T2DM pathophysiology Flashcards
describe basic pathophysiology of T2DM?
genetic predisposition combined with environmental factors (obesity) leads to insulin resistance
how does insulin resistance progress?
compensatory Beta cell hyperplasia - causes normoglycaemia > beta cell failure (early) - causes impaired glucose tolerance > beta cell failure (late) - diabetes
what is the ominous octet?
8 defects found in T2DM decreased incretin effect increased glucagon secretion increased hepatic glucose production decreased insulin secretion neurotransmitter dysfunction decreased glucose uptake increased glucose reabsorption increased lipolysis
who does a high BMI cause a higher risk of diabetes in?
women
Asians
3 stages in the natural history of t2dm?
susceptibility
adaptation
failure
how does C peptide change over time?
is lost over time as beta cell mass is lost
what causes micro and macro vascular disease in T2DM?
chronic hyperglycaemia causes microvascular disease
insulin resistance causes macrovascular disease
what other non diabetic conditions cause insulin resistance? what does this mean?
polycystic ovary syndrome
indian/Pakistani origin
most overweight people
- means macrovascular disease can occur even without diabetes
how is CVD risk from diabetes best managed?
statins
antihypertensives
how can diabetes be diagnosed if symptomatic?
single test - random blood glucose (RBG)
more tests needed if asymptomatic
can diabetes be prevented?
yes
via lifestyle
relationship between insulin sensitivity and insulin secretion?
as sensitivity decreases, secretion increases and vice versa
normal curve as both are balanced
diabetes causes variation from curve
first steps in t2dm diagnosis?
lifestyle advice
metformin
blood pressure control if needed
how is hypertension controlled in diabetes?
same as normal
important as risk to kidneys
metformin mechanism of action?
decreases hepatic gluconeogenesis
increases peripheral glucose uptake
how does metformin affect diabetes outcome?
doesn't affect weight makes you more sensitive to insulin reduces HbA1c by 0.8-2% doesn't cause hypoglycaemia when used as monotherapy can reduce CVD risk
side effects of metformin?
GI effects - some cant tolerate it
lactic acidosis
target for HbA1c?
SIGN = 53 NICE = 48
what can affect target?
age
if diagnosed at young age then try and reach lower target as chance of CV event during working life
what factors can lead to failure to reach glycaemic targets?
young female obese not at BP or lipid targets more complex therapies poor adherence to meds, lifestyle etc
SIGN guidelines for T2 diabetes management?
1 = metformin/SURs (if MF intolerant or losing weight) 2 = SURs/TZD (if risk of hypoglycaemia or no CCF) / DPPV (if weight gain a concern) 3 = TZD/DPPIV (if wgt gain a concern)/GLP-1 (if BMI >30)
what is the mechanism of SURs?
blocks beta cell Katp channels
increases 1st and 2nd phase insulin secretion
effects of SURs on diabetes outcome?
decrease HbA1c by 1-2%
cause weight gain
increase hypoglycaemia
adverse effects of SURs?
abnormal LFTs
increased CHD
how are SURs best used?
more efficient at lower doses (80-120mg)
GLP-1 vs DPPIV inhibitors?
GLP causes a slightly larger decrease in GLP-1
GLP-1 cause more of a drop in weight
GLP-1 causes higher rate of hypoglycaemia
same rate of microvascular disease
GLP-1 lowers BP
how do SGLT-2 inhibitors work?
inhibit SGLT-2 which therefore reduces free uptake of glucose in the kidneys so you pass it out in urine
- therefore cause weight loss
mechanism of action of glitazones?
PPARgamma activator
increases peripheral glucose uptake
how do glitazones affect diabetes outcome?
decrease HbA1c by 0.6-1.5%
cause weight gain (larger number of smaller fat cells)
adverse effects of glitazones?
higher fracture risk (more fat in bone)
hepatotoxicity
fluid retention
HbA1c targets?
if <40 = 48
if >70 = 53-75
standard treatment for every diabetic with history of CVD?
metformin + SGLT2
good drug for diabetics with non alcoholic fatty liver disease?
pioglitazone
what is the most commonly used SUR?
gliclazide
