Diabetes 2/15 Flashcards
impaired fasting glucose
after overnight fast, BG between 100-125
impaired glucose tolerance
after ingestion of 75 g of G and 2 hours later–> BG 140-199
WHO criteria for diegnosis of DM
random BG>200 in 2 settings OR
fasting BG>126 in 2 settings OR
OGTT 2 hours after ingestion of 75g of oral glucose–> BG>200
The primary event in DMII
reduced sensitivity of insulin responsive tissue
diagnostic of DMI
insulitis and near total depletion of beta cells
chronic complicatiosn of DM
generally seen 10-15 years after onset and lack of hyperglycemic control
3 pathways to complications
1) formation of advanced glycation end products (AGE) by nonezymatic glycosylation
2) polyol pathways
3) activation of protein kinase C (PKC)
AGE bind to RAGE receptors on inflammatory cells,endothelium and vascular smooth muscles resultin in:
release of cytokines
generation of ROI in endothelial cells
increased procoagulation
enhanced proliferation of vascular smooth muscles and ECM
AGE cross link ECM proteins–>
collagen1 cross linking–>decrease elasticity of large vessels
collagen4 cross linking in basement membrane–> decrease adhesion and extravasation of fluid
cross-linked proteins are resistant to proteolytic digestion so more get deposited
modified matrix component trap non-glycated materials like LDL and albumen–> thickening of BM
Glucose–>sorbitol (polyhydroxyl alcohol or polyol)
–>fructose
polyols accumulate in tissues that have insulin independent glucose transport like lens, nerve, kidney and blood vessels
this leads to increased intracellular osmolarity–> swelling
damage to schwann cells by:
accumulated sorbitol decrease intracellular myo-inositol level–> decreased phosphoinositide metabolism–> decreased PKC–> decreased ATPase activity–> segmental demyelination and microaneurysms in retinal capillary pericytes
sorbitol pathway
GLU+NADPH+H–>(aldose reductase) sorbitol+NADP
sorbitol+NAD–>(sorbitol dehydrogenase) fructose+ NADH+H
NADPH is depleted–> less glutathione can be reduced to GSH–> increased oxidative stress
aldose reductase inhibitors
can prevent cataracts and neuropathy
intracellular hyperglycemia increase synthesis of DAG which activates PKC–>
increases production of proangiogenic VEGF–> retinopathy
increases vasoconstrictor endothelin-1
decreases vasodilator of endothelial NO synthase
increases fibrogenic TGF-beta–> thickening of BM
increases procoagulant PAI-1
increases proinflammatory molecules by endothelium
pancreas of nondiabetic newborns of diabetic mothers
see increase in numbers of islets due to hyperplasia from exposure to hyperglycemia–> risk of hypoglycemia after birth
most common causes of death in diabetics
MI>ESRF
DM can lead to thicker glomerular BM
although thicker,BM more leaky
decreased negative charge (decreased heparan sulfate)
increased fibronectin and collagen4
clinically see proteinurea sometimes in nephrotic range
capsular drop and fibrin cap
capsular drop= eosinophilic,PAS+, deposits in parietal layer of bowman’s capsule–> charecteristic of DM
fibrin cap=eosinophilic deposits under visceral epithelium of bowman’s capsule–> not specific of DM
efferent arteriolosclerosis
is diagnostic of DM
renal papillary necrosis
more prevalent in diabetic but not limited to them
most common infections in diabetics
candida vulvovaginitis
cellulitis
rhinocerebral mucormycosis= rare, complicates DKA, black nasal turbinates, bloody nasal discharge, periorbital edema, internal jugular and venous sinus thrombosis, death very rapid