Pathology of diabetes mellitus

Question 1

What genes are thought to contribute to type 1 diabetes and what is their function?

Answer 1

HLA genes

Help T cells to recognise self from non self

Question 2

What occurs as a result of the autoimmune attack on pancreatic b cells?

Answer 2

lymphocyte infiltration and destruction of the b cells leading to scarring and reduced insulin production

Question 3

List some environmental triggers thought to contribute to type 1 diabetes and explain 1

Answer 3

chemicals

virus - molecular mimicry as their antigens mimic those found on pancreatic b cells

Question 4

What is the general cause of type 2 diabetes and what is this due to?

Answer 4

failure for b cells to produce enough insulin to meet demands of the body
reduced tissue sensitivity to insulin - insulin resistance
inability to secrete very high levels of insulin

Question 5

Main environmental factor of type 2 DM and cause

Answer 5

central upper body visceral fat

eat too much and exercise too little

Question 6

Why does obesity lead to increased FFA in blood?

Answer 6

overweight adipocytes are probably “stressed” and release FA

Question 7

Why does obesity lead to decreased insulin receptor sensitivity?

Answer 7

unclear why

Question 8

What is the consequence of having insulin receptors which do not work efficiently?

Answer 8

some Glc gets into cell and some does not
need more insulin to get same amount of glucose into cells
pancreas must secrete more insulin

Question 9

True or false - in a person with central adiposity (not yet diabetes) the pancreas needs to secrete more insulin to move glucose into cells

Answer 9

true

Question 10

Even in a person with obesity and hyperinsulinaemia if the body can do what then diabetes will not occur

Answer 10

produce enough insulin

Question 11

Genes important in type 2 DM (+ those which are NOT)

Answer 11

implicated genes for poor b cell high end function

Not HLA, or central adiposity genes

Question 12

If you have many genes promoting high end insulin secretion and central adiposity will you develop type 2 DM?

Answer 12

probably not

Question 13

Why may a slim person who puts on a little bit of weight develop type 2 DM?

Answer 13

high dose of genes resulting in inability to even modestly raise insulin

Question 14

Lists some long term complications of DM and whey they may arise

Answer 14

risk of CVD and MI
reduced life by 5-10 years
poor glycaemic control

Question 15

What is the main complication in diabetes?

Answer 15

damage to vessels

Question 16

Briefly explain large vessel disease in diabetes

Answer 16

glucose attaches to LDL so stops it binding as tightly to its receptors on hepatocytes
LDL and lipid in serum = hyperlipidaemia
accelerates atherosclerosis –> MI, stroke, CHD

Question 17

Briefly explain (not yet in specifics) small vessel disease in diabetes

Answer 17

endothelial cells line lumen which make a basal lamina (collagens) to sit on with a subendothelial space between which molecules flux in and out off
smooth muscle is around basal lamina and in diabetes molecules cannot flux back out of cell so build up of trapped molecules and basal lamina thickened

Question 18

What is another name for arteriolar disease and its complications

Answer 18

hyaline change

narrowing of arterioles throughout body leading to ischaemia

Question 19

Where is hyaline change particularly damaging?

Answer 19

kidney
periphery
eyes
arterioles which supply nerves

Question 20

What happens to capillaries in small vessel disease?

Answer 20

increased connective tissue around these eg glomerulus in kidney

Question 21

List some morbidities diabetics are at risk of

Answer 21

amputation
blindness
end stage renal disease

Question 22

What is the main cause of small vessel disease?

Answer 22

glycosylation

Question 23

What is glycosylation and when is it reversible/irreversible

Answer 23

glucose added to proteins
reversible at first
irreversible if covalent bonds form - AGE

Question 24

2 forms of glycosylation leading to small vessel disease

Answer 24

collagen glycosylated

cross linked proteins

Question 25

Where is collagen normally found in small vessels?

Answer 25

basal lamina

Question 26

Does normal collagen bind albumin?

Answer 26

no

Question 27

Does glycosylated collagen bind albumin?

Answer 27

yes

Question 28

consequence of glycosylated collagen binding to albumin

Answer 28

accumulation of albumin in subendothelial space of arterioles and is trapped

Question 29

Why do the proteins cross link and the consequence?

Answer 29

normal basal lamina proteins are easily removed
glycosylated and bind neighbouring proteins
rigid cross linked proteins cannot easily be removed

Question 30

Do cross linked proteins persist or undo if normoglycaemia occurs?

Answer 30

persist