Diabetes Mellitus

1. Diabetes Mellitus

2. Definition • Diabetes Mellitus is a group of Metabolic Diseases • characterized by Hyperglycemia resulting from • defects in insulin secretion, insulin action, or both. American Diabetes Association

3. Diabetes: Clinical Features • Symptoms: • Polyuria • Polydipsia = thirst • Polyphagia= appetite • Asthenia & Loss of weight • Signs: No specific signs may be signs of complications

4. “Leonard Thompson (14 year old boy) & Elizabeth Hughes (aged 14 years), were the first patients to be treated with insulin in 1922.

5. “Fredrick Banting (1921), successfully, extracted insulin, gaining the Nobel prize for this great discovery”.

6. “Claude Bernard and Von Mering (1889), discovered in the same year that pancreatectomy causes diabetes”

7. “Mathew Dobson (1776), identified glycosuria.

8. “ Thomas Willis (1621 - 1679), discovered the sweetness of urine, hence, the name Diabetes Mellitus arised”

9. “ Diabetes was long thought to be a kidney disease (Greek & Arabic Methodology).

10. Predisposing FactorsIDDM • Heredity. • Histocomptability. • Virus infection. • Seasonality. • Cell-mediated immunity.

11. Insulin Synthesis PrePro Insulin Split at position 61/62 Pro Insulin Insulin C peptide

12. Insulin Secretion Curve Biphasic insulin response to a constant glucose stimulation (IVGTT - hyperglycemic Clamp) Insulin rate Basal Time (min) 4 60

13. Fate of Absorbed Glucose Glycogenesis G Muscle Cells 50 % Glycolysis Liver Cells 30 % Glycogenesis G Glycolysis Lipogenesis G Fat Cells 5 % Glycolysis

14. Hormonal Regulation Blood Glucose Level < 110 mg/L Glucagons Growth Hormone Adrenaline Cortisol Insulin Hypoglycaemic Hormone Counter regulatory Hormones

15. Diabetes Estimates and Projection

16. Classification of Diabetes Mellitus • Primary Diabetes • Type 1 insulin dependent diabetes • Type 2 non insulin dependent diabetes

17. Classification of Diabetes Mellitus • Secondary Diabetes • Gestational diabetes • Malnutrition related diabetes • Diabetes resulting from: • Pancreatic disease • Hormonal diseases • Drug/chemical induced • Genetic syndromes

18. METABOLIC ASPECTS

19. Key Organs of Diabetes Pancreas insulin secretion disorder Muscle Liver in hepatic glucose production in glucose storage Hyperglycemia

20. Peripheral Abnormalities Muscles Liver Fat tissues Gluconeogenesis Glycogenogenosis Glycolysis Glycolysis Lipogenesis Lipolysis Gluconeogenesis Glycogenogenesis FFA Glucose production Glucose Storage Hyperglycaemia

21. Pathogenesis of diabetes: metabolic features Genetic predisposition Insulin resistance Defective insulin secretion Hyperglycemia

22. Impaired Insulin Secretion

23. Causes of Impaired Insulin Secretion • Decrease in number of Beta cells by 40-50 % {In Insulin resistance states, the number is either normal or increased}

24. Causes of Impaired Insulin Secretion Amyloid deposits Amylin : amyloid material secreted by B cells Interferes with the recognition of the glucose signal

25. Causes of Impaired Insulin Secretion • Reduced activity of the glucokinase • ATP production reduced inside B cells • Closure of K channel decreases • Entry of Calcium reduced • release of Insulin reduced

26. Insulin Resistance

27. Receptor defect Post Receptor defect Types of Insulin Resistance

28. Types of Insulin Resistance • Receptor defect • Decrease in the affinity • Decrease in number (rare)

29. Types of Insulin Resistance • Post receptor defect Glucose Transporters Intra cellular utilization Enzymatic activity

30. Gluco-toxicity Insulin secretion disorder Chronic Hyperglycemia Insulin resistance

31. Vascular Complications

32. Vascular complications • Micro-vascular complications • Macro-vascular complications

33. Micro-vascular complications • Retinopathy • Nephropathy • Neuropathy

34. Macro-vascular complications • CHD • CVD • PAD 10 years accelerated

35. Treatment Of Diabetes

36. Treatment of diabetes: • Life style modification • Insulin • Oral hypoglycemic agents

37. Life style modification • Diet control • Exercise • Smoking cessation

38. Diet Control

39. DIET CONTROL • All diabetic patients should be on diet control.Diet control is a must either the patient is taking insulin or oral therapy. • Over weight should be reduced .

40. DIET CONTROL • Diet control should be tried at first before the next step [insulin or tablets] especially in obese patients, When diet fails drugs are indicated.

41. DIET CONTROL • The diet for a diabetic patient is not so different from the healthy diets for the whole population. • Simple sugars Carbohydrate [as sucrose], should be limited for the diet of diabetic patients.

42. DIET CONTROL • Carbohydrate content should be in a fiber-rich diet [for example fruits containing fibers as apples]. ….. because the fiber content of diet delays absorption of carbohydrates avoiding the rapid elevation of blood glucose levels.

43. DIET CONTROL Calories : • Calories should be tailored to the need of the patient. Diet should contain: • Carbohydrates → 50 - 55% • Fat→ 30-35% • Protein →10 - 15%

44. INSULIN

45. Indication of Insulin • Type 1 diabetes • Unstable diabetes • Type 2 diabetes failed on SUs. • Pregnant diabetic patients • Surgery (all diabetic patients) • Diabetic coma

46. Oral Hypoglycemic agents

47. Oral hypoglycemic agents • Biguanides • Sulfonylureas • α- glucosidase inhibitors • Thiazolidinediones • Prandial glucose regulator

48. Biguanides • Biguanides are derivatives of the antimalarial agent Chloroguanide. Which is found to have hypoglycemic action. • The most commonly used member of biguanides is Metformin [Cidophage].

49. Biguanides • Indication: • Type 2 diabetes failed on diet • Metformin can be given alone or in combination with sulfonylureas or Insulin

50. Biguanides • Mode of action Biguanides [Metformin] is an Antihyperglycemic and not Hypoglycemic agent. • It does not stimulate pancreas to secrete insulin and does not cause hypoglycemia (as a side effect) even in large doses. • Also it has no effect on secretion of Glucagon or Somatostatin.