Microvascular Disease

To better understand the rationale for glucose control it is useful to review the role of hyperglycemia in the development of the long-term microvascular complications. After the discovery of insulin it was noted that patients with insulin-dependent diabetes who lived longer tended to develop retinopathy. It was not clear at the time as to whether these were usual changes of the disease or whether they were related to the level of hyperglycemia. Early pathological studies in animals indicated a relationship between elevated blood glucose levels and retinopathy. Currently a number of different mechanisms have been implicated in the pathogenesis of the microvascular disease and this has been studied extensively in diabetic retinopathy and nephropathy. Chronic duration of the disease, a number of metabolic abnormalities including hyperglycemia, and genetic factors all play a role in causing the microangiopathy. Diabetic retinopathy has been most thoroughly studied because it is one of the first complications that can be detected clinically. The early changes of diabetic retinopathy include the formation of capillary microaneurysms with increased permeability and thickening of the capillary basement membrane. However, even before these changes are evident, there are changes in endothelial cell function that can affect capillary blood flow. With poor glycemic control there is progression of the retinopathy from background changes to preproliferative and then proliferative retinopathy. Eventually this can lead to bleeding from rupture of the neovascularization with the end stage of blindness.

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