Chronic diabetic complications: the body's adaptive response to hyperglycemia gone awry?

In the last two decades, diabetes mellitus has reached epidemic proportions in the United States. Most of the recent increase in prevalence of diabetes involves type 2 disease and is a result of an alarming increase in prevalence of obesity, although type 1 diabetes may also be on the rise. Advances in treatment have essentially eliminated ketoacidosis as a cause of death and led to better glycemic control than ever before. Consequently, diabetics now live a longer life, allowing many of them to develop the chronic complications of the disease. Here we review the evidence that a maladaptive response to hyperglycemia contributes to diabetic neuropathy, a major microvascular complication. We postulate that the same response may also be the culprit for the other chronic complications of diabetes.