot problems in patients with type 2

diabetes.


Patient recruitment was described in Chapter 2. A convenience sample of adults with type

2 diabetes participating in the Fremantle Diabetes Study Phase II (FDSII) was recruited to

the present study from August to October 2012 inclusive. Recruited patients were

consecutively assigned to Group A (written information) or Group B (interactive group

education). At the initial visit, a standardized detailed bilateral foot assessment was

performed (by MB) and a Foot Score out of 90 was generated based on presence and

severity of 15 podiatric disorders (see Appendix D). This was the primary variable of

interest in the present study. Patients also completed a modified Nottingham Assessment

of Functional Foot Care (NAFFC) survey. This is a validated assessment tool designed to

evaluate foot care behaviours in people with diabetes after exposure to an education

program (N. Lincoln et al., 2007). They also completed a 6-item attitudes survey, and were

invited to comment on foot care-related worries in diabetes.

For the purposes of the present study, 10 of the 29 NAFFC questions were selected to

simplify the questionnaire and to make it relevant to Australian culture and climate,

specifically: “Do you examine your feet?”, “Do you check your shoes before you put them

on?”, “Do you wash your feet?”, “Do you dry between your toes?”, “Do you use

moisturizing cream on your feet?”, “Do you wear shoes without socks/stockings?”, “Do

you walk around the house barefoot?”, “Do you walk outside barefoot?”, “Do you use

corn remedies/corn plasters if you get a corn?”, and “Do you put a dry dressing on a graze,

cut or burn when you get one?” (see Appendix E). A 0-3 integer scale based on the

frequency of the individual foot health-related behavior was used to quantify responses,

with maximum score (indicating excellent functional foot care) of 30.

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For the 6-item attitude survey, patients were also asked to categorize their responses to the

following statements or questions: “Foot problems are more likely to lead to complications

in people with diabetes”, “Do you think you are likely to develop foot complications?”, “I

feel well informed about the risks of developing diabetes related foot complications”,

“How well do you understand how to prevent diabetic foot complications?”, “Would you

like more information about diabetes foot complications?”, and “How often do you feel

overwhelmed with the demands of living with diabetes?” (see Appendix F).

4.2.1 Interventions

These interventions chosen for the present study are available to patients with diabetes in

the state of Western Australia (WA) through the consumer organisation Diabetes WA.

Patients in Group A were provided with a detailed information booklet entitled My feet and

diabetes: A pictorial guide to be read in their own time. This resource contained five illustrated

sections relating to foot care information, recommended foot care activities, footwear

problems and selection, and foot care tools with accompanying simple explanatory text (see

Appendix G).

Patients allocated to Group B were asked to attend a single audio-visual education session

as part of a group of 10-15 people. These sessions were co-ordinated by a credentialed

diabetes educator (JD) and ran for approximately 90 minutes. They were based on the

interactive Footsmart education program developed by Diabetes WA which provides

information under the headings i) foot facts, ii) diabetes complications, iii) how diabetes

affects your feet, iv) how to care for your feet, v) how to choose a shoe, vi) how to check

your feet, and problems to look for. No written information was provided in this arm of

the study.

4.2.2 Follow-up assessment

Patients were invited to a review three months after recruitment. At this follow-up

appointment, their feet were re-examined and a Foot Score was assigned. Patients also

completed the modified NAFFC survey and the 6-item attitudes survey.


An initial pilot study was performed in which a Foot Score was generated in 25 patients

with diabetes who attended for FDS review but who were not recruited to the present

study. Based on a mean change (∆) in Foot Score of 3 with a standard deviation of 6, a

sample size of 64 in each group was needed to reject the null hypothesis that the

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population means were equal, with 80% power and probability of a type I error (α) of 0.05

(Dupont & Plummer, 1990). After allowing for 10% attrition, the target sample size was

70 participants per group.

Statistical analyses were performed using IBM SPSS Statistics 21 (IBM Corporation,

Somers, NY, USA). Normality was assessed using Shapiro-Wilk normality tests and

examination of histograms. Data are summarised as mean±SD, median [interquartile range]

or percentages. Two sample comparisons for normally-distributed variables were by

Student‟s t-tests or paired t-tests. Mann Whitney U-tests or Wilcoxon signed rank tests

were used for non-normally distributed variables. Responses to questions 1 and 4 of the

attitudinal survey were dichotomised into agreement (agree/strongly agree) or disagreement

(disagree/strongly disagree) for analysis. Comparisons of proportions were by Fisher‟s

exact or McNemar‟s or McNemar-Bowker tests. Percentage change in Foot Score and

NAFFC Survey score was calculated by subtracting the score at study entry from the score

at three months, dividing the result by the entry score, and multiplying by 100. Associations

between changes in foot and survey scores by group were assessed by Student‟s t-test and

linear regression, adjusting for baseline values. Generalised linear modelling (GLM) was

used to test whether the changes over time in the responses to the Foot and Survey Scores

and Attitudes Survey differed significantly by group. A binomial probability distribution

with logit link was used for binary variables and an ordered logistic model with multinomial

probability distribution and cumulative logit link function for multinomial responses. A

two-tailed significance level of 0.05 was used.

4.4 Results

We recruited 154 patients (78 to Group A and 76 to Group B) who, compared with the

863 eligible but non-recruited FDSII participants, were of similar age (68.1±10.3 vs.

67.9±11.1 years, P=0.81) and sex (59.7% vs. 52.5% male, P=0.11), and had a similar

duration of diabetes (11.4 [5.3-18.6] vs. 10.3 [5.1-17.9] years, P=0.53). Details of the

recruited patients at entry categorized by allocated intervention are shown in Table 4-1.

There were no significant between-group differences in age, sex, ethnicity, diabetes

duration, diabetes control or history of diabetes education in the previous 12 months.

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Table 4-1. Patient characteristics at trial entry by allocated intervention.

Group A Group B P-value

Number 78 76 Age (years) 69.5 ±10.5 66.3 ±10.0 0.06 Male (%) 52.6 67.1 0.07 Diabetes duration (years) 12.2 [6.9-19.2] 9.4 [4.4-18.5] 0.12 Ethnicity (%)

Anglo-Celt Southern European

Other European Asian

Mixed/Other

60.3 3.8 5.1 7.7 23.1

59.2 7.9 11.8 5.3 15.8

0.35

Diabetes treatment (%) Diet

Oral agents Insulin

Insulin+oral agents

11.5 38.5 5.1 44.9

19.7 40.8 2.6 36.8

0.43

Waist:hip ratio 0.97±0.07 0.95±0.10 0.41 Attended diabetes education in the past year (%)

No Yes

48.0 52.0

60.0 39.4

0.14

4.4.1 Intervention effects

Of the recruited patients, 148 (96%) attended the 3-month follow-up assessment. Five

participants did not re-attend (one from Group A and four from Group B) and their

scores/responses from baseline were carried forward in the intention to treat (ITT)

analysis. For the single participant who was recruited but did not attend the baseline

assessment, follow-up scores/responses were carried backwards.

At baseline, the Foot Score was significantly greater in Group A (P=0.012; see Table 4-2)

but there was no between-group difference at 3 months (P=0.73). The mean change (∆) in

Foot Score was significantly greater for Group A than Group B (-1.8 (95% CI: -2.4 to -1.2)

vs. -0.1 (-0.7 to 0.4), P<0.001). The Foot Score decreased by a mean of 15.9% in Group A

relative to the baseline value, but increased by 8.7% in Group B (between-group difference

24.5 (95% CI 6.7-42.4)%, P=0.007; see Table 4-2). After adjustment for the baseline value,

the Foot Score was 1.2 (0.4-1.9) greater at 3 months in Group A relative to Group B.

The responses to the NAFFC Survey in the two groups were not significantly different at

baseline (P=0.97). There was a trend to higher scores in both groups at 3 months (see

Table 4-2), but neither the mean change in NAFFC Survey score nor the mean percentage

change was significantly different by group (P≥0.13), including after adjustment for the

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baseline score. There was no association between change in Foot Score and ∆NAFFC

Survey score after adjustment for baseline values of each (P=0.21).

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Table 4-2. Baseline, and absolute and percentage change (∆), in Foot Score and NAFFC survey score by allocated intervention.

Group A Group B P-value (Baseline)

P-value (∆)

P-value

(% ∆)

Baseline Mean ∆ (95% CI) over 3 months

% ∆ over 3 months

Baseline Mean ∆ (95% CI) over 3

months

% ∆ over 3 months

Foot Score 8.3 ±3.6 -1.8 (-2.4 to -1.2) -15.9 6.8 ±3.6 -0.1 (-0.7 to 0.4) 8.7 0.012 <0.001 0.007

NAFFC score

17.0 ±4.5 0.3 (-0.5 to 1.0) 5.9 17.0 ±4.4 1.0 (0.4 to 1.7) 8.3 0.97 0.13 0.29

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The responses to the attitudes survey by group are summarised in Table 4-3. There was

near complete awareness of the increased risk of foot complications in diabetes (Question

1) which did not change over time. In terms of personal risk of foot complications

(Question 2), approximately one-third of patients in each group felt that they were unlikely

to develop foot complications before intervention (P=0.56) and these proportions did not

change over time (P=0.86). Most patients in both groups felt well informed about the risks

of developing diabetes-related foot complications at baseline (Question 3) and there were

further increases in these proportions at 3 months (P≤0.039), but there was no difference

in this change between the groups (P=0.52). In relation to prevention (Question 4), self-

reported understanding of preventive measures was low in about one-third of patients in

both groups before intervention. This proportion did not change in Group A (P=0.07) but

had fallen significantly in Group B at 3 months (P<0.001). Most patients in both groups

wanted more information regarding foot care before intervention (Question 5) and these

proportions decreased significantly (both P<0.001), but there was no difference in this

change by group (P=0.63). More participants in Group B were often overwhelmed by the

demands of living with diabetes (Question 6) and there was a significant reduction in this

proportion at 3 months (P=0.020), but the between group difference in change in response

to this question after intervention did not reach statistical significance (P=0.08).

Responses to the open-ended question regarding worries about diabetes foot complications

were classified under the common themes of amputation, ulceration, mobility and other.

Amputation was by far the most important concern at study entry, with 32% worried about

this as a consequence of diabetes, while 5% were worried about ulceration and 8% were

worried about impacts on mobility. These figures did not change after intervention (38%,

5% and 11%, respectively, P=0.39) (see Figures 4-1 and 4-2).

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Table 4-3. Attitudes survey responses at baseline and at 3 months by intervention group.

Question/Statement Response options Group A P-value Group B P-value P-value*

Baseline 3 months Baseline 3 months

Foot problems are more likely to lead to complications in diabetes (%)

Agree/Strongly agree Disagree/Strongly disagree

97.4 2.6

97.4 2.6

1.0 98.7 1.3

100.0 0.0

- 0.57

Do you think you are likely to develop foot complications? (%)

Not likely Quite likely Very likely

32.1 51.3 16.7

33.3 55.1 11.5

0.56 36.8 50.0 13.2

42.1 43.4 14.5

0.53 0.86

I feel well informed about the risks of developing diabetes related foot complications (%)

Agree/Strongly agree Disagree/Strongly disagree

80.5 19.5

90.0 9.1

0.039 81.6 18.4

96.1 3.9

0.003 0.52

How well do you understand how to prevent foot complications? (%)

Very well Moderately well Not at all well

10.3 56.4 33.3

20.5 53.8 25.6

0.07 14.5 52.6 32.9

32.9 59.2 7.9

<0.001 0.031

Would you like more information on foot care in diabetes? (%)

Yes No

97.4 2.6

66.7 33.3

<0.001 85.5 14.5

59.2 40.8

<0.001 0.63

How often do you feel overwhelmed with the demands of living with diabetes? (%)

Never Rarely Sometimes Often

30.8 38.5 26.9 3.8

32.1 37.2 23.1 7.7

0.72 26.3 32.9 26.3 14.5

26.3 42.1 27.6 3.9

0.020 0.08

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Figure 4-1. Responses to open-ended question regarding worries about diabetes foot

complications before education.

Figure 4-2. Responses to open-ended question regarding worries about diabetes foot

complications after education.

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4.5 Discussion

The present data suggest that provision of detailed written foot care information is more

effective than interactive education in improving overall foot health as assessed by an

aggregate Foot Score in patients with type 2 diabetes. However, interactive education may

improve patient understanding of key preventive measures more than written information.

These data suggest that perhaps the combination of illustrated written material and an

interactive group session could provide the best approach to foot care education in

community-based patients with type 2 diabetes.

The Foot Score was developed as a summary measure of abnormalities that are readily

detectable in usual practice but which have implications for the development of more

serious complications and associated morbidity (Ledoux et al., 2005; Murray et al., 1996;

Reiber et al., 1999). Most of the patients in both groups had relatively low Foot Scores at

baseline, consistent with the community-based nature of the sample, but there was still

improvement in Group A during the three months after intervention. Available data on

patient education resources suggest that communication tools in most formats (verbal,

written, video, provider-delivered and computer-based) increase patient understanding but

are more likely to do so if interactive (Trevena, Davey, Barratt, Butow, & Caldwell, 2006),

but the interactive education did not improve the Foot Score.

There are several possible explanations for the observation that written material was more

effective at improving overall foot health than interactive group education. First, Group A

patients were able to refer to the information provided during follow-up and this may have

prompted more sustained awareness of self-care including preventive measures. Second,

the risk of messaging confusion is inherent in interactive education (Sakraida & Robinson,

2009), including misunderstanding of technical terms and illustrative data, insufficient time

to process information, and non-attentiveness. It is of potential relevance to these first two

explanations that intensive group education in the study conducted by Barth and colleagues

(Barth et al., 1991) was not associated with improved compliance with foot care advice at

three months post-intervention. Third, it is possible that, although we adjusted for baseline

Foot Score and still found a significant between-group difference, the higher mean value in

Group A at baseline itself prompted a greater improvement in subsequent self-care.

In a retrospective study of patients receiving standard outpatient diabetes care versus group

education, improvements in foot appearance were noted in the intervention group,

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specifically fewer skin problems such as dryness, fissures and blisters, that reflected

improvements in some foot care behaviours including drying between toes after washing

and wearing socks with shoes (Sun et al., 2009). This result might appear contrary to the

present findings but it should be emphasized that all the participants had already received

foot care advice as part of conventional education at diagnosis and perhaps also through

subsequent interactions with diabetes nurse educators and/or podiatrists as part of

Australian primary care management (Menz, 2009). This is reflected in the observation

that most patients in both groups felt well informed about the risks of developing diabetes-

related foot complications at baseline, but most also wanted more information regarding

foot care with both interventions having reduced this need significantly at the three-month

review.

Although responses to the NAFFC Survey did not change in either group as a result of the

interventions, the questions asked do not provide data on how rigorously foot care

preventive and treatment measures are implemented. The data suggest that patients in

Group A improved their Foot Score through more attentive rather more frequent

preventive and remedial foot health measures. The mean baseline NAFFC was 17 out of

30 (or 57%) in both groups of patients in the present study, which is similar to mean scores

of 52 out of 87 (60%) in the 65 without neuropathy and 55 (63%) in the 14 with

neuropathy who comprised the outpatient sample of patients with type 2 diabetes in whom

the full NAFFC was validated (N. Lincoln et al., 2007). These data suggest that the

patients were not atypical in their responses to the NAFFC questionnaire.

The significant finding from the attitudes survey was that interactive education increased

the percentage of patients who felt that they understood how to prevent foot

complications of diabetes while this change was directionally similar but did not reach

statistical significance in Group A. Although the improved self-reported understanding of

preventive measures was not paralleled by a reduction in Foot Score at the three month

review in Group B, it is likely that implementation of these better understood measures

would have been helped by written information as provided to Group A, but an

examination of this hypothesis was beyond the scope of the present study.

Approximately one third of patients spontaneously raised amputation as a specific concern

and this proportion did not change after interventions designed to enable better foot

health. Consistent with this finding, a similar proportion of patients felt overwhelmed by

the demands of diabetes at least sometimes. These data show that community-based

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patients with type 2 diabetes are aware of the serious nature of foot complications but may

need support with self-management that minimises the risk of their occurrence. This

includes those who think they are unlikely to develop foot complications (around one in

seven of the present sample), and a targeted framework now exists to guide foot care

education among patients categorised as low risk (McInnes et al., 2011).

This study had limitations. The Foot Score has not yet been validated but will be utilised in

future studies of foot outcomes in the present patients. We used a modified version of the

validated NAFFC survey tool to improve both compliance with study procedures and

relevance to an Australian context. Participants were followed for only three months and

this may have been insufficient time for assessment of changes in foot health or foot care

behaviours. Nevertheless, some studies have shown benefits for multi-faceted educational

intervention over a similar period (Corbett, 2003), while those employing longer follow-up

periods have not always shown durable or delayed improvement (Barth et al., 1991). We

did not include a group who received no intervention but the aim was to compare specific

active interventions. Although participants in Group A were clearly instructed to read the

information provided to them, there was no absolute guarantee that this occurred. Finally,

we did not recruit indigenous Australians because the foot care information utilised did not

include culturally acceptable language and images, which has been recognised as an

important component of imparting health care messages to Aboriginal Australians (Schoen,

Balchin, & Thompson, 2010; Watson, Obersteller, Rennie, & Whitbread, 2001). The

strengths of the study include its community-based, representative sample and a very low

attrition rate with 96% of participants returning for follow-up.

The present data suggest that the combination of detailed written and interactive verbal

instruction on foot health, such has been employed successfully in small scale studies

(Corbett, 2003), should complement conventional diabetes education. More intensive and

thus more expensive personalised interventions, including specific involvement of health

care professionals outside of usual care, may have even better outcomes (Litzelman et al.,

1993), but are likely to be difficult to fund and implement widely. We recommend that, as

in the present study, written material developed with consumer input and interactive

sessions delivered by experienced and dedicated educators, are both feasible and affordable

in most countries.

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115

Chapter Five

A longitudinal study of foot ulceration and its risk

factors in community based patients with type 2

diabetes: The Fremantle Diabetes Study

116

117

A longitudinal study of foot ulceration and its risk

factors in community based patients with type 2

diabetes: The Fremantle Diabetes Study

5.1 Introduction

Foot ulcers contribute significantly to the morbidity, mortality and cost associated with

diabetes (A. J. Boulton, 2008). Accurate estimates of the prevalence and incidence of foot

ulceration complicating type 2 diabetes have, however, been difficult to obtain (W. J.

Jeffcoate & Harding, 2003; Margolis & Jeffcoate, 2013). Available data from largely

primary care studies suggest that the point prevalence of an active ulcer is up to 1.8% (de

Sonnaville et al., 1997; Kumar et al., 1994), with an annual incidence ranging from 1.0% to

4.1% (Singh et al., 2005). Such estimates can, however, be influenced by how foot ulcers

are defined and ascertained, as well as by racial/ethnic differences in propensity to foot

ulceration (C.A. Abbott et al., 2005; Lavery et al., 2003), and between-sample differences in

the management of diabetes and associated foot disease that are strongly influenced by

socio-economic and behavioural factors (Margolis & Jeffcoate, 2013).

Similarly, risk factors for diabetic foot ulcers have been incompletely characterized

(Crawford et al., 2013; Crawford et al., 2007; Monteiro-Soares et al., 2012). In recent meta-

analyses (Crawford et al., 2007; Monteiro-Soares et al., 2012) diagnostic tests and physical

signs that detect DPN and excessive plantar pressure were consistently associated with

future diabetic foot ulceration, but the role of other candidate risk factors including HbA1c

and ankle brachial index (ABI) were not. Differences in methodology including design

(retrospective vs. prospective), sources of patients (clinic vs. community), attrition rates,

durations of follow-up, definitions and ascertainment of foot ulcer, standardization of data

collection, cut-points for interpretation of diagnostic tests, and availability of potential

explanatory variables for multivariate assessment of independent associates, are all barriers

to effective pooling of data (Crawford et al., 2007; Monteiro-Soares et al., 2012). Indeed,

very few individual studies have included a full range of predictive variables in their

analyses (Monteiro-Soares et al., 2012), a deficiency that has prompted international

collaboration aimed at performing a more detailed systematic review (Crawford et al.,

2013).

118

Issues with ascertainment are highlighted by the observation that a significant proportion

of diabetic patients can develop foot ulcers, including those that persist for more than three

weeks, that heal without healthcare system intervention (Iversen et al., 2008). This reflects

patient delay in seeking help (Prompers, Huijberts, Apelqvist, et al., 2008; A. P. Sanders et

al., 2013), especially by those who do not regard an ulcer as a serious complication of

diabetes (A. P. Sanders et al., 2013). Given the problems associated with complete

identification of all ulcers in a longitudinal natural history study and the inconsistent

findings from previous studies, the aims of the present study were to i) determine the

prevalence and associates of foot ulceration in patients with type 2 diabetes from a large

representative community-based cohort detected through active screening, and ii) identify

the incidence and predictors of all foot ulceration severe enough to require hospitalisation

during up to 17 years of follow-up of the same cohort.


A description of the FDS and data collection procedure is provided in Chapter 2. Of 2,258

diabetic patients identified from a variety of sources between April 1993 and June 1996,

1,426 (63%) were recruited to FDSI and 1,296 had clinically-diagnosed type 2 diabetes.

Eligible patients who declined participation were a mean of 1.4 years older than

participants, but their sex distribution, the proportion with type 2 diabetes and their use of

blood glucose-lowering therapies were similar (T. M. Davis et al., 2013).

Each FDSI patient underwent comprehensive assessment at entry and was invited to return

for similar assessment on an annual basis over a minimum of five years (T. M. Davis et al.,

2013). Questionnaire data included demographic, socioeconomic, diabetes-specific and

general health data, with ethnic background based on self-selection, country/countries of

birth and parents‟ birth and language(s) spoken at home. Patients provided fasting blood

and urine samples for automated biochemical analyses in a single nationally-accredited

laboratory. A physical examination was performed by a trained registered nurse and

included a detailed bilateral foot assessment including palpation for the pedal pulses

(dorsalis pedis and posterior tibial), measurement of ankle brachial indices (ABI),

assessment of PSN using the clinical features of the Michigan Neuropathy Screening

Instrument (MNSI) (Feldman et al., 1994) and general foot inspection to detect the

presence or absence of ulceration (defined, for the purposes of the present study, as

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located at or below the level of the malleoli), deformity, corns or callus, skin fissures,

infections and nail pathology.

Chronic complications were identified by standard criteria (W. A. Davis et al., 2006).

Peripheral sensory neuropathy (PSN) was defined as a score of >2/8 on the clinical

portion of the MNSI. Peripheral arterial disease (PAD) was considered present if the ABI

was ≤0.90 on either leg or a diabetes-related amputation was present. Intermittent

claudication was ascertained by determining whether pain in the calves came on during

walking, caused the patient to slow down or stop, and resolved with rest. Self-reported

stroke and transient ischaemic attack were amalgamated with prior hospitalisations to

define baseline cerebrovascular disease status. Patients were considered to have coronary

heart disease if there was a self-reported history of, or hospitalisation for, myocardial

infarction, angina, coronary artery bypass grafting, angioplasty and/or definite myocardial

infarction on electrocardiogram. A subject was considered to have retinopathy if any grade

of retinopathy, including maculopathy, was detected by direct and/or indirect

ophthalmoscopy in one or both eyes and/or on more detailed assessment by an

ophthalmologist. The estimated glomerular filtration rate (eGFR) was calculated using the

Chronic Kidney Disease Epidemiology Collaboration equation (Levey et al., 2009).

5.3 Data linkage

A government register records details of all deaths and hospital admissions in Western

Australia and is part of WADLS. The Confidentiality of Health Information Committee

approved linkage with the FDS database. These sources provided hospital admissions

from the beginning of the study until 31st December 2011.

5.4 Hospitalisation for foot ulcer

All hospital admissions, whether public or private, for foot ulceration were identified using

relevant International Classification of Disease (ICD) procedure codes (ICD-9-CM and

ICD-10-AM). ICD-10-AM primary diagnosis codes E10.73, E11.73, E13.73 and E14.73

were coded as a foot ulcer with verification from the casenotes if required. Casenote

review was also performed in all patients with ICD-10-AM codes L97 and I70.23, and,

since ICD-9-CM codes did not include a specific diagnosis code for diabetes-related foot

ulcer, those with codes 707.1 and 440.23.

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The computer package IBM SPSS Statistics 20 (IBM Corporation, Somers, NY, USA) was

used. Data are presented as proportions, means±SD, geometric mean (SD range), or in the

case of variables that did not conform to a normal or ln-normal distribution, median

(interquartile range [IQR]). For independent samples, two way comparisons for

proportions were by Fisher‟s exact test, Student‟s t test for normally distributed variables,

and the Mann-Whitney U-test for variables that were not normally distributed. A two-

tailed P-value <0.05 was considered significant. Multiple logistic regression modelling was

used to determine independent associates of prevalent foot ulceration. Cox proportional

hazards modelling (forward conditional variable entry, entry and removal with P<0.05 and

>0.10, respectively) was used to determine independent predictors of first-ever foot ulcer.

All clinically plausible variables with P<0.20 were considered for model entry. In addition,

MNSI-defined neuropathy was used as an indicator for all other measures of DPN. The

crude incidence of first-ever diabetes related foot ulcer was determined in patients without

foot ulcer at study entry by dividing the number of first-ever diabetes related foot ulcers

after study entry, by the patient-years of follow up to first-ever ulcer or death or end-

December 2010, whichever came first.

5.6 Results

At baseline, the mean age of the 1,296 patients was 64.0±11.3 years, 48.6% were male, and

they had a median [interquartile range] diabetes duration of 4.0 [1.0-9.0] years. Four

participants had bilateral below-knee amputations at study entry and were excluded from

further analysis. Sixteen of the remaining 1,292 patients had a foot ulcer identified at FDS

entry, representing an active foot ulcer prevalence of 1.2% (95% CI: 0.7%-2.1%). The

characteristics of the patients with foot ulcers at baseline are compared with those without

an ulcer in Table 5-1. Those with an ulcer were older, had longer diabetes duration, were

more likely to be insulin-treated and taking antihypertensive medication and less likely to

have exercised in the past two weeks. In relation to complications, they had higher urinary

albumin:creatinine ratios and there were greater proportions with DPN, intermittent

claudication, PAD and a history of vascular bypass surgery for PAD.

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Table 5-1. Baseline characteristics of Fremantle Diabetes Study patients with type 2

diabetes by foot ulcer status.

No foot ulcer Foot ulcer P-value

Number 1276 16

Age (years) 63.9±11.3 73.4±8.4 0.001

Male (%) 48.7 37.5 0.46


Ethnicity (Anglo-Celt/Southern European/Other; %)

61.3/17.9/20.8 62.5/12.5/25.0 0.88

Education level (% greater than primary level) 74.0 68.8 0.58

Alcohol consumption (standard drinks/day) 0 [0-0.8] 0 [0-0] 0.12

Smoking status (never/ex-/current; %) 45.0/40.0/15.0 20.0/53.3/26.7 0.09

Any exercise in the past 2 weeks (%) 72.5 43.8 0.02

Diabetes duration (years) 4.0 [1.0-9.0] 13.0 [10.0-23.0] <0.001

Fasting plasma glucose (mmol/L) 8.5 [6.9-10.8] 8.8 [6.4-11.7] 0.74

HbA1c (%) 7.4 [6.4-8.8] 8.0 [6.5-9.7] 0.35

HbA1c (mmol/mol) 57 [46-73] 64 [48-83] 0.35

Diabetes treatment (diet/oral agents/insulin±oral; %)

32.4/56.1/11.6 6.3/50.0/43.8 0.001

Prior diabetes education (%) 67.7 75.0 0.79

Prior podiatry attendance (%) 30.2 50.0 0.10

Height (m) 1.65±0.10 1.63±0.09 0.33


Abdominal obesity by waist circumference (%) 64.7 56.3 0.60



Pulse pressure (mmHg) 70±20 77±25 0.17

Anti-hypertensive treatment (%) 50.3 87.5 0.004

Lipid-modifying therapy (%) 10.9 0.0 0.40

Aspirin therapy (%) 21.9 31.3 0.37


Serum HDL-cholesterol (mmol/L) 1.1±0.3 1.1±0.3 0.43

Serum LDL-cholesterol (mmol/L) 3.4±0.9 3.6±1.3 0.39


Urinary albumin:creatinine (mg/mmol) 3.1 (0.7-13.4) 4.9 (1.7-14.2) 0.048

Estimated glomerular filtration rate <60mL/min/1.73m2 (%)

34.3 56.3 0.11

Retinopathy (any) (%) 16.1 33.3 0.08

Neuropathy (%) 30.0 92.9 <0.001

Self-reported intermittent claudication (%) 13.1 81.3 <0.001

Peripheral arterial disease (%) 28.8 57.1 0.03

Cerebrovascular disease (%) 9.8 12.5 0.67

Ischemic heart disease (%) 29.2 43.8 0.27

History of vascular bypass before first visit (%) 1.0 12.5 0.01

Abnormal foot appearance at FDS assessment (%) 6.8 62.5 <0.001

Values are proportions, mean±SD, geometric mean (SD range), or median [interquartile range].

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In multiple logistic regression analysis, the strongest independent associates of an active

ulcer at baseline were intermittent claudication, DPN and diabetes duration (Table 5-2).

Antihypertensive therapy was weakly but positively associated with foot ulcer, consistent

with confounding by indication.

Table 5-2. Significant independent associates of foot ulcer at study entry.

Of the 1,272 type 2 patients without a prior history of hospitalisation for, or a prevalent,

foot ulcer, 79 (6.2%) had a first-ever hospitalisation for foot ulcer during 15,154 patient-

years of follow up, representing an incidence of 5.21 (95% CI 4.13-6.50) per 1,000 patient-

years. In men, the incidence of first-ever foot ulcer was 6.01 (4.33-8.12) per 1,000 patient-

years compared with 4.53 (3.19-6.25) per 1,000 patient years in women (P=0.21). The

mean age at which participants first developed a foot ulcer was 65.0±9.5 years. Compared

with participants who did not develop a foot ulcer during follow-up, those with incident

ulceration had longer diabetes duration, worse glycaemic control and higher systolic and

pulse pressures, and were more likely to have DPN, retinopathy, intermittent claudication,

PAD, cerebrovascular disease and a history of vascular bypass surgery (see Table 5-3).

Odds ratio (95% CI) P-value

Intermittent claudication 17.24 (3.66-81.23) <0.001

Diabetes duration (for increase of 5 years) 1.58 (1.12-2.23) 0.009

Neuropathy 15.84 (1.95-128.81) 0.010

Antihypertensive therapy 11.16 (1.13-95.44) 0.028

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Table 5-3. Baseline characteristics of Fremantle Diabetes Study participants with type 2

diabetes by incident foot ulcer status during follow-up.

No incident foot ulcer Incident foot ulcer P-value

Number 1,193 79

Age (years) 63.8±11.4 65.5±9.4 0.13

Male (%) 48.2 53.2 0.42


Ethnicity (Anglo-Celt/Southern European/Other; %)

61.3/617.7/21.0 62.0/20.3/17.7 0.71

Education level (%, greater than primary level)

73.8 76.6 0.69

Alcohol consumption (standard drinks/day) 0.0 [0.0-0.4] 0.0 [0-1.5] 0.18

Smoking status (never/ex-/current, %) 45.5/39.8/14.7 38.5/42.3/19.2 0.36

Any exercise in the past 2 weeks (%) 72.5 73.7 0.90

Diabetes duration (years) 4.0 [0.9-8.0] 5.4 [2.8-12.0] 0.001

Fasting plasma glucose (mmol/L) 8.3 [6.8-10.7] 9.4 [7.4-12.2] 0.015

HbA1c (%) 7.4 [6.4-8.8] 7.9 [6.9-9.6] 0.003

HbA1c (mmol/mol) 57 [46-73] 63 [52-81] 0.003

Diabetes treatment (diet/oral agents/insulin±oral; %)

33.3/55.6/11.0 19.2/61.5/19.2 0.009

Prior diabetes education (%) 68.2 60.8 0.17

Prior podiatry attendance (%) 29.7 34.6 0.37

Height (m) 164.7±9.7 166.7±10.0 0.08


Abdominal obesity by waist circumference (%)

64.1 72.2 0.18



Pulse pressure (mmHg) 70±20 76±17 0.007

Anti-hypertensive treatment (%) 50.1 53.2 0.64


Serum HDL-cholesterol (mmol/L) 1.06±0.32 1.06±0.34 0.95

Serum LDL-cholesterol (mmol/L) 3.44±0.90 3.43±0.92 0.85


Lipid-modifying therapy (%) 11.0 10.1 1.00

Aspirin therapy (%) 22.0 19.0 0.67

Urinary albumin:creatinine (mg/mmol) 3.0 (0.7-12.8) 5.2 (1.1-25.2) 0.001

Estimated glomerular filtration rate <60mL/min/1.73m2 (%)

33.2 49.4 0.006

Retinopathy (any) (%) 14.1 42.9 <0.001

Neuropathy (%) 29.0 43.5 0.014

Self-reported intermittent claudication (%) 12.1 24.1 0.005



Ischemic heart disease (%) 29.0 31.6 0.61

History of vascular bypass before first visit (%)

0.8 3.8 0.03

Values are proportions, mean±SD, geometric mean (SD range), or median [interquartile range]

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In a Cox proportional hazards model (see Table 5-4), independent predictors of time to

first-ever diabetes related foot ulcer were retinopathy, cerebrovascular disease, intermittent

claudication, PSN, alcohol consumption, eGFR, PAD, HbA1c and pulse pressure.

Table 5-4. Cox proportional hazards model of baseline predictors of time to first-ever

diabetes-related foot ulceration during follow up.

Hazard ratio (95% CI) P-value

Any retinopathy 3.86 (2.26-6.59) <0.001

Cerebrovascular disease 3.76 (1.97-7.19) <0.001

Intermittent claudication 2.77 (1.52-5.04) 0.001

Neuropathy 2.24 (1.35-3.71) 0.002

HbA1c (for a 1.0% increase) 1.22 (1.07-1.40) 0.003

Alcohol consumption (for a 1 standard drink/day increase)

1.16 (1.05-1.27) 0.003

Estimated glomerular filtration rate <60 mL/min/1.73m2

2.12 (1.30-3.51) 0.004

Peripheral arterial disease 1.85 (1.10-3.13) 0.021

Pulse pressure (for a 5 mmHg increase) 1.07 (1.00-1.14) 0.038

5.7 Discussion

The present data, from a large, well characterized cohort with long-duration follow-up,

confirm the important contribution of DPN to foot ulceration (Crawford et al., 2007;

Monteiro-Soares et al., 2012), but also show that peripheral vascular disease is a significant

independent risk factor. Neuropathy detected by the clinical MNSI score was associated

with a substantial increase in risk of a prevalent foot ulcer but, in the more informative

prospective arm of the study, it also predicted a more than two-fold increase in incident

hospitalisation for ulceration. The symptom of intermittent claudication was also a

significant independent variable for both prevalent and incident foot ulcer, and other

manifestations of PAD (ABI ≤0.90 or a diabetes-related amputation) and more widespread

atherosclerosis (cerebrovascular disease and increased pulse pressure) were also predictors

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of incident hospitalisation for ulceration together with retinopathy, renal impairment,

HbA1c and alcohol consumption.

The baseline active foot ulcer prevalence of 1.2% was lower than the 1.4-1.8% reported in

other studies (C. A. Abbott et al., 2002; de Sonnaville et al., 1997; Kumar et al., 1994).

Although these latter estimates were within the 95% CI (0.7%-2.1%), it is likely that the

lower prevalence in the present study was a reflection of the community-based nature of

the FDS cohort compared with individuals who were recruited from primary or secondary

care attendances. The incidence of hospitalisation for foot ulcer of 5.21 per 1,000 patient-

years is understandably much lower than overall incidence rates of 30-71 per 1,000 patient-

years reported in a variety of other studies (Boyko et al., 2006; Boyko et al., 1999; Lavery et

al., 2003). Similarly, cumulative annual incidence rates reported in the literature range from

1.0% to 4.1% (Singh et al., 2005) compared to only 0.6% in the present study. Given

problems with ascertainment of all incident ulceration (Iversen et al., 2008; Prompers,

Huijberts, Apelqvist, et al., 2008; A. P. Sanders et al., 2013), we restricted cases to the

severe end of the spectrum, specifically those requiring hospitalisation. Based on the

present data and those of others (C. A. Abbott et al., 2002; Boyko et al., 2006; de

Sonnaville et al., 1997; Kumar et al., 1994; Lavery et al., 2003), we estimate that between

one in seven and one in ten foot ulcers requires hospitalisation.

Neuropathy, or markers of neuropathy including insensitivity to monofilament testing,

absent ankle reflexes, elevated vibration perception threshold and composite indices other

than MNSI such as the neuropathy disability score, have been consistently reported as a

strong independent predictors of foot ulceration in the present and other studies (C. A.

Abbott et al., 2002; C. A. Abbott et al., 1998; Boyko et al., 1999; Crawford et al., 2007;

Kastenbauer, Sauseng, Sokol, Auinger, & Irsigler, 2001; Monteiro-Soares et al., 2012;

Young et al., 1994). The association between markers of PAD and foot ulceration has

been less clear (Crawford et al., 2007). The present data, from one of the largest and

longest-running studies to date, show a robust link between PAD symptoms (intermittent

claudication) and both prevalent and incident ulcer, supporting findings from a number of

other studies (Monteiro-Soares et al., 2012). For incident ulcer hospitalisation, PAD

primarily ascertained through measurement of the ABI was also a significant independent

risk factor, suggesting that symptoms of vascular insufficiency may be absent or not

detected because of neuropathy in some patients at risk of foot ulceration.

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Other manifestations of macrovascular disease were independently associated with incident

ulcer hospitalisation, specifically cerebrovascular disease and an increased pulse pressure. It

is likely that there are patients in whom a presentation with a manifestation of more

generalized atherosclerosis, such as with a stroke, precedes foot ulceration in contrast to

other patients in whom PAD is the major macroangiopathic complication of type 2

diabetes. Consistent with the present data, a self-reported history of stroke has been

identified previously as an independent determinant of foot ulceration in a large Norwegian

study (Iversen et al., 2008). Increased pulse pressure may predispose to complications such

as foot ulceration through an increase in microvascular pressure due to underlying reduced

elasticity of the larger arteries in combination with diabetes-related impaired vascular

autoregulation (Knudsen et al., 2002). In an Italian cohort study of more than 1,900

people, pulse pressure was also an independent risk factor for ulceration in association with

other variables (including diabetes duration, HbA1c, PSN and lower limb arteriopathy) that

were predictive in the present study (Monami et al., 2009).

Retinopathy was a strong predictor of incident hospitalisation with foot ulcer in the present

cohort. Other studies have shown a direct (Walters, Gatling, Mullee, & Hill, 1992) or

indirect (Boyko et al., 2006) association between retinopathy and foot ulceration. It is

possible that shared risk factors with neuropathy and PAD, such as long diabetes duration,

poor glycaemic control, dyslipidaemia and hypertension (Antonetti, Klein, & Gardner,

2012) may underlie co-linearity in the multivariate analyses, but there is also evidence that

inadequate small blood vessel perfusion, which correlates with retinopathy, is a major cause

of the inability to heal small wounds that eventually results in foot ulcer formation

independently of neuropathy and macrovascular disease (Ngo et al., 2005). Reduced visual

acuity associated with retinopathy may also result in delayed recognition of the presence

and/or severity of a foot ulcer, thus increasing the likelihood of progression to

hospitalisation.

Renal impairment was also an independent predictor in the incident foot ulcer Cox model.

The same independent doubling of the risk of foot ulceration in patients with renal

impairment has been shown by other authors (Margolis et al., 2008), who postulated that

hyperglycaemia-associated damage to mesangial cells and podocytes, which have limited

ability to replenish compared with cells of the dermis, might be an early marker of

subsequent dermal skin leading to foot ulceration. However, patients with renal

impairment may also be predisposed to foot ulceration through a variety of other factors

such as leg oedema, anaemia and altered nutrition (Ndip, Rutter, et al., 2010). An increase

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in HbA1c was a predictor of first-ever hospitalisation for foot ulceration in this cohort,

consistent with other studies (Bennett, Stocks, & Whittam, 1996; Boyko et al., 2006; Lavery

et al., 2003). As this was independent of chronic micro- and macrovascular complications,

it could reflect an adverse impact of foot ulceration on diabetes self-management

(including lifestyle factors such as exercise as well as treatment adherence) prior to

hospitalisation or the effects of foot ulceration and perhaps associated infection on prior

glycaemic control.

There was a strong independent association between alcohol consumption and incident

hospitalisation with foot ulcer in the present study. Alcohol has been found previously to

be a risk factor for foot ulcer in several small-scale largely cross-sectional studies with <200

patients and limited other potential explanatory variables (Altenburg et al., 2011; Bresater,

Welin, & Romanus, 1996; Kastenbauer et al., 2001; Mantey, Foster, Spencer, & Edmonds,

1999). As the present association was independent of neuropathy, it is likely that the

adverse effects of alcohol on nutrition and on wound healing may be responsible. We have

found previously that alcohol consumption was also associated with tendon rupture in the

FDS cohort (Zakaria, Davis, & Davis, 2013), and alcohol-related inhibition of fibroblast

proliferation and collagen synthesis may underlie both tendon injury and progression of

foot ulceration.

This study had limitations. We did not have either measures of excessive plantar pressure

(Crawford et al., 2007; Monteiro-Soares et al., 2012) or a detailed assessment of the

adequacy of footwear (Jan Apelqvist et al., 1990) factors that have been found to be

prognostically important in other studies, but they are not routinely available in a usual care

setting. Although ascertainment of prevalent ulcer was relatively robust, the predictors of

foot ulcers requiring hospitalisation may be different to those underlying less severe

ulceration. The strengths of the present study include the prospective design, large patient

numbers, long duration follow-up, detailed baseline assessment and capture of endpoints

through a validated data linkage system (Holman et al., 2008) applied to a stable population

base (Bradshaw, Jamrozik, Jelfs, & Le, 2000).

The present study, which is amongst the largest and longest duration longitudinal study yet

undertaken, shows that foot ulceration is a common complication of type 2 diabetes that

can progress to hospitalisation in a significant proportion of cases. DPN and PAD are

modifiable risk factors if identified early in the progression of disease, confirming the

results of previous studies (C. A. Abbott et al., 2002; C. A. Abbott et al., 1998; Boyko et al.,

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1999; Crawford et al., 2007; Kastenbauer et al., 2001; Monteiro-Soares et al., 2012; Young

et al., 1994), but alcohol use, poor glycaemic control and renal impairment are other

treatable precipitants. The associations between retinopathy, raised pulse pressure and foot

ulceration raise the potentially important issue of local microvascular changes as

contributors to pathogenesis, while alcohol may also have toxic effects on skin and

subcutaneous structures that promote ulcer progression. All these risk factors should be

considered carefully in the assessment and management of patients with type 2 diabetes

who are at risk of, or who present with, foot ulceration.

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Chapter Six

Temporal changes in prevalence and associates of foot

ulceration in patients with type 2 diabetes: The

Fremantle Diabetes Study

130

131

Temporal changes in prevalence and associates of foot

ulceration in patients with type 2 diabetes: The

Fremantle Diabetes Study

6.1 Introduction

Diabetes management and prognosis have changed significantly over the past two decades.

There is evidence that blood glucose-lowering strategies have become more intensive in

countries such as the US (Dodd et al., 2009), the UK (Calvert, Shankar, McManus, Lester,

& Freemantle, 2009), and Australia (T. M. E. Davis et al., 2012), that other vascular risk

factors including hypertension and dyslipidaemia are also now better managed (T. M. E.

Davis et al., 2012; Ford, 2011a; Kuznik & Mardekian, 2011), and that outcomes such as

cardiovascular events and preventable hospitalisations in general have been reduced as a

result (Ford, 2011b; Hoerger et al., 2009; J. Wang et al., 2009). In the case of diabetes-

related foot disease, most population-based studies have shown a decline in LEA rates

(Holstein et al., 2000; Karakoc, Ersoy, Arslan, Toruner, & Yetkin, 2004; Schofield, Yu, Jain,

& Leese, 2009; Vamos et al., 2010; van Houtum, Rauwerda, Ruwaard, Schaper, & Bakker,

2004; J. Wang et al., 2009), but some have shown no change (Buckley et al., 2012;

McCaslin, Hafez, & Stansby, 2007; Trautner, Haastert, Spraul, Giani, & Berger, 2001).

Equivalent temporal data relating to changes in foot ulceration complicating diabetes, a

potent precursor of LEA (Singh et al., 2005), are sparse. The decline in LEA rates

observed in most geographical contexts could reflect better management of established

foot ulcers by multi-disciplinary care that improves offloading, debridement, treatment of

bacterial infection and revascularization (M. Edmonds, 2013; Nesbitt, 2004), rather than a

reduction in foot ulcer incidence over time through improvements in glycaemia and non-

glycaemic vascular risk factors (R. A. Malik, Tesfaye, & Ziegler, 2013). In the light of issues

complicating standardised ascertainment of foot ulceration and its risk factors (Crawford et

al., 2013; Crawford et al., 2007; Monteiro-Soares et al., 2012), valid examination of

temporal changes in foot ulcer incidence and its determinants requires active surveillance

of, and detailed data collection from, representative community-based patient cohorts.

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The aims of the present study were, therefore, i) to determine whether the prevalence of

foot ulceration changed in well-characterised cohorts with type 2 diabetes resident in a

large urban Australian population between 1993-1996 and 2008-2011, and ii) to assess the

relationship between any changes in established risk factors for ulceration and its

prevalence over the same period.


A description of the FDS and data collection procedure is provided in Chapter 2. We

identified 2,258 eligible FDSI subjects during the three-year period between 1993 and 1996

in the local population of 120,000 (crude diabetes prevalence 1.9%) and recruited 1,426

(63%). In the case of FDSII, 4,793 diabetic patients were identified over the same time

period between 2008 and 2011 from a population of 153,000 (crude prevalence 3.1%) and

1,668 (35%) were recruited including 390 surviving FDSI patients. For FDSI, 1,296

(90.9%) of the recruited cohort had type 2 diabetes and, for FDSII, the equivalent figure

was 1,509 (89.4%). These two cohorts had similar age, gender distribution, type of diabetes

and race/ethnicity to those of the non-recruited patients (T. M. Davis et al., 2013).

Each FDSI participant was assessed in detail at baseline and invited to attend annual

reviews for ≥5 years. For FDSII, comprehensive baseline assessments are followed by face-

to-face assessments biennially with questionnaire follow-up in alternate years. We

performed only a comparative analysis of baseline data from both phases in the present

study. This was primarily because we wished to determine whether, using the most

complete cross-sectional FDS data available, changes in foot ulcer prevalence and

associates over the 15 years between recruitment periods but, in addition, we have

previously published data relating to the prevalence and incidence of foot ulcer in FDSI

patients followed for up to 18 years (Baba M, Davis WA, & Davis TM, 2014) while the

average follow-up in FDSII is currently only 4.5 years (T. M. Davis et al., 2013).

All FDS face-to-face assessments comprise a comprehensive questionnaire, physical

examination and standard fasting biochemical tests (T. M. Davis et al., 2013). For both

phases, diabetes type was assessed from diabetes treatment history, BMI, age at diagnosis,

nature of first presentation, and/or self-identification, and case records were consulted for

evidence of ketonemia, as well as islet cell antibody (ICA), GAD antibodies, serum insulin

and C-peptide levels, if available. Ethnic background was assessed from self-selection,

country/countries of birth and parents‟ birth, language(s) spoken at home and, for FDSII,

country of grandparents‟ birth. In the case of foot assessment, intermittent claudication

was ascertained by determining whether pain in the calves came on during walking, caused

133

the patient to slow down or stop, and resolved with rest. In addition to other procedures, a

trained nurse performed palpation of the pedal pulses (dorsalis pedis and posterior tibial),

measurement of the ankle brachial index (ABI), assessment of DPN using the clinical

features of the MNSI (Feldman et al., 1994), and general foot inspection to detect the

presence or absence of ulceration (defined, for the purposes of the present study, as

located at or below the level of the malleoli), deformity, corns or callus, skin fissures,

infections and nail pathology.

Chronic complications were ascertained using standard criteria (Norman et al., 2006).

PAD was considered present if the ABI was ≤0.90 on either leg or a diabetes-related

amputation was present. DPN was defined as a score of >2/8 on the clinical portion of

the MNSI. Self-reported stroke and transient ischemic attack were amalgamated with prior

hospitalisations to define baseline cerebrovascular disease status. Patients were considered

to have coronary heart disease if there was a self-reported history of, or hospitalisation for,

myocardial infarction, angina, coronary artery bypass grafting, angioplasty and/or definite

myocardial infarction on electrocardiogram. A subject was considered to have retinopathy

if any grade of retinopathy, including maculopathy, was detected by direct and/or indirect

ophthalmoscopy in one or both eyes and/or on more detailed assessment by an

ophthalmologist. The estimated glomerular filtration rate (eGFR) was calculated using the

Chronic Kidney Disease Epidemiology Collaboration equation (Levey et al., 2009).

Biochemical testing in both phases of the FDS was carried out in the same nationally

accredited diagnostic biochemistry laboratory. Between-run imprecision for all methods

was <3.5%, except for urine albumin and serum HDL-cholesterol in FDSII, for which it

was <5.0%. Serum LDL-cholesterol was estimated using the Friedewald equation. For

assays that had changed between 1993 and the present, calibration equations were applied

to standardize all concentrations to current assays used for FDSII (T. M. E. Davis et al.,

2012).


The computer package IBM SPSS Statistics 21 (IBM Corporation, Somers, NY, US) was

used for statistical analysis. Data are presented as proportions, mean±SD, geometric mean

(SD range), or, median and interquartile range [IQR] in the case of variables that do not

conform to the normal or log-normal distribution. For independent samples, two way

comparisons for proportions were performed by Fisher exact test, Student‟s t-test for

normally distributed variables, and the Mann-Whitney U-test for variables that were not

normally distributed. A two-tailed P-value of <0.05 was considered significant. Multiple

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logistic regression was used to determine independent associates of prevalent foot

ulceration, with all clinically plausible variables P<0.20 considered for entry into the model.

Generalised linear modelling with adjustment for age, sex and ethnicity was used to

determine whether baseline associates had changed between phases.

6.4 RESULTS

6.4.1 Patient characteristics

Demographic, socioeconomic, anthropometric and diabetes-specific details of participants

with type 2 diabetes recruited to the two phases are summarised in Table 6-1. Those in

FDSII were older and there were proportionately more males than females than in FDSI.

There were fewer Anglo-Celts and Southern Europeans, but a greater proportion of

Aborigines and those with an ethic/racial background outside the major groups. The

FDSII patients were diagnosed at a younger age and had a longer duration of diabetes.

More FDSII participants had received an education beyond primary school level and more

were in paid employment compared to those in FDSI. They consumed more alcohol but

fewer reported that they were current smokers. Subjects in FDSII were more likely to have

a higher BMI and be overweight or obese by waist to hip ratio.

135

Table 6-1. Baseline characteristics of FDSI compared with FDSII participants with type 2 diabetes.

FDSI FDSII Difference (95% CI) P-value*

Number 1,296 1,509

Age (years) 64.0±11.3 65.4±11.7 1.4 (0.56 to 2.3) <0.001

Sex (% male) 48.6 51.8 3.2 (0.5-6.9) 0.032

Ethnic background (%): Anglo-Celt

Southern European

Other European

Asian

Aboriginal

Other

61.4

17.7

8.5

3.4

1.5

7.5

52.6

12.9

7.4

4.3

7.1

15.8

-8.9 (-5.2 to -12.5)

4.9 (2.2 to 7.5)

-1.1 (-0.9 to 3.1)

-0.9 (-0.2 to 0.5)

5.6 (4.1 to 7.1)

8.4 (6.0 to 10.7)

<0.001

<0.001

0.20

0.14

<0.001

<0.001

Age at diabetes diagnosis (years) 57.9±11.7 55.6±12.4 2.3 (1.4 to 3.2) <0.001

Duration of diabetes (years) 4.0 [1.0-9.0] 8.0 [2.7-15.4] 3.8 (3.1 to 4.3) <0.001

Education beyond primary level (%) 74.0 86.8 12.8 (9.8 to 15.7) <0.001

Paid employment (%) 17.5 31.0 13.6 (10.4 to 16.7) <0.001

Married/de facto relationship (%) 65.7 62.7 3.0 (0.6 to 6.5) 0.79

Alcohol use (standard drinks/day) 0 [0-0.8] 0.1 [0-1.2] 0.25 (0.1 to 0.4) 0.003

Smoking status (%): Never

Ex-

Current

44.7

40.2

15.1

45.4

43.9

10.7

0.7 (0.4 to 3.0)

3.6 (0 to 7.3)

-4.5 (-2.0 to -6.9)

0.054

0.29

<0.001

BMI (kg/m2) 29.6±5.4 31.3±6.1 1.7 (1.3 to 2.1) <0.001

Obese by waist circumference (%)† 64.5 70.9 6.4 (2.9 to 9.9) <0.001

Overweight/obese by waist:hip ratio (%)‡ 74.2 82.7 8.5 (5.5 to 11.5) <0.001

Fasting serum glucose (mmol/L) 8.0 [6.5-10.3] 7.2 [6.2-8.9] 0.79 (0.57 to 1.01) <0.001

HbA1c (%) 7.2 [6.2-8.5] 6.8 [6.2-7.7] 0.32 (0.20-0.40) <0.001

Diabetes treatment (%): Diet

Oral agents

Insulin±oral agents

31.9

56.0

12.1

24.6

53.4

22.0

-7.3 (-4.0 to -10.7)

-2.6 (-1.1 to -6.3)

10.0 (7.1 to 12.7)

<0.001

0.075

<0.001

Systolic blood pressure (mmHg) 151±24 146±22 -5.0 (-3.4 to -6.8) <0.001

Diastolic blood pressure (mmHg) 80±11 80±12 0.27 (-0.60-1.14) 0.66

On antihypertensive therapy (%) 50.9 72.6 21.7 (18.2-25.2) <0.001

On renin-angiotensin blockers (%) 0.0 31.5 31.5 (28.9-34.0) <0.001

Total serum cholesterol (mmol/L) 5.5±1.1 4.4±1.1 -1.1 (-1.0 to -1.2) <0.001

Serum HDL cholesterol (mmol/L) 1.06±0.3 1.24±0.3 0.18 (0.15 to 0.20) <0.001

Serum LDL cholesterol (mmol/L) 3.3±0.91 2.3±0.9 -1.0 (-0.9 to -1.1) <0.001

Serum triglycerides (mmol/L) 2.2 (1.2-3.9) 1.5 (0.9-2.5) -0.9 (-0.7 to -1.0) <0.001

On lipid modifying treatment (%) 10.5 67.5 56.9 (54.0-59.8) <0.001

Taking aspirin (%) 22.0 36.6 14.6 (11.2-17.9) <0.001

Microalbuminuria or worse (%) 56.4 40.0 -16.4 (-12.7 to 20.0) <0.001

eGFR <60 mL/min/1.73m2 (%) 34.7 30.5 -4.1 (-0.7 to –7.6) <0.001

Any retinopathy (%) 16.4 22.4 6.0 (3.0-9.0) 0.001

Peripheral sensory neuropathy (%) 30.8 58.2 27.4 (23.8-31.1) <0.001

Coronary artery disease (%) 29.6 27.8 -1.8 (-5.1 to 1.6) 0.32

Cerebrovascular disease (%) 10.0 8.5 -1.4 (-3.6 to 0.7) 0.21

Peripheral arterial disease (%) 29.3 22.6 -6.7 (-3.5 to -10.0) <0.001

Intermittent claudication (%) 14.0 9.2 -4.8 (-2.4 to -7.1) <0.001

History of vascular bypass (%) 1.2 3.2 1.9 (0.8 to 3.1) 0.001

Foot ulcer at baseline (%) 1.2 1.5 -0.3 (-0.12 to 0.6) 0.86

Past hospitalisation for foot ulcer (%) 0.4 1.8 1.4 (0.7 to 2.2) <0.001

Data are proportions, mean±SD, geometric mean (SD range), median [IQR] or mean difference (95% CI). *Age-, sex- and ethnicity-adjusted for the interaction between phases. †Waist circumference ≥102.0cm for males and ≥88.0cm for females. ‡Waist:hip ratio ≥0.95 for males and ≥0.80 for females.

136

Fasting serum glucose and HbA1c were significantly lower in FDSII subjects who were also

more likely to be treated with insulin (see Table 6-1). Systolic blood pressure and serum

lipid profiles were better in FDSII participants but there were significantly more taking

antihypertensive therapy (especially renin-angiotensin system blocking drugs) and lipid-

lowering therapies (statin drugs in the majority). Although fewer FDSII patients had

microalbuminuria and an eGFR <60 mL/min/1.73 m2 than those in FDSI, they were more

likely to have retinopathy and neuropathy. They were, however, less likely to have

intermittent claudication and PAD.

6.4.2 Baseline foot ulcer prevalence and associates

At baseline in FDSI, 16 foot ulcers were identified representing a prevalence of 1.2%, while

for FDSII there were 23 foot ulcers at baseline (1.5%; P=0.62 by χ2 test). The age-, sex- and

ethnicity-adjusted difference between the phases for foot ulcer prevalence was also not

significant (-0.3 (-0.12 to 0.6)%, P=0.86; see Table 6-1). However, a greater number of

FDSII participants had been hospitalised previously with a foot ulceration (1.8% vs 0.4%

in FDSI, P<0.001; see Table 6-1). In multiple logistic regression analysis, the strongest

independent associates of an active ulcer at FDSI baseline were intermittent claudication,

diabetes duration and DPN (see Table 6-2 and reference (Baba M et al., 2014)).

Table 6-2. Independent associates of foot ulcer at baseline in FDSI and FDSII. Odds ratios

(ORs) and 95% confidence intervals (CI) are shown.

FDSI FDSII

OR (95% CI) P-value OR (95% CI) P-value

Prior hospitalisation for foot ulcer 13.19 (6.65-56.82) <0.001


Diabetes duration (for increase of 5 years)

1.58 (1.12-2.23) 0.009 1.40 (1.13-1.74) 0.002

Neuropathy 15.84 (1.95-128.81) 0.010 11.20 (1.48-84.90) 0.019

Antihypertensive therapy 11.16 (1.13-95.44) 0.028

Aboriginal racial background 3.37 (1.07-10.62) 0.038

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Antihypertensive therapy was weakly but positively associated with foot ulcer, consistent

with confounding by indication. In the case of FDSII, diabetes duration and DPN were

significant independent associates of foot ulceration at baseline (see Table 6-2) but

previous hospitalisation for a foot ulcer and Aboriginality were also influential in the

logistic regression model.

When FDSI and FDSII data were combined, those with a foot ulcer were older and more

likely to be Aboriginal, and they had been diagnosed at a younger age and had a longer

duration of diabetes than those without foot ulceration (see Table 6-3). They were

significantly less likely to be in paid employment and married or in a de facto relationship,

and they were more likely to be current smokers. There were no between-group differences

in measures of overweight/obesity or in glycaemia but those with a foot ulcer were more

likely to be insulin-treated. There was a lower mean diastolic but similar mean systolic

blood pressure in the foot ulcer group, consistent with a wider pulse pressure, but no

differences in serum lipid parameters or their treatment. All microvascular and

macrovascular complications were more frequent in the foot ulcer group.

138

Table 6-3. Baseline characteristics of pooled FDSI and FDSII participants with or without

a foot ulcer.

No foot ulcer Foot ulcer P-value

Number 2,754 39

Age (years) 64.7±11.5 68.5±12.1 0.04

Sex (% male) 50.3 48.7 0.87

Ethnic background (%): Anglo-Celt

Southern European

Other European

Asian

Aboriginal

Other

56.9

15.1

7.8

4.0

4.1

12.1

48.7

10.3

12.8

0.0

17.9

10.3

0.009

Age at diabetes diagnosis (years) 56.7±12.1 51.0±13.4 0.003

Duration of diabetes (years) 5.0 [1.8-12.9] 15.7 [9.5-28.3] <0.001

Education beyond primary level (%) 80.9 74.4 0.31

Paid employment (%) 25.1 5.1 0.002


Alcohol use (standard drinks/day) 0.1 [0.0-0.8] 0.0[0.0-1.3] 0.38

Smoking status (%): Never

Ex-

Current

45.3 42.2 12.5

36.8 42.1 21.1

0.024

BMI (kg/m2) 30.5±5.9 30.0±4.8 0.61

Obese by waist circumference (%)† 67.9 71.8 0.73

Overweight/obese by waist:hip ratio (%)‡ 78.6 86.8 0.32

Fasting serum glucose (mmol/L) 7.5 [6.3-9.6] 7.0 [6.0-10.2] 0.51

HbA1c (%) 7.0 [6.2-8.1] 7.2 [6.4-8.6] 0.30

Diabetes treatment (%): Diet

Oral agents

Insulin±oral agents

28.3 54.7 17.0

10.3 46.2 43.6

<0.001



On antihypertensive therapy (%) 62.3 82.1 0.012

On renin-angiotensin blockers (%) 16.9 20.5 0.52


Serum HDL cholesterol (mmol/L) 1.15±0.34 1.19±0.35 0.55

Serum LDL cholesterol (mmol/L) 2.8±1.0 2.5±1.4 0.06

Serum triglycerides (mmol/L) 2.2±2.2 2.0±1.5 0.67

On lipid modifying treatment (%) 41.2 41.0 1.0

Taking aspirin (%) 29.7 38.5 0.29

Microalbuminuria or worse (%) 47.4 66.7 0.02

eGFR <60 mL/min/1.73m2 (%) 19.0 30.8 0.10

Any retinopathy (%) 19.2 41.2 0.003

Neuropathy (%) 45.1 94.6 <0.001

Coronary artery disease (%) 19.3 33.3 0.039



Intermittent claudication (%) 10.9 46.2 <0.001

History of vascular bypass (%) 2.0 15.4 <0.001

Past hospitalisation for foot ulcer (%) 0.8 20.5 <0.001

Data are proportions, mean±SD, geometric mean (SD range), median [IQR] or mean difference (95% CI). †Waist circumference ≥102.0cm for males and ≥88.0cm for females. ‡Waist:hip ratio ≥0.95 for males and ≥0.80 for females.

139

In multiple logistic regression analysis, the independent associates of an active ulcer at

baseline in the pooled FDSI and FDSII datasets included, as in the analysis of the

individual cohorts, diabetes duration and DPN (see Table 6-4), but prior hospitalisation for

foot ulcer, intermittent claudication and Aboriginal racial background were also

independently associated with prevalent foot ulcer. After adjusting for these independent

variables in the most parsimonious model, FDS phase as a simple binary variable was not

significant (odds ratio [95% confidence interval] for FDSII vs FDSI 0.62 [0.28-1.37],

P=0.24).

Table 6-4. Independent associates of foot ulcer at baseline in pooled FDSI and FDSII

samples. Odds ratios (ORs) and 95% confidence intervals (CI) are shown.

6.5 Discussion

Detailed data from two representative FDS patient cohorts drawn from the same

community 15 years apart show that, despite significant improvements in glycaemia and

non-glycaemic cardiovascular risk factors through increased use of medications such as

insulin, statins and angiotensin converting enzyme inhibitors, the prevalence of foot

ulceration complicating type 2 diabetes had not changed over time. In addition, FDS phase

was not an independent associate of foot ulcer in pooled multivariable analysis. The

expected strong associations between foot ulcer and diabetes duration, DPN and

intermittent claudication as a manifestation of PAD were observed, but Aboriginality also

proved an independent risk factor. Prior hospitalisation for foot ulcer was also a significant

determinant. Since FDSII patients were significantly more likely to have all of these risk

factors apart from intermittent claudication, we hypothesize that improvements in foot

OR (95% CI) P-value

Prior hospitalisation for foot ulcer 9.48 (3.52-25.56) <0.001


Diabetes duration (for increase of 5 years)

1.40 (1.17-1.66) <0.001

Peripheral sensory neuropathy 12.04 (3.36-59.79) 0.001

Aboriginal racial background 4.05 (1.46-11.22) 0.007

140

care since FDSI, such as government-funded podiatry access and earlier referral for

peripheral arterial revascularization, have attenuated the potential for foot ulcers to develop

in susceptible FDSII patients.

As reported previously (Baba M et al., 2014) the baseline foot ulcer prevalence of 1.2% in

FDSI ascertained by active screening was slightly below the 1.4-1.8% found in other

studies conducted in the 1990s (C. A. Abbott et al., 2002; de Sonnaville et al., 1997; Kumar

et al., 1994), and the present data show that the prevalence in FDSII (1.5%) was towards

the bottom of this range. The relatively low frequency in the two cohorts was probably a

reflection of the community-based nature of the FDS compared with studies involving

individuals recruited from primary or secondary care attendances (C. A. Abbott et al., 2002;

de Sonnaville et al., 1997; Kumar et al., 1994). Although we may have detected some foot

ulcers which would not have led to healthcare system intervention (Iversen et al., 2008), it

is likely that most patients would attend their primary care physician or hospital clinic if

they developed this potentially serious complication, with the attendant potential for bias in

referred patient samples (Crawford et al., 2013).

Peripheral sensory neuropathy has been consistently reported as a strong independent

associate of foot ulceration in the present and other (C. A. Abbott et al., 2002; C. A.

Abbott et al., 1998; Boyko et al., 1999; Crawford et al., 2007; Kastenbauer et al., 2001;

Monteiro-Soares et al., 2012; Young et al., 1994) studies. The odds ratios in both FDSI

and FDSII for DPN were similar to those reported previously, but it is of interest that this

complication was almost twice as common in FDSII type 2 patients as in FDSI

participants. This may relate to the older age and longer duration of diabetes in FDSII, but

diabetes duration was itself an independent associate of foot ulceration in both cohorts and

the pooled analysis. Diabetes duration has been identified as an independent determinant

(Bresater et al., 1996; Tapp, Shaw, de Courten, et al., 2003; Walters et al., 1992; Young et

al., 1994) or has been adjusted for in multivariate models (de Sonnaville et al., 1997; Kumar

et al., 1994) in most studies, but has had no association with foot ulceration in some others

(Bennett et al., 1996; Boyko et al., 2006).

A history of intermittent claudication as a marker of PAD was significantly associated with

foot ulcer in multivariable analyses of FDSI and pooled data. The relationship between

PAD and foot ulceration in previous studies has been less consistent than that of DPN

(Crawford et al., 2007), but the weight of evidence suggests that it is a major determinant

(Monteiro-Soares et al., 2012). Both intermittent claudication and PAD assessed by ABI

were less frequent in FDSII vs FDSI patients, probably reflecting better cardiovascular risk

141

factor management (including less frequent smoking) and the significantly greater

percentage of patients who had undergone prior vascular bypass surgery for PAD in

FDSII. These factors may explain why neither intermittent claudication nor PAD was an

independent associate of foot ulcer in the FDSII multivariable model. A past history of

foot ulceration was an independent associate of foot ulcer in FDSII and the pooled data,

consistent with the results of other studies (C. A. Abbott et al., 2002; Boyko et al., 2006).

This may have been a precursor to the relatively high number of patients in FDSII who

had undergone vascular bypass surgery for PAD and may have contributed to better

cardiovascular risk factor management in FDSII patients.

Aboriginality was an independent associate of foot ulcer in analyses of both FDSII and

pooled data. It was also close to inclusion in the FDSI multivariable model (P=0.082) but

there were relatively few such patients. There were more than five times as many

Aboriginal participants in FDSII than FDSI, primarily because of strategies to increase

recruitment through culturally sensitive means (T. M. E. Davis et al., 2012). The

Aboriginal patients in both FDS phases had more adverse cardiovascular risk profiles than

other racial/ethnic groups, including substantially greater proportions of smokers, but the

present analyses show that Aboriginality was a risk factor for foot ulcer after adjusting for

these disparities. The present data are consistent with a study showing that Aboriginal

patients make up the majority of hospitalisations for diabetes-related foot complications in

rural Australian centres (Ewald, Patel, & Hall, 2001), and suggest that factors such as

podiatric education, and choice and use of footwear, may also be suboptimal in urban-

dwelling indigenous patients with type 2 diabetes (Maple-Brown, Brimblecombe, Chisholm,

& O'Dea, 2004; Watson et al., 2001).

Given that four out of the five variables that were strongly and independently associated

with prevalent foot ulcer in the pooled analysis (previous hospitalisation for ulcer, diabetes

duration, DPN and Aboriginality) were all significantly more common in the FDSII cohort,

it appears surprising that the prevalence of ulceration was not also more frequent at

baseline in this more recent cohort. This apparent discrepancy implies that that there are

factors that have changed between FDS phases that attenuate the risk of foot ulcer

regardless of conventional determinants. This may include the initiation of government-

subsidised diabetes care plans implemented through primary care that were initiated in

2004, through which there has been a progressive and substantial increase in podiatry

referrals (Menz, 2009). This development and perhaps increased awareness of the

importance of diabetes-related foot health, may have contributed to the earlier referral for

142

the peripheral vascular revascularisation that was more common amongst FDSII

participants.

This study had limitations. We attempted to maintain the same procedures for assessment

of DPN and PAD, with periodic quality assurance checks of trained staff, but it is possible

that there was a between-phase change in aspects of data collection requiring subjective

assessment. As previously acknowledged (Baba M et al., 2014), we did not have either

measures of excessive plantar pressure (Crawford et al., 2007; Monteiro-Soares et al., 2012)

or a detailed assessment of the adequacy of footwear (Jan Apelqvist et al., 1990), factors

that have been found to be prognostically important in other studies, but they are not

routinely available in a usual care setting. The strengths of the present study include the

prospective design, large participant numbers, inclusion of Aboriginal people, long duration

follow-up, and detailed standardised baseline assessments in each phase.

The present study shows that the prevalence of, and major risk determinants of, foot

ulceration have not changed in community-based patient cohorts assessed 15 years apart

between 1993-2001 and 2008-2011. The relatively adverse risk factor profile in FDSII

participants suggests that there have been favourable influences such as improved

provision of government-subsidised podiatry services and greater utilisation of

revascularisation procedures between FDS phases. The complex interaction between these

various factors may vary between and within countries, reflecting the heterogeneity of LEA

rates in other studies (Buckley et al., 2012; Margolis & Jeffcoate, 2013; McCaslin et al.,

2007; Trautner et al., 2001). However, the present Australian data provide indirect

evidence that strategies to improve community- and hospital-based foot care for patients

with type 2 diabetes are beneficial.

143

Chapter Seven

Overview and recommendations for future research

144

145

Overview and recommendations for future research

7.1 Overview

Diabetes mellitus is increasing in prevalence (Shaw et al., 2010; Wild et al., 2004) and foot

complications contribute disproportionately to the burden of care (W. A. Davis et al.,

2006). There is an urgent need to improve outcomes for patients with diabetes-related foot

problems, through a better understanding of its epidemiology, enhancement of patient

recognition and awareness of foot problems, and improvements in foot care education.

The findings presented in this thesis describe investigations of self-awareness of foot health

status, a comparison of two types of foot care education and the epidemiology of foot

ulceration in type 2 diabetes over a 17 year period.

To date, few studies have been conducted on self-awareness of foot health status in a

community based cohort of patients with type 2 diabetes. Awareness of foot health, and

recognition of potential precursors to serious foot complications, is central to reducing the

incidence and severity of foot problems. Indeed, improving individual and community

awareness of the high risk foot in diabetes is a key recommendation of the West Australian

Model of Care for the High Risk Foot (Department of Health, 2010). For patients with

multiple risk factors for serious complications, it is particularly important that they are able

to recognise and respond to changes immediately, as the likelihood of ulceration and

amputation is much greater. A cross-sectional study was conducted, presented in Chapter

3, investigating awareness of foot health, and found that most patients with type 2 diabetes

and DPN consider their feet are normal, and almost half of patients with PAD also

considered that their feet were normal. The findings suggest that these patients may be at

high risk of complications such as foot ulceration. Foot abnormalities, such as dry skin,

callous and fissures were not recognised as abnormal, suggesting that these features are

often unnoticed, disregarded or downplayed. These gaps in patient understanding of

common precursors to future potential foot complications of diabetes need to be

addressed in diabetes education programs, which should emphasise the value of

ascertaining and reversing patient unawareness of neurovascular and other clinical foot

abnormalities. From a clinician viewpoint, we also advocate for increased attention to the

importance of foot health, and the responsibility of clinicians to prioritise foot health

assessment as part of the clinical examination.

146

The results of the intervention comparing two methods of foot care education, presented

in Chapter 4, demonstrated that written information was more effective at improving foot

health, whereas interactive education was more effective at helping patients understand

how to prevent foot complications, suggesting that foot care education may be most

successful when including both written and oral information. Although longer term

outcomes of the intervention beyond the 3 month follow up period were not investigated,

the results argue for the wider implementation of combined foot care education methods

in the community. In practical terms, clinicians and educators should encourage patients to

attend interactive educational programs, and increase their utilisation of written educational

foot care resources, when managing patients with diabetes.

In Chapter 5, the findings of an initial retrospective detailed investigation of foot ulcer data

from a community based cohort of patients with type 2 diabetes, were presented. The

prevalence of foot ulceration at baseline in Phase I was 1.2%, and the incidence of

hospitalisation for those without prior/prevalent foot ulceration was 5.21 per 1000

patients-years. Predictors of time to first-ever diabetes related foot ulceration included

microvascular and macrovascular abnormalities such as peripheral sensory neuropathy,

retinopathy, cerebrovascular disease, PAD, pulse pressure and intermittent claudication,

but also included other factors such as glycaemic control, estimated glomerular filtration

rate, and alcohol consumption. Within the context of previous research, these findings

support the established role of neuropathy and vasculopathy as major modifiable predictors

of foot ulceration (C. A. Abbott et al., 2002; C. A. Abbott et al., 1998; Boyko et al., 1999;

Crawford et al., 2007; Kastenbauer et al., 2001; Monteiro-Soares et al., 2012; Young et al.,

1994), but also provide evidence for the previously unconfirmed influence of glycaemic

control, renal impairment and alcohol consumption. The findings verify that diabetic foot

ulceration is a common end-stage complication of type 2 diabetes that can progress to

hospitalisation in a significant proportion of cases.

In Chapter 6, results of the follow up retrospective analysis comparing prevalence of foot

ulceration between subjects recruited to Phase I (1993-1996) and Phase II (2008-2011), and

independent associates of prevalent foot ulceration, were presented. It was anticipated that

the prevalence of foot ulceration would be lower in Phase II, due to improvements in the

care and control of diabetes over the 17 year period between the two recruitment phases.

Despite significant improvements in glycaemic control and PAD, and the introduction of

government subsidised podiatry care plans for patients with diabetes in 2004, there was no

statistical difference in the prevalence of foot ulceration (P=0.52). This may have been due

to the Phase II cohort being older, with a longer duration of diabetes, and an increased

147

prevalence of DPN. In addition, more subjects presented with abnormal feet, which

reflected a large increase in the presence of foot deformity, skin or nail problems and

infections, which may have increased the risk of foot ulceration. Using pooled data from

Phase I and II, associates of baseline foot ulceration were prior hospitalisation for foot

ulcer, peripheral sensory neuropathy, intermittent claudication, duration of diabetes and

ATSI ethnicity. After adjusting for these independent variables, FDS phase did not add

significantly to the model, suggesting the same processes are leading to ulceration across

time.

7.2 Recommendations for future research

7.2.1 Awareness of foot health

The research presented in this thesis demonstrates that in patients with type 2 diabetes,

common observable foot problems such as deformity, dry skin, callus, fissures and

infections were not associated with perceived abnormal foot health status. The present

study was cross-sectional in nature, and thus future research investigating how foot health

awareness changes over time is warranted. A useful addition to the findings would be a

comparison of foot health awareness between patients with type 1 and 2 diabetes. Given

the disparities between age of diagnosis in these groups of patients, it is likely that type 1

patients would have a history of greater exposure to, and opportunities for, diabetes

education and this may impact on awareness of foot health.

Another aspect pertaining to foot health awareness that may warrant investigation in future

research is an evaluation of existing foot health awareness campaigns on patient outcomes.

For example, Foot Health Month is an annual awareness campaign coordinated by The

Australasian Podiatry Council (APodC). Throughout the designated month, the APodC

produces and distributes promotional material to podiatrists throughout Australia for use

in clinical practice. Although this campaign is not specifically directed at patients with

diabetes, an evaluation of its impact on foot health awareness would be worthwhile. For

patients with diabetes, more specialised awareness campaigns and self-management

initiatives are recommended (Department of Health, 2010). Thus, to further support an

increasing awareness of foot health in diabetes, future research efforts might focus on the

development, implementation and evaluation of targeted and comprehensive diabetic foot

awareness campaigns.

148

7.2.2 Diabetic foot care education

This study suggests that a combination of both written and verbal information may provide

the most beneficial method of foot care education. However, recruiting a larger sample

and using a validated foot health assessment tool would strengthen the validity of the

findings. Future research might compare a combined foot care education program of

written and verbal education with a single method of oral education or written education,

or both. In addition, it would be valuable to investigate these methods of education and

their outcomes over a longer time frame. The study was limited to a three month follow-

up period, which may be insufficient for observable changes to learned foot care

behaviours. A follow-up period of 12 months or longer may be a more suitable time frame

to detect changes in behaviour. An examination of the impact of these education programs

in different ethnic groups would also provide a more comprehensive review of diabetic

foot care education. Given the high prevalence of diabetes among Australian Aborigines

(T. M. Davis, McAullay, Davis, & Bruce, 2007), and the significantly greater rates of

diabetes related lower limb amputation (Norman, Schoen, Gurr, & Kolybaba, 2010), there

is a need to evaluate the impact of culturally appropriate foot care education (Norman et

al., 2010; Schoen et al., 2010). This would include the development and evaluation of

educational resources that recognise cultural identity, in order to effectively convey health

care messages. Recent research suggests that health promotion materials utilising

traditional Aboriginal art, language and symbolism, are more acceptable to Aboriginal

people, and are therefore more likely to be effective in imparting health care information

(Schoen et al., 2010).

7.2.3 Foot ulcer prevalence, incidence and predictors

The findings from this prospective observational study of the prevalence, incidence and

predictors of foot ulceration in type 2 diabetes are an important contribution to the current

body of literature. It would be beneficial however, to include other foot related variables in

future FDS foot assessments, such as plantar pressure measurements, joint ROM, and

footwear assessment, to confirm their role in foot ulceration as these factors have been

identified as prognostically important in previous research (Jan Apelqvist et al., 1990).

149

7.3 Conclusion

It is clear that diabetic foot complications in all their forms are a major burden on

individuals and health care providers, and can be disabling complications of diabetes (A. J.

Boulton, Vileikyte, et al., 2005). The research in this thesis has, in an Australian

community-based cohort, identified the following key findings:

Awareness of foot health among patients with type 2 diabetes is poor. Patients

who consider their feet normal have evidence of DPN and PAD, suggesting that in

a background of diabetes, patient perceptions of their own foot health is unreliable.

Patient awareness of foot health should be assessed during a clinical examination

and further foot care education provided if there are gaps in patient comprehension

of precursors to more serious foot problems.

A comparison of written and oral diabetes foot care education identified that a

combination of both forms of education may be most beneficial to patients with

regard to foot health status, and confidence in caring for their feet. In light of these

findings, the delivery of foot care education programs in the community may need

to be reviewed or modified, however further research is necessary.

In Phase I of the FDS, prevalence of foot ulceration was 1.2%, the incidence of

ulceration was 5.21 per 1000 patient-years, and the independent associates of foot

ulceration were intermittent claudication, diabetes duration, DPN and

antihypertensive therapy. The independent predictors of time to first-ever diabetes

related foot ulcer were retinopathy, cerebrovascular disease, intermittent

claudication, DPN, alcohol consumption, eGFR, PAD, HbA1c and pulse pressure.

The findings also suggest that diabetes related foot ulceration is a common end-

stage complication of diabetes.

Subsequent analysis of foot ulcer data collected 15 years later in the Phase II cohort

of the FDS found no significant difference in foot ulcer prevalence, despite

significant improvements in glycaemic and non-glycaemic cardiovascular risk

factors. This may be attributable to improvements in foot care since Phase I,

including government funded podiatry access, the establishment of

multidisciplinary diabetic foot clinics, and early referral for peripheral arterial

150

revascularisation. Consistent with Phase I, the unchanged independent associates

of ulceration identified in Phase II were diabetes duration and peripheral sensory

neuropathy, but Aboriginality and prior hospitalisations for foot ulcer also became

significant risk factors. These findings will assist in the early identification of

patients at risk of ulceration.

7.4 Concluding remarks

In a large cohort of community-based patients with type 2 diabetes, patient awareness

of their foot health was characterised, two forms of foot care education were evaluated,

and the prevalence, incidence and predictors of foot ulceration was identified. To

realise the potential of the findings presented in this thesis, and to encourage practical

change in the clinical setting, ongoing collaboration with clinicians and diabetes

educators will be necessary. Nonetheless, the outcomes of this research support

efforts to reduce the impact of diabetes related foot complications, and indicate a good

foundation for future research in this area.

151

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APPENDICES

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Appendix A

FDS Clinical Assessment Form

Neurological Assessment (Feet)

Appearance of feet:

Left Right

Appearance Normal Abnormal

Tick one or more:

Deformed

Dry skin/Callus

Infection/Fissure

Other (specify)

……………………………

……………………………

Normal Abnormal

Tick one or more:

Deformed

Dry skin/Callus

Infection/Fissure

Other (specify)

……………………………

……………………………

Ulceration Absent Present Absent Present

Participant’s ID:________________

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Sensory testing (feet)

Ankle Jerks Left Right

…… ……

0= Absent 1= Present 2= + 3= ++ 4= +++ 5= Clonus

Biothesiometer Left Right

(P1 1st MPJ) ……. …….

(Apex Hallux) ……. …….

1 = Normal (<20V) 2 = Reduced (20 – 30V) 3 = Impaired (>30V)

Light Touch (cotton wool) Left Right

……. ……...

1 = Normal 2=Abnormal (toes) 3=Abnormal (Mid foot) 4=Abnormal (ankles) 5=Abnormal

(above)

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Monofilament testing Left Right

……. ……...

1 = Normal 2=Abnormal (toes) 3=Abnormal (Mid foot) 4=Abnormal (ankles) 5=Abnormal

(above)

Pulses of Ankles and Brachial bilateral

Peripheral pulses:

(Y=present, N=absent)

Left Right

Dorsalis pedis

Posterior tibial

(If can’t get the above)

Popliteal

Peripheral circulation (Doppler):

Left Right

Pressure (mmHg) Pressure (mmHg)

Posterior tibial

Dorsalis pedis

Brachial

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Appendix B

Awareness Questionnaire

FOOT HEALTH SURVEY

Q1. Do you think that your feet are normal (eg. circulation, sensation, skin and nails)?

(Please circle Yes OR No below)

1. Yes 2. No

Q2. Have you had any problems with your feet in the last 12 months? (Please circle Yes OR No below)

1. Yes 2. No

If YES, who noticed the problem/s? (Please circle ONE only)

1. I noticed it myself 2. A Health Professional noticed it (eg. GP, Podiatrist, Nurse etc) 3. A Health Professional and myself both noticed it

What was the problem/s? ___________________________________________________________________________ ___________________________________________________________________________

Q3. Do you have numbness, tingling or pain in your feet? (Please circle Yes OR No below)

1. Yes 2. No

Q4. Do you have poor circulation in your feet? (Please circle Yes OR No below)

1. Yes 2. No

Q5. Do you have a foot ulcer? (Please circle Yes OR No below)

1. Yes 2. No

Q6. Are there any other problems you have noticed in your feet in the last 12 months?

(Please circle Yes OR No below)

1. Yes 2. No If YES, please specify ________________________________________________________________

Thank you for completing our survey!

ID: _______________ Date: _____________

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Appendix C

Flow diagram – Educational intervention

Randomised to receive written

information (n=78)

Completed trial (n=72), ITT analysis (n=76)

responses carried forward

3 month review Lost to follow up (n=4) 1 deceased

1 interstate

1 failed to attend (FIFO)

1 withdrew

3 month review Lost to follow up (n=1)

1 hospitalised

Completed trial (n=77), ITT analysis (n=78)

responses carried forward

400 randomly selected and sent

invitation to participate

FDS database eligible (n=1551) (Type 2)

Eligible (n=1017)

307 no response 2 declined

154 recruited Randomised to intervention or control groups

Randomised to receive group education

(n=76)

Excluded (n=534):

Deceased (91), failing health (3), withdrew

from FDSII (136), not fluent in English (153),

cognitive impairment/dementia (65),

Aboriginal (86)

Additional 65 letters sent

1 failed to attend for the

education session but

attended for follow up

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Appendix D

Foot Score

FDS Foot Score

Nail conditions (Evident on one or more toenails) Rating: 0=absent, 1=mild, 2=moderate, 3=severe

1. Onychomycosis and/or Other nail infection Left 0 1 2 3 ___ Nail dystrophy (destruction, thickening, discolouration) Right 0 1 2 3 ___

2. Onychocryptosis (Ingrown toenail/s) Left 0 1 2 3 Redness, swelling, discomfort at sulcus/sulci Right 0 1 2 3 ___

3. Subungual lesion/s Left 0 1 2 3 Bruising, discolouration under nail Right 0 1 2 3 ___

4. Involuted nail/s Left 0 1 2 3 Curvature of nail plate/s Right 0 1 2 3 ___

Combined Total___ Common skin conditions

1. Heloma durum/heloma molle (Corns) Left 0 1 2 3 Localised hard thickened area of skin over a joint or prominence Right 0 1 2 3 ___

2. Hyperkeratosis (Callous) Left 0 1 2 3 Diffuse hardening of skin Right 0 1 2 3 ___

3. Skin fissures Left 0 1 2 3 Cracks/breaks/splits in the skin eg. Heels, plantar joints Right 0 1 2 3 ___

4. Anhydrosis Left 0 1 2 3 General skin dryness, reduced elasticity Right 0 1 2 3 ___

5. Skin trauma/cuts/abrasions/blisters Left 0 1 2 3 Recent or healing Right 0 1 2 3 ___

Combined Total___ Other conditions and infections

1. Dermatitis/Eczema/Psoriasis/Dermopathy (feet or legs) Left 0 1 2 3 Includes redness, itch, blisters, plaques, circumscribed lesions Right 0 1 2 3 ___

2. Interdigital maceration Left 0 1 2 3 Moisture/whitening of skin between toes Right 0 1 2 3 ___

3. Tinea pedis Left 0 1 2 3 Vesicular, Papulosquamous) Right 0 1 2 3 ___

4. Verruca pedis Left 0 1 2 3 Single, multiple, mosaic Right 0 1 2 3 ___

Combined Total___ Complications

1. Ulcer/s Left 0 1 2 3 Wound with superficial loss of tissue (+/-infection) Right 0 1 2 3 ___

2. Gangrene Left 0 1 2 3 3. Evidence of tissue death (one or more toes) Right 0 1 2 3 ___

Combined Total___

Grand Total _________

ID: __________________

Date: ________________

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Appendix E

Modified NAFF

Foot Care Survey

We would like to know what you do to look after your feet. Please circle the answer that best reflects what you actually do. Please answer every question.

Q1. Do you examine your feet?

More than once a day Once a day 4-6 times per week Once a week or less

Q2. Do you check your shoes before you put them on?

Often Sometimes Rarely Never

Q3. Do you wash your feet?

More than once a day Once a day Most days a week A few days a week

Q4. Do you dry between your toes?

Always Often Sometimes Rarely/Never

Q5. Do you use moisturising cream on your feet?

Daily Once a week About once a month Never

Q6. Do you wear shoes without socks/stockings?


Q7. Do you walk around the house barefoot?


Q8. Do you walk outside barefoot?


Q9. Do you use corn remedies/corn plasters if you get a corn?


Q10. Do you put a dry dressing on a graze, cut or burn when you get one?


ID: __________________

Date: ________________

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Appendix F

Attitudes Survey

Now we would like to ask you to respond to some statements and questions about how you feel about diabetes. Please circle the answer that best reflects how you feel, or provide a written answer where required.

Q11. Foot problems are more likely to lead to complications in people with diabetes.

Strongly agree Agree Disagree Strongly disagree

Q12. Do you think you are likely to develop foot complications?

Very likely Quite likely Not likely Q13. Why do you think this? ……………………………………………………………………………………………………………………………………………………………………………………………………………………………… Q14. How often do you feel overwhelmed with the demands of living with diabetes?


Q15. I feel well informed about the risks of developing diabetes-related foot complications (eg. A

foot ulcer)

Strongly Agree Agree Disagree Strongly Disagree

Q16. How well do you understand how to prevent diabetic foot complications? Very well Moderately well Not at all well Q17. Would you like to have more information about diabetes foot complications? (Please circle ONE only) Yes No Q18. What worries you most when you think about diabetes foot complications?

…………………………………………………………………………………………………………………………………………………………..…………………………………………………………….……

Thank you very much for taking part in our survey!

ID: __________________

Date: ________________

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Appendix G

My Feet and Diabetes - foot care booklet

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Documents

Foot health in diabetes mellitus: Epidemiological and