Week 4 Pathogenesis of Glucose Glucose Intolerance and DM Lecture Flashcards
rank these progressions: insulin resistance, diabetes, glucose intolerance
insulin resistance–>impaired glucose tolerance–>diabetes
what are the two “forms” that glucose intolerance manifests in when testing?
IFG: impaired fasting glucose, measures glucose levels after fasting (if they are abnormally high, Diabetes)
IGT: Impaired glucose tolerance, does blood sugar get abnormally high after the glucose tolerance test?
what A1C levels confirms diabetes?
A1C>6.5%
why is low blood sugar not as big a problem as high blood sugar?
the only hormone that regulates high blood sugar is insulin whereas low blood sugar is regulated by Glucagon, Epinephrine, Cortisol, Growth Hormone
what is the bodies first line of defense against insulin resistance? for how long does this occur
increase insulin secretion (glucose will appear normal), this only occurs until beta cells cant compensate and insulin declines
define insulin resistance
decreased ability of the body to use insulin
which adipokines are anti-hyperglycemic? 2
leptin, adiponectin
which adipokines are pro-hyperglycemic? 2
TNF-alpha, IL-6
How are FFAs a big component of hyperglycemia?
Large adipocytes (large visceral/android adipocity)=more FFAs are released. The more FFAs in circulation the more FA oxidation occurs. In the skeletal muscle, the increased FA oxidaiton decreases glucose utilization (no need for glucose derivived ATP). In the Liver, the increased FA oxidation favors gluconeogenesis.
Insulin resistance is thought to be a result of a combination of…(2)
genetics, obesity (adipokines, increased FFAs)
at the cellular level how does insulin resistance manifest (2)
receptor levels (the amount of receptor) and/or RTK activity in skeletal muscle are reduced (poor intracellular signaling)
which ethnic groups are more prone to diabetes? (3)
asian, african-americans, hispanic
which medications increase insulin resistance? 2
Glucocorticoids (steroids/anti-infalammatory), immunosuppresants, others
what is the incretin effect?
effect seen when glucose is administered orally vs IV. when given orally incretins are activated and insulin spikes. This is not seen when given IV
what is acanthosis?
darkening of skin folds seen in individuals with insulin resistance
what are four clinical features of insulin resistance? 5
central obesity, acanthosis, hypertension, dyslipidemia (elevated lipids), metabolic syndrome
what causes acanthosis?
high levels of insulin bind IGF receptors and stimulate growth of keratinocytes and dermal fibroblasts
what is the most effective way to prevent insulin resistance from progressing to diabetes?
Lifestyle change. a loss of weight and subsequent regain will still be more beneficial than medications alone
A patient comes in with symptoms of type I diabetes (low insulin, hyperglycemic), upon genetic screening you determine they have MODY, what is the best course of action? why?
give them sulfonurea to treat their defect in sulfonurea receptor on B cells. this will “repair” their insulin defect
a person has a neoplasm on his pancreas that is removed with surgery, a small portion of healthy pancreas was also removed. should the doctor advise the patient to watch his glucose levels? what type of diabetes should be watched our for?
yes, only a small amount of the pancreas is made up B cells (~2-5%). any loss of pancreas puts a person at risk for developing diabetes. Type I diabetes
A woman is diagnosed with polycistic ovary syndrome, what do you have to look out for?
along with its association with obesity, irregular menses, and reduced fertility these individuals are at a greater risk for insulin resistance. regular glucuose tolerance/A1C tests.
what causes gestational diabetes?
placental hormones (human placental lactogen) promotes insulin resistance by increasing the amount of glucose in the blood
how does elevated glucose lead to insulin resistance??
increased glucose increases the amount of insulin that needs to be produced. constituitevly high levels of insulin/glucose eventually decreases the amount of insulin that is produced (pre-diabetes–>T2DM)
if a woman has gestational diabetes, even if it goes away after the pregnancy what is their chance of acquiring diabetes down the road?
30%
