Week 4 Pathogenesis of Glucose Glucose Intolerance and DM Lecture

Question 1

rank these progressions: insulin resistance, diabetes, glucose intolerance

Answer 1

insulin resistance–>impaired glucose tolerance–>diabetes

Question 2

what are the two “forms” that glucose intolerance manifests in when testing?

Answer 2

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?

Question 3

what A1C levels confirms diabetes?

Answer 3

A1C>6.5%

Question 4

why is low blood sugar not as big a problem as high blood sugar?

Answer 4

the only hormone that regulates high blood sugar is insulin whereas low blood sugar is regulated by Glucagon, Epinephrine, Cortisol, Growth Hormone

Question 5

what is the bodies first line of defense against insulin resistance? for how long does this occur

Answer 5

increase insulin secretion (glucose will appear normal), this only occurs until beta cells cant compensate and insulin declines

Question 6

define insulin resistance

Answer 6

decreased ability of the body to use insulin

Question 7

which adipokines are anti-hyperglycemic? 2

Answer 7

leptin, adiponectin

Question 8

which adipokines are pro-hyperglycemic? 2

Answer 8

TNF-alpha, IL-6

Question 9

How are FFAs a big component of hyperglycemia?

Answer 9

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.

Question 10

Insulin resistance is thought to be a result of a combination of…(2)

Answer 10

genetics, obesity (adipokines, increased FFAs)

Question 11

at the cellular level how does insulin resistance manifest (2)

Answer 11

receptor levels (the amount of receptor) and/or RTK activity in skeletal muscle are reduced (poor intracellular signaling)

Question 12

which ethnic groups are more prone to diabetes? (3)

Answer 12

asian, african-americans, hispanic

Question 13

which medications increase insulin resistance? 2

Answer 13

Glucocorticoids (steroids/anti-infalammatory), immunosuppresants, others

Question 14

what is the incretin effect?

Answer 14

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

Question 15

what is acanthosis?

Answer 15

darkening of skin folds seen in individuals with insulin resistance

Question 16

what are four clinical features of insulin resistance? 5

Answer 16

central obesity, acanthosis, hypertension, dyslipidemia (elevated lipids), metabolic syndrome

Question 17

what causes acanthosis?

Answer 17

high levels of insulin bind IGF receptors and stimulate growth of keratinocytes and dermal fibroblasts

Question 18

what is the most effective way to prevent insulin resistance from progressing to diabetes?

Answer 18

Lifestyle change. a loss of weight and subsequent regain will still be more beneficial than medications alone

Question 19

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?

Answer 19

give them sulfonurea to treat their defect in sulfonurea receptor on B cells. this will “repair” their insulin defect

Question 20

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?

Answer 20

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

Question 21

A woman is diagnosed with polycistic ovary syndrome, what do you have to look out for?

Answer 21

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.

Question 22

what causes gestational diabetes?

Answer 22

placental hormones (human placental lactogen) promotes insulin resistance by increasing the amount of glucose in the blood

Question 23

how does elevated glucose lead to insulin resistance??

Answer 23

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)

Question 24

if a woman has gestational diabetes, even if it goes away after the pregnancy what is their chance of acquiring diabetes down the road?

Answer 24

30%

Question 25

what is stress diabetes? what does it cause?

Answer 25

hyperglycemia associated with critical illness (Trauma, burn, ICU). Results in increased inflammatory cytokines, cortisol and catecholamine and subsequent increase in glycogenolysis and gluconeogenesis. this raises blood sugar and may induce insulin resistance

Question 26

what are two endocrine disorders that can lead to diabetes?

Answer 26

cushing’s syndrome (excess cortisol), acromegaly (excess Growth hormone)

Question 27

you are a doctor and a patient presents with pre-diabetes and insulin resistance. You can only prescribe one thing, what do you prescribe?

Answer 27

Lifestyle change. (weight loss)

Question 28

A patient shows up with full blown T2DM, what medication do you prescribe? why?

Answer 28

metformin. helps reduce insulin resistance. (one of the only/best meds to do this). Metformin is used as a monotherapy and in combination with other drugs

Question 29

an elderly patient and a younger patient both have type II diabetes. which one can you more “safely’ shoot for a lower A1C?

Answer 29

the younger patient. they have more of an ability to rebound and the risk/effects of hypoglycemia would not be as severe

Question 30

a person has just been diagnosed with type II diabetes, how do you portray this news?

Answer 30

start with the basics (not too much info at once), give them an initial weight loss goal of 5-10% (reachable short term goals)

Question 31

an extremely obese person has type II diabetes, although you want to reduce their calorie intake significantly, you do not want to go below..

Answer 31

800 cal/day. diet should never drop below this