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
Diabetes islet infiltration
Type I - T lymphocytes (insulitis)
Type II - Amyloid
Alpha cells
Glucagon
Beta cells
Insulin
Delta cells
Somatostatin
Type I island histo
T lymphocytes
- No beta cells
- Normal alpha and delta
Diabetic atherosclerosis
Same as regular atherosclerosis
-MI is most common cause of death
Diabetic microangiopathy
Diffuse thickening of basement membranes
Diabetic glomeruli (3)
-Capsular drops, fibrin caps, K-W lesions (mesangial matrix)
Diabetic renal damage (3)
- Hyalinization (mucopolysaccharides), thickening of aff/eff arterioles
- Renal papillary necrosis
- Recurrent pyelonephritis
Diabetic nephrotic syndrome cause
Diffuse glomerulosclerosis (diffuse mesangial sclerosis) -DIffuse BM thickening and mesangial matrix deposition
Chronic pyelonephritis histo
Thyroidization of the kidney tubules
Diabetic comas
Type I - ketoacidosis
Type II - hyperosmolar nonketotic coma (dehydration from sustained osmotic diuresis)