treatment of type 2 diabetes Flashcards
(47 cards)
aims of management
- treat symptoms
- prevent microvascular complications
- prevent cardiovascular complications
- screen for complications early while treatable
diet changes
- aim is to lose 5-10kg in one year
- reduce refined sugar intake
- reducing fat intake
- increase fruit and veg intake
- reducing salt
- safe and sensible alcohol consumption
how low should glucose aim to be
- low enough to stop symptoms
- prevent complications - HbA1c <7%
aim of HbA1c target for type 2
53mmol/mol (7%)
what are some insulin secretagogues
- sulphonylureas
- DPP4 inhibitors
- GLP-1RA
what are some insulin sensitizers
- metformin
- thiazolidinediones
molecular mechanism of metformin
- inhibition of complex 1 of the mitochondrial respiratory chain
- fall in cellular ATP
- rise in ADP/ATP ratio
- lowers hepatic glucose production
- increases gut glucose utilisation and metabolism
where is metformins site of action
- requires active transport by organic cation transporters
- these are present in the intestines, liver and kidneys
what is the usual dose of metformin
500mg bd
max dose 1g bd
side effects of metformin
- GI intolerance
- diarrhoea
- bloating
- abdo pain
- dyspepsia
- metallic taste in mouth
- metformin associated lactic acidosis
what is done to reduce side effects of metformin
initiate slowly
-500mg od 1 week and increase by 500mg od per week
or use modified release formation
why does metformin associated lactic acidosis happen
metformin increases lactic acid production
- lactate is normally cleared by the liver and kidneys
- in acute kidney injury metformin is associated with greater risk of lactic acidosis
is metformin first line
yes
what are the 2nd generation sulphonylureas
- gliclazide
- glipizide
- glimepiride
- glibenclamide
mechanism of action of sulphonylureas
- SUs bind to SUR1
- closure of ATP sensitive K channels
- rise in membrane potential triggers voltage gated calcium channel
- calcium influx leads to insulin exocytosis
do sulphonylureas increase or decrease weight
increase
risk of sulphonylureas
hypoglycaemia
most common sulphonylurea in UK
gliclazide
who do we need to be cautious with when prescribing sulphonylureas
- elderly
- where hypoglycaemia would be a risk (driving, working up ladders etc)
what type of ligands are thiazolidinediones
PPARgamma
-results in switching on 100s on genes
what does TZDs mainly have an effect on
adipose tissue
what is TZDs effect on adipocytes
- increase differentiation from pre-adipocytes to adipocytes
- increased fat mass
- lipid seal - FFA (free fatty acids) uptake removed fat from liver and muscle, reduces lipotoxicity
- increases adiponectin which acts on liver to increase insulin sensitivity
- net result is increased insulin sensitivity
who are TZDs particularly potent in
obese women
TZDs affect on blood pressure and weight
increase in weight
reduction in blood pressure
