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
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