16. Type II diabetes mellitus Flashcards
which specific-tissues does DM cause long-term damage to?
- retina
- kidneys
- nerves
- arteries
what is macrovascular disease?
ischaemic heart disease and cerebrovascular disease (stroke)
what only occurs in diabetes?
microvascular disease
what is not seen in T2DM that is seen in T1DM?
ketosis
what should a normal 2-hour glucose be in an oral glucose tolerance test?
less than 7.8mmol/l
at what glucose values does a patient have DM?
- fasting glucose is over 7mmol/l
- 2hr glucose is over 11mmol/l
outline the epidemiology of T2DM
- 10% of 60 year olds suffer from diabetes (and most suffer from T2DM)
- seen with increasing age
- prevalence varies depending on ethnicity and environment
- T2DM is occurring and being diagnosed younger
- greatest in ethnic groups that have moved from rural to urban lifestyles
what is the pathophysiology of T2DM?
- genes, intrauterine environment and adult environment have a role
- most T2DM patients are insulin resistant
- most patients have an insulin secretion defect
how many hereditary forms of Maturity Onset Diabetes of the Young (MODY) are there?
8 forms
what is MODY?
- a genetic disease (autosomal dominant)
- all patients have a positive family history and no obesity
- ineffective pancreatic B cell insulin production
what are adipocytokines?
hormones made by fat cells that are a mechanism of T2DM
what is dyslipidaemia and what is associated with it? what does it lead to?
dyslipidaemia involves abnormal handling of cholesterol
it is associated with insulin resistance
it leads to macrovascular disease
why is light birth associated with diabetes in adulthood?
there are genes that are susceptible to epigenetic manipulation in-utero
what does T2DM present with?
- obesity
- insulin resistance and insulin secretion deficit
- hyperglycaemia and dyslipidaemia
- acute and chronic complications (though less than T1DM) e.g. hyperosmolar coma (acute), ischaemic heart disease and retinopathy (chronic)
- osmotic symptoms
- infections (yeast and microorganisms thrive in high glucose environments)
- screening test
what causes diabetic dyslipidaemia?
very low density lipoprotein triglycerides
these are produced from triglycerides in adipocytes that break down and release glycerol and non-esterified fatty acids. the fatty acids go to the liver where they contribute to low density lipoprotein triglyceride production
what is a common side effect of diabetes treatment? treatment with what gives the exception?
weight gain
metformin is the only drug associated with weight maintenance/loss
what two things alter and express defects or differences that can result in diabetes?
- maternal microbiota
- adipocytokines
what are the complications of T2DM?
- microvascular: retinopathy, nephropathy, neuropathy
- macrovascular: ischaemic heart disease, stroke, renal artery stenosis
- metabolic: lactic acidosis, hyperosmolar complications
how is T2DM managed?
- education
- diet
- pharmacological treatment
- complication screening
why should T2DM be treated?
- symptoms can be alleviated
- chances of acute metabolic complications can be reduced
- chances of long term complications can be reduced
how should the diet of patients with T2DM change?
- controlled calories
- increased exercise
- reduce refined carbohydrate
- increase complex carbohydrate
- reduce fat
- increase unsaturated fat
- increase soluble fibre
- monitor salt intake
what needs to be treated and monitored in T2DM?
- weight (using an orlistat or surgery)
- glycaemia
- blood pressure
- dyslipidaemia
how is glycaemia treated?
- metformin and insulin
- sulphonylureas and metaglinides
- a-glucosidase inhibitors
- thiazolidinediones (act on central adiposity)
- GLP-1 and DPP4 inhibitors
- SGLT2 inhibitors
what can improve diabetes control?
gastric bypass
why is metformin used to treat T2DM?
- acts as an insulin sensitiser
- reduces insulin resistance
- given when diet alone has not succeeded
- safe (except some GI side effects)
why are sulphonylureas used to treat T2DM?
sulphonylureas block ATP sensitive K+ channels even when there is little glucose, to induce insulin release (normally uptake of glucose leads to channel blockage)
if the patient has functional b-cells this will allow insulin secretion
why is acarbose (alpha glucosidase inhibitor) used to treat T2DM?
- prolongs oligosaccharide absorption in the gut
- allows insulin secretion to cope
why are thiazolidinediones used to treat T2DM?
- act as an insulin sensitiser, mainly peripheral effects
- improves glycaemia and lipids
what are the side effects of sulphonyurea, acarbose and thiazolidinediones?
sulphonyurea - hypoglycaemia, weight gain
acarbose - flatus
thiazolidinediones - peripheral weight gain, hepatitis, heart failure
what is the incretin effect?
food stimulates more insulin secretion if given orally rather than intravenously
what roles does GLP-1 have in the body?
- stimulates insulin and suppresses glucagon
- restores b-cell glucose sensitivity
- increases satiety
how can the effects of GLP-1 be clinically manipulated?
GLP-1 agonists
- injectable
- decrease glucagon concentration and glucose concentration
- result in weight loss
Gliptins (DPPG-4 inhibitors - DPPG-4 degenerates GLP-1)
- increases half life of GLP-1
- increases GLP-1 concentration
- decreases glucagon concentration and glucose concentration
- neutral on weight
why are SGLT-2 inhibitors used to treat T2DM?
- reduce glucose reabsorption
- increase polyuria and polydipsia to control glucose
- inhibits the Na-glucose transporter to increase glycosuria
- causes HBA1C to be lower
what are the other aspects of diabetic control?
- anti-hypertensive treatment to control BP
- increasing HDL and reducing cholesterolaemia to treat diabetic dyslipidaemia
how is diabetes screened?
look at glucose, fasting glucose and stimulated glucose in high risk individuals
