Path 8 Diabetes Flashcards
Type 2 diabetes definition
Progressive insulin secretory defect
Diabetes Dx
Fasting plasma glucose > 126
HbA1C > 6.5%
Random glucose > 200
Prediabetes
Increased risk of CV disease
Proinsulin
Cleaved into insulin and c-peptide
Insulin anabolic functions
- Promote lipogenesis, inhibit lipolysis
- Promote AA uptake and protein synthesis
- Inhibit protein degradation
Glucose receptors
GLUT-2 on B cells for insulin production
GLUT-4 on normal cells stimulated by insulin
DM type I genetics
HLA-DR3 or DR4
-less genetic influence than in Type II
Insulin resistance
- Found 10-20 years before onset of DM
- Universal in obese diabetics
4 ways obesity contributes to Insulin Resistance
- FFA inhibit insulin signaling
- FFA engage inflammation
- Adipocytokinins (resistin)
- PPARy
B-cell dysfunction
Amylin deposition
Islet degeneration
Monogenetic DM
MODY (maturity-onset diabetes of the young) caused by many individual mutations
3 DM complication mechanisms
- Non-enzymatic glycosylation
- Protein Kinase C activation
- Intracellular hyperglycemia & polyol disturbance
AGEs
Advanced Glycosylation End Products
-Damage long lived proteins
PKC mechanism
Neovascularization (retinopathy)
-Intracellular hyperglycemia activates DAG -> PKC -> VEGF
Intracellular hyperglycemia & polyols mechanism
Lens, kidneys, blood vessels, nerves don’t require insulin for glucose transport
-Hyperglycemia -> Sorbitol (polyol via Aldose Reductase) -> Fructose -> Water influx, oxidative stress