Complications of diabetes Flashcards
What are the 6 general complications of diabetes?
microvascular: diabetic retinopathy, diabetic nephropathy, diabetic neuropathy
macrovascular: stroke, heart disease, peripheral vascular disease
How does hyperglycemia lead to complications of diabetes?
multiple pathways, mostly related to increased ROSs
- incr. aldose reductase causes sorbitol accumulation. sorbital can cause neural problems and changes Na-K-ATPase activity
- incr. DAG and Protein kinase C activity: alters the contractility and responsiveness of smooth muscle. changes endothelial cell permeability.
- altered non-enzymatic glycosylation: activates endothelial and macrophage AGE (advanced glycosylation end products) receptors. changes lipid, basement membrane, and matrix proteins
- glucose-dependent epigenetic changes
How can DM cause blindness?
proliferative retinopathy causing hemorrhage and retinal detachment
macular edema- retinal thickening dt accumulation of fluid
cataracts
glaucoma
What is the pathogenesis of diabetic retinopathy?
- microthrombi causing capillary nonperfusion and reduced retinal blood flow. this leads to hyposia and VEGF production. may increase permeability or hemorrhage
- pericyte death and microaneurysms: can cause tight junction loosening, leakage, hemorrhage, and exudates
How does VEGF contribute to diabetic retinopathy?
causes blood retinal barrier breakdown and macular edema
also causes retinal neovascularization
risk factors for diabetic retinopathy
duration, puberty, gycemic control, HTN, lipids, pregnancy
what are two fancy treatment for diabetic retinopathy?
also pan-retinal photocoagulation- kills of peripheral retina to reduce oxygen needs of the retina as a whole and spare important center part from ischemia
also anti-VEGF agents:Avastin/bevacizumab. or ranibiumab
management of diabetic retinopathy
- annual eye exams after yr 5 in DM1 and every yr in DM2 and every trimester in preg with established retinopathy
- BP control
- glycemic control
- laser or anti-VEGF (Anti-VEGF especially for diabetic macular edema)
pathology of diabetic nephropathy
glomerular basement membrane changes and mesangial expansion
classically causes diabetic nodules
What changes occur in the kidney as a result of hyperglycemia? What other factors are important in determining diabetic nephropathy
growth of kidney, changes to renal hemodynamics, and changes to the chemical composition of glomerular components
genetics, as well as glucose control, matter for determining the course of diabetic nephropathy
What is the natural history of diabetic nephropathy?
What is the course of DN in terms of protein in the urine
type 2s get there fast than type 1s- though this may be because type 2 diabetics may be diabetic for a long time before their diagnosis
course: normoalbuminuria to microalbuminuria (50%). Fot these, about half develop overt proteinuria. and some of these get end stage renal disease.
incr. BP and risk of CV disease increase as you move along this progression
What factors promote progression of diabetic nephropathy
genetics, BP, albuminuria, metabolic control, smoking
What drugs can help prevent diabetic nephropathy and how do you treat overt diabetic nephropathy
Prevention: ACE-Is, ARBs
Treatment: BP control, ACE-Is, glycemic control, protein restriction, renal or pancreatic transplant?
diabetic nephropathy may be reversible within 10 yrs after a pancreatic transplant
What is the pathology of diabetic neuropathy?
early axonal thickening, then a decrease in microfilaments and capillary narrowing. eventually, axon loss
What is the pathophysiology of diabetic neuropathy?
neuronal ishcemia with incr. VEGF and decrease in NO-dependent vasorelaxation
glycemic death: aldose reductase, edema, loss of neurotrophic factors, etc.
