Type 2 Diabeetus Flashcards
What % of the population has pre-diabeetus?
At least 50%
Note: Hyperglycemia is characteristic, and independent of which Type of diabetes that you have
Which is the best way to screen for DM? Why? What issue does it have?
Best/easiest way is to check the HgbA1c because you don’t need to fast and it is a 3 mo average, so it is not dependent upon time of day.
It is not as sensitive.
Fast Facts on Diabetes
- 29.1 million have diabetes, and 21 million know that they have it (but about 30% don’t know)
- 86 million have pre-diabetes….
Role of obesity
- Reflects sedentary lifestyle and poor food choices
- Makes you more likely to be insulin resistant
- It has steadily increased across the US, so has incidence of diabetes
Role of color
Anybody that isn’t white has a higher chance of diabetes
Some things about the body being a fine-tune regulator
- Go from 5 grams of glucose to 7 grams of glucose
- Hormones go awry but we can clinically manipulate these
- Every tissue can store or use carbohydrate to let you take in 20 g/day but still maintain 5 g/day
Best criteria for having T1D vs T2D?
Usually:
- young
- thin
- normal lipid panel (this is probably the most useful)
- will require insulin for treatment
Gestational diabetes
- 2nd and 3rd trimester makes you insulin resistant
- Fasting >95 mg/dL
- 1 hr > 180 mg/dL
- 2 hr > 155 mg/dL
- 3 hr > 140 mg/dL
Consequences both for mother and baby. Try to be aggressive but conservative
If you have this, will go back to normal glucose tolerance, but then you have increased risk over the next 5-10 years for developing T2D
Pathogenesis of T2D
Genes + Environment
Normal –> insulin resistance (sedentary lifestyle and eat too much = increased demand on beta cells and exacerbate the resistance) –> decreased insulin secretion –> T2D
Metabolic defects in T2D
- Eat glucose, liver makes glucose –> Hyperglycemia
- Muscle has inability to use glucose up
- Insulin secretion cannot keep up
Schema of insulin action
- IR = Heterotetramer that insulin binds to
- Insulin receptor becomes a tyrosine kinase - phosphorylates itself first
- Attracts IRS to the cell membrane and secondarily phosphorylates them
- Signal through PI3K and Akt for: glycogen synthesis, glucose uptake
Risk factors for T2DM
- FHx of DM
- HTN or dyslipidemia
- Central obesity (if 30 y/o screen annually)
- Gestational diabetes
- Birthweight more than 9 lbs. or SGA*
- Ethnicity (AA, Hispanic, NA, Pacific Islander)
Difference in pre or post-prandial testing
- post-prandial more common than fasting being elevated
2. as progresses, then can’t keep up and fasting is also elevated
How much B-cell function lost at diagnosis?
Usually about 50%
If treated with metformin and/or sulfonylureas then you can go to 5 years with 75% of B-cell function loss. 10-20 years out, they need to take insulin.
What happens in the liver?
- Insulin controls hepatic gluconeogenesis
- Hepatic glucose output goes up or down based upon fed status. If have T2DM then insulin is not suppressing hepatic glucose output, then fat cells break down and feed FFA, and muscles send AA to liver to make into glucose/accelerate glucose production
How to measure peripheral glucose uptake
- insulin into 1 arm - should lead to store glucose in arm
- measure in the other arm to figure out how much to infuse to keep sugar stable
T2D - need lots of insulin to get any glucose stored
Hormonal control in T2D
- CHO meal eaten
- Glucose goes up
- Insulin barely rises
- Glucagon actually goes up (stimulates HGO)
Incretin effect
GLP-1 and GIP made in the gut and affects the C-peptide level/augments post-meal insulin secretion.
MODY
Maturity Onset Diabetes of Young
- Beta cell disorder
Normal:
- GLUT2 transporter
- Glucose goes down gradient, makes ATP, blocks K+/ATP channel, allows Ca++ to enter. Get 1st phase insulin secretion –> signals insulin containing granules and leads to 2nd phase.
MODY:
- Beta cell never knows it is in a high glucose state
- Another defect is insulin transcription
- Can treat with an agent that blocks K+/ATP channel
Diabetic emergencies
- DKA
- Hypoglycemia Unawareness
Hypoglycemia is still a major cause of death… more risky than hyperglycemia
Insulin is the only hormone that decreases glucose
Brain’s role in judging what’s going on..
- Can only metabolize either insulin or ketone bodies
2. Has 4 hormones (counter-regulatory proteins to increase glucose)
DKA
- Pathogenesis: absolute or relative lack of insulin, increased counter-regulatory hormones
- Ketone body production: increased FFA flux from adipocytes, intrahepatic glucagon/epi induced increased carnitine acyltransferase and decreased malonyl CoA activity permitting mitochondrial ketone body production (MUST reverse this to clear DKA)
- Hyperosmolar Hyperglycemia Syndrome: Osmotic diuresis, decreased free water
Combo of insulin deficiency and increased FFA; and glucagon excess –> accelerated ketogenesis
Hypoglycemia
- Sx begin when plasma blood glucose falls to 50-60 mg/dL
- When do you feel hypoglycemic? Test then and see whether or not they are. If they aren’t they may not be sensing sugars at that level.
- Will be blunted with frequent hypoglycemia (brain compensates and makes you feel fine because you don’t want to die)
- Easy to get insulin dose wrong and cause hypoglycemia
Hypoglycemic Unawareness:
…. fill this in from lecture
Hypoglycemia not caused by DM
- Ethanol
- Insulinoma
- Poor nutrition
Morbidity from DM
- Cardio disease
- # 1 cause of blindness
- # 1 cause of ESRD
- # 1 cause of non-traumatic amputations
Macrovascular disease
More common, more severe, more deadly
(most common cause of hospitalization, inc risk of CVD disease)
Fewer heart attacks overall, but still 2-6% increase
Who lives longer after a heart attack with diabetes? M or F?
Men
Metabolic syndrome
Factors accelerating atherosclerosis in diabetes
- glucose intolerance
- small, dense LDL
- increased TG
- decreased HDL (unfavorable lipid profile)
- increased prothrombotic agent (PAI-1)
- increased blood pressure
