Pathophysiology of microvascular complication of

diabetes
The underlying driver of microvascular disease is tissue exposure .to chronic hyperglycaemia
Landmark clinical trials such as the UK Prospective Diabetes Study
(UKPDS) and Diabetes Control of Complications Trial (DCCT) have
established a clear relationship between microvascular disease and
.glucose control
Microvascular disease tends to occur predominantly in tissues where glucose uptake is independent of insulin activity (eg kidney,
retina and vascular endothelium) because these tissues are exposed
to glucose levels that correlate very closely with blood glucose
.levels
The development of disease is the result of a combination of direct glucose-mediated endothelial damage, oxidative stress due to
superoxide overproduction, and the production of sorbitol and
advanced glycation end-products due to the prevailing state of
.hyperglycaemia
These metabolic injuries cause altered blood flow and changes in endothelial permeability, extravascular protein deposition and
.coagulation resulting in organ dysfunction
Current evidence demonstrates a clear relationship between blood pressure (BP) and progression of nephropathy and
retinopathy. These are now established as independent risk factors
.for microvascular disease progression

Result of microvascular complication of diabetes

Diabetes mellitus can lead to many acute and chronic complications. The chronic complications are mainly the result of
longstanding damage to blood vessels. These complications are
grouped as microvascular due to basement membrane thickening or
macrovascular due to accelerated atherosclerosis. The major
microvascular complications are diabetic retinopathy, nephropathy,
and neuropathy. The diabetic foot ulcer shown is the result of
.longstanding peripheral neuropathy

Diabetic retinopathy is progressive damage to the retina from longstanding diabetes mellitus that, if untreated, will lead to
progressive vision loss and blindness. Microvascular basement
membrane thickening impairs the diffusion of oxygen and nutrients
to the retina, activating a cascade of events leading to neovascular
proliferation. The abnormal growth of friable blood vessels on the
retina produces microaneurysms (short arrow) that may rupture,
leading to blot or flame-shaped hemorrhages (arrowhead). Hard
exudates (long arrow) are caused by the breakdown of the bloodretina barrier allowing for serum proteins and lipids to leak out and
.accumulate on the retinal surface
Fluorescein angiograms allow for a better examination of the retinal vasculature. Sodium fluorescein is injected into the venous
system and serial photographs of the retina are taken over time.
The photographs are taken in black-and-white to provide better
contrast for the vasculature. The angiogram shown demonstrates
.leakage of dye secondary to poor capillary integrity
Macular edema is presumed to be the result of functional damage and necrosis to the retinal capillaries. It is a sign of longstanding
retinal disease and over time leads to blindness. Macular edema is
characterized by retinal thickening and the presence of hard
exudates near the fovea, as shown. In the United States, diabetic
retinopathy is the most common cause of blindness and macular
.edema is the major contributor
Diabetic retinopathy is classified on a spectrum from nonproliferative to proliferative depending on the extent of retinal
changes and the degree of microvascular growth. In advanced
disease, progressive hemorrhage obscures a patient's visual fields,
leading to vision loss. The image shown is an example of what a
patient with advanced diabetic retinopathy may see when looking at
a scene of 2 young children. Image courtesy of the National Institute
of Health