diabetes mellitus

1. Diabetes mellitus

3. Criteria

4. Classification Type I � (Insulin-dependent) 15% B cells destruction, leading to absolute insulin deficiency Juvenile sudden onset Body weight normal or reduced Tendency to ketosis and ketoacidosis Absolute need for insulin treatment

5. Classification Type II � NIDDM � 85%. Associated with obesity Onset is later in life, >30 years, gradual Insulin in blood is normal or elevated Ketoacidosis is rare Some patients with type I may masquerade as type 2

6. Classification Secondary DM � (secondary to other dis.) Destructive lesions of the pancreas (pancreatitis, tumors, hemochromatosis) Endocrine diseases (Cushing syndrome, acromegaly). Drugs � diuretics and corticosteroids. Genetic syndromes

7. Normal morphology The islets of Langerhans � 2% of the mean pancreatic gland � 1-2g A cells � glucagon B cells � insulin D cell � somatostatin PP cells � pancreatic polypeptide

8. Aetiology of Type I DM Disease of multifactorial autoimmune causation. Genetic predisposition: (HLA-DR3/4 in 98%) Autoimmunity. Aberrant expression of class II MHC antigen by B cells. Viral infection (mumps, coxsackie B, retroviruses, rubella, CMV, EBV)

9. Mechanisms of B cell destruction T lymphocytes mediated Damage by cytokines Autoantibodies (cytoplasmic, cell-surface, insulin and glutamic acid decarboxylase)

10. Type I

11. Type I (autoantibody)

12. Pathogenesis of Type I DM

13. Epidemiology Unknown or rare in Japanese, Indians, Chinese, and American Indians. White population in North America and Europe � 14/100,000 population.

14. Aetiology of Type II diabetes Defects in both insulin secretion and insulin action. Genetic factors: there is a familial tendency but there are no HLA associations. Progressive decline in B-cell function. Hyperglycemia itself contributes to B cell dysfunction � glucose toxicity.

15. Insulin resistance Mutations in insulin receptors, glucose transporters, and signaling proteins.Over-eating, aging, some medications. Normoglycemia can be maintained in case of B-cell dysfunction with retain insulin sensitivity and vice versa.

16. Islets in Type II Diabetes:

17. Epidemiology of Type II DM Originally rare in many populations Dramatically increased with modernization of life The highest prevalence rates in Pima Indians and Micronesians � 35% The lowest rate in Eskimos 1.3-1.9%

19. Acute complications Hypoglycemia: 30% of insulin-treated patients experience coma at least once. More often during sleep. Excessive doses of insulin or delayed ingestion of food. Sweating, tremor, palpitations, incoordination and unconsciousness. Responds quickly to glucose ingestion

20. Acute complications Diabetic ketoacidosis: main cause of death in type I DM patients under 20 years of age. Many cases occur in newly identified patients. Nausea, vomiting, thirst, polyuria, acidotic respiration. It is often precipitated by infection or another concurrent illness.

21. Acute complications Hyperosmolar non-ketoacidotic coma: Affects the middle-aged or elderly who have undiagnosed type II DM Precipitating factors � infection, diuretic therapy and glucose-rich drinks. Coma is more common than in case of ketoacidosis.

22. Chronic complications

23. Chronic complications

24. Microangiopathy Pathogenesis: Hyperglycemia chronic Glycosylation of basement membrane proteins ? Leaky blood vessels. Thick and Leaky blood vessels. Narrow lumen Ischemic Organ damage...

25. Nephropathy 35% of type I patients develop nephopathy. Microalbuminuria (30-300mg/day) Proteinuria (0,5 g/day) reflects widespread vascular damage. Hypertension of renal origin. Peripheral vascular disease, neuropathy, and retinopathy are universal in these patients and if is not present the nephropathy is unlikely.

26. Nephropathy Diffuse thickening of the glomerular capillary basement membrane. Abnormal mesangium with fibrin casps.

27. Nephropathy Nodular diabetic glomerulosclerosis Kimmelstiel-Wilson nodules.

28. Nephropathy

29. Neuropathy Risk is linked to the duration of DM. In patients attending a diabetic clinic: 25% reported symptoms 50% found to have neuropathy using a simple test 90% posotive to more sophisticated test Micro: Axonal degeneration with segmental demyelination Narrowing of the vasa nervorum as one of the factors

30. Neuropathy - forms Distal symmetric sensory or sensorimotor neurupathy. Focal or multifocal asymmetric neuropathy. Diabetic autonomic neuropathy (inmpotence, diarrhea, absent sweating in the feet)

32. Third cranial nerve palsy

33. Diabetic Amyotrophy

34. The diabetic foot Ischemic and neuropathic ulceration. Traumatic damage in the presence of sensory loss Spread infection to bone can cause osteomyelitis

35. Diabetic gangren

36. Diabetic retinopathy More severe in type I diabetes but onset after 5 or more years. Type II previously unrecognized patients may have retinopathy at presentation The prevalence increases with the duration of D Visual impairment is caused by proliferative R in type I DM and by maculopathy in type II All diabetic patients should have regular ophtalmic examination.

37. Retinopathy Non Proliferative Microaneurysms, Dot blot hemorrhages Hard and soft exudates Cotton wool � infarcts Macular edema. Proliferative. Neovascularization Large hemorrhages Retinal detachment.

38. Retinopathy

39. Macroangiopathy Atherosclerosis Dyslipidemia ? HDL Non-Enzymatic Glycosylation ? Platelet Adhesiveness ? Thromboxane A2 ? Prostacyclin Endothelial damage ? Atherosclerosis MI, CVA

40. Diabetic dyslipidemia Hypertriglyceridemia Elevation of VLDL Predominance of small, dense LDL particles. Decreased HDL concentration

41. Infections in Diabetes: Increased glucose � good growth condition for bacteria. (alone is not the cause) Decreased function of neutrophils and lymphocytes � glycosylation. Glycosylation of immune mediators. Ab Decreased metabolism � low immunity. Capillary thickening � impaired inflammation. Ischemia & infarctions. Diabetes ? State of immunosuppression.

42. Lungs Miscellaneous bacterial infections. Tuberculosis � increased risk and rapidly progressive.

43. Skin Trophic changes, due to neuropathy and microangiopathy. Carbuncles from increased susceptibility to infection. Diabetic dermatopathy and xanthelasmas

44. Diabetic bulla

45. Diabetic dermatophathy Atrophic, slightly depressed lesions on the legs.

46. Necrobiosis Lipoidica Sharply circumscribed, multicolored plaques on the anterior and lateral surfaces of the legs and arms.

47. Eruptive xantoma Sign of diabetes out of control

48. Monitoring Glycosylated hemoglobin Hgb A1 � is a hemoglobin molecule with a single glucose molecule attached. Normal value is 3-6% (up to 20% in diabetics) Indicator of diabetes control during the preceding 3 months Glycosylated serum proteins (fructosamine) C-peptide ( 3 weeks )

49. Diabetes and pregnancy Diabetic patients should be closely supervised during pregnancy Women with type I diabetes should normalize HbA1c to avoid the risk of congenital malformations Gestational diabetes mellitus is glucose intolerance first recognized during pregnancy.

50. Pathogenesis: Pathophysiologically type II DM. Pregnancy is a state of insulin resistance. HPL blocks insulin receptors Increased Insulin needs in pregnancy. Insulin release is enhanced in preg. Increased insulin ? hunger ? over eating. Insulin release decreases insulin receptors. When the pregnancy is over and the insulin needs return to normal, the diabetes usually disappears.

51. Maternal Complications: Higher risk of hypertension, Preeclampsia, Infections, Cesarean section, Future diabetes.

52. Fetal Complications: Macrosomia, neural tube defects, neonatal hypoglycemia, Hypocalcemia, hypomagnsemia, Birth trauma Prematurity syndromes Childhood and adolescent obesity

53. Think of diabetes whenever you see an older patient with myocardial infarction, angina, stroke, cataracts, glaucoma, peripheral neuropathy, obesity, proteinuria, foot ulcers, infections, "nervousness", etc., etc.