Type 2 Diabetes Flashcards
Which diabetes is more common
T2d - 90% of cases
What parameters looked at for diagnosis
Fasting plasma glucose
And hbac1 (avg bgc over 2-3 months)
Why is it called a complex disease
Many genetic factors and environmental factors
How many validated snp variants which increase risk slightly
3 but around 400 found altogether
Give an example of a validated variant
PPARG / y - allowing insulin sensitivity usually and reg of adipogenesis
Did the study find there were gene x diet interactions in t2d
No they were independent risk factors which had no additive effect together
Which gene pathway polygenic risk score was highest
B cell dysfunction
Which had bigger impact on risk
Genes around 50% vs 38% for diet
Did poor diet increase risk
Yes by 30%
Which twin defect is in t2d pathogenesis
Insulin resistance and b cell dysfunction
What imbalance is there
More resistance than sensitivity. So more insulin can’t compensate for the resistance = BGC high
What does insulin usually do
Glycogenesis in liver and muscle
Decrease gluconeogenesis
Reduce fat breakdown/lipolysis from adipose tissue (which increases fat flow into liver)
What does insulin sensitivity of liver cause it to form
De novo lipogenesis (insulin activates tf - see nafld)
What sort of issues seen in insulin resistance eg in muscle
Glut4 imapired so glucose can’t form glycogen
Also impaired glycogen synthase
What has evidence found about exercise and glut4
It improves translocation of glut4 = less glucose more glycogen
Which 2 toxicities impair b cells
Lip toxicity and Glucotoxicity
What do they both induce when high in blood
Induce b cell apoptosis
As well as decrease insulin expression in response to glucose
How does glucotoxicity affect the tf and repressors for insulin expression
Oxidative stress / ros generation
Why is lipotoxicity dependant on glucose
Because need glucose and insulin both to induce de novo lipogenesis
Why can’t the fa be oxidised after lipogenesis and so what forms instead
Malonyl coa blocks cpt1
More vldl-TG release = issues on pancreas
Explain the twin cycle pathogenesis
Calorie excess and decreased insulin sensitivity eg from genetics
Need more insulin release from pancreas because more glucose
Insulin and the high BGC will cause liver de novo lipogenesis
Lipid fat accumulates
Lipid becomes insulin resistant from the fat
Glucose can’t be controlled = no glycogenesis
Plus more vldl-tg release
Pancreatic fat builds and glucose = gluco and lipotoxicity
Reduced insulin response to glucose
What fa found in vldl which causes pancreatic b dysfunction by de differentiation
Palmitate / palmitic acid
What by products of de novo lipogenesis blocks IRS-1 signalling I.e causing liver insulin resistance
Diacglycerol
What could be some reasons for IR in skeletal muscle which is the smoking gun along with calorie excess
History or t2d, obesity, hypertension and ageing
