What regulates glucose homeostasis?
- hepatic release of glucose
- tissue utilization of glucose
- hm control of glu by insulin and glucagon
What is a marker of endogenous insulin? what is the significance of this?
C peptide, it allows you to tell the difference between insulin administered vs made by self
What is type 1 diabetes? When do symptoms occur?
- Autoimmune disease due to failure of T cell self tolerance
- Immune mediated destruction of islet cells → once 90% of islet cells are destroyed you begin to get sx
What causes type 2 DM?
Insulin resistance + Beta cell dysfunction
Why is obesity a risk for T2DM?
- excess adipose results in free fatty acids, inflammation, and adipokines accumulating
- adipokines and ffa disrupt paths that enable insulin uptake
- inflammation causes direct damage to beta cells and can also disrupt cell uptake of insulin
What is MODY? Cause?
- maturity onset diabetes of the young
- Resembles T2DM clincally but happens in the young, blood insulin may be high normal or low
- NO autoantibodies
- nonketotic
- Most often caused by mutations resulting in los of function of glucokinase
Risks to the fetus if mom has gestational diabetes?
- neonatal hypoglycemia → seizure → brain damage
- macrosomia
- congenital malformation
- still birth
Classic triad of T1DM?
- polyphagia
- polyuria
- polydipsia
- severe → DKA
How do you differentiate T1DM and T2DM?
- autoantibodies
- 90% white kids have
- <50% west african descent and Latinx populations have, so it is difficult to tell 1 from 2
- HLA typing
- HLA DR/DQ on chr 6
DKA triad?
- hyperglycemia
- ketonemia
- metabolic acidosis
How does epinephrine impact glucose?
Body can’t use glucose so it accumulates in the blood
How does a stressful situation (infections) induce DKA in a diabetic patient?
- With high epinephrine the body isn’t able to utilize glucose
- Glucagon gets released promoting gluconeogenesis
- Insulin deficiency promotes FFA generating ketones
- as glucose and ketones accumulate in blood kidneys begin to dump that → osmotic diuresis
- leading to shock and dehydration which causes more epinephrine to be released repeating the cycle
How do you test for DKA?
Accumulation of ketones in the urine
What is Hyperglycemic Hyperosmotic syndrome? What are the symptoms?
- acute hyperglycemic crisis in T2DM resulting from a prolonged insulin deficiency
- increased gluconeogenesis
- decreased glucose uptake in peripheral tissue
- Glucose >600
- severe dehydration
- Hyperosmolality → coma
- Impaired renal fxn
- NO ketones
Compare DKA and HHS.
- anion gap acidosis
- osmolality
- hyperglycemia
- ketonemia
what is Hemoglobin A1C, what is the use, and target?
- glycosylated form of hemoglobin that takes a month to form
- it measures long term diabetic control
- target is <6.5-7.0
What are the risks assoc. with chronic hyperglycemia?
- stroke
- MI (most common COD)
- lower extremity gangrene (100x higher risk)
Advanced glycatedd end products?
- breakdown product of glucose
- modify and crosslink proteins (makes it abnormal) as they accumulate and they can act on receptors in endothelial cells to create cellular dysfunction and damage
What is the leading cause of ESRD in the US?
Diabetic nephropathy
What are the three primary pathologic conditions seen in diabetic nephropathy?
- Glomerular sclerosis:
- thickening of basement membrane
- disruption of protein cross links that make membrane effective filter → leak large molecules into urine
- Renal vascular lesions:
- arteriolosclerosis
- Pyleonephritis
What are the pathologic changes seen in diabetic nephropathy?
- Nodular mesangial matrix accumulation in glomeruli called Kimmelstiel Wilson disease
- Also grossly see diffuse nephrosclerisis due to the underlying microscopic changes
How do you test for diabetic nephropathy
Urine albumin Creatinine ratio testing is the gold standard (UACR)
Describe neovasculariztion seen with diabetic retinopathy?
- Hypoxia leads to VEGF overexpression →
- Hemorrhage →
- Blindness
Besides diabetic retinopathy what are other occular complications of diabetes?
Cataracts and glacuoma
