The Pathology of Diabetes

Question 1

What are the three main tissues that respond to insulin?

Answer 1

liver, fat and skeletal muscle

Question 2

What are the three main actions of insulin in the cell?

Answer 2

adding GLUT-4 transporters to the cell membrane, PI-3K signalling pathway, MAPK signalling pathway

Question 3

What is the acute complication of hyperglycaemia in T1D?

Answer 3

diabetic ketoacidosis

Question 4

What is the acute complication of hyperglycaemia in T2D?

Answer 4

hyperosmolar coma

Question 5

What are the three main types of chronic complications of hyperglycaemia?

Answer 5

macrovascular, microvascular and cellular

Question 6

What are the macrovascular effects of chronic hyperglycaemia and why do they occur?

Answer 6

atheroma - occurs because of increased production of atherogenic lipoproteins in the liver, suppression of lipid uptake in peripheral tissue, abnormal endothelial function, the associated hyperlipidaemia and hypertension in DM

Question 7

What are the major clinical problems associated with the microvascular effects of chronic hyperglycaemia?

Answer 7

nephropathy, retinopathy, delayed wound healing

Question 8

What causes the microvascular effects of chronic hyperglycaemia?

Answer 8

glycosylation of proteins

Question 9

What other problems occur in the kidney apart from diabetic arteriolosclerosis?

Answer 9

infection, necrosis and atherosclerosis in the renal arteries

Question 10

What are the typical histological lesions in diabetic nephropathy?

Answer 10

Kimmelsteil-Wilson nodules, hyaline arteriolosclerosis and infarcts

Question 11

What causes diabetic retinopathy?

Answer 11

ischaemia due to microvascular injury

Question 12

Why is wound healing a major problem in diabetics?

Answer 12

impaired perfusion, lack of sensation means injury is more likely, poor immune response means more susceptible to infection

Question 13

What are the three pathways which cause the damage to tissues in chronic hyperglycaemia?

Answer 13

advanced glycation end products, activation of protein kinase C, intracellular hyperglycaemia and abnormal polyol pathways

Question 14

What causes advanced glycation end products?

Answer 14

reaction between glucose and amino groups of proteins

Question 15

What is the receptor for AGEs and what happens when the receptor is activated?

Answer 15

the receptors are called RAGE and they are located on inflammatory cells, endothelial cells and vascular smooth muscle

Question 16

What are the receptor mediated effects of AGEs?

Answer 16

release of pro inflammatory cytokines and growth factors from macrophages, generation of ROS from endothelial cells, increased pro-coagulant activity in endothelial cells, proliferation and matrix production by vascular smooth muscle cells

Question 17

What are the non receptor mediated effects of AGEs?

Answer 17

cross linking of type I collagen in vessel walls altering their dynamics, cross linking of type IV collagen in basement membranes thickening the basement membrane, resistance to degradation, trap other proteins including LDLs

Question 18

What causes peripheral neuropathy?

Answer 18

AGE related damage leading to loss of axons, polyol related damage, neuronal ischaemia due to microvascular damage