Thursday, July 5, 2007

Diabetes

Primary

- Type I (insulin dependent, IDDM)

- Type II (non-insulin dependent, NIDDM)

non-obese NIDDM

obese NIDDM

- Maturity-onset diabetes of the young (MODY) - genetic defect of Beta cells



Secondary

- chronic pancreatitis

- post pancreatectomy

- hormonal tumors (pheochromocytoma, pituitary tumor)

- drugs (corticosteroids)

- hemochromatosis

- genetic disorder



Glucose + GLUT-2 signals Beta cells to produce insulin


Insulin signals target cells to produce GLUT-4 for glucose transport


Type I IDDM

- HLA-D gene (DP, DQ, DR) - class II MHC renders Beta cells immunogenic


Type II NIDDM

- derangement in Beta cell secretion of insulins

- decreased response of peripheral tissues to respond to insulin

- also leads to irreversible Beta cell injury

- obesity, insulin insensitivity

- gestational diabetes (obesity, pregnancy)

- amylin - normally produced with Beta cells copackaged with insulin

- in NIDDM, accumulate in sinusoidal space outside the Beta cell

=> eventually become like amyloid


amyloid - insoluble fibrous protein aggregation

- physically disrupt tissue architecture



Complications of diabetes (seen in both type I and II)

- microangiopathy, retinopathy

- nephropathy, etc.


Nonenzymatic glycosylation

- degree of enzymatic glycolytation at blood glucose

Reversible vs. Irreversible glycolylation

irreversible advanced glycosylation end products (AGE)

early glycosylation products rearrange intead of dissociating

AGE crosslinking with LDL in blood vessel or albumin in renal glomeruli

-> decrease protein removal, increase protein deposit

AGE binding to receptors of blood cells

-> procoagulation