Microvascular Complications

Question 1

Mechanism for hyperglycemia induced tissue damage

Answer 1

hyperglycemia –> repeated acute changes in cellular metabolism + cumulative long-term changes in stable macromolecules –> tissue damage + accelerating factors (e.g. hypertension)

Question 2

Molecular pathways implicated in pathogenesis of diabetic tissue damage (4)

Answer 2

polyol pathway, advanced glycosylation end products (AGE), pKC activation, hexosamine pathway

Question 3

Molecular pathways implicated in pathogenesis of diabetic tissue damage - polyol

Answer 3

decreased NADPH due to altered function of aldose reductase –> decreased glutathione –> oxidative stress

Question 4

Molecular pathways implicated in pathogenesis of diabetic tissue damage - advanced glycosylation end-products (AGE)

Answer 4

modification of intra/extracellular proteins resulting in increased cytokines and growth factors

Question 5

Molecular pathways implicated in pathogenesis of diabetic tissue damage - PKC

Answer 5

decreased endothelial nitric acid synthase, increased endothelin1,tgfbeta,pai1,vegf,nfkb –> vasoconstriction, coagulation, angiogenesis, inflammation

Question 6

Molecular pathways implicated in pathogenesis of diabetic tissue damage - hexosamine pathway

Answer 6

diversion from glycolysis –> increased nacetyl glucosamine –> altered gene expression of cytokines

Question 7

Diabetic retinopathy

Answer 7

most common cause of blindness in US –> most t1d affected at 20 years, 50-80% of t2d at 20 years

Question 8

T/F diabetic retinopathy tends to onset after diagnosis of t2d

Answer 8

F –> before diagnosis of t2d and after diagnosis of t1d

Question 9

Pathophysiology of diabetic retinopathy

Answer 9

dysregulated retinal blood flow, oxidative stress and inflammation, edema, microthrombosis, growth factors leading to proliferation, genetic, hypertension, dyslipidemia, medications

Question 10

Two categories of retinopathy

Answer 10

non proliferative (mild/moderate/severe) + proliferative (early/high-risk/severe)

Question 11

Macular edema

Answer 11

can occur at any stage of retinopathy –> “clinically significant macular edema”

Question 12

Clinical findings of mild retinopathy

Answer 12

microaneurysms, dot hemorrhages, hard exudate (lipid leakage within macrophages)

Question 13

Clinical findings of moderate/severe retinopathy

Answer 13

soft exudate (cotton wool spots - nerve fiber layer infarct), venous beading, intraretinal microvascular abnormalities (tortuous capillaries, occluded vessels)

Question 14

dot hemmorhage

Answer 14

mild retinopathy

Question 15

cotton wool spot

Answer 15

moderate/severe retinopathy

Question 16

Defining feature of proliferative retinopathy vs non-proliferative retinopathy

Answer 16

neovascularization –> new vessels are fragile and can hemorrhage (also has preretinal and vitreous hemorrhage, fibrosis, ischemia)

Question 17

Prevention of retinopathy

Answer 17

glycemic control, antihypertensive therapy (maybe lipid lowering, antiplatelet, and carbonic anhydrase inhibitors)

Question 18

Glycemic control is highly effective in prevention/slowing of retinopathy in t1d

Answer 18

prevention –> less pronounce in slowing

Question 19

Tx of NPDR/CSME

Answer 19

NPDR with CSME (non prolif + clinically sig macular edema) = focal laser photocagulation

Question 20

Tx of high risk/severe PDR

Answer 20

panretinal photocoagulation, intravitreal glucocorticoids, VEGF inhibitor

Question 21

Indications for vitrectomy

Answer 21

non clearing vitreous hemorrhage, traction retinal detachment involving fovea, non responsive pdr

Question 22

Diabetic nephropathy

Answer 22

most common cause of kidney failure in US, independent risk factor for cv and overall mortality

Question 23

Pathologic changes of nephropathy

Answer 23

glomerular disease (mesangial expansion, glomerular basement thickening, glomerular sclerosis) + albuminuria (micro or protein/macro)

Question 24

Prevention of nephropathy

Answer 24

glycemic control, bp control, tx of dyslipidemia, measurement of spot urin microalbum/creatinine ratio

Question 25

Tx of nephropathy

Answer 25

ace inhibitor/angiotensin ii receptor blocker (improves or normalizes), hypertensive agents, dietary restriction, weight loss

Question 26

T/F ace inhibitors and angiotensin ii receptor blockers can prevent onset of microalbuminuria

Answer 26

F

Question 27

Mx of action of ACE inhibitors and ARB

Answer 27

dilation of efferent arteriole --> reduction of glomerular pressure --> decreased urinary protein

Question 28

Diabetic neuropathy

Answer 28

most common microvascular complication --> polyneuropathy is most common

Question 29

Peripheral neuropathy

Answer 29

most common diabetic neuropathy --> distal, symmetric (stocking glove distribution) sensory loss > motor loss, worse at night

Question 30

Clinical findings of polyneuropathy

Answer 30

sensory loss, loss of ankle reflexes/ vibration loss> pain/temp loss

Question 31

diff dx of polyneuropathy

Answer 31

alcohol, b12, uremia, hypothyroidism

Question 32

Tx of painful neuropathy

Answer 32

anticonvulsants, tca's, snris, topical agents, opioids, antioxidants, tens

Question 33

CV autonomic neuropathy

Answer 33

resting tachycardia/loss of ps tone, exercise intolerance, postural hypertension, silent MI

Question 34

GI autonomic neuropathy

Answer 34

esophageal enteropathy (GERD, LES relaxation), gastroparesis, diabetic enteropathy, gallbladder atony and enlargement

Question 35

Gastroparesis

Answer 35

delayed gastric emptying/symptoms = early satiety, vomiting, nausea, worsening of glycemic control, asymptomatic

Question 36

Tx of gastroparesis

Answer 36

glycemic control, eating less fat and non-digestible fiber, prokinetic agents

Question 37

Genitourinary autonomic neuropathy

Answer 37

urinary retension (utis and overflow incontinence), ED, retrograde ejaculation, female sexual dysfunction

Question 38

Peripheral autonomic neuropathy/sudomotor neuropathy

Answer 38

impaired perspiration, peripheral edema, callus formation/ulcers, contributor to neuroarthropathy

Question 39

T/F neuropathy in diabetes can affect single nerves

Answer 39

T --> cranial nerves (e.g. bells palsy), peripheral nerves (e.g. carpal tunnel), or mononeuritis multiplex (multiple nerves)

Question 40

Diabetic amyotrophy

Answer 40

an example of radiculopathy with motor neuropathy of l2-l4- -> acute, asymmetric pain followed by weakness of butt and proximal leg

Question 41

Truncal polyradiculopathy

Answer 41

sever abdominal pain in band like pattern T4-T12

Question 42

Tx of NPDR without CSME

Answer 42

risk factor management