UPDATE ON DIABETES AND INSULIN THERAPY BY Dr.M.SYED SULAIMAN.M.D; PHYSICIAN & DIABETOLOGIST

1. UPDATE ON DIABETES AND INSULIN THERAPYBYDr.M.SYED SULAIMAN.M.D;PHYSICIAN & DIABETOLOGIST

2. DIABETES ENVIRONMENT IN INDIA Diabetes is no more an epidemic, it is a PANDEMIC. Diabetes related complications pose greatest risk of morbidity and mortality.

4. BURDEN OF DIABETES : MORBIDITY • DIABETIC RETINOPATHY #1 Cause of blindness in working age adults • DIABETIC NEPHROPATHY #1 Cause of ESRD • DIABETIC NEUROPATHY AMPUTATIONS #1 Cause of non-traumatic amputations of lower Extremity. • DIABETIC VASCULAR DISEASE 2 to 6 fold higher risk of CVD

5. DEFINITION Diabetes Mellitus is a group of metabolic diseases characterized by Hyperglycemia resulting from defects in Insulin secretion, Insulin action, or both.

6. ETIOLOGIC CLASSIFICATION OF DIABETES MELLITUS • 1.Type 1 Diabetes • Immune mediated • Idiopathic • 2.Type 2 Diabetes

7. 3.Other specific types: a. Genetic defects of b-cell function b. Genetic defects in insulin action c. Disease of exocrine pancreas d. Endocrinopathies e. Drug/chemical induced f. Infection g. Uncommon immune mediated h. Other Genetic Syndromes 4. GESTATIONAL DIABETES MELLITUS(GDM)

8. ETIOLOGY OF TYPE 2 DM IMPAIRED INSULIN SECRETION & INSULIN RESISTANCE GENES AND ENVIRONMENT GENES & ENVIRONMENT IMPAIRED INSULIN SECRETION IMPAIRED INSULIN SECRETION + INSULIN RESISTANCE INSULIN RESISTANCE IMPAIRED GLUCOSE TOLERANCE IMPAIRED GLUCOSE TOLERANCE TYPE 2 DM

9. DIAGNOSTIC CRITERIA OF DIABETES IFG -Impaired Fasting Glucose IGT -Impaired Glucose Tolerance

10. What is pre diabetes? • Abnormalblood glucose Values which is clearly Above the normal values but less than the Values diagnostic of Diabetes [IMPAIRED GLUCOSE METABOLISM]

11. MAJOR RISK FACTORS FOR TYPE 2 DM 1. Age>45 2. Race / Ethnicity (Asian / Asian American / Hispanics / etc) 3. Obesity (>30kg/m) 4. Family h/o Diabetes 5. Sedentary lifestyle 6. h/o GDM or delivered a baby weighing>4.5kg 7. PCOS

12. ACUTE METABOLIC COMPLICATIONS OF DIABETES MELLITUS A.) DIABETIC KETOACIDOSIS B) HYPEROSMOLAR HYPERLYCEMIC STATE C) HYPOGLEMIA

13. Diabetes Mellitus and chronic complications • Diabetes is a vascular disease • Affects both small and medium sized arteries (micro vascular &macro vascular)

14. MICRO VASCULAR Retinopathy Nephropathy Neuropathy Chronic complications Macrovascular CVD CAD PVD

15. MANAGEMENT • Diet • Exercise • Insulin • Oral Antidiabetic Drugs • DPP 4 Inhibitors • Amylin Analogues

16. ORAL ANTI DIABETIC DRUGS • Secretogauges a) Sulphonylurias b) Non sulphonylurias • Biguanides • Alpha Glucosidase Inhibitors( A G I ) • Thiozolidinediones • DPP 4 Inhibitors • Amylin Analogues • Exenatide

17. SECRETOGOUGES • Sulphonyluria Groups • First Generation SU 1.Tolbutamide 2.Chlorpropamide • Second Generation SU 1.Glibenclamide(Daonil,Euglucon) 2.Glipizide(Glynase,Dibizide) 3.Gliclazide(Diamicron,Reclide) 4.Glimipride(Amaryl,Glipride,Glimer)

18. SECRETOGOGUES Currently available secretogogues stimulate Insulin secretion by causing closure of ATP dependent Potassium channel in Islet β cells.

19. NON SU SECRETOGOGUES Meglitinides Repaglinide(Novonorm)

20. INSULIN SENSITIZERS • Agents from this group enhances the effect of endogenous Insulin. • A reduction in Insulin resistance at each and every stage of diabetes will improve Glucose metabolism. • Biguanide(Metformin),Thiozolidinediones(PIO,ROSI)

21. BIGUANIDES • METFORMIN(Glyciphage,Glycomet). • Primary site of action:Liver. • Reduces hepatic glucose output. • Reduce fasting hyperglycemia.

22. THIOZOLIDINEDIONES Troglitazone Rosiglitazone(Rezult,Enselin) Pioglitazone(Pioz,Pioglit) Primary site of action : Adipose Cells, Skeletal muscles.

23. AGI • Acarbose(Glucobay,Acarb) • Miglitol(Misobit,Mignor) • Voglibose(Volibo,Volix) • Blocks alpha glucosidase enzyme • Targets postprandial hyperglycemia

24. DPP 4 Inhibitors(Dipeptidyl Pepsidase 4) • Nateglinide • Citagliptin • Vidagliptin • DPP 4 Inhibits GLP 1.Thus extends Insulin action. • Improves satiety,Increases β cell production,Inhibits β cell apoptosis delays gastric emptying,stimulate Insulin release

25. AMYLIN ANALOGUES • Pramlintide

26. INSULIN • First hormone to be • Discovered • Introduced in clinical practice • Structurally characterized • Synthesized – chemically • Biosynthesized – by rDNA technology

27. Insulin – Definitive Therapy for Diabetes • In diabetes there is impaired insulin secretion and impaired insulin action • Exogenously administered Insulin can overcome both defects • Thus insulin is the definitive therapy for all types of diabetes

28. INSULINABSOLUTE INDICATIONS • Regular Use • Type 1 Diabetes Patients • Type 2 Diabetes Patients with OHA failure • - Primary • - Secondary • Intermittent Use • Type 2 diabetes patients during • - major surgery • - pregnancy, labour and delivery • - myocardial infarction • - acute infections • - acute metabolic crisis like hyperosmolar non ketotic coma and lactic acidosis • Gestational diabetesmellitus

29. Type 1 DM Insulin Therapy • Initiating insulin therapy in uncomplicated ambulatory Type 1 patients • Initiating insulin therapy in ill patients with altered sensorium

30. Type 1 DM Insulin Therapy : Initiation • In uncomplicated ambulatory Type 1 patients • Patients should preferably be admitted to hospital • Initiate with short-acting insulin [0.5 IU/Kg body weight per day] divided over 3 doses/day given pre-meal; subcutaneously

31. Type 1 DM Insulin Therapy : Initiation • If hospital admission is not possible, close continuous monitoring of the patient is necessary • After adequate control is obtained with the above treatment a minimum of twice daily regimen with a short and intermediate-acting insulin may be given as per individual patient requirement

32. ACTION PROFILE OF INSULIN

34. ACTION PROFILE OF INSULIN

36. ACTION PROFILE OF INSULIN

38. ACTION PROFILE OF INSULIN

40. ACTION PROFILE OF INSULIN

42. TYPES OF INSULINS

43. REGIMENS • Should maintain normal blood glucose levels (Normoglycemia) • Mimic normal physiological profile • Regimens vary in Type 1 and type 2 diabetes because of different pathophysiology

45. INSULIN REGIMENS – Type 1 Diabetes • Insulin secretion totally absent • Insulin administration tailored to match demand (food intake) • Need for multiple injections • Popular Regimens * Basal Bolus: Ideal but difficult to implement * Split mix therapy: Popular regimen; Patients find mixing insulins difficult • Premixed Insulins: Most popular regimen world- wide and in India • Right mix of compliance and control • Insulin required • - 0.4 - 0.6 i.u/kg body weight/day • - Regimen depends on blood glucose profiles

46. BASAL BOLUS THERAPY • At least four injections/day • Intermediate injection at bedtime • soluble insulin before breakfast, lunch and dinner • Regular blood monitoring must • Requires highly motivated patient

48. SPLIT MIX REGIMENS • Two injections (intermediate + soluble) per day • before breakfast and before bedtime • Proportion/dosage of insulin titrated based on blood glucose profile • Mixing insulin is tedious and problematic