Insulin sensitivity in humans: alterations during drug administration and in essential hypertension

Hypertension has a high prevalence among patients with noninsulin-dependent diabetes mellitus as well as in obese subjects, and glucose intolerance is emerging as a common feature to these conditions. There is increasing evidence that essential hypertension in nonobese, nondiabetic patients can be an insulin-resistant state per se. In view of the known acute effects of insulin on renal sodium retention, transcellular cation transport and perhaps also on sympathetic system, a possible involvement of insulin resistance in the genesis of essential hypertension deserves consideration. This point is of particular relevance not only because of the possible pathogenetic link between insulin resistance and high blood pressure, but also because of the potential metabolic interactions of certain drugs, especially in hypertensive diabetics. The oral glucose tolerance test, the glucose clamp and the minimal model approach represent three different methodological approaches that have been used to estimate insulin sensitivity in the intact organism. These methods differ with regard to their sensitivity, comparability and complexity. Although the oral glucose tolerance test has been widely used as standard approach to investigate drug-induced glucose intolerance, it does not provide a specific measure of insulin responsiveness. The insulin clamp introduced by Andres allows a direct quantification of insulin sensitivity, but its methodological complexity has limited its application in humans. The minimal model approach allows an accurate estimate and facilitates the assessment of insulin sensitivity under clinical conditions.