1. Diabetes Mellitus Pathology and complications

2. Diabetes Mellitus  Metabolic disease affecting CHO, protein and fat metabolism due to insulin deficiency or inefficiency.

3. Diagnostic criteria Any one of the following 3 criteria: A random blood glucose>200 mg/dL, with classical signs & symptoms A fasting blood glucose>126 mg/dL on more than one occasion An abnormal oral glucose tolerance test (OGTT), in which blood glucose>200 mg/dL 2 hrs after a standard carbohydrate load

4. Classification Type 1 diabetes mellitus* Type 2 diabetes mellitus* Other specific types: Genetic defects of beta-cell function Genetic defects in insulin action Diseases of the exocrine pancreas ◦ Chronic pancreatitis ◦ Trauma/pancreatectomy ◦ Neoplasia ◦ Cystic fibrosis ◦ Hemochromatosis ◦ Fibrocalculous pancreatopathy ◦ Others Endocrinopathies ◦ Acromegaly ◦ Cushing's syndrome ◦ Glucagonoma ◦ Pheochromocytoma ◦ Hyperthyroidism ◦ Somatostatinoma ◦ Aldosteronoma ◦ Others Drug- or chemical-induced ◦ Pentamidine ◦ Nicotinic acid ◦ Glucocorticoids ◦ Thyroid hormone ◦ Diazoxide ◦ Beta-adrenergic agonists ◦ Thiazides ◦ Phenytoin ◦ Alfa-interferon ◦ Others …contd

5. Classification… Other genetic syndromes sometimes associated with diabetes ◦ Down syndrome ◦ Klinefelter's syndrome ◦ Turner's syndrome ◦ Wolfram syndrome ◦ Friedreich's ataxia ◦ Huntington's chorea ◦ Lawrence-Moon Beidel syndrome ◦ Myotonic dystrophy ◦ Porphyria ◦ Prader-Willi syndrome ◦ Others Infections ◦ Congenital rubella ◦ Cytomegalovirus ◦ Coxsackie virus B ◦ Others Uncommon forms of immune- mediated diabetes Gestational diabetes mellitus

6. TYPE I Type II 1. AgeUnder 25 years.Above 40 years. 2. B. Cell mass.ReducedNot reduced. 3. Insulin secretion ReducedNot reduced 4. Etiology1.Autoimmune destruction of the β.cells. 1.Insulin resistance. 2.β cell dysfunction- decreased insulin secretion

7. * Pathological lesions: 1. Pancreas: - In type I: the pancreas is atrophic. M/P: degranulated and destroyed B.cells, lymphocytic infiltration and fibrosis. - In type II: the pancreas is normal. M/P: normal in early stage, later on shows hyalinosis.

8. In this high-power view, an islet surrounded by normal pancreatic acini is seen. The islet shows extensive deposition of a pink homogeneous material that has the features of amyloid. This change is often, but not always, seen in long-standing type II diabetes

9. 2. Vascular changes: 1. Diabetic macroangiopathy: Accelerated atherosclerosis in aorta, large and medium sized arteries. Hyaline arterioloscelrosis: hyaline thickening of the arterioles due to deposition of hyaline material. 2. Diabetic microangiopathy: Diffuse thickening of the basement membranes due to deposition of hyaline material. Involves predominantly the capillaries of, retina, renal glomeruli, and peripheral nerves. Leads to diabetic nephropathy, retinopathy and neuropathy.

10. * Complications of diabetes mellitus: I. Acute complications: 1.Diabetic ketoacidosis 2.Hypoglycemic coma 3.Hyperosmolar hyperglycemic state (HHS) II. Chronic complications: a. Microvascular  Retinopathy  Nephropathy  Neuropathy b. Macrovascular  Cerebrovascular.  Cardiovascular.  Peripheral vascular disea Enhanced susceptibility to infections of the skin, tuberculosis, pneumonia and pyelonephritis.

11. A. Macro-vascular Complications: Accelerated atherosclerosis involving the aorta and large- and medium-sized arteries ( esp-renal arteries) Myocardial infarction, caused by atherosclerosis of the coronary arteries, is the most common cause of death in diabetics. Gangrene of the lower extremities. Hypertension due to Hyaline arteriolosclerosis.

12. ATHEROSCLEROSIS OF AORTA

13. MYOCARDIAL INFARCTION

14. GANGRENE OF TOES AND LOWER LIMB

15. Microvascular complications are specific to diabetes and related to long standing hyperglycaemia. In diabetes, the microvasculature shows both functional and structural abnormalities. The structural hallmark of diabetic microangiopathy is thickening of the capillary basement membrane. B. Microvascular Complications

16. Many chemical changes in basement membrane composition have been identified in diabetes, including increased type IV collagen and its glycosylation (i.e. binding of glucose to wall of blood vessels).

17. The main functional abnormalities include increased capillary permeability and disturbed platelet function. Increased capillary permeability is manifested in the retina by exudation and in the kidney by increased urinary losses of albumin. Platelets from diabetic patients show an exaggerated tendency to aggregate, perhaps mediated by altered prostaglandin metabolism.

18. Diabetic retinopathy

19. Background( preproliferative) DR Microaneurysm - earliest sign Macular edema Exudates Dot and blot hemorrhages Cotton wool spots Proliferative DR Neovascularization- neovascular membrane may lead to Vitreous hemorrhage Retinal detachment

20. Normal Retina

22. Diabetic Retinopathy Cotton wool spots

23. Other Eye Complications - Cataracts. - Glaucoma

24. CATARACT

25. Vitreous Bleeding

26. Diabetic Nephropathy (DN)

27. - Diabetic nephropathy is defined by persistent albuminuria (>300 mg/day), decrease glomerular filtration rate and rising blood pressure. - About 20 – 30% of patients with diabetes develop diabetic nephropathy

28. Characteristics of nephropathy Three lesions are encountered: (1) Glomerular lesions; (2) Renal vascular lesions, principally arteriolosclerosis and atherosclerosis; and (3) Pyelonephritis, including necrotizing papillitis.

29. Morphology Morphology Gross — Fine granular scarring-Bilateral contracted kidneys Microscopy— 1. Glomerular lesions Capillary BM thickening Diffuse mesangial sclerosis--dis>10yrs Nodular glomerulosclerosis— ‘’Kimmelstiel-Wilson lesion’’-PAS+ nodules in periphery of glomeruli 2. Renal vascular lesions- Hyaline arteriosclerosis of both aff & eff arterioles 3. Pyelonephritis, including necrotizing papillitis

30. The gross appearance of the kidney varies, depending on the type of vascular lesion. Typically, as seen here, kidneys with diabetic glomerulosclerosis show diffuse, fine granularity of the cortical surface, resulting from destruction and scarring of the glomeruli.

31. Low-power view shows hyaline thickening of the arterial wall and evidence of tubular destruction, seen as an increase in the interstitial fibrous tissue. One of the glomeruli in this field has been totally replaced by scar tissue, and hence, it appears acellular and hyalinized. The two other glomeruli show nodular glomerulosclerosis

32. Nodular glomerulosclerosis (Kimmelstiel-Wilson lesion)

33. PAS stain highlights the glycoprotein-rich basement membrane in Bowman capsule and the mesangial nodules.

34. Diabetic Neuropathy

35. 1. Sensorimotor neuropathy. 2. Autonomic neuropathy.

36. Sensorimotor Neuropathy Distal symmetric polyneuropathy of the lower extremities that affects both motor and sensory function, but particularly the latter. Numbness, paresthesia's- ‘’glove and stocking’’ Feet are mostly affected, hands are seldom affected. Complicated by ulceration (painless). Charcot arthropathy,

37. Complications of Sensorimotor neuropathy

38. Autonomic Neuropathy  Postural hypotension.  Diabetic diarrhea.  Erectile dysfunction.

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