Pathology of Diabetes Mellitus

Question 1

What does a normal pancreas look like?

Answer 1

Lobules of glandular tissue surrounded by fat

Question 2

How much of islet cells are beta cells?

Answer 2

2/3rds

Question 3

What do beta cells secrete?

Answer 3

Insulin

Question 4

What is involved in the glucose metabolism pathway?

Answer 4

Increased glucose so increased insulin
Which increases glucose uptake into cells and decreases glucose in serum

Question 5

What genes can cause diabetes mellitus type I?

Answer 5

Human Leukocyte Antigen (HLA) molecules - help cells recognises self from non self
So cannot distinguish own cells from other so autoimmune attack on beta cells

Question 6

What does autoimmune attack on islet cells cause?

Answer 6

Lymphocyte infiltration of islets - destruction of beta cells
Decreases insulin production so increases glucose in blood

Question 7

Does environment cause diabetes mellitus type I?

Answer 7

Environmental triggers plus genes can lead to the destruction of beta cells

Question 8

Describe the aetiology of type II diabetes mellitus

Answer 8

Combination of reduced tissue sensitivity to insulin and inability to secrete very high levels of insulin
So failure of beta cells to meet increased demand for insulin in body

Question 9

What is the environmental cause of type Ii diabetes mellitus?

Answer 9

Expanded upper body visceral fat mass - increased adipocytes due to increased intake of food and lack of exercise

Question 10

What does expanded upper body visceral fat mass result in?

Answer 10

Increased free fatty acids in blood as adipocytes under stress
This leads to decreased insulin receptor sensitivity

Question 11

What does decreased insulin receptor sensitivity lead to?

Answer 11

Decreased removal of glucose form blood
So pancreas needs to secrete more insulin to move glucose into cells for person with central adiposity

Question 12

What does central adiposity lead to?

Answer 12

Hyperinsulinemia

Question 13

How does the body cope with peripheral insulin resistance?

Answer 13

Need pancreas to produce more and more insulin
Not diabetic if increase in insulin is substantial

Question 14

What genes are involved in type II diabetes mellitus?

Answer 14

Implicated genes are for poor beta cell ‘high end’ insulin secretion
So if only a few abnormal - lots of insulin can still be produced
If variants for lower insulin production then can’t produce large amounts

Question 15

What are the 2 factors causing type II diabetes mellitus?

Answer 15

Insulin secretion genetically can only be increased so far in a person who’s weight gain has slowed down for their insulin receptors

Question 16

What is an exception in type II diabetes mellitus?

Answer 16

Slim person gains small amount of weight but have very high dosage of genes resulting in inability to even modestly raise insulin

Question 17

What part of type II diabetes mellitus is reversible?

Answer 17

Adipose fat

Question 18

What are some long term complications of DM?

Answer 18

Annual mortality is 5.4% so double non-diabetics
Life expectancy decreased by 5-10yrs
MI is commonest cause of death
result from prolonged poor glycaemia control

Question 19

What is the main complication of DM?

Answer 19

Large vessel disease - arteries
Small vessel disease - arterioles and capillaries

Question 20

What does DM accelerate in large vessels?

Answer 20

Atherosclerosis
Coronary heart disease, MI and stroke increased risk

Question 21

How is atherosclerosis acclerated?

Answer 21

Glc attaches to low density lipoprotein so stop lipoprotein from binding to receptor on liver cells tightly - lipoprotein stays in blood - hyperlipidaemia then atherosclerosis

Question 22

What sits on endothelial lining?

Answer 22

Makes basal lamina for collagen to sit on

Question 23

What happens to small vessels in diabetes mellitus?

Answer 23

Molecules flux into subendothelial space but find it hard to flux back to blood - build up of trapped molecules
Basal lamina also becomes thicker

Question 24

What builds up between subendothelial space?

Answer 24

Accumulation of plasma proteins and connective tissue

Question 25

What is hyaline change?

Answer 25

Arteriolar disease
Process occurs throughout body
Narrow arteriole so poor blood flow so ischaemia
Very damaging in kidney, peripheral tissues, eyes and nerve supply

Question 26

What is the risk of hyaline change?

Answer 26

Amputation
End stage renal disease
Blindness

Question 27

What small vessel disease happens in capillaries?

Answer 27

Increased connective tissue around capillaries

Question 28

What is a nodule of connective tissue called?

Answer 28

Kimmelsteil Wilson lesion

Question 29

Explain glycosylated collagen and small vessels

Answer 29

Collagen in in normal basal lamina and normal collagen does not bind to albumin
Glycosylated collagen does bind to albumin so accumulation in subendothelial space

Question 30

Explain cross linked proteins and small vessels

Answer 30

Normal basal lamina proteins do not crosslink and can be easily removed
Glycosylated proteins bind to neighbouring proteins - rigid crosslink which cant be easily removed - persistence

Question 31

What does glycosylation cause?

Answer 31

Accumulation of trapped plasma proteins
Accumulation of cross linked basal lamina proteins

Question 32

When does large and small vessel disease in DM occur?

Answer 32

Typically irreversible when established
Occurs in setting of prolonged poor diabetic control