Lecture 8: Type II Diabetes

Question 1

Mature Onset Diabetes of the Young

Answer 1

Heterogenous disorder
Due to heterozygous monogenic mutations of one out of 10 genes
Onset early in life
Autosomal dominant inheritance
Defect in insulin secretion

Question 2

Genetic Component of MODY

Answer 2

6 Genes found

Mutations found in HNF-4alpha, glucokinase, insulin promoter factor

Question 3

Treatment of MODY

Answer 3

Not progressive or slowly progressive
- Responsive to diet, and/or anti-hyperglycemic agents for years to decades
May eventually develop insulin dependence

Question 4

T2D

Answer 4

• Incidence varies widely
• Prevalence of diabetes correlates with standard weight, but not all T2D patients are obese
• Insulin resistance and beta cell dysfunction are core defects
• Progressive disease

Question 5

Insulin Resistance

Answer 5

Inability of insulin to produce usual effects at circulating concentrations
Surpress hepatic glucose production by inhibiting gluconeogenesis or glycogenolysis and promote glucose uptake, especially in muscle
- Relationship between insulin sensitivity and beta cell insulin response is not linear
- Progression from normal glucose tolerance to T2D transitions through impaired glucose tolerance in red region

Question 6

Fatty Acid Role

Answer 6

Increase levels in intracellular DAG due to lipogenesis/decreased fatty acid oxidation
Causes inactivation of insulin receptor to cause insulin resistance
Mouse models suggest that liver and beta cells are key to glucose tolerance

Question 7

Beta Cell Failure

Answer 7

Hyperglycemia
Oversecretion of insulin to compensate for insulin resistance
Lipotoxicity, glucotoxicity

Question 8

Genetics

Answer 8

GWAS reveals many linkages, but only explains a minority with the disease
- Some genes include FTO, IRS1, PPARG

Question 9

Surgeries Reversing Diabetes

Answer 9

Surgeries done for people with BMI>40, poor dietary and lifestyle management, and acceptable surgical risk
Remission as high as 70%
Restrictive procedures include- Lapriscopic adjustable band, Vertical banded gastroplasty, Roux en Y gastric Bypass (can be done lapriscopically, more complications, more weight loss)

Question 10

Theory on Cause of Diabetes

Answer 10

Genes responsible for obesity and insulin resistance interact with environmental factors, resulting in the development of obesity and insulin resistance
- Beta cells with genetic defect may not be able to hand the increased hyperglycemia associated with insulin resistance