Hyperglycemia is a key factor in both beta cell death and dysfunction as well as in development of microvascular disease. The hypothesis described in this paper suggests that pancreatic microvascular endothelial dysfunction and subsequent microvascular disease of the pancreas causes islet ischemia. This subtle ischemia is the cause of initial dysfunction and subsequent apoptosis of B cells which is preceding development of type 2 diabetes. Moreover, the subtle beta cell ischemia will continue to diminish the beta cells' ability to secrete the increasing amount of insulin needed as the insulin resistant state progresses into type 2 diabetes. This vicious cycle might perpetuate type 2 diabetes.
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