Risk of Type 2 Diabetes and It’s Risk of Type 2 Diabetes and It’s Complications Along The Continuum Complications Along The Continuum

of Fasting Plasma Glucoseof Fasting Plasma Glucose

Gregory A. Nichols, PhDGregory A. Nichols, PhD

Collaborative Diabetes Education Conference Collaborative Diabetes Education Conference for Health Professionalsfor Health Professionals

January 30, 2010January 30, 2010

DisclosuresDisclosures Employed by Kaiser Permanente Center for Health Employed by Kaiser Permanente Center for Health

Research, Portland, OregonResearch, Portland, Oregon

Government Research Funding:Government Research Funding:– National Institute of Diabetes and Digestive and Kidney Disorders National Institute of Diabetes and Digestive and Kidney Disorders

(NIDDK)(NIDDK)

– Agency for Healthcare Research and Quality (AHRQ)Agency for Healthcare Research and Quality (AHRQ)

Industry Funding:Industry Funding:– GlaxoSmithKlineGlaxoSmithKline

– Novo NordiskNovo Nordisk

– Novartis PharmaceuticalsNovartis Pharmaceuticals

– Tethys BioscienceTethys Bioscience

– Takeda Pharmaceuticals North AmericaTakeda Pharmaceuticals North America

OverviewOverview

Part I - Diabetes and “Pre-diabetes”Part I - Diabetes and “Pre-diabetes”

Part II - Fasting Glucose as a Diabetes Part II - Fasting Glucose as a Diabetes Risk FactorRisk Factor

Part III – Nondiabetic Fasting Glucose Part III – Nondiabetic Fasting Glucose as a Risk Factor for Complications of as a Risk Factor for Complications of DiabetesDiabetes

Part I Part I Diabetes and “Pre-diabetes”Diabetes and “Pre-diabetes”

A brief history of the definition of a A brief history of the definition of a diabetes diagnosisdiabetes diagnosis

Defining other forms of dysglycemiaDefining other forms of dysglycemia

Diagnosing DiabetesDiagnosing Diabetes

Oral Glucose Tolerance Test (OGTT)Oral Glucose Tolerance Test (OGTT) 2-hour post-load 2-hour post-load >> 200mg/dl 200mg/dl

Fasting Plasma Glucose (FPG)Fasting Plasma Glucose (FPG) Prior to 1997, Prior to 1997, >> 140 mg/dl 140 mg/dl

Now, Now, >> 126 mg/dl 126 mg/dl

HbA1c HbA1c >> 6.5% (as of 2010) 6.5% (as of 2010)

These tests measure different things and often These tests measure different things and often identify different peopleidentify different people

Other Forms of DysglycemiaOther Forms of Dysglycemia(“Pre-Diabetes”)(“Pre-Diabetes”)

Impaired Glucose Tolerance (IGT)Impaired Glucose Tolerance (IGT)OGTT 2-hour post-load 140 - 199 mg/dlOGTT 2-hour post-load 140 - 199 mg/dl

Impaired Fasting Glucose (IFG)Impaired Fasting Glucose (IFG)From 1997-2003, 110 - 125 mg/dlFrom 1997-2003, 110 - 125 mg/dl

Since 2003, 100 - 125 mg/dlSince 2003, 100 - 125 mg/dl

HbA1c 5.7 – 6.4%HbA1c 5.7 – 6.4%

Summary of Part ISummary of Part I

Diabetes is a “category” on the continuum of Diabetes is a “category” on the continuum of glucose and is based on the point at which glucose and is based on the point at which riskrisk of diabetic retinopathy becomes elevatedof diabetic retinopathy becomes elevated

IFG and IGT are categories on the continuum IFG and IGT are categories on the continuum of glucose that were designed to represent of glucose that were designed to represent increased increased riskrisk of developing diabetes of developing diabetes

Part II - Part II - Fasting Glucose as a Fasting Glucose as a Diabetes Risk FactorDiabetes Risk Factor

Impaired Fasting Glucose (IFG) and Risk of Impaired Fasting Glucose (IFG) and Risk of DiabetesDiabetes

Normal Plasma Glucose and Risk of DiabetesNormal Plasma Glucose and Risk of Diabetes

Glucose, other Risk Factors, and Risk of Glucose, other Risk Factors, and Risk of DiabetesDiabetes

Risk of Progression Risk of Progression From IFG to DiabetesFrom IFG to Diabetes

PopulationYears of

F/UIsolated

IFGIFG &

IGT

Hoorn Study (1998) Dutch 5.8-6.5 33.0% 64.5%

Paris Prospective Study (2001) French 2.5 2.7% 14.9%

Vaccaro et al. (1999) Italian 11.5 9.1% 44.4%

Shaw et al. (1999) Mauritius 5.0 21.6% --

Gabir et al. (2000)Pima

Indians 5.0 -- 41.2%

Gimeno et al. (1998)Brazilian-Japanese 7.0 -- 72.7%

Baltimore Longitudinal Study on Aging (2003) U.S. 10.0 -- 25.0%

Sample SelectionSample Selection

28,335 KPNW non-diabetic members with at 28,335 KPNW non-diabetic members with at least two FPG tests 100-125 mg/dl between least two FPG tests 100-125 mg/dl between 1994 and 20031994 and 2003

5,452 with a prior test < 100 mg/dl5,452 with a prior test < 100 mg/dl

4,526 had first abnormal value 100-1094,526 had first abnormal value 100-109

926 had first abnormal value 110-125926 had first abnormal value 110-125

Follow-up through 12/31/05 Follow-up through 12/31/05

Study SampleStudy Sample

Added IFG (100-109 mg/dl)

Original IFG (110-125

mg/dl) p value

Number (%) of Subjects 4,526 (83.0%) 926 (17.0%) --

Age at IFG Incidence 59.7 (11.1) 57.9 (11.6) <0.0001

Percent Female 48.1% 53.9% 0.001

Systolic Blood Pressure 134 (13) 136 (13) 0.017

Diastolic Blood Pressure 79 (7) 80 (7) 0.033

Body Mass Index 31.0 (6.3) 33.2 (7.2) <0.0001

HDL Cholesterol 51 (15) 48 (14) <0.0001

Triglycerides 190 (215) 212 (138) 0.004

LDL Cholesterol 126 (30) 121 (31) <0.0001

Nichols et al., Diabetes Care 2007;30:228-233

Nichols et al., Diabetes Care 2007;30:228-233.

Proportion of Subjects Progressing to Diabetes, Proportion of Subjects Progressing to Diabetes, Months Until Progression, Months Until Progression,

and Rate of Progression, by IFG Stageand Rate of Progression, by IFG Stage

Did Not Did Not Progress to Progress to

Original IFGOriginal IFGProgressed to Progressed to Original IFGOriginal IFG TotalTotal

Initial IFG Initial IFG Stage was Stage was

Added IFGAdded IFGInitial IFG Stage Initial IFG Stage was Original IFGwas Original IFG TotalTotal

Total, All Total, All SubjectsSubjects

nn

(%)(%)

3,7533,753

(82.9%)(82.9%)

773773

(17.1%)(17.1%)4,5264,526

773773

(45.5%)(45.5%)

926926

(54.5%)(54.5%)1,6991,699 5,4525,452

Progressed to Progressed to DiabetesDiabetes

201 201

(5.4%)(5.4%)

164164

(21.2%)(21.2%)

365365

(8.1%)(8.1%)

164164

(21.2%)(21.2%)

249249

(26.8%)(26.8%)

413413

(24.3%)(24.3%)

614614

(11.3%)(11.3%)

Mean (SD) Months Mean (SD) Months from 1from 1stst FPG FPG Measure to Measure to Progression to Progression to DiabetesDiabetes

31.131.1

(23.2)(23.2)

54.154.1

(27.6)(27.6)

41.441.4

(25.8)(25.8)

29.529.5

(25.9)(25.9)

28.728.7

(26.5)(26.5)

29.029.0

(26.2)(26.2)

36.336.3

(27.9)(27.9)

Diabetes Incidence Diabetes Incidence per Yearper Year

0.910.91 3.243.24 1.341.34 5.165.16 5.875.87 5.565.56 1.951.95

Added IFG (100-109 mg/dL) Original IFG (110-125 mg/dL)

Nichols et al., Diabetes Care 2007;30:228-233.

Predictors of Progression to DiabetesPredictors of Progression to Diabetes

Risk Ratio 95% CI p value Risk Ratio 95% CI p value

Progressed to Original IFG 3.11 2.43 – 3.98 <0.0001 -- -- --

Initially Added IFG -- -- -- 1.12 0.88 - 1.42 0.352

Initial FPG (per mg/dl) 1.08 1.04 - 1.13 0.0003 1.07 1.04 - 1.10 <0.0001

Age (per 10 Years) 0.92 0.86 - 0.99 0.020 0.92 0.87 – 0.98 0.015

Female Sex 1.47 1.11 - 1.93 0.007 1.33 1.02 - 1.72 0.032

Current Smoker 1.51 1.15 - 1.99 0.003 1.17 0.89 - 1.53 0.255

BMI (per kg/m2) 1.04 1.02 - 1.06 <0.0001 1.03 1.02 - 1.05 <0.0001

Systolic BP (per 5mmHg) 1.10 1.04 - 1.16 <0.0001 1.08 1.03 - 1.14 0.001

HDL-C (per 5mg/dl) 0.88 0.83 - 0.93 <0.0001 0.88 0.84 - 0.93 <0.0001

LDL-C (per 5mg/dl) 0.97 0.95 - 0.99 0.003 0.99 0.97 - 1.01 0.411

Triglycerides (per 50mg/dl) 1.01 1.00 - 1.02 0.026 1.03 1.01 - 1.04 0.0003

Progression from IFG 100-109 Progression from IFG 110-125

Adapted from Nichols et al., Diabetes Care 2007;30:228-233

SummarySummary Patients with IFG progress to diabetes at a rate of Patients with IFG progress to diabetes at a rate of

1.3-5.6% per year1.3-5.6% per year

Those who progress do so in 29-59 months, and Those who progress do so in 29-59 months, and more rapid progression prior to diabetes is a more rapid progression prior to diabetes is a warning signwarning sign

High BMI and low HDL-C are the strongest non-High BMI and low HDL-C are the strongest non-glucose predictors of progressionglucose predictors of progression

Each mg/dl of fasting glucose increases risk of Each mg/dl of fasting glucose increases risk of progression to diabetes by 7-8%progression to diabetes by 7-8%

Next QuestionNext Question

Does the apparently linear relationship Does the apparently linear relationship between fasting glucose and progression to between fasting glucose and progression to diabetes extend below 100 mg/dl? diabetes extend below 100 mg/dl?

Sample SelectionSample Selection 46,578 KPNW members with FPG < 100 46,578 KPNW members with FPG < 100

mg/dl between 1997 and 2000mg/dl between 1997 and 2000

No diabetes or previous FPG No diabetes or previous FPG >> 100 mg/dl 100 mg/dl

Categories of baseline FPG:Categories of baseline FPG:< 85 mg/dl< 85 mg/dl85-89 mg/dl85-89 mg/dl90-94 mg/dl90-94 mg/dl95-99 mg/dl95-99 mg/dl

Followed through 4/30/07 for development of Followed through 4/30/07 for development of diabetes (mean of 81 months)diabetes (mean of 81 months)

Study SampleStudy Sample

< 85 mg/dL85-89 mg/dL

90-94 mg/dL

95-99 mg/dL

n (%)

8,705 (18.7%)

10,983 (23.6%)

13,704 (29.4%)

13,186 (28.3%)

Age* 55.4 (11.0) 56.6 (10.7) 57.8 (11.0) 59.1 (11.1)

% Male* 28.7% 35.5% 42.9% 49.4%

BMI* 28.0 (5.8) 28.6 (5.8) 29.2 (5.9) 29.9 (6.0)

Systolic BP* 128 (19) 130 (18) 131 (19) 134 (19)

Diastolic BP * 79 (10) 79 (10) 80 (10) 81 (10)

HDL-Cholesterol* 57 (17) 56 (17) 54 (16) 52 (16)

LDL-Cholesterol* 123 (34) 126 (34) 129 (35) 130 (34)

Triglycerides* 142 (122) 147 (115) 156 (106) 164 (114)

Adapted from Nichols et al., Am J Med 2008;121:519-524

Cumulative Diabetes Incidence by Cumulative Diabetes Incidence by Category of Normal Fasting GlucoseCategory of Normal Fasting Glucose

0

2

4

6

8

10

12

0 6 12 17 21 24 28 32 35 38 41 45 48 51 55 58 62 66 70 74 77 81 85 89 92 98 102 108

Months of Follow-up

Cu

mu

lati

ve

In

cid

en

ce

(%

)

95-99 mg/dL

9.9/1,000 person-years

95% CI, 9.3 - 10.690-94 mg/dL

5.6/1,000 person-years95% CI, 5.1 - 6.1

85-89 mg/dL

3.6/1,000 person-years95% CI, 3.2 - 4.1

< 85 mg/dL

3.1/1,000 person-years95% CI, 2.6 - 3.5

log-rank p<0.0001

Nichols et al., Am J Med 2008;121:519-524

Hazard Ratios of Diabetes Incidence Hazard Ratios of Diabetes Incidence Adjusted for Risk FactorsAdjusted for Risk Factors

2.33(1.95 - 2.79)

1.49(1.23 - 1.79)

1.08(0.87 - 1.33)1.00

(referent)

0.00

1.00

2.00

3.00

< 85 mg/dL 85-89 mg/dL 90-94 mg/dL 95-99 mg/dL

Baseline Fasting Plasma Glucose Category

Ha

za

rd R

ati

o

Nichols et al., Am J Med 2008;121:519-524.

Cox Regression of Diabetes Cox Regression of Diabetes Incidence (Continuous FPG)Incidence (Continuous FPG)

Hazard Ratio 95% CI p value

Fasting Plasma Glucose (per mg/dL) 1.06 1.05 - 1.07 <0.0001

Age (per year) 1.01 1.00 - 1.02 <0.001

Male Sex 1.01 0.90 - 1.13 0.837

BMI (per kg/m2) 1.08 1.07 - 1.09 <0.0001

Systolic BP (per 5 mmHg) 1.02 1.01 - 1.03 0.008

HDL-Cholesterol (per 5 mg/dL) 0.90 0.88 - 0.92 <0.0001

LDL-Cholesterol (per 10 mg/dL) 0.97 0.96 - 0.99 0.0001

Triglycerides (per 50 mg/dL) 1.09 1.07 - 1.10 <0.0001

Current Smoker 1.37 1.22 - 1.54 <0.0001

Diagnosed Cardiovascular Disease 1.65 1.40 - 1.93 <0.0001

Diagnosed Hypertension 1.51 1.35 - 1.68 <0.0001Nichols et al., Am J Med 2008;121:519-524

Characteristics of Patients Who Characteristics of Patients Who Developed DiabetesDeveloped Diabetes

< 85 mg/dL 85-89 mg/dL 90-94 mg/dL 95-99 mg/dL

Age 56.6 (9.7) 57.4 (9.5) 58.7 (10.4) 59.1 (10.5)

% Male 42.9% 45.5% 46.5% 49.8%

BMI 32.7 (6.7) 33.5 (7.2) 33.4 (7.3) 33.0 (6.8)

Systolic BP 134 (18) 137 (18) 136 (20) 136 (19)%

Diastolic BP 82 (10) 82 (11) 82 (11) 82 (10)

HDL-Cholesterol 49 (15) 46 (15) 47 (14) 47 (14)

LDL-Cholesterol 123 (37) 124 (36) 127 (37) 125 (34)

Triglycerides 239 (364) 213 (257) 212 (149) 209 (131)

Current Smoker 27.4% 25.8% 25.0% 22.0%

Cardiovascular Disease 9.7% 8.3% 11.9% 11.7%

Hypertension 41.1% 49.6% 43.7% 43.6%

Months to Diabetes 59.0 (28.3) 54.6 (28.3) 54.4 (28.3) 53.8 (29.9)

Mean FPG at Diagnosis 150 (63) 145 (52) 141 (53) 142 (51)

Adapted from Nichols et al., Am J Med 2008;121:519-524

Characteristics of Patients who Did and Characteristics of Patients who Did and Did Not Develop DiabetesDid Not Develop Diabetes

Developed Diabetes No Diabetes p value

Age 58.5 (10.3) 57.4 (10.9) <0.0001

% Male 47.6% 40.1% <0.0001

BMI 33.2 (7.0) 28.8 (5.8) <0.0001

Systolic BP 136 (19) 131 (19) <0.0001

Diastolic BP 82 (10) 80 (10) <0.0001

HDL-Cholesterol 47 (14) 54 (16) <0.0001

LDL-Cholesterol 125 (36) 128 (34) 0.005

Triglycerides 213 (191) 151 (109) <0.0001

Current Smoker 23.9% 20.2% <0.001

Cardiovascular Disease 11.1% 6.0% <0.0001

Hypertension 44.2% 25.8% <0.0001

Nichols et al., Am J Med 2008;121:519-524

SummarySummary

Elevated risk of diabetes is associated with Elevated risk of diabetes is associated with higher values of “normal” fasting glucose, higher values of “normal” fasting glucose, perhaps to as low as 87 mg/dlperhaps to as low as 87 mg/dl

The 6% increase in risk per mg/dl was similar The 6% increase in risk per mg/dl was similar to the 7% found among patients with IFGto the 7% found among patients with IFG

The same risk factors consistently predict The same risk factors consistently predict diabetes regardless of FPGdiabetes regardless of FPG

Diabetes Risk and Diabetes Risk and The Metabolic SyndromeThe Metabolic Syndrome

Fasting Glucose Fasting Glucose >> 100 mg/dl 100 mg/dl

BP BP >> 130/85 mmHg 130/85 mmHg

Triglycerides Triglycerides >> 150 mg/dl 150 mg/dl

HDL-C < 40/50 mg/dlHDL-C < 40/50 mg/dl

Waist circumference Waist circumference >> 102/88 cm 102/88 cm

Age/sex Adjusted Incidence of Diabetes, by Presence of Individual Metabolic Syndrome Components

8.8(8.2 - 9.4)

21.9(21.2 - 22.7)

8.4(7.9 - 8.9)

26.2(25.3 - 27.1)

11.5(11.0 - 12.0)

27.6(26.5 - 28.7)

13.1(12.6 - 13.6)

29.1(27.8 - 30.4)

7.1(6.7 - 7.4)

47.0(45.4 - 48.7)

0.0

10.0

20.0

30.0

40.0

50.0

Inci

den

ce p

er 1

,000

per

son

-yea

rs (9

5% C

I)

Age/sex Adjusted Incidence of Diabetes by Number of Metabolic Syndrome Components

1.0

10.0

100.0

-1 0 1 2 3 4 5Number of Risk Factors

Inci

denc

e per

1,

000

pers

on-y

ears

(9

5% C

I)

Low HDL High TG Hypertension Obesity IFG

Summary of Part IISummary of Part II

Risk of diabetes associated with fasting Risk of diabetes associated with fasting glucose is continuousglucose is continuous

Other metabolic risk factors that are Other metabolic risk factors that are commonly associated with elevated glucose commonly associated with elevated glucose play important but largely supplementary play important but largely supplementary rolesroles

Part III – Nondiabetic Fasting Part III – Nondiabetic Fasting Glucose as a Risk Factor for Glucose as a Risk Factor for Complications of DiabetesComplications of Diabetes

Cardiovascular DiseaseCardiovascular Disease

Microvascular Diseases: Microvascular Diseases:

Nephropathy Nephropathy

Retinopathy Retinopathy

NeuropathyNeuropathy

Heart FailureHeart Failure

Medical CostsMedical Costs

Glucose and CVD EventsGlucose and CVD Events

Fasting glucose is (probably) associated with Fasting glucose is (probably) associated with CVDCVD

Coutinho et al. (1999): 20 studies, RR 1.33 (1.06-Coutinho et al. (1999): 20 studies, RR 1.33 (1.06-1.67) for 75 vs. 110 mg/dl1.67) for 75 vs. 110 mg/dl

Levitan et al. (2004): 34 studies, RR 1.27 (1.13-Levitan et al. (2004): 34 studies, RR 1.27 (1.13-1.43) comparing top and bottom categories, 1.43) comparing top and bottom categories, possible threshold effect at 100 mg/dlpossible threshold effect at 100 mg/dl

Danaei et al. (2006): 1 in 5 deaths from ischemic Danaei et al. (2006): 1 in 5 deaths from ischemic heart disease are attributable to higher-than-heart disease are attributable to higher-than-optimum blood glucose optimum blood glucose excludingexcluding deaths deaths attributable to diabetesattributable to diabetes

Glucose and Microvascular DiseaseGlucose and Microvascular Disease

No data on neuropathyNo data on neuropathy

Diabetes diagnosis based on increased Diabetes diagnosis based on increased prevalence of retinopathy, which is present prevalence of retinopathy, which is present for up to 7 years prior to diagnosisfor up to 7 years prior to diagnosis

Cox et al. (2005) - No relationship between Cox et al. (2005) - No relationship between IFG/IGT and CKD, but strong association IFG/IGT and CKD, but strong association with diabeteswith diabetes

IFG and Heart FailureIFG and Heart Failure

FPG test in 1997 or 1998 < 126mg/dlFPG test in 1997 or 1998 < 126mg/dl

Age 50 or older and no evidence of diabetes Age 50 or older and no evidence of diabetes or CHFor CHF

10,113 subjects with IFG (100-125mg/dl)10,113 subjects with IFG (100-125mg/dl)

10,113 subjects with glucose < 100mg/dl 10,113 subjects with glucose < 100mg/dl matched on sex and 5-year age groupmatched on sex and 5-year age group

Followed for ~6.5 yearsFollowed for ~6.5 years

IFG and Heart FailureIFG and Heart Failure

1.08(1.03-1.13)

1.12(1.00-1.25)

1.19(1.04-1.36)

0.25

1

1.75

Per 10mg/dl 100-109 mg/dl 110-125 mg/dl

Baseline Fasting Plasma Glucose

Haz

ard

Rat

io

1.00

Nichols et al., Journal of Diabetes and Its Complications 2009;23:224-228

IFG and Heart Failure (2)IFG and Heart Failure (2)

1.01(0.87-1.16)

1.08(0.97-1.22)1.01

(0.97-1.07)

0.25

1

1.75

Per 10mg/dl 100-109 mg/dl 110-125 mg/dl

Baseline Fasting Plasma Glucose

Haz

ard

Rat

io

1.00

Nichols et al., Journal of Diabetes and Its Complications 2009;23:224-228

Comorbidities and Risk of DiabetesComorbidities and Risk of Diabetes

IFG IFG (n=15,732)(n=15,732)

NPG NPG (n=40,962)(n=40,962)

Relative Risk Relative Risk of Diabetes*of Diabetes*

Cardiovascular DiseaseCardiovascular Disease 18.5%18.5% 11.6%11.6%1.69 1.69

(1.58-1.82)(1.58-1.82)

Chronic Kidney DiseaseChronic Kidney Disease 8.7%8.7% 6.7%6.7%1.45 1.45

(1.32-1.60)(1.32-1.60)

Heart FailureHeart Failure 3.4%3.4% 1.8%1.8%2.13 2.13

(1.88-2.41)(1.88-2.41)

History of DepressionHistory of Depression 20.5%20.5% 20.6%20.6%1.41 1.41

(1.32-1.50)(1.32-1.50)

*Controlling for fasting plasma glucose

Medical Care CostsMedical Care Costs

Diabetes is enormously expensiveDiabetes is enormously expensive

If a diabetes diagnosis is an arbitrary If a diabetes diagnosis is an arbitrary point on a continuum of glucose, then point on a continuum of glucose, then wouldn’t costs also be elevated at sub-wouldn’t costs also be elevated at sub-diabetic levels of hyperglycemia (relative diabetic levels of hyperglycemia (relative to those with normal glycemia)?to those with normal glycemia)?

Incremental Cost of Diabetes Incremental Cost of Diabetes Before and After DiagnosisBefore and After Diagnosis

Costs for Non-Diabetes Control

Group

Incremental Costs for Diabetes

$0

$1,000

$2,000

$3,000

$4,000

$5,000

$6,000

$7,000

$8,000

Co

st o

f Car

e (U

S$1

998)

Year -5 Year -4 Year -3 Year -2 Year -1 Year +1 Year +2 Year +3

Year Before or After Recognition

Nichols et al. Diabetes Care 2000;23:1654-1658

Costs of Impaired Fasting GlucoseCosts of Impaired Fasting Glucose

$1,497 $1,569 $1,747

$1,923 $1,991$2,045

$937$1,057

$1,174

$-

$1,000

$2,000

$3,000

$4,000

$5,000

$6,000

< 100mg/dL (n=28,335) 100-109mg/dL (n=18,738) 110-125mg/dL (n=12,878)

PharmacyOutpatientInpatient

$4,357$4,617

$4,966

Nichols and Brown, Diabetes Care 2005;28:2223-2229

Costs of Impaired Fasting Glucose (2)Costs of Impaired Fasting Glucose (2)

$1,157$1,547 $1,746

$1,790

$1,979$2,039

$852

$1,054

$1,175

$-

$1,000

$2,000

$3,000

$4,000

$5,000

$6,000

Stayed Below 100mg/dL(n=23,621)

100-109mg/dL (n=18,738) 110-125mg/dL (n=12,878)

PharmacyOutpatientInpatient

$3,799

$4,580

$4,960

Nichols and Brown, Diabetes Care 2005;28:2223-2229

Incremental Costs of Incremental Costs of Normal Fasting GlucoseNormal Fasting Glucose

$1,148$1,716

$2,164$2,599

$1,794

$1,940

$2,103

$2,613

$843

$803

$1,040

$1,356

$-

$1,000

$2,000

$3,000

$4,000

$5,000

$6,000

$7,000

Stayed Below100mg/dL (n=23,621)

Progressed to 100-109mg/dl (n=1,741)

Progressed to 110-125mg/dl (n=462)

Progressed toDiabetes (n=485)

PharmacyOutpatientInpatient

$3,755

$3,900

$4,488

$6,796

Nichols and Brown, ADA 65th Scientific Sessions;2005:Abstract #117-OR

SummarySummary

The risk of developing diabetes is strongly The risk of developing diabetes is strongly associated with level of fasting glucoseassociated with level of fasting glucose

That risk is That risk is continuouscontinuous, or at least extends , or at least extends well below the point at which glucose is well below the point at which glucose is considered abnormalconsidered abnormal

Summary (2)Summary (2)

Other metabolic risk factors that are Other metabolic risk factors that are commonly associated with elevated glucose commonly associated with elevated glucose play important but largely supplementary play important but largely supplementary rolesroles

Non-diabetic levels of glucose increase the Non-diabetic levels of glucose increase the risk of “diabetic” complications as well as risk of “diabetic” complications as well as costs of medical carecosts of medical care

ConclusionConclusion

The relationships between glucose, other The relationships between glucose, other metabolic disturbances, diabetes, and it’s metabolic disturbances, diabetes, and it’s complications are complex and confoundedcomplications are complex and confounded

Categorizing glucose helps us understand Categorizing glucose helps us understand these interrelationships, but limits our ability these interrelationships, but limits our ability to predict riskto predict risk