T2DM pathophysiology

Question 1

describe basic pathophysiology of T2DM?

Answer 1

genetic predisposition combined with environmental factors (obesity) leads to insulin resistance

Question 2

how does insulin resistance progress?

Answer 2

compensatory Beta cell hyperplasia - causes normoglycaemia > beta cell failure (early) - causes impaired glucose tolerance > beta cell failure (late) - diabetes

Question 3

what is the ominous octet?

Answer 3

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

Question 4

who does a high BMI cause a higher risk of diabetes in?

Answer 4

women

Asians

Question 5

3 stages in the natural history of t2dm?

Answer 5

susceptibility
adaptation
failure

Question 6

how does C peptide change over time?

Answer 6

is lost over time as beta cell mass is lost

Question 7

what causes micro and macro vascular disease in T2DM?

Answer 7

chronic hyperglycaemia causes microvascular disease

insulin resistance causes macrovascular disease

Question 8

what other non diabetic conditions cause insulin resistance? what does this mean?

Answer 8

polycystic ovary syndrome
indian/Pakistani origin
most overweight people
- means macrovascular disease can occur even without diabetes

Question 9

how is CVD risk from diabetes best managed?

Answer 9

statins

antihypertensives

Question 10

how can diabetes be diagnosed if symptomatic?

Answer 10

single test - random blood glucose (RBG)

more tests needed if asymptomatic

Question 11

can diabetes be prevented?

Answer 11

yes

via lifestyle

Question 12

relationship between insulin sensitivity and insulin secretion?

Answer 12

as sensitivity decreases, secretion increases and vice versa
normal curve as both are balanced
diabetes causes variation from curve

Question 13

first steps in t2dm diagnosis?

Answer 13

lifestyle advice
metformin
blood pressure control if needed

Question 14

how is hypertension controlled in diabetes?

Answer 14

same as normal

important as risk to kidneys

Question 15

metformin mechanism of action?

Answer 15

decreases hepatic gluconeogenesis

increases peripheral glucose uptake

Question 16

how does metformin affect diabetes outcome?

Answer 16

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

Question 17

side effects of metformin?

Answer 17

GI effects - some cant tolerate it

lactic acidosis

Question 18

target for HbA1c?

Answer 18

SIGN = 53
NICE = 48

Question 19

what can affect target?

Answer 19

age

if diagnosed at young age then try and reach lower target as chance of CV event during working life

Question 20

what factors can lead to failure to reach glycaemic targets?

Answer 20

young
female
obese
not at BP or lipid targets
more complex therapies
poor adherence to meds, lifestyle etc

Question 21

SIGN guidelines for T2 diabetes management?

Answer 21

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)

Question 22

what is the mechanism of SURs?

Answer 22

blocks beta cell Katp channels

increases 1st and 2nd phase insulin secretion

Question 23

effects of SURs on diabetes outcome?

Answer 23

decrease HbA1c by 1-2%
cause weight gain
increase hypoglycaemia

Question 24

adverse effects of SURs?

Answer 24

abnormal LFTs

increased CHD

Question 25

how are SURs best used?

Answer 25

more efficient at lower doses (80-120mg)

Question 26

GLP-1 vs DPPIV inhibitors?

Answer 26

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

Question 27

how do SGLT-2 inhibitors work?

Answer 27

inhibit SGLT-2 which therefore reduces free uptake of glucose in the kidneys so you pass it out in urine
- therefore cause weight loss

Question 28

mechanism of action of glitazones?

Answer 28

PPARgamma activator

increases peripheral glucose uptake

Question 29

how do glitazones affect diabetes outcome?

Answer 29

decrease HbA1c by 0.6-1.5%

cause weight gain (larger number of smaller fat cells)

Question 30

adverse effects of glitazones?

Answer 30

higher fracture risk (more fat in bone)
hepatotoxicity
fluid retention

Question 31

HbA1c targets?

Answer 31

if <40 = 48

if >70 = 53-75

Question 32

standard treatment for every diabetic with history of CVD?

Answer 32

metformin + SGLT2

Question 33

good drug for diabetics with non alcoholic fatty liver disease?

Answer 33

pioglitazone

Question 34

what is the most commonly used SUR?

Answer 34

gliclazide