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Hyperglycemia does it by increasing the rate of transformation of NAD to NADH. Hypoxia makes it difficult for cells to turn NADH back to NAD. In both conditions the increased NADH is recycled back to NAD by processes that produce free radicals, chemically reactive compounds that can damage tissue. Williamson and his coauthors propose that long-term use of these processes causes the damage seen in diabetes.
Diabetes is a metabolic disorder that affects how the body uses food for energy due to insulin resistance. Diabetes affects the metabolism as well as the immune system. The disease causes the immune system to destroy insulin producing cells within the pancreas. The immune response is also much lower in people who have diabetes so they are more susceptible to getting infections that could result in the loss of a limb.