Pre-diabetes, metabolic syndrome, and cardiovascular risk.

Pre-diabetes represents an elevation of plasma glucose above the normal range but below that of clinical diabetes. Pre-diabetes can be identified as either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). The latter is detected by oral glucose tolerance testing. Both IFG and IGT are risk factors for type 2 diabetes, and risk is even greater when IFG and IGT occur together. Pre-diabetes commonly associates with the metabolic syndrome. Both in turn are closely associated with obesity. The mechanisms whereby obesity predisposes to pre-diabetes and metabolic syndrome are incompletely understood but likely have a common metabolic soil. Insulin resistance is a common factor; systemic inflammation engendered by obesity may be another. Pre-diabetes has only a minor impact on microvascular disease; glucose-lowering drugs can delay conversion to diabetes, but whether in the long run the drug approach will delay development of microvascular disease is in dispute. To date, the drug approach to prevention of microvascular disease starting with pre-diabetes has not been evaluated. Pre-diabetes carries some predictive power for macrovascular disease, but most of this association appears to be mediated through the metabolic syndrome. The preferred clinical approach to cardiovascular prevention is to treat all the metabolic risk factors. For both pre-diabetes and metabolic syndrome, the desirable approach is lifestyle intervention, especially weight reduction and physical activity. When drug therapy is contemplated and when the metabolic syndrome is present, the primary consideration is prevention of cardiovascular disease. The major targets are elevations of cholesterol and blood pressure.