Pathology of Diabetes Mellitus complications

Question 1

What proportion of Islet cells are beta cells, responsible for insulin production?

Answer 1

2/3

Question 2

What genes have found to be affected in type I DM?

Answer 2

HLA

Question 3

Describe the aetiology of type I DM

Answer 3

• Cannot distinguish own cells from other cells à autoimmune attack on pancreatic B cells
• Autoimmune attack on islet cells via lymphocyte infiltration of islets (insulitis) causing the destruction of B cells, and therefore decreased insulin production
• This destruction of beta cells leads to decreased insulin production, and therefore increased glucose concentration in the blood as it is no longer taken up by fat and muscle cells

Question 4

Describe the aetiology of type II DM

Answer 4

Combination of:

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

= a failure of the B cells to meet an increased demand for insulin in the body

Question 5

How does obesity lead to insulin receptor sensitivity?

Answer 5

• Expanded upper body visceral fat mass (pot belly) results in increased free fatty acids in blood (Note - patient is not yet diabetic) as ‘overweight’ adipocytes are probably ‘stressed’ and release fatty acids
• This leads to decreased insulin receptor sensitivity, though it is not clear why the fatty acids interfere with the insulin receptor pathway, meaning the insulin receptors no longer work efficiently
• This means more insulin must be secreted from the to get the same amount of glucose into cells (=hyperinsulinaemia)

Question 6

What is the most common cause of death in diabetics?

Answer 6

Myocardial infarction

Question 7

What mechanism explains large vessel complications associated with DM?

Answer 7

Glucose molecules stop low-density lipoprotein from binding its receptor (on liver cells) tightly. Low density lipoprotein is not removed by liver cells causing lipoprotein and lipids to stay in blood, leading to hyperlipidaemia land the development of atherosclerotic fatty plaques

Question 8

What mechanism underlies arteriole complications in DM?

Answer 8

In Diabetes Mellitus – molecules flux into subendothelial space of arteriole walls but find it hard to flux back to blood, leading to a build up of ‘trapped’ molecules under endothelial cells. Also, basal lamina also becomes thickened

Question 9

What 2 mechanism underly capillary complications in DM?

Answer 9

Glucose added to proteins and eventually form Advanced Glycosylation End-products (AGE’s)

Collagen is glycosylated - Collagen is found in normal basal lamina. Albumin can sometimes get into subendothelial space. Normal collagen does not bind albumin, so albumin fluxes out of space and there is no accumulation of albumin in subendothelial space of arterioles. Glycosylated collagen does bind albumin, leading to an accumulation of albumin in subendothelial space of arterioles. Albumin is trapped in subendothelial space of arterioles

Proteins are cross-linked - Many normal basal lamina proteins do not crosslink and can be removed easily, but glycosylated proteins bind their neighbouring proteins. Rigid, cross-linked protein cannot easily be removed, leading to persistence of proteins in arteriole walls despite it patient returns to normoglycaemia

Question 10

Is vessel disease reversible?

Answer 10

• Typically irreversible when established

* Occurs in setting of prolonged, poor diabetic control