Type 2 Diabetes Flashcards
what are the key physiological changes in T2DM?
insulin resistance
beta cell dysfunction
what happens in a normal person when insulin binds to a receptor on a cell?
triggers production of glucose transport proteins to allow glucose to enter the cell
what happens if someone is insulin resistant?
receptor is not as responsive to the insulin molecule & therefore less glucose enters the cell causes a build up of glucose in blood
PCOS
polycystic ovarian syndrome
what is beta cell dysfunction?
major defect in individuals with T2DM, reduced ability of beta-cells to secrete insulin in response to hyperglycaemia
what happens initially for increasing insulin resistance?
initially the beta cells compensate
what does insulin resistance lead to?
glucotoxicity (hyperglycaemia)
lipotoxicity (elevated FFA, TG)
what do glucotoxicity & lipotoxicity lead to?
declining beta cell function
which body shape is most commonly associated with T2DM?
apple body shape
what is the metabolic syndrome?
high blood pressure
high triglycerides
low HDL
insulin resistance
what 4 complications of T2DM can be present at time of diagnosis?
retinopathy
neuropathy
erectile dysfunction
nephropathy
what 4 lifestyle changes can be made to help with T2DM?
weight loss
exercise
smoking cessation
improve diet
which ethnicity have lower BMI targets due to increased risk of diabetes?
SE Asian populations
what can we do to help patients better their self-management?
education
behaviour change
motivational interviewing
personal information sharing
health literacy
the wide range or skills & competencies that people develop to seek out, comprehend, evaluate & use health information & concepts to make informed choices, reduce health risks & increase quality of life
give an example of a biguanide?
metformin
give some examples of sulphonylureas
glicazide
glibenclamide
glimeparide
give an example of thiazolidinediones
pioglitazone
what is metformin derived form
guanidine
what does metformin do
improves sensitivty to insulin
what are the doses of metformin tablets that can be given
500mg
850mg
1000mg
what is the normal starting dose of metformin?
500mg od or bd
what are the effects of metformin
reduces HbA1c by lowering insulin resistance
prevents microvascular & macrovascular complications
when metformin is used as a monotherapy, does it cause hypos?
no
is metformin do in pregnancy?
nothing it’s safe
what does metformin do to BP?
minor reduction
what does metformin to to triglycerides & LDL?
reduces them
what GI side effects does metformin do?
anorexia, nausea, vomiting, diarrhoea, abdo pain, taste disturbance
what substances does metformin interfere with?
Vit. B12 & folic acid absorption
what other adverse affects can metformin do?
rarely lactic acidosis
liver failure
rash
at what eGFR/serum creatinine should metformin be stopped?
eGFR 150
at what level of eGFR should metformin dose be halved?
30-45 ml/min
what is 1st line management of T2DM?
lifestyle changes
what is 1st line therapeutic in T2DM?
metformin
what are the 2 most widely used sulphonylureas (SUs)?
glicazide
glipizide
what effects do SUs have?
reduced HbA1c
more rapid reduction in hyperglycaemia compared to insulin sensitisers
prevents microvascular & macrovascular complications
how do SUs work?
increase insulin secretion
what are the adverse affects of SUs?
hypoglycaemia
weight gain
GI upset
headaches
when would SUs be first line?
in underweight T2DM
what are the rarer adverse effects of SUs?
hypersensitivity
blood dyscrasias
live dysfunction
when should SUs be avoided?
severe renal or hepatic failure
why was rosiglitazone taken off the market?
concerns over increased risk of MI
what are the effects of thiazolidinedones (TZDs)?
reduces HbA1c
prevents macrovascular complications
do TZDs cause hypos?
not if used without an SU
what happens to weight with TZDs?
increase is very common
what is the effect of TZDs on heart conditions?
reduces heart attacks but will make heart failure worse
how do TZDs work?
increase insulin sensitisation
what MSK problem do glitazone drugs increase the risk of?
hip fractures
give an example of an SGLT2 inhibitor?
dapagliflozin
empagliflozin
give an example of a drug based on incretins (GLP-1 receptors agonists)?
exenatide
exendin
liraglutide
lixisenatide
what is the incretin effect?
the amount of glucose given intravenously to bring the glucose blood level to the same as that of oral glucose will stimulate less insulin to be produced
what are incretins?
intestinal secretions of insulin or hormones that help this
what cells secrete GIP?
K cells
what cells secrete GLP-1?
L cells
what is the issue for patients with GLP-1 receptor agonists?
they have to be given by injection
give an example of a glitazone
pioglitazone
what are the benefits of GLP-1 receptor agonists?
promote insulin secretion from pancreas without hypoglycaemia
suppress glucagon
decrease gastric emptying (early satiety)
act on hypothalamus to reduce appetite, results in weight loss
what are the problems with GLP-1 receptor agonists?
nausea
injectable
pancreatitis
give an example of a drug based on incretins (DPP4 inhibitors)?
vildagliptin
sitagliptin
saxagliptin
linagliptin
what are the benefits of DPP4 inhibitors?
promote insulin secretion from pancreas without hypoglycaemia suppress glucagon weight neutral can be taken orally nausea not as bad as other drugs
what are the problems with DPP4 inhibitors?
not that potent
no weight loss
pancreatitis
where in the body do SGLT2 inhibitors act?
in the kidneys to reduce uptake of sugar by about one quarter
what’s the downside of SGLT2 inhibitors?
causes sugar in the urine which increases thrush & UTIs
what insulin regimen is used in T2DM?
basal inulin
