Diabetes Mellitus

Question 1

Types of diabetes

Answer 1

1. Primary (Idiopathic) Diabetes
   - Type I - β-cell destruction, absolute insulin deficiency
   - Type II - β-cell dysfunction, peripheral insulin resistance with relative insulin deficiency
2. Secondary Diabetes
   - chronic pancreatitis & post-pancreatectomy
   - hormonal tumours
   - drugs
   - haemochromatosis
   - genetic disorders
   - gestational DM

Question 2

Features & pathogenesis of type 1 DM

Answer 2

• autoimmune disease
• islet destruction caused primarily by immune effector cells reacting against endogenous β-cell antigens
• genetic predisposition + environmental insult (eg viral inf) - immune response against normal/altered β-cells - autoimmune attack (β-cell destruction)

Question 3

Pathogenesis of type 2 DM

Answer 3

• genetic predisposition - pri β-cell defect (impaired insulin secretion) + envt (obesity)
• peripheral tissue insuline resistance - inadequate glucose utilisation
• hyperglycemia - β-cell exhaustion

Question 4

Changes in the pancreas in DM

Answer 4

• reduction in number & size of islets
• leukocytic infiltration of islets
• amyloid replacement of islets

Question 5

Clinical features of DM

Answer 5

Type 1

• onset 30y
• obese
• normal/increased blood insulin
• no islet cell antibodies
• ketoacidosis rare

Question 6

Islet cells in DM

Answer 6

Type 1

• insulitis early
• marked atrophy & fibrosis
• β-cell depletion

Type 2

• no insulitis
• focal atrophy & amyloid
• mild β-cell depletion

Question 7

Complications of diabetes

Answer 7

1. Macrovascular - large & med sized muscular arteries
   - accelerated atherosclerosis, htn, mi
2. Microvascular - small vessels
   - cerebral vascular infarcts, hemorrhage
   - retinopathy, cataracts, glaucoma
   - nephrosclerosis, glomerulosclerosis, pyelonephritis
   - peripheral neuropathy, autonomic neuropathy
   - peripheral vascular atherosclerosis, arteriosclerosis
   - gangrene, infections

Question 8

Pathogenesis of complications of diabetes

Answer 8

1. Nonenzymatic glycosylation
   - glucose attaches to amino group of protein - irreversible advanced glycosylation end-products
   - cross link w collagen & albumin - thickening of BM
   - also traps LDLs - accelerate atherogenesis
   - AGEs bind to AGE receptors of cells - release cytokines, growth factors, increase endothelial permeability, proliferation & synthesis of ecm
2. Intracellular hyperglycemia - disturbance in polyol pathways
   - affects tissues that do not req insulin for glucose transport
   - increased intracellular glucose - conversion to sorbitol by aldose reductase - fructose - increased oxidative stress + osmotic pressure - tissue damage