Type II diabetes Flashcards
type II diabetes
a complex metabolic disease characterized by high blood glucose resulting from insulin resistance combined with increasing insulin deficiency.
what form of diabetes is the most common?
type II
symptoms of type II diabetes
increased thirst, hunger, urination fatigue infections weight loss blurred vision
greatest risk factor for type II diabetes
obesity
type 2 diabetes is caused by a combination of
genetic factors
environmental factors
evidence for genetic basis of T2D
concordance in monozygotic twins: 70%
concordance in dizygotic twins: 30%
insulin resistance
the body’s cells (liver and muscle) have a diminished ability to respond to the action of insulin.
characteristic features of type two
insulin resistance
decreased insulin secretion
first stage of T2
insulin resistance
how the pancreas compensates insulin resistance
the pancreas secretes increasing amounts of insulin to maintain adequate sugar movement into cells.
what occurs first: insulin resistance or decreased insulin synthesis/secretion?
insulin resistance
the best predictor for T2
insulin resistance
metabolic syndrome causes the development of
metabolic syndrome
metabolic syndrome symptoms
hyperinsulinemia T2D obesity hypertension LDL
prediabetes
when insulin resistance leads to increased blood glucose levels.
It leads to T2D
elevated glucose impairs and destroys
beta cells
causes of decreased insulin secretion
a decline in the cellular secretory rate (in beta cell function)
a decrease in beta cell mass (the product of beta cell size and number)
Is more known about the genetics of T1 or T2?
T1
Pathogenesis of T2D is more complicated than T1D since more metabolic pathways are involved.
two gene candidates
hepatocyte nuclear transcription factor
peroxisome proliferator activated receptor gamma.
First important diabetes gene to be identified
TCFF7L2
an allele of an intronic SNP
What TCF7L2 is associated with
impaired beta cell function (and insulin secretion), but not insulin resistance.
How TCF7L2 increases risk of T2D
SNP T allele exhibits stronger enhancer activity compared to non-risk G allele.
Nuclear DNA binding protein HMGB1 interacts with TCF7L2 in human islets (bound more SNP T allele than to G allele).
Exapmple of a loci containing variants that confer T2D risk in addition to the TCF7L2 gene
a non synonymous polymorphism in the zinc transporter SLC30A8, which is expressed exclusively in insulin producing beta cells.
what do most of the genes identified by GWAs involve in?
beta cell dysfunction than insulin resistance.
percentage of T2 SNPs that are intergenic or intergenic or intronic
80 - 90%
