Lecture 3 Pathology of Diabetes Mellitus and its Complications

Question 1

2/3rds of Islet cells are ___

Answer 1

B cells

Question 2

What doe B cells secrete

Answer 2

Insulin into blood

Question 3

What is the function of insulin

Answer 3

Drives glucose into adipocytes and decreases glucose in the serum

Question 4

Define type I Dibetes

Answer 4

Pancreas produces little or no insulin

Question 5

Aetiology of Type I diabetes

Answer 5

• Molecules that help T cells recognise self from non-self = HLA molecules
• Cannot distinguish own cells from other cells  autoimmune attack on pancreatic B cells
• Autoimmune attack on islet cells = insulitis = destruction of B cells due to lymphocyte infiltration  destruction of islets  scarred islet  decreased insulin increase of Glc

Question 6

Environmental causes of type I diabetes

Answer 6

 Chemicals
 Bacteria in gut altered in infancy
 Viral infection- molecules on viral surface mimic molecules on outside of B cells and immune cells attack

Question 7

Aetiology of Type II Diabetes

Answer 7

1. Reduced tissue sensitivity to insulin (insulin resistance)
2. Inability to secret very high levels of insulin

Question 8

Environmental cause of Type II Diabetes

Answer 8

• Environment- expanded upper body visceral fat mass (pot belly)
 Increased intake of food
 Lack of exercise
 Increased free fatty acids in blood (no yet diabetic) because of stressed adipocytes
 Increased FFA which leads to decreased insulin receptor sensitivity
 Now more insulin is needed to get same amount of glucose into cells
 Pancreas secretes more insulin to move glucose into cells in person with central adiposity
 This leads to raised glucose and insulin levels then have to markedly increase to make glucose go back to normal levels

Question 9

Central adiposity leads to___

Answer 9

Increase FFA
Insuline receptor compels is disrupted
Glucose cannot be taken up into cell 
May still have genes that enable them to produce enough insulin to compensate 
If not this leads to type II diabetes

Question 10

Long term complication of Diabetes

Answer 10

Myocardial Infarction
Reduced life expectancy
Acceleration of atherosclerosis

Question 11

What does prolonged poor glycemic control lead to acceleration of atherosclerosis

Answer 11

• Glucose + LDL = inability of protein to bind to receptor in liver to remove it for processing
• LDL is not removed in blood  Hyperlipidaemia  atherosclerosis

Question 12

What leads to microvascular ischaemia

Answer 12

• Molecules flux in subendothelial space but find it hard to flux back to blood
• Basal becomes thickened
• Narrows arteriole  poor blood flow  Iscahemia
• Hyaline charge
• Very damaging in kidney, peripheral tissues ,foot, eyes and in arterioles supplying nerves
• Glomerulus in kidney
• Nodule of connective tissue called Kimmelstiel-Wilson lesion

Question 13

Prolonged glucose in subendothelial space leads to

Answer 13

 Glycosylated collagen does bind to albumin = accumulation of albumin in subendothelial space of arterioles
 Proteins are cross-linked
 Cannot be easily removed
 Persistence even if return to normoglycaemia