Insulin Resistance/Compensatory Hyperinsulinemia, Essential Hypertension, and Cardiovascular Disease

Abstract

In 1966, Welborn et al. (1) studied 19 nondiabetic patients with essential hypertension and demonstrated that these individuals had significantly higher plasma insulin concen- trations compared with a normotensive control group. Al- though these observations suggested that the prevalence of resistance to insulin-mediated glucose disposal would be increased in patients with essential hypertension, it wasn't until approximately 20 yr later that several research groups demonstrated that this was the case (2-7). Although the relationship between insulin resistance, hyperinsulinemia, and essential hypertension has been extensively studied in the past 15 yr, questions continue to be raised as to the nature of the link between these variables. Indeed, there is not even consensus as to whether or not there is a physiological re- lationship between insulin resistance/compensatory hyper- insulinemia and blood pressure regulation. Another issue, and perhaps of greater clinical relevance, is whether the insulin resistance/compensatory hyperinsulin- emia that is frequently present in patients with essential hypertension plays any role in the increased prevalence of cardiovascular disease (CVD) that is the major cause of mor- bidity and mortality in this clinical syndrome. The goals of this review are to address both of these issues. To begin with, the evidence in support of a role for insulin resistance and compensatory hyperinsulinemia in the patho- genesis of essential hypertension will be summarized. In addition, an argument will be made that insulin resistance and its manifestations play major roles in the development of CVD in patients with essential hypertension. In both in- stances, only experimental evidence obtained in human be- ings will be considered. Finally, although it remains an issue of major scientific importance, a discussion of the possible mechanistic links between insulin resistance and hyperin- sulinemia will not be addressed.