Diabetes II Flashcards
(59 cards)
3 main effects of chronic hyperglycemia
- Glycation of proteins
- Accumulation of sorbital inc ells
- Increased/inappropriate activation of protein kinase C
Glycation of proteins due to hyperglycemia results in
Glucose binds to protein chain and can cause slow, permanent cross linking that leads to pathology.
Abnormal cross linking.
It affects hemoglobin and collagen in vessel walls.
Causes microvascular dysfunction.
Accumulation of sorbital in cells causes
Cellular edema. May cause cataracts and nerve dysfunction due to swelling.
Increased/inappropriate activation of protein kinase C causes
Vasoconstriction of smooth muscle
Vascular permeability–> leaky vessels
Basement membrane thickening
Abnormal angiogenesis
how can glycation of proteins lead to AGEs (advanced glycation end products)
If glucose binds to protein, it can cause an enzyme activity change and increase oxidative stress/inflammatory reactions in days- weeks. (early glycation products)
In months- years, they can transition to advances glycation end products that are permanent. The proteins cross link and lead to pathology.
Another name for glycation process
Maillard reaction
What occurs during early glycation products
Occurs in days-weeks from glucose binding to protein in days to weeks. Causes oxidative and inflammatory reactions.
How does sorbitol cause edema
Once sorbitol is produced inside a cell, it cannot get out. It attracts water that remains in the cell. This causes edema and injury.
What increases sorbitol levels in cells?
If glucose levels are elevated, they will diffuse more readily into cells. Cells only use 3% for energy. The remaining extra glucose is converted to sorbitol. Sorbitol cannot travel outside the cell- trapped. Water loves sorbital, so water enters the cell and causes edema.
Hyperglycemia causes an increase in ___, which causes an increase in PKC
DAG diacylglycerol
Increase in PKC results in what?
Blood flow abnormailities Angiogenesis Capillary occlusion Vascular occlusion ^^ all affect eyes
Also:
pro-inflam gene expression
Oxidative stress
How does diabetes mellitus affect macrovascular
Coronary artery disease- CAD, MI, CHF
Peripheral artery disease- amputations
Cerebrovascular disease- Transient ischemic attacks, stroke
Other- Immunosuppression and hearing loss due to neuropathy
2 most common causes of death in people with Type II DM
Coronary artery disease, cerebrovascular disease (stroke)
Peripheral artery disease (ex of macrovascular complication)
Atherosclerosis in major arteries of legs– causes downstream problems in lower legs/feet. May cause ulcerations and gangrene infections. Need amputations.
Prevalence of cerebrovascular disease with DM increases with
Duration of disease
Insulin resistance –> hyperglycemia –> ____ –> Accelerated atherosclerosis –> Vascular damage
Endothelial dysfunction due to blood vessel problem
Microvascular chronic complications of DM
Retinopathy
Neuropathy
Nephropathy
Root cause of microvascular complications
Endothelial glycation damages endothelium. Results in a thickening of the basement membrane, which decreases oxygen transmission.
Loss of pericytes causes a small out pouching of blood vessel- micro aneurysm that will leak blood.
Glycated platelets and RBC will stick to damage endothelium and can form thrombosis that may obstruct blood vessels and cause ischemia or rupture and cause exudate/blood leakage.
Prevalence of diabetic retinopathy
28-33%
Diabetic Nephropathy
Leading cause of renal failure due to glomerulosclerosis (scarring of glomerulus)
Most common cause of death in type 1 diabetics
Increases albumin in urine
Sclerosis vs stenosis
Sclerosis= scarring Stenosis= narrowing
Diabetes is the number 1 cause of
End stage renal disease- will qualify pt for medicare
Most common cause of death in type 1 diabetic
Diabetic nephropathy
Leading cause of renal failure
Diabetic nephropathy by gomerulosclerosis- scarring.
