Diabetes affects approximately 17 million Americans, or an estimated 6.2% of the U.S. population. Of these, approximately 6 million cases are undiagnosed. An additional 16 million Americans have the prediabetic condition of impaired glucose tolerance. The prevalence of diabetes has increased sixfold in the past 40 years. Chronic complications of diabetes are a major medical concern. Diabetes is the sixth-leading cause of death in the U.S., with over 200,000 deaths per year from the disease and related complications. Approximately 80% of all patients with diabetes die of cardiovascular disease. In the U.S., diabetes is responsible for 15% of all blindness, 35% of all end-stage renal disease, and 50% of all nontraumatic amputations.
Diabetes is a progressive disorder. Under normal circumstances, when blood glucose concentrations are high, the pancreas secretes the hormone insulin, promoting transport of glucose into cells and reducing release of glucose by the liver. In insulin resistance, however, cells of the peripheral tissues become progressively more resistant to insulin and less able to take in glucose. Over time, pancreatic b-cells lose their ability to produce insulin in sufficient quantities to overcome insulin resistance, a condition known as “impaired glucose tolerance” or “pre-diabetes.” Reduced glucose uptake, coupled with increased hepatic glucose production, yields rising blood glucose levels and results in hyperglycemia, especially after meals (postprandial hyperglycemia). The combination of insulin resistance and insulin deficiency ultimately may result in persistent hyperglycemia, or frank type 2 diabetes. Type 2 diabetes (formerly called non-insulin-dependent diabetes mellitus) accounts for approximately 90% to 95% of diabetes diagnoses.
Often, several years — perhaps a decade — may elapse between onset of insulin resistance and diagnosis of hyperglycemia or diabetes. During that time, high levels of circulating glucose and associated lipid abnormalities can cause extensive damage to blood vessels, nerves, and other tissues. This damage produces the life-threatening complications of diabetes. These complications fall into two main groups: micro- and macrovascular disorders. Microvascular (small vessel) complications include retinopathy (often leading to blindness), kidney disease (sometimes requiring dialysis), and neuropathy. Reduced blood supply to peripheral tissues can damage nerves and cause weakness, numbness, and increased risk of epidermal ulceration, especially in the legs and feet, which may require amputation. Macrovascular (large vessel) complications include hypertension, atherosclerosis, and thrombosis. (The term “syndrome X” — also known as insulin resistance syndrome or cardiovascular dysmetabolic syndrome — has been applied to describe this cluster of metabolic alterations. They include hyperinsulinemia, dyslipidemia, hypertension, and abdominal obesity.) Because diabetes complications can begin early in the course of the disease — even before symptoms develop — early detection of diabetes is essential.