Pathology of diabetes mellitus Flashcards
What genes are thought to contribute to type 1 diabetes and what is their function?
HLA genes
Help T cells to recognise self from non self
What occurs as a result of the autoimmune attack on pancreatic b cells?
lymphocyte infiltration and destruction of the b cells leading to scarring and reduced insulin production
List some environmental triggers thought to contribute to type 1 diabetes and explain 1
chemicals
virus - molecular mimicry as their antigens mimic those found on pancreatic b cells
What is the general cause of type 2 diabetes and what is this due to?
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
Main environmental factor of type 2 DM and cause
central upper body visceral fat
eat too much and exercise too little
Why does obesity lead to increased FFA in blood?
overweight adipocytes are probably “stressed” and release FA
Why does obesity lead to decreased insulin receptor sensitivity?
unclear why
What is the consequence of having insulin receptors which do not work efficiently?
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
True or false - in a person with central adiposity (not yet diabetes) the pancreas needs to secrete more insulin to move glucose into cells
true
Even in a person with obesity and hyperinsulinaemia if the body can do what then diabetes will not occur
produce enough insulin
Genes important in type 2 DM (+ those which are NOT)
implicated genes for poor b cell high end function
Not HLA, or central adiposity genes
If you have many genes promoting high end insulin secretion and central adiposity will you develop type 2 DM?
probably not
Why may a slim person who puts on a little bit of weight develop type 2 DM?
high dose of genes resulting in inability to even modestly raise insulin
Lists some long term complications of DM and whey they may arise
risk of CVD and MI
reduced life by 5-10 years
poor glycaemic control
What is the main complication in diabetes?
damage to vessels
Briefly explain large vessel disease in diabetes
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
Briefly explain (not yet in specifics) small vessel disease in diabetes
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
What is another name for arteriolar disease and its complications
hyaline change
narrowing of arterioles throughout body leading to ischaemia
Where is hyaline change particularly damaging?
kidney
periphery
eyes
arterioles which supply nerves
What happens to capillaries in small vessel disease?
increased connective tissue around these eg glomerulus in kidney
List some morbidities diabetics are at risk of
amputation
blindness
end stage renal disease
What is the main cause of small vessel disease?
glycosylation
What is glycosylation and when is it reversible/irreversible
glucose added to proteins
reversible at first
irreversible if covalent bonds form - AGE
2 forms of glycosylation leading to small vessel disease
collagen glycosylated
cross linked proteins
Where is collagen normally found in small vessels?
basal lamina
Does normal collagen bind albumin?
no
Does glycosylated collagen bind albumin?
yes
consequence of glycosylated collagen binding to albumin
accumulation of albumin in subendothelial space of arterioles and is trapped
Why do the proteins cross link and the consequence?
normal basal lamina proteins are easily removed
glycosylated and bind neighbouring proteins
rigid cross linked proteins cannot easily be removed
Do cross linked proteins persist or undo if normoglycaemia occurs?
persist
