type 2 diabetes mellitus Flashcards
define T2DM
- state of chronic hyperglycaemia sufficient to cause long-term damage to specific tissues
- not ketosis prone
- involves weight, lipids, BP
describe fasting glucose in diabetes
fasting glucose above 7mmol/L
what is MODY?
- autosomal dominant
- mutations in TF glucokinase gene = produces ineffective beta cell insulin secretion
- no obesity
what can the pathophysiology of T2DM be influenced by?
- genetics
- intrauterine environment
- adult environment
- epigenetic changes in intrauterine environment can affect functioning of developing genes
what is T2DM caused by?
- insulin resistance
- insulin secretion deficits
what specifically about the intrauterine environment can greatly inc. chance of developing T2DM?
intrauterine growth restriction
how does insulin resistance lead to macrovascular disease?
- insulin resistance
- dyslipidaemia
- inc. mitogenic pathway
- hypertrophy and inc. in BP
- macrovascular disease
if dyslipidaemia leads to macrovascular disease, what does hyperglycaemia lead to?
microvascular
why would everyone get T2DM at some point?
- insulin production dec. with age
- we become more resistant with age
- at some point, insulin resistance and secretion lines bisect
- cannot make enough insulin for our resistance
what is hyperglycaemia clamp?
- in people that are developing T2DM, they will have some insulin production
- but lose their first phase response to glucose
- make insulin but takes longer
what are the 1st and 2nd phase responses in insulin secretion?
1st phase: stored insulin that is ready to be released when stimulated
2nd phase: produced and secreted insulin over time
describe the inc. blood glucose in T2DM
- deficient insulin means HGO continues after eating food
- deficient insulin also meands glucose cannot move into muscles and fat
what happens to fatty acids in insulin resistance?
- fatty acids cannot be used to make glcose
- instead are made into VLDLs which are atherogenic
- liver not inhibited to make new glucose in gluconeogenesis or breakdown glycerol into glucose
how is the gut microbiota involved?
- associated with obesity, insulin resistance, T2DM, inflammation, adipocytokine pathwayys
- via host signalliing
- various lipopolysaccharides are fermented by gut bacteria to short chain FFAs, enter host circulation, modulate bile acids
how do people with T2DM found?
- osmotic symptoms
- infections (hyperglycaemia)
- screnning tests
- often found at presentation of complications
what can these complications be?
- microvascular
- macrovascular
- metabolic
- from treatment (hypo attack)
how do you manage T2DM?
- education
- diet
- pharmacological treatment
- complication screening
in what ways, should the diet be changed?
- control total calorie intake/ inc. exercise
- reduce fat as proportion of calories
- reduce refined carbs
- inc. complex carbs, unsat fat
how do you monitor T2DM?
- weight
- glycaemia
- BP and dyslipidaemia
name the 5 different drug treatments for T2DM
- orlistat: pancreatic lipase inhibitor
- metformin: biguanide, insulin sensitiser
- sulphonylureas: makes existing pancreas secrete more insulin
- alpha glucosidase inhibitors: delays glucose absorption
- thiazolidinediones: acts on adipocytes and insulin sensitizer peripherally in fat and muscles
describe metformin
- biguanide class (oral anti-hyperglycaemic drugs)
- insulin sensitiser
- used in overweight pt when diet has succeeded
- reudces HGO and inc. peripheral glucose disposal
what are the side effects of metformin?
GI effects
don’t use if severe liver/cardiac failure
or mild renal failure
describe sulphonylurea
e. g. Glibenclamide
- acts on beta cell and act to inc. insulin secretion
- blocks ATP-sensitive K channel
- cause influx of Ca
- used in lean patients with T2DM
which patients are sulphonylureas used in?
lean patients
with T2DM
