Diabetes 2/15

Question 1

impaired fasting glucose

Answer 1

after overnight fast, BG between 100-125

Question 2

impaired glucose tolerance

Answer 2

after ingestion of 75 g of G and 2 hours later–> BG 140-199

Question 3

WHO criteria for diegnosis of DM

Answer 3

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

Question 4

The primary event in DMII

Answer 4

reduced sensitivity of insulin responsive tissue

Question 5

diagnostic of DMI

Answer 5

insulitis and near total depletion of beta cells

Question 6

chronic complicatiosn of DM

Answer 6

generally seen 10-15 years after onset and lack of hyperglycemic control

Question 7

3 pathways to complications

Answer 7

1) formation of advanced glycation end products (AGE) by nonezymatic glycosylation
2) polyol pathways
3) activation of protein kinase C (PKC)

Question 8

AGE bind to RAGE receptors on inflammatory cells,endothelium and vascular smooth muscles resultin in:

Answer 8

release of cytokines

generation of ROI in endothelial cells

increased procoagulation

enhanced proliferation of vascular smooth muscles and ECM

Question 9

AGE cross link ECM proteins–>

Answer 9

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

Question 10

Glucose–>sorbitol (polyhydroxyl alcohol or polyol)

–>fructose

Answer 10

polyols accumulate in tissues that have insulin independent glucose transport like lens, nerve, kidney and blood vessels

this leads to increased intracellular osmolarity–> swelling

Question 11

damage to schwann cells by:

Answer 11

accumulated sorbitol decrease intracellular myo-inositol level–> decreased phosphoinositide metabolism–> decreased PKC–> decreased ATPase activity–> segmental demyelination and microaneurysms in retinal capillary pericytes

Question 12

sorbitol pathway

Answer 12

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

Question 13

aldose reductase inhibitors

Answer 13

can prevent cataracts and neuropathy

Question 14

intracellular hyperglycemia increase synthesis of DAG which activates PKC–>

Answer 14

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

Question 15

pancreas of nondiabetic newborns of diabetic mothers

Answer 15

see increase in numbers of islets due to hyperplasia from exposure to hyperglycemia–> risk of hypoglycemia after birth

Question 16

most common causes of death in diabetics

Answer 16

MI>ESRF

Question 17

DM can lead to thicker glomerular BM

Answer 17

although thicker,BM more leaky

decreased negative charge (decreased heparan sulfate)

increased fibronectin and collagen4

clinically see proteinurea sometimes in nephrotic range

Question 18

capsular drop and fibrin cap

Answer 18

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

Question 19

efferent arteriolosclerosis

Answer 19

is diagnostic of DM

Question 20

renal papillary necrosis

Answer 20

more prevalent in diabetic but not limited to them

Question 21

most common infections in diabetics

Answer 21

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