Diabetic complications n shizz Flashcards
Legacy effect
tight blood glucose control for 4-5 yrs early in the disease process leads to decreased CVevents 10-20 yrs later
What contributes to all microvascular and macrovascular complications of diabetes?
Hypertension!!
- can dramatically decrease complications with BP control
Metabolic syndrome is a constellation of:
- insulin resistance
- visceral adiposity
- HTN
- dyslipidemia
- T2D glucose intolerance
-Hyperinsulinemia is associated with metabolic syndrome
Ways that high insulin can have an effect on vessel walls
dyslipidemia
Insulin is a GF that has direct effect on vessel wall
Vascular wall response to diabetes
- abnormal endothelial cell fxn
- abnormal vascular sm cell fxn
- inflammation and decreased fibrinolysis
Abnormal endothelial cell fxn associated with diabetes
- abnl clotting factor prod: DECREASED tPA and INCREASED PAI-I
- adhesion molecules present (platelets/leukocytes)
- decreased endo dep. vasomotion
- increased cytokine and chemokind prod
Abnl vascular SM cell fxn associated with diabetes
- enhanced vascular SM prolif + migration
- Increased production of matrix proteins, cytokines, GFs
- Altered contractile fxn
(very similar to endo cell fxn that is altered in diabetes)
Inflammation and decreased fibrinolysis associated with diabetes
- platelet adhesion and activation
- monocyte adhesion and macrophage activation and invasion into subintimal space
- expression of cytokines and chemokines
- foam cell formation and activation of MMPs
AGEs effects due to hyperglycemia
Advanced glycosylation end products
well est. role in diabetic complications in: nephropathy, vasculopathy, and retinopathy
Hyperglycemia can result in elevation in PKC, what are some complications?
PKC –> production of ECM proteins collagen and fibronectin by renal and vascular cells –> BM thickening
Increased expression of ICAMs
Increased PAI-I
Inreased VEGF
Defective production of NO
Leading cause of blindness in US
diabetes –> retinopathy (microvascular complication)
Retinopathy progression:
most 1. retinopathy begins with pericyte dropout
- loss of autoregulation of bf to retinal capillary bed
- capillary dropout, BM thickening, leakage of intravascular fluids –> exudates
- abnormal BF create hypoxic stress + stimulate cytokines + GFs –> stim neovascularization and proliferative retinopathy
What stage of diabetic retinopathy should intervention be taken?
Severe pre-proliferation
- panretinal photocoagulation is tx to prevent/decreased visual loss.
first line therapy for retinopathy, for recurrent, and refractory retinopathy
first line:
- focal/modified photocoagulation
- intravitreal pharmacotherapies added if more advanced
persistent/recurrent
- repeat photocoagulation
- Intravitreal triamcinolone acetonide or antivascular VEGF agent
refractory
- pars plana vitrectomy (PPV)
Nephropathy assoc with diabetes
BM thickening,
mesangial proliferation,
glomerular destruction
but most diabetes does not lead to CKD/kidney failure, but it is the leading cause of it.
