01-07 DM Type 2 Flashcards
1) To learn the epidemiology of Type 2 diabetes: prevalence, ethnicity, age and the risk factors 2) To learn the natural history of the pathophysiology of Type 2 diabetes 3) To learn the concept of insulin resistance and how it can be measured 4) To learn the roles of the hormones insulin, glp1 and adiponectin in Type 2 diabetes 5) To learn the roles of the liver, fat cells, GI tract and islet cells in the pathophysiology of Type 2 diabetes 6) To illustrate the interplay of genetics and env
definition of DM2
Type 2 diabetes is a metabolic disorder characterized by blood glucose concentrations that are high enough to lead to diabetes microvascular complications despite continued pancreatic secretion of insulin.
Prevalence of diabetes in those
—20-39
—40-59
—>60
20-39: 3%
40-59: 11%
>60: 23%
Describe the natural hx of DM2 (think back to graph w/ father and daughter)
birth-puberty: nl insulin & glucose levels
puberty: sex steroids cause ~insulin resistance
—insulin levels rise to maintain euglycemia
40s+: pancreas cannot keep up with insulin demand
—hyperglycemia sets in —> DM2
—late stage: pancreas actually harmed, insulin levels begin to fall
Heritability to DM2?
Highly heritable
—most pts will have a + FMHx
—In identical twins, there is essentially 100 % concordance for DM2, but inheritance seems to require many genes
MODY
"Maturity onset diabetes of the young" —Autosomal dominant inheritance —Dx before age 25 —Degree of hyperglycemia varies —Highly responsive to sulfonureas —MODY-2 is a A.D. mutation in glucokinase, discovery of which taught us that the pancreatic beta cells sense insulin
Sex differences?
M : F ratio = 1:1
IV Glucose tolerance test (IVGTT)
tells you how well body disposes of excess glucose
—not specific re: whether that’s due to insulin resistance or ↓ insulin production
—glucose bolus given
—IV insulin given ~1hr later
—frequent monitoring of both levels
—expect pts to show an initial burst of endogenous glucose and then to also show a response to the exogenous insulin
Glucose Clamp technique
Give continuous insulin infusion
—then start infusing glucose at a level high enough to maintain euglycemia
—Should take a lot of sugar to maintain normal level
—In DM2 pts, it will only take a little bit of sugar b/c that huge bolus of insulin is so ineffective due to RESISTANCE
—i.e. this doesn’t tell us anything about beta cells’ ability to secrete insulin or monitor [insulin]
[IMAGE q8]
Muscle glucose uptake in exercise
is insulin independent!
—walk after dinner = ~4units!
effect of insulin on the liver
Insulin does NOT regulate the uptake of glucose by the liver
—It regulates the OUTPUT of glucose from the liver by inhibiting glycogenolysis
—Fasting glucose is a good measure of liver glucose output
—In a normal pt: pre-prandial output is normal and post-prandial is low
—in a DM2 pt: liver glucose output is elevated all the time!
effect of insulin on fat tissue
—Insulin regulates glucose uptake by fat tissue, but fat tissue takes up only a small amount of the glucose taken up after a meal
—Insulin regulates the OUTPUT of FFAs from fat cells
—High levels of FFAs enhance or may even cause insulin resistance
adiponectin
—fat is endocrine tissue!
—release by fat cells and directly increases insulin sensitivity
—DM2 pts have low levels of adiponectin
—thought of as DM Rx, but hepatotox probs
leptin
—another fat cell-released hormone
—satiety signal that increases as amt of fat increase
—Obese and DM patients have ↑ [leptin] but must have some resistance
GLP1
glucagon-like peptide 1 —released post-prandially from jejunum —↑ insulin release —↑ insulin responsiveness —↓ glucagon release —↓ rate of stomach emptying —↓ appetite
insulin release with same amt of glucose give p.o. vs. i.v.
much more release when given p.o.
—likely due to incretins like GLP1
