Selective aspects of the insulin resistance syndrome.

There is increasing recognition of new features in the insulin resistance syndrome and its association with new disease states or treatment modalities. Recent additions to the list of features in the insulin resistance syndrome include elevated non-esterified fatty acids, abnormalities in visceral fat metabolism, elevated uric acid, elevated hematocrit, endothelial dysfunction, abnormalities in glucocorticoids, and differences in the phenotypic expression of the syndrome between men and women. A critical factor that may be inherent in the syndrome is the distribution and metabolism of visceral fat. This finding is also accompanied by the recognition of the role of non-esterified fatty acids as a cause of many of the risk factors in the insulin resistance syndrome. Elevated non-esterified fatty acids contribute to hypertension, glucose intolerance and increased arteriosclerosis. Elevated cortisol levels and disrupted metabolism, as well as abnormalities in the hypothalamic-pituitary-adrenal axis are seen in the insulin resistance syndrome. In women, adipose cells express fewer glucocorticoid receptors and less of the enzyme that metabolizes cortisol, 11beta-hydroxysteroid dehydrogenase. Several inflammatory factors such as tumor necrosis factor-alpha may be an etiologic link in the risk found in the insulin resistance syndrome. Certain cases of the syndrome appear to be related to specific drug therapies (steroids, immunosuppressive agents and antiretroviral agents), as seen in transplant patients and HIV-infected individuals.