Mechanisms for early microvascular injury in obesity and type II diabetes.

Obesity in the absence of hyperglycemia carries a low risk for microvascular disease compared with type II diabetes. The occurrence of hyperglycemia seems to be an important, if not the most important, distinction between obesity and obesity plus diabetes mellitus for microvascular disease. In vitro and in vivo human and animal studies of the early microvascular consequences of hyperglycemia indicate an immediate detrimental suppression of vasodilatory microvascular mechanisms that might be even worse with pre-existing obesity. The overall concept emerging from a very large research base is that hyperglycemia activates protein kinase C, increases oxidant formation, elevates constrictor prostanoid species to the detriment of beneficial prostanoids, and suppresses flow-mediated regulation with the nitric oxide generated by endothelial cells. The end result is decreased blood flow and loss of microvascular reactivity to endothelial-dependent vasodilatory stimuli that persists for 3 to 6 hours.