SPAGGDocument Title Diabetes Management in Palliative Care

Document Date March 2015

Document Purpose and Intended Audience

The aim of these guidelines is to ensure staff are informed and able to manage diabetes in end of life care:

Avoiding hypoglycaemia. Limiting symptomatic hyperglycaemia. Avoiding unnecessary CBG checks and complex

insulin regimes. Avoiding metabolic decompensation and

recognising, and considering treatment of, diabetes-related emergencies[

These guidelines are suitable for use in both primary community care and in the in patient setting

Authors Rebecca Dawber ST3 Palliative Medicine East of England Deanery, Dr Philip Dyer Diabetologist HEFT and Chantal Meystre, Consultant Palliative Medicine HEFT

1SPAGG Diabetes Management in Palliative Care v3.0 2015

References 1. Boon N, Colledge N, Walker B, Hunter J (2006).Davidson’s Principles and Practice of Medicine. 20th edition.

2. Rowles S, Kilvert A, Sinclair A: on behalf of the Association of British Clinical Diabetologists (2011) ABCD position statement on diabetes and end of life care. Practical Diabetes International. 28 (1); 26-27.

3. Watson M, Lucas C, Hoy A, Wells, J (2009). Oxford Handbook of Palliative Care (Oxford Medical Handbooks).

4. Joint Formulary Committee (2012) British National Formulary (BNF) 64.

5. Husbands, E. (2008) Clinical Care Guidelines: Management of Diabetes Mellitus in Palliative Medicine. Birmingham: Pan-Birmingham Palliative Care Network.

6. HEFT guidelines for DKA and HHS (available via Birmingham HEFT intranet).

7. HEFT guielines for hypoglycaemia (available via Birmingham HEFT intranet).

8. Poulson J. (1997) The management of diabetes in patients with advanced cancer. Journal of Pain and Symptom Management. 13(6):339-46

9. End of Life Diabetes Care: A Strategy Document Commissioned by Diabetes UK. Full Strategy Document Commissioned by Diabetes UK second edition October 2013

10.Pan Birmingham Cancer Network (2012). Guideline for the use of symptom control (West Midlands Palliative Care Physicians), 5th Edition. Available via Birmingham Heartlands Hospital intranet.

11.Davis SN, Umpierrez GE. Diabetic ketoacidosis in type 2 diabetes mellitus--pathophysiology and clinical presentation...Nat ClinPractEndocrinolMetab. 2007 Nov;3(11):730-1. Epub 2007 Sep 11.

12.David S. Oyer, Ajul Shah, and Susan Bettenhausen How to Manage Steroid Diabetes in the Patient with Cancer.. J Support Oncol 2006;4:479–483

13.Guidelines for Diabetes in Palliative Care, Marie Curie Hospice Solihull, Dr N Baker, Dr C Meystre

Consultation Process Guideline review of existing SPAGG guideline for diabetes, local hospice guideline, Diabetes lead Heart of England Foundation Trust, and review of new literature by Dr R Dawber, Dr C Meystre on behalf of palliative care, and Dr Dyer on behalf of the diabetes team.

Draft guideline sent to SPAGG expert group for comment

Monitoring Monitoring of guideline implementation locally

2SPAGG Diabetes Management in Palliative Care v3.0 2015

Review Date March 2018

Approval Signatures:

SPAGG chair

SPAGG deputy chair

SPAGG secretary

M.Astlett

J.Dominey

N.Khan

Date Approved by SPAGG: March 2015

Date submitted to Area Prescribing Committee:

Guidance Name

Version History

Version Date Summary of change/ process

3.0 2015 Chantal Meystre (Marie Curie Hospice), Rebecca Dawber (SpR Palliative Medicine. Adaption from Pan Birmingham NHS Palliative Care Network Guidelines and extensive review in conjunction with HEFT diabetologist Dr. Philip Dyer

2.0 2012 Diana Webb (John Taylor Hospice), Nicky Baker (Marie Curie Hospice)

1.0 2009 Emma Husbands, amended by Nial McCarron

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Diabetes Management in Palliative Care

These guidelines have been adapted from the Pan-Birmingham NHS Palliative Care Network-produced guidelines.

Introduction

Diabetes is a clinical syndrome characterised by an absolute or relative lack of insulin[1]. Lack of insulin affects the metabolism of carbohydrate, fats and protein, and can cause significant disturbances of water and electrolyte homeostasis [1]. Death can result from acute metabolic decompensation [1]. Calculations based on the prevalence of diabetes indicate that 6-9% of the dying will have diabetes [2].

In type 1 diabetes mellitus (T1DM) there is autoimmune destruction of insulin secreting beta cells in pancreatic islets[1], and it accounts for 5-10% of diabetes. Patients with T1DM have an absolute deficiency of insulin and will always be on subcutaneous insulin replacement, without which they will die [2]. Insulin is needed to allow uptake of glucose from the blood into cells for it to be used as an energy source. In its absence the body has to change from utilising carbohydrate for energy to using fatty acids. Breakdown of these fatty acids creates ketone bodies, which are acidic and cause nausea, vomiting and metabolic acidosis. This is called diabetic ketoacidosis (DKA) and this is a life-threatening diabetic emergency [6] [see appendix 1].

Type 2 diabetes mellitus (T2DM) occurs because although the pancreas is producing insulin, there is resistance to its effect[1]. This accounts for 90% of diabetes. They may be treated with dietary modification or oral anti-diabetic drugs (OADs) initially. Over time, as the beta cells struggle to make more insulin to maintain normal blood glucose, the cells eventually cannot sustain the demand and patients with T2DM also develop insulin deficiency[1]. 20% of patients with T2DM ultimately develop profound insulin deficiency and require insulin replacement [1]. This does not mean that they then develop T1DM, they are patients with T2DM who require insulin. Patients with T2DM are prone to developing hyperglycaemic hyperosmolar state (HHS) which has a high mortality[1]. They also can develop DKA and up to 50% of episodes of DKA occur in T2DM[11]. HHS develops over a longer period of persistent hyperglycaemia with patients having a very high blood sugar and they become severely dehydrated [see appendix 1].

The mechanism of action, dose range, efficacy and elimination route of OADs for T2DM, along with their associated side effects, are listed in appendix 2. The types of the commonly used insulin are listed in appendix 3.

The use of steroids in high doses is common in advanced cancer. These agents have a direct hyperglycaemic effect which starts very early after ingestion, and they also increase appetite[3]. One in five patients on high dose steroids develop steroid-induced diabetes and the hyperglycaemia is dose dependent[3].

Patients with pancreatic cancer are prone to developing diabetes due to destruction of pancreatic tissue[3]. Pancreatic cancer may present with diabetes[3].

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Patients with existing diabetes and their families may have spent years try to achieve tight glycaemic control and they may have difficulty understanding that strict glycaemic control can be detrimental to quality of life, and that long term complications of diabetes become irrelevant when the end of life is near [2]. It is therefore important to consider the patient and families wishes and to counsel appropriately[2].

Rationale

The aim of these guidelines for management of diabetes in end of life care is to: Avoid hypoglycaemia. Limit symptomatic hyperglycaemia. Always consider checking blood glucose (CBG) if the condition of a

patient with diabetes changes, or if the patient has symptoms consistent with hyper- or hypo- glycaemia[5].

Avoiding unnecessary CBG checks and complex insulin regimes. Avoid metabolic decompensation and recognise, and consider

treatment of, diabetes-related emergencies[9]. Ensure the patient is on the lowest dose of steroid – risk vs. benefit.

Management will be different for each patient and will need to be reviewed as their condition changes – for example as their oral intake and weight changes. Evidence based research into diabetes care in the terminal phase does not exist [5].

Target Capillary Blood Glucose for patients with a prognosis of months or less

8.0-15.0 mmol/L

Definitions

Hypoglycaemia

Defined as CBG below 4.0mmol/L[7]

Symptoms include pallor, sweating, tremor, tachycardia, loss of concentration, aggression/confusion, fits, transient neurological deficit, reduced conscious level [7].

Causes of hypoglycaemia in the palliative care population[2,3]: weight loss anorexia renal failure (drugs not metabolised) liver failure (decreased glycogen and gluconeogenesis) [2,3]

Hyperglycaemia

Defined as CBG above 15.0mmol/L for the purpose of this guideline.

Symptoms include thirst, dry mouth, confusion, drowsiness, polyuria and lethargy [8]. Generally overt symptoms develop with blood glucose concentrations are above

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15.0mmol/L[8]. Treatment should be instituted if there are symptoms[8]. Which treatment depends on the individual case.

Causes of hyperglycaemia in palliative care population are as follows [2,3]: stress response to illness disturbance of glucose metabolism caused by certain malignancies steroid use coexistent infection pre-existing diabetes pancreatic cancer

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1

1 7

SPAGG Diabetes Management in Palliative Care v3.0 2015

Patient in the dying phaseAim to avoid hypoglycaemia and symptomatic

hyperglycaemia

Steroid-Induced Diabetes If not already stopped, stop

steroids Do not monitor CBG Stop all anti-diabetic

medication

Type 1 Diabetes Stop rapid acting and pre-mixed insulin Change to long acting (LA) analogue insulin

(e.g. Lantus) given once daily at half their current basal insulin* dose

Type 2 Diabetes Stop all anti-diabetic

medication Do not monitor CBGs

Check CBG once daily before insulin dose. If CBG: 8.0-15.0mmol/L stop monitoring <8.0mmol/L or >15.0mmol/L continue to monitor

and alter insulino <8.0mmol/L reduce Lantus by 20%o >15.0mmol/L increase Lantus by 20%

BASAL INSULINThese include Humulin-I, Insulatard, Lantus or Levemir

Not eating, significant weight loss, nausea and vomiting, significant renal or liver disease.

Type 1 DiabetesPrognosis days/weeks

Use once daily long-acting insulin (Lantus) at 50% of basal insulin dose.

Manage as hypoglycaemia as per trust guidelines. Reduce insulin dose by 50%.

CBG≥4.0-8.0mmol/LCBG<4.0mmol/L

If patient unconscious and in dying phase, refer to algorithm for the dying phase.

Eating and drinking, no significant weight loss, no nausea and vomiting, normal renal and liver function.

Continue current insulin regimeTarget CBG 8.0-15.0mmol/LAlter insulin dose by 20% increments or decrements to achieve this.CBG>15.0mmol/L

Use once daily long-acting insulin (Lantus) at the current basal dose.Titrate up insulin by 20% every 3 days if CBG remains above 15mmol/L.

Target CBG 8.0-15.0 mmol/LOnce CBG in target continue the regime and monitor CBG once daily.

*BASAL INSULINThese include Humulin-I, Insulatard, Lantus or Levemir

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*BASAL INSULINThese include Humulin-I, Insulatard, Lantus or Levemir

Type 2 DiabetesPrognosis days/weeks

Not eating, significant weight loss, nausea and vomiting, and renal or liver dysfunction.

Eating and drinking, no significant weight loss, no nausea and vomiting, normal renal or liver function.

CBG >4.0-8.0mmol/LUse once daily long-acting insulin (Lantus) at 50% of basal insulin dose.

Continue current treatment regime. Target CBG 8.0-15.0 mmol/L.Increase or decrease as below to achieve the target CBG.

Insulin Controlled

CBG<4.0mmol/LManage as hypoglycaemia as per trust guidelines. Reduce insulin dose by 50%.

Stop any oral anti-diabetic agents (OADs)If on once daily long-acting insulin reduce by 50%.If on pre-mixed BD insulin give 50% of the total dose as once daily long-acting insulin (Lantus) once daily with breakfast.Monitor CBG twice daily for 48 hours

Tablet Controlled

Stop metformin and pioglitazone.Monitor CBG twice daily for 48 hours.

CBG<4.0mmol/LManage hypoglycaemia as per trust guidelines.Stop any other OADs i.e. suphonylureas.

CBG 4.0-8.0mmol/LHalf the dose of sulphonylurea.If CBG remains 4.0-8.0 mmol/L stop remaining dose of sulphonylurea.

CBG>15.0mmol/LIncrease or start Gliclazide 40mg BD and titrate up by 40 mg BD increments every 3 days (max 120 mg BD). Check CBG once daily pre-evening meal.

If CBG remains >15.0mmol/L.Start long acting insulin 0.2 units/kg once daily with breakfast.

Target CBG 8.0-15.0 mmol/LOnce CBG in target continue current regime and monitor CBG once daily.

CBG >15.0mmol/LUse once daily long-acting insulin (Lantus) at the current basal dose.Titrate up insulin by 20% every 3 days if CBG remains above 15mmol/L.

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Pre-existingT2DM on OAD Monitor CBG as usual. If not monitoring check

CBG 2 hours post lunch once daily.Pre-existing T2DM on insulin or T1DM Monitor CBG at least twice daily

No history of diabetes AND Dexamethasone >4mg per day Check CBG 2 hours post lunch daily

Starting Steroid TreatmentAlways give the smallest dose and reduce

whenever possible

CBG≤15.0mmol/L

Check CBG only if symptomatic of hyperglycaemia or hypoglycaemia

CBG>15.0mmol/L

Start Gliclazide 40 mg BD with breakfast and lunch.Titrate up by 40 mg BD increments every 3 days (max 120 mg BD). If able to tolerate use metformin 500mg BD and titrate to 1g BD.If CBG still >15.0 mmol/L start Humulin-I or Insulatard 0.2 units/kg with breakfast.

CBG >15mmol/L

Increase total daily insulin dose by 20% (split this equally between each insulin dose).

CBG >15mmol/L

Increase usual OADs e.g. Gliclazide by 40mg BD increments every 3 days (max 120mg bd).

If CBG still >15.0 mmol/L start Humulin-I or Insulatard 0.2 units/kg with breakfast.

Target CBG <15.0 mmol/LOnce CBG in target continue current regime and monitor CBG once daily.

DETAILED MANAGEMENT

Prognosis - Years [5]

Treatment should be in line with national guidelines [9] and glycaemic target should be individualised.

Diabetes care should be provided by the primary or secondary care depending on patient need such as type of diabetes and complications i.e. T1DM and those with advanced diabetes-related complications should be managed in secondary care.

Prognosis – Months

Type 1[5]: Usual insulin regime. Aim for CBG 8.0-15.0 mmol/L [9]. Treat diabetic emergencies as per national guidelines (JBDS and NHS Diabetes). Check CBG if condition changes or patient becomes unwell. If oral intake decreasing reduce insulin regime (initially by 20% and further 20%

decrements every 3 days thereafter until CBG is within target range) to minimise the risk of an hypoglycaemic episodes.

Liaise with diabetes team if unsure or difficulties arise.

Type 2[5]: Aim for CBG of 8.0-15.0 mmol/L[9]. Consider stopping treatment – benefit vs. burden of treatment. Liaise with diabetes team if unsure or difficulties arise.

Diet controlled No routine monitoring. Only check CBG if unwell or if symptoms of hyperglycaemia develop. Give treatment for confirmed hyperglycaemia with symptoms.

o gliclazide 40mg BD (1st line) and titrate up to maximum of 120mg BD or metformin 500mg BD (2nd line) and titrate up to maximum of 1g BD. If concerned about hypoglycaemia and unable to tolerate metformin use sitagliptin 50mg OD titrate to a maximum 100mg OD.

OAD controlled No routine monitoring. If unwell or symptomatic of hyper- or hypo- glycaemia check CBG. Treat diabetic emergencies as per national guidelines (JBDS and NHS Diabetes). If oral intake reducing initially half the dose of OAD(s) and if CBG below target range

still (8.0-15.0 mmol/L) then stop medications completely to reduce the risk of hypoglycaemia.

If symptomatic hyperglycaemia increase the OAD i.e. if on gliclazide (1st line) titrate up to maximum of 120mg BD (40mg BD increments every 3 days). If on metformin increase to 1g BD (max). If on maximum suggested doses of OADs start a new class of OAD (see table 1).

Insulin controlled

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If on regular insulin regime – aim for CBG 8.0-15.0mmol/L If unwell check CBG and treat diabetic emergencies as per national guidelines

(JBDS and NHS Diabetes). If oral intake reducing:

1. Change to once daily long-acting (LA) analogue insulin (see appendix 5)2. Stop all OADs.

If hyperglycaemia is a problem, increase LA analogue insulin by 20% (but by no more than 10 units) every 3 days.

Liaise with diabetes team if unsure or difficulties arise.

Prognosis - Days/Weeks

Always consider a diabetic emergency when assessing whether someone is imminently dying[5] and tailor advice to the individual patient.

Type 1[5,10]: Aim is to avoid hypoglycaemia and symptomatic hyperglycaemia. Just because a patient is not eating does not mean they do not need insulin. They

still require their basal insulin requirement to prevent the development of ketosis. All basal insulins should be converted to once daily LA insulin analogues (see

appendix 5) Once daily CBG (pre-evening meal) can be done and sometimes may be

discontinued – considering the individual case. If imminently dying, insulin can be stopped after discussion with patient and/or

relatives. If patient eating and drinking, no significant weight loss, no nausea and vomiting,

normal renal or liver function, continue normal insulin regime as long as CBG in target range. Titrate insulin by 20% increments to achieve this.

Doses of insulin should be decreased in the presence of :1. Decreased oral intake2. Weight loss3. Nausea and vomiting4. Renal/liver impairment

See table below in this instance.

CBG ACTION THEN<4.0mmol/L Manage as hypoglycaemia as per Trust

guidelines(see appendix 4)Reduce current total insulin dose by 50%.

4.0-8.0mmol/L Reduce LA insulin analogue by 50%. Check CBG daily pre-evening meal. If remains <8.0 mmol/L give another 20% dose reduction.

8.0-15.0mmol/L Reduce LA insulin analogue by 50%. Check CBG daily pre-evening meal.

>15.0mmol/L Continue regular LA insulin analogue and check daily CBG. If persistently high, increase LA insulin analogue by 20% increments (but by no

If LA insulin increased and CBG still >15.0 mmol/L, need further increase in LA insulin

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more than 10 units) every 3 days. analogue. Titrate insulin every 3 days by 20% increments until within target range.

If unconscious and imminently dying – see advice for the dying phase.

Note: it is easier to use LA insulin analogues once daily rather than twice daily intermediate insulin as the basal insulin.

Type 2[5,10]:Doses may need to be decreased in the presence of:

1. Decreased oral intake2. Weight loss3. Nausea and vomiting4. Renal/liver impairment

Diet controlled If CBG<15.0 mmol/L do not recheck unless symptomatic of hyperglycaemia.

OAD controlled If eating and drinking, no nausea or vomiting, and no renal of liver impairment,

continue current treatment regime. Target CBG 8.0-15.0 mmol/L. If poor oral intake, nausea and vomiting, renal or liver impairment, stop glitazones

and metformin and monitor CBG twice daily (pre-breakfast and pre-evening meal) for 48 hours and manage as per table below.

If CBG>15.0 mmol/L, start gliclazide or if already on gliclazide convert to standard release regime and titrate up to maximum dose in 40mg BD increments.

Liaise with diabetes team if unsure or difficulties arise. Follow table below.

CBG ACTION THEN<4.0mmol/L Treat as hypoglycaemia (see

appendix 4)Stop OADs

4.0-8.0mmol/L Reduce sulphonylurea dose by 50%.

If CBG still 4.0-8.0 mmol/L, stop sulphonylurea.

8.0-15.0mmol/L Monitor CBG daily pre-evening meal.

If CBG remains 8.0-15.0 mmol/L no change required.

>15.0mmol/L If not on gliclazide start 40mg BD. If already on gliclazide convert to standard release regime and titrate up by 40mg BD increments to maximum dose of 120mg BD. Monitor CBG daily pre-evening meal.

If CBG not controlled on maximum suggested dose of gliclazide, start LA analogue insulin OD (0.2 units/kg) and titrate by 20% units increments (but by no more than 10 units) every 3 days.

If unconscious and imminently dying – stop CBG checks, stop insulin and see advice for the dying phase.

Insulin controlled

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If eating and drinking, no nausea and vomiting, no renal or liver impairment, continue current treatment regime. Target CBG 8.0-15.0 mmol/L. Increase or decrease as below to achieve the target CBG.

If not eating and drinking, nausea and vomiting, renal or liver impairment, see table below.

Follow table below.

CBG ACTION THEN<4.0 mmol/L Manage as hypoglycaemia

(see appendix 4)Stop all SA insulin and stop OADs.Change to LA analogue insulin and reduce insulin dose by 50% (see appendix 5).

4.0-8.0 mmol/L Stop all SA insulin and stop OADs.Change to LA analogue insulin and reduce insulin dose by 50% (see appendix 5).

If CBG still <8.0 mmol/L repeat step.

8.0-15.0 mmol/L Continue the current insulin dose.Monitor CBG daily pre-evening meal.

Monitor CBG daily pre-evening meal.

>15.0 mmol/L Increase LA analogue insulin by 20% (but by no more than 10 units).

Monitor CBG daily pre-evening meal.

If CBG still >15.0 mmol/L continue to titrate up insulin every 3 days by 20% unit increments (but by no more than 10 units).

If unconscious and imminently dying – stop CBG checks, stop insulin and see guidance for patients in the dying phase.

Steroid-Induced [5] :

Always reduce or stop steroid if possible.

Monitoring The most sensitive time to test for hyperglycaemia is 2 hours after lunch[12].

HyperglycaemiaDefined as a CBG>15.0 mmol/L for the purpose of this guideline.

Target Capillary Blood Glucose on Treatment8.0-15.0 mmol/L

Pre-existing DiabetesActions if hyperglycaemia develops:Diet controlled

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Start gliclazide 40mg BD (1st line) or metformin 500mg BD (2nd line) for duration of steroid treatment. Increase gliclazide by 40 mg BD increments or metformin by 500mg BD increments to maximal dose.

If on maximal dose of OAD start either Insulatard or Humulin-I insulin with breakfast 0.2 units/kg.

OAD controlled Increase in usual OAD (e.g. metformin by 500mg BD increments or gliclazide by 40

mg BD increments). If on maximal dose of OAD start either Insulatard or Humulin-I insulin with breakfast 0.2 units/kg.

Insulin controlled Increase insulin dose by 20% increments (but by no more than 10 units) every 3

days.

Liaise with diabetes team if unsure or difficulties arise.

No Pre-existing Diabetes[10]: Check CBG 2 hours after lunch daily after starting >4mg per day dexamethasone, or

after changing dose for at least 4 days. If CBG ≤15.0mmol/L only recheck CBG if symptomatic of hyperglycaemia. If CBG >15.0mmol/L start gliclazide 40mg BD (1st line) or metformin 500mg BD (2nd

line) for the duration of steroid treatment. Increase gliclazide by 40 mg BD increments or metformin by 500mg BD increments to maximal dose. Continue to check CBG daily.

If imminently dying stop insulin and anti-diabetic medications, and check CBG only if symptomatic of hyperglycaemia.

In the dying phase:

Type 1 Stop all rapid acting and pre-mixed insulin. Change to long-acting insulin analogue at half their current basal insulin dose. Check CBG once daily before insulin dose. If CBG 8-15mmol/L stop monitoring. If CBG <8mmol/L reduce once daily insulin analogue by 20% and continue to

monitor. If CBG >15mmol/L increase once daily long-acting insulin by 20%. Once stable stop monitoring.

Type 2 diabetes Stop all anti-diabetic medication. Stop monitoring CBG.

Steroid induced Stop steroids. Stop all antidiabetic medications. Stop monitoring CBG.

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References:

14.Boon N, Colledge N, Walker B, Hunter J (2006).Davidson’s Principles and Practice of Medicine. 20th edition.

15.Rowles S, Kilvert A, Sinclair A: on behalf of the Association of British Clinical Diabetologists (2011) ABCD position statement on diabetes and end of life care. Practical Diabetes International. 28 (1); 26-27.

16.Watson M, Lucas C, Hoy A, Wells, J (2009). Oxford Handbook of Palliative Care (Oxford Medical Handbooks).

17.Joint Formulary Committee (2012) British National Formulary (BNF) 64.18.Husbands, E. (2008) Clinical Care Guidelines: Management of Diabetes Mellitus in

Palliative Medicine. Birmingham: Pan-Birmingham Palliative Care Network.19.HEFT guidelines for DKA and HHS (available via Birmingham HEFT intranet).20.HEFT guielines for hypoglycaemia (available via Birmingham HEFT intranet).21.Poulson J. (1997) The management of diabetes in patients with advanced cancer.

Journal of Pain and Symptom Management. 13(6):339-4622.End of Life Diabetes Care: A Strategy Document Commissioned by Diabetes UK.

Full Strategy Document Commissioned by Diabetes UK second edition October 2013

23.Pan Birmingham Cancer Network (2012). Guideline for the use of symptom control (West Midlands Palliative Care Physicians), 5th Edition. Available via Birmingham Heartlands Hospital intranet.

24.Davis SN, Umpierrez GE. Diabetic ketoacidosis in type 2 diabetes mellitus--pathophysiology and clinical presentation...Nat ClinPractEndocrinolMetab. 2007 Nov;3(11):730-1. Epub 2007 Sep 11.

25.David S. Oyer, Ajul Shah, and Susan Bettenhausen How to Manage Steroid Diabetes in the Patient with Cancer.. J Support Oncol 2006;4:479–483

26.Guidelines for Diabetes in Palliative Care, Marie Curie Hospice Solihull, Dr N Baker, Dr C Meystre

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Appendix 1:

Taken from Diabetic Ketoacidosis (DKA) and Hyperglycaemia Hyperosmolar State (HSS) Guideline, Heart of England NHS Trust guideline.

Diabetic ketoacidosis (DKA)Definition:Diabetic ketoacidosis is defined by severe uncontrolled diabetes with ketonaemia/ketonuria, metabolic acidosis and usually hyperglycaemia.Clinical Symptoms and Signs of DKA:

Hyperventilation Deep sighing breathing Dehydration Abdominal pain Vomiting Impaired consciousness

Diagnostic Criteria: Glucose > 11.0 mmol/L HCO3 < 15.0 mmol/L Venous pH (if measured) < 7.3 Ketonaemia> 3.0 mmol/L Ketonuria (if unable to measure capillary ketones measured) > 2+

Management available via Heart of England Foundation Trust Intranet Guidelines.

Hyperglycaemic Hyperosmolar state (HHS)Characteristic of HHSHypovolaemia+Marked hyperglycaemia (>30.0 mmol/L) without significant hyperketonaemia (<3.0mmol/L) or acidosis (pH>7.3, bicarbonate>15 mmol/L)+Osmolality >320 mosmol/kg

Focal neurological signs may accompany coma. There usually is no ketosis, however, the patient may have a lactic acidosis.In patients with marked hyperglycaemia (>40.0mmol/L) or >60years Hyperosmolar Hyperglycaemic States (HHS) is more likely than DKA. Always calculate the osmolality by the formula: 2Na+glucose + urea and if this is >320 the probable diagnosis is HHS.

Management available via Heart of England Foundation Trust intranet guidelines.

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Class of Agent Names Mechanism of Action Starting Dose

Maximum Dose

Main Elimination Route

Precautions

Biguanides Metformin insulin resistance↓ hepatic glucose output ↑ peripheral glucose utilisation↑glucose turnover between intestine and liver

500mg bd 1g bd Renal GI intolerance Lactic acidosis (rare) Renal impairment, any hypoglycaemic condition

Sulphonylureas Gliclazide

Gliclazide SR

Directly ↑insulin secretionBinds to SUR1 - stimulates β-cells by closure of K+-ATP channels

80mg od

30mg od

160mg bd

120mg od

Renal 60% HypoglycaemiaSelection restricted by severe liver or renal disease, or porphyria

Meglitinides Nateglinide

Repaglinide

Directly ↑ insulin secretionBinds to benzamido site on SUR1 - stimulates β-cells by closure of K+-ATP channels Rapid onset, short duration of action

60 mg with each meal

0.5g with meals

540 mg

16g

Hepatic

Hepatic

Lesser risk of hypoglycaemia (fewer and less severe than with sulphonylureas) Liver or severe renal disease

Gliptins (DPP-4 inhibitors)

Sitagliptin

Linagliptin

↑ insulin secretionInhibition of DPP-4 allows increased t½ for incretins, which potentiate nutrient-induced insulin secretion

50mg od

5mg od

100mg od Renal

Faecally excreted

Small risk of hypoglycaemia (seldom severe), mostly when used with other glucose- lowering agents Substantial renal or liver disease

Glitazones Pioglitazone ↑ insulin actionStimulate PPARγ↑adipogenesis Alter glucose-fatty acid cycle

30mg od 45mg od Hepatic Heart failure, oedema, fluid retention, anaemia, fractures Cardiac disease, severe liver or renal disease

Alpha-Glucosidase Inhibitors

Acarbose Inhibiting the digestion of carbohydrates by inhibiting a-glucosidase

50mg od 100mg tds Renal 35% The major drawback of acarbose is the fact that it is often associated with a lot of flatulence.

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Appendix 2. Oral diabetic medications

Appendix 3: Types of InsulinTrade Name Source Delivery System Taken Time Action Profile

Marked in hourly intervalsRapid-acting Insulin AnaloguesNovorapid Analogue Vial and Syringe

3 ml cartridges in a re-usable penPre filled disposable pen system (Flexpen)

Just before / with / just after food NOVORAPID

HUMALOG

ACTRAPIDHUMULIN S

INSULATARDHUMULIN I

LANTUSLEVEMIR

HUMULIN M3HUMALOG MIX 25

NOVOMIX 30

Short-acting Human InsulinsActrapid Human Vial and Syringe For use only in VRIII

or FRIII

NOVORAPIDHUMALOG

ACTRAPIDHUMULIN S

INSULATARDHUMULIN I

LANTUSLEVEMIR

HUMULIN M3HUMALOG MIX 25

NOVOMIX 30

Intermediate-acting Human InsulinsHumulin I Human Vial and Syringe

3 ml cartridges in a re-usable penPre filled disposable pen system (Kwikpen)

30 mins before food

NOVORAPIDHUMALOG

ACTRAPIDHUMULIN S

INSULATARDHUMULIN I

LANTUSLEVEMIR

HUMULIN M3HUMALOG MIX 25

NOVOMIX 30

Intermediate-acting Biphasic and Rapid-acting Analogue InsulinsHumalog Mix25 Analogue 3 ml cartridges in a re-usable pen

Pre filled disposable pen system (Kwikpen)

Just before / with / just after food

NOVORAPIDHUMALOG

ACTRAPIDHUMULIN S

INSULATARDHUMULIN I

LANTUSLEVEMIR

HUMULIN M3HUMALOG MIX 25

NOVOMIX 30NovoMix 30 Analogue 3 ml cartridges in a re-usable penPre filled disposable pen system (Flexpen)

Just before / with / just after food

Long-acting Insulin AnaloguesLantus

Levemir

Analogue Vial and Syringe3 ml cartridges in a re-usable penPre filled disposable pen system (Solostar)

Once a day anytime but at the same time each day

No peak of action

19SPAGG Diabetes Management in Palliative Care v3.0 2015

Appendix 4: Management of hypoglycaemia[7,9]

Hypoglycaemia is a blood glucose of 4.0mmol/L or less. Wherever possible, check blood glucose level prior to

treatment. If patient asymptomatic, repeat test.

4.0mmol/L 3.0mmol/L 2.0mmol/L 1.0mmol/L

MILD P a tie n t c o n s c io us a n d ab le to

s w a llo w Trem bling, sweating, hungry, ting ling, headache, anxiety,

palpitations, nausea, fo rgetfu lness

MODERATE P a tie n t c o n sc io us a nd a b le to

s w a llo w , b u t in ne e d o f as s is tanc e D ifficulty concentrating, confusion, weakness, g iddiness , drows iness,

unsteady, headache, d izziness, d ifficu lty focusing and speak ing

SEVERE P a tie n t u n a b le to s w a llo w .

U nconscious or fitting SEEK URGENT M EDICAL HELP

STEP 1 |

U SE H Y PO B O X Ad m inister 10g - 20g fast

acting g lucose* 3-5 x G lucoTabs (4g glucose per

tablet) or

1 x 59m l bottle of G luco Juice

U SE H Y PO B O X Ensure gag reflex is present.

Adm inister 1-2 tubes of G lucoG el (10g glucose per tube)

If no gag reflex use IV or IM route

Check airw ay P lace patient in recovery

po sitio n I n t r a v e n o u s 2 5 0 m l 1 0 %

G lu c o s e O r

In tra m u s cu la r in je c t io n o f G lu c a g o n 1m g if no IV access.

W ait 15 m inutes and recheck glucose levels, and record. If reading is still below 4 .0m m ol/L, or if no physical im provem ent, repeat STE P 1

O nce patien t is conscious, give s ips of G lucose L iquid B last or Lucozade. Recheck glucose leve l every 15 m inutes to ensure increase to at least 4 .0m m ol/L STEP 2

REPEAT STEP 1 twice in total (except only use Glucagon only once). If after this if glucose still below 4.0mmol/L give intravenous bolus of 10% Glucose 150ml and start and infusion of 10% Glucose at 50-100ml/h to maintain CBG between 6-10mmol/L. Once 3 consecutive hourly readings are above 10.0mmol/L stop the infusion. If volume is a concern use 20% glucose (ideally centrally) at half the volume of 10% STEP 3

ALW AYS FOLLOW UP W ITH A SLOWLY DIGESTED/ STARCHY C ARBO HYDR ATE C heck g lucose leve l. O nce it is at 4 .0m m ol/L or over and patient is recovered, eat a m inim um of 20g s low ly d igested/starchy carbohydrate e .g. 2 x s lice /sandw ich of low G l b read (ideally m ultigra in or granary), two d iges tive b iscu its , 2 S hredded w heat. R echeck glucose levels after 15 m inutes. NOT E: D O NO T om it insulin dose if due, how ever dose rev iew m ay be requ ired .

STEP 4

W HAT TO DO ABOUT THE ANTIDIABETIC M EDIC ATION 1. R eview C BG read ing for the last 2 previous da ys 2 . R eview the tim e anti-d iabetic m edication w as adm inistered i.e . w as it g iven before m eals (24h E P AC on E P) 3 . If adm inistered at the incorrect tim e (i.e . >60 m inutes after food) - do not change the dose o f the antid iabetic

m edicatio n B U T speak to the ward nurs ing s taff. Severe Hypoglycaemia - if on ora l agents s top sulphon ylureas particu larly. If on insulin reduce the appropriate dose b y 50% . C ontact to the Inpatient D iabetes T eam . D O N O T G IV E G LU C A G O N – increases the ac tion of SU s Moderate Hypoglycaem ia - if on ora l agents reduce sulphon ylureas particu larly. If on insu lin reduce the appropria te dose by 30% Mild Hypoglycaemia - if has occurred on the previous 2 da ys red uce the dose of the ora l a gents particu larly S ulphon ylureas rather than M etform in. If on insu lin reduce the appropriate dose by 20% . If no t occurred on 2 previous da ys do not change doses.

Be aware that IM glucagon can be ineffective in the starved patient as it depends on adequate liver stores of glycogen to work [3,9].

20SPAGG Diabetes Management in Palliative Care v3.0 2015

Appendix 5:

Conversion of twice daily mixed insulin to once daily long-acting insulin[5,10]:

Pre-mixed insulin has a proportion of intermediate-acting insulin in it. For example Novomix 30 has 70% intermediate-acting insulin. Humalog 25 has 75% intermediate-acting insulin.Calculate the total daily amount of intermediate-acting insulin and give 80%of this amount as LA insulin analogue such as Lantus once daily. If blood glucoseare low i.e. 4.0-6.0 mmol/L, use 50% of the original intermediate-acting dose.

For exampleIf the patient normally takes 20 units BD Novomix30, this totals 40 units of insulin in 24 hours as it is a BD preparation. This is a mixture of intermediate and short acting insulin.70% of Novomix30 is intermediate-acting, so the patient takes 28 units of intermediate-acting insulin daily (0.70 x 40 units).

To calculate the new dose, we want 80% of the existing intermediate-acting daily insulin dose, which is 22 units (0.80 x 28 units = 22 units).If hypoglycaemic we need to give 50% of the daily intermediate-acting insulin dose. This equals 14 units (0.50 x 28 units = 14 units)

21SPAGG Diabetes Management in Palliative Care v3.0 2015