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When to Start Insulin Doctors and Nurses Working Together Dr Ketan Dhatariya Consultant in Diabetes and Endocrinology Norfolk and Norwich University Hospital.

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Presentation on theme: "When to Start Insulin Doctors and Nurses Working Together Dr Ketan Dhatariya Consultant in Diabetes and Endocrinology Norfolk and Norwich University Hospital."— Presentation transcript:

1 When to Start Insulin Doctors and Nurses Working Together Dr Ketan Dhatariya Consultant in Diabetes and Endocrinology Norfolk and Norwich University Hospital NHS Trust

2 Good Timing!

3 Why is it the 14 th of November? Fred Banting – one of the co-discoverers of insulin Fred Banting – one of the co-discoverers of insulin Born on 14 th November 1891 Born on 14 th November 1891

4 We’re All Trying to Achieve The Same Thing – But Using Different Approaches

5 Some Definitions Type 1 Type 1 Type 2 Type 2 Others (not mentioned any more) Others (not mentioned any more)

6 Two Main Types Type 1 Type 1 Autoimmune destruction of the β cells of the Islets of Langerhans in the pancreas. This leads to an absolute insulin deficiency. Insulin treatment is therefore mandatory Autoimmune destruction of the β cells of the Islets of Langerhans in the pancreas. This leads to an absolute insulin deficiency. Insulin treatment is therefore mandatory Previously known as IDDM or juvenile onset diabetes Previously known as IDDM or juvenile onset diabetes

7 Two Main Types Type 2 Type 2 Impaired insulin action (insulin resistance) and eventually, impaired insulin secretion as well Impaired insulin action (insulin resistance) and eventually, impaired insulin secretion as well Usually treated with oral medication initially, then may move onto insulin Usually treated with oral medication initially, then may move onto insulin Formerly known as NIDDM or maturity onset diabetes Formerly known as NIDDM or maturity onset diabetes

8 Epidemiology Diabetes currently affects approximately 3 to 4% of the population Diabetes currently affects approximately 3 to 4% of the population 90% of whom have type 2 diabetes 90% of whom have type 2 diabetes Lifetime risk of developing diabetes is about 10% Lifetime risk of developing diabetes is about 10%

9 Why is it Important? Poorly controlled diabetes leads to accelerated cardiovascular morbidity and mortality Poorly controlled diabetes leads to accelerated cardiovascular morbidity and mortality A combination of microvascular and macrovascular disease A combination of microvascular and macrovascular disease Thom T et al Circulation 2006;113(6):e85-151

10 Some Good News Health Consumer Power House Euro Consumer Diabetes Index Sept 2008

11 UKPDS HbA 1c Median Values HbA 1c (%) Years from randomisation Conventional Intensive 6.2% upper limit of normal range

12 Data From 3.3M Danes Schramm TK et al Circulation 2008;117:

13 An (?Uncontroversial) Starting Point People with type 1 diabetes need to be referred to the specialist hospital team at the time of suspected diagnosis People with type 1 diabetes need to be referred to the specialist hospital team at the time of suspected diagnosis Many people continue to be followed up in secondary care. Many people continue to be followed up in secondary care. This depends heavily on the competence and confidence of the primary care team – and the support offered by secondary care This depends heavily on the competence and confidence of the primary care team – and the support offered by secondary care

14 Non-Insulin Hypoglycaemic Agents α glucosidase inhibitors α glucosidase inhibitors Metaglinides Metaglinides Metformin Metformin Sulphonylureas Sulphonylureas Thiazolidindiones Thiazolidindiones GLP – 1 analogues GLP – 1 analogues DPP IV inhibitors DPP IV inhibitors

15 α Glucosidase Inhibitors There is only 1 – acarbose There is only 1 – acarbose Intestinal disaccharidase inhibitor Intestinal disaccharidase inhibitor Taken one with each meal Taken one with each meal If they don’t eat, no need to take the tablet If they don’t eat, no need to take the tablet HbA1c reduction of % HbA1c reduction of %

16 Metaglinides There are 2 – repaglinide and nateglinide There are 2 – repaglinide and nateglinide Work by binding to the sulphonylurea receptor and ‘squeezing’ the β cell to release insulin Work by binding to the sulphonylurea receptor and ‘squeezing’ the β cell to release insulin They stimulate first-phase insulin release in a glucose-sensitive manner They stimulate first-phase insulin release in a glucose-sensitive manner HbA1c reduction of % HbA1c reduction of %

17 Metformin Derived from the plant known as Goat's Rue, French Lilac, Italian Fitch or Professor-weed (Galega officinalis)

18 Metformin First choice oral hypoglycaemic agent for people with type 2 diabetes, regardless of BMI First choice oral hypoglycaemic agent for people with type 2 diabetes, regardless of BMI Works by decreasing hepatic gluconeogenesis, decreasing gut glucose uptake and increasing peripheral insulin sensitivity Works by decreasing hepatic gluconeogenesis, decreasing gut glucose uptake and increasing peripheral insulin sensitivity Metformin does not (or very rarely) give people hypos, because it works by preventing blood glucose levels rising rather than by lowering glucose levels Metformin does not (or very rarely) give people hypos, because it works by preventing blood glucose levels rising rather than by lowering glucose levels HbA1c reduction of 1.0 – 2.0% HbA1c reduction of 1.0 – 2.0%

19 Sulphonylureas Have been around since the 1950’sHave been around since the 1950’s Act by binding to the SU receptor causing an influx of Ca 2+ and an exocytosis of insulin containing vesiclesAct by binding to the SU receptor causing an influx of Ca 2+ and an exocytosis of insulin containing vesicles Use limited to individuals with a BMI < 25 or in whom metformin is contraindicatedUse limited to individuals with a BMI < 25 or in whom metformin is contraindicated HbA1c reduction of 1.0 – 2.0% HbA1c reduction of 1.0 – 2.0%

20 Thiazolidinediones Work by increasing peripheral insulin sensitivity at a nuclear level on peroxisome proliferator- activated receptor γ (PPAR γ ) Work by increasing peripheral insulin sensitivity at a nuclear level on peroxisome proliferator- activated receptor γ (PPAR γ ) HbA1c reduction of % HbA1c reduction of % Several controversies thus use is declining Several controversies thus use is declining Increased CV death rates Increased CV death rates Increased fracture rates Increased fracture rates Increased rates of macular oedema Increased rates of macular oedema Nissen SE NEJM 2007;356(24): Loke Y et al In press Ryan EH et al Retina 2006; 26(5):562-70

21 GLP-1 and DPP-IV Nauck MA et al. Diabetologia 1993;36:741–744; Larsson H et al. Acta Physiol Scand 1997;160:413–422; Nauck MA et al. Diabetologia 1996;39:1546–1553; Flint A et al. J Clin Invest 1998;101:515–520; Zander et al. Lancet 2002;359:824–830. GLP-1 secreted upon the ingestion of food cell: Enhances glucose-dependent insulin secretion in the pancreas 1.  -cell: Enhances glucose-dependent insulin secretion in the pancreas 3.Liver: reduces hepatic glucose output 2.α-cell: Suppresses postprandial glucagon secretion 4.Stomach: slows the rate of gastric emptying 5.Brain: Promotes satiety and reduces appetite

22 Their Effects Are Additive HbA 1 C Time

23 The Goalposts Are Changing HbA 1 C targets are coming down HbA 1 C targets are coming down The tighter the control, the likelihood of developing complications reduces – to a point The tighter the control, the likelihood of developing complications reduces – to a point

24 EVERY 1% reduction in HbA 1c REDUCED RISK* 1% Deaths from diabetes –21% Heart attacks –14% Microvascular complications –37% Peripheral vascular disorders UKPDS 35. BMJ 2000;321:405–12 Lessons from UKPDS: Better Control Means Fewer Complications –43% *p<0.0001

25 How Many Guidelines? EASD / ADA EASD / ADA Nathan et al Diabetes care 22/10/08 epub ahead of publication Nathan et al Diabetes care 22/10/08 epub ahead of publication NICE NICE ullguideline.pdf ullguideline.pdf Royal College of Physicians Royal College of Physicians 8fa4-4d0b f2e77edc2ca.pdf 8fa4-4d0b f2e77edc2ca.pdf

26 Recent ADA / EASD Guidelines Nathan DM et al Diabetes Care 22/10/08 epub online

27 NICE Advice Accessed 9th November 2008

28 RCP Management of Type 2 diabetes – May 2008 Accessed

29 Tighter Control This means that oral agents alone may not be sufficient and that insulin needs to be added This means that oral agents alone may not be sufficient and that insulin needs to be added

30 Consider the Following Scenarios 60 year old, CVA, blind, dense hemiplegia, lives in a nursing home, fully dependent 60 year old, CVA, blind, dense hemiplegia, lives in a nursing home, fully dependent 80 year old, plays golf daily, travels the world extensively with their 60 year old partner looking for ‘excitement’ 80 year old, plays golf daily, travels the world extensively with their 60 year old partner looking for ‘excitement’ QOF is not ‘situation specific’ QOF is not ‘situation specific’

31 Insulin Should be started when the HbA 1 C is ≥ 7.5% on maximal oral hypoglycaemics Should be started when the HbA 1 C is ≥ 7.5% on maximal oral hypoglycaemics Pregnancy Pregnancy Steroids Steroids Intercurrent illness Intercurrent illness

32 Now You’ve made Your Decision A few questions A few questions Which insulin? Which insulin? What dose? What dose? What regime? What regime? What do I do with the tablets? What do I do with the tablets? Should I address their weight first?? Should I address their weight first??

33 Insulins Soluble (short acting) Soluble (short acting) NPH (intermediate) NPH (intermediate) Once daily Once daily Mixtures Mixtures Insulin analogues – ultra short, long and mixtures Insulin analogues – ultra short, long and mixtures

34 EASD / ADA Recommendations Start with once daily basal insulin Start with once daily basal insulin Which type of insulin depends on when BG levels are highest Which type of insulin depends on when BG levels are highest If there are no contraindications – stay on night time insulin, with day time metformin or SU’s If there are no contraindications – stay on night time insulin, with day time metformin or SU’s Keep regularly increasing the dose until the fasting blood glucose is less than 7.0 mmol/L Keep regularly increasing the dose until the fasting blood glucose is less than 7.0 mmol/L Holman RR et al N Engl J Med 2007;357: Bretzel RG et al Lancet 2008;371: ; Nathan DM et al Diabetes Care 22/10/2008; epub Riddle MC Endocrine and Metabolic Clinics of North America 2005;34:77-98; Pala L et al Diabetes Res Clin Pract 2007;78:

35 Other Options Twice daily mixtures are commonly used but may be associated with greater weight gain than once daily injections Twice daily mixtures are commonly used but may be associated with greater weight gain than once daily injections Three times daily mixtures are also common on the continent Three times daily mixtures are also common on the continent In people who have unpredictable lifestyles, a basal bolus regime may be appropriate In people who have unpredictable lifestyles, a basal bolus regime may be appropriate

36 ADA/EASD Insulin Initiation Guidelines Nathan DM et al Diabetes Care 22/10/08 epub online

37 There are Other Algorithms At:Lantus – starting at 10 IU / day At:Lantus – starting at 10 IU / day Davies M et al Diabetes Care 2005;28:

38 Potential Implications Driving Driving Insurance Insurance

39 Recent Data ACCORD (Action to Control Cardiovascular Risk in Diabetes) ACCORD (Action to Control Cardiovascular Risk in Diabetes) ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) VADT (Veteran’s Administration Diabetes Trial) VADT (Veteran’s Administration Diabetes Trial) NEJM 2008;358(24): NEJM 2008;358(24): Duckworth WC et al Diabetes Care 2001;24:

40 Tighter Glycaemic Control Does NOT Influence Outcomes Getting HbA1C to less that 7.0% added no benefit Getting HbA1C to less that 7.0% added no benefit In ACCORD it lead to a higher mortality rate In ACCORD it lead to a higher mortality rate Lots of reasons – including better risk factor management Lots of reasons – including better risk factor management

41 Increased Use of Adjunctive Agents Charlton J et al Diabetes Care 2008;31(8):

42 Things That Make the Most Difference Smoking OR 2.87 Smoking OR 2.87 Raised ApoB/ApoA1 ratioOR 3.25 Raised ApoB/ApoA1 ratioOR 3.25 History of hypertensionOR 1.91 History of hypertensionOR 1.91 DiabetesOR 2.37 DiabetesOR 2.37 Abdominal obesityOR 1.12 Abdominal obesityOR 1.12 Psychosocial factorsOR 2.67 Psychosocial factorsOR 2.67 Daily fruit and veg intakeOR 0.7 Daily fruit and veg intakeOR 0.7 Regular alcohol consumptionOR 0.9 Regular alcohol consumptionOR 0.9 Regular physical activityOR 0.86 Regular physical activityOR 0.86 Yusuf et al Lancet :

43 In Summary There are a lot of medications to try first There are a lot of medications to try first Weight loss is a cornerstone to delaying insulin Weight loss is a cornerstone to delaying insulin To ensure the best outcomes for your patients with diabetes To ensure the best outcomes for your patients with diabetes Be Aggressive! Be Aggressive! Treat Early! Treat Early! Being on insulin is not ‘failure’ Being on insulin is not ‘failure’

44 Thank you for your attention


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