Insulin resistance, obesity and hypertension: an overview.

Insulin resistance and hyperinsulinemia are consid ered important risk factors for the development of hy pertension, and there is a significant association be tween hypertension and insulin resistance in both obese and nonobese individuals (Ferrannini et al. 1987, Modan et al. 1985, Sowers et al. 1991a). That this re lationship persists even in the absence of obesity or overt glucose intolerance (Ferrannini et al. 1987) sug gests a more fundamental relationship between hy pertension and insulin resistance. However, it is not clear whether this relationship results from a direct manifestation of insulin resistance per se or to hyper insulinemia secondary to the insulin resistance. This symposium focused primarily on the pathophysiology and clinical implications of hypertension in insulinresistant states and on differentiating the role of hy perinsulinemia vs. that of target organ insulin resis tance in mediating the hypertension characteristic of Type II diabetes as well as of obesity. The term Syndrome X was introduced by Reaven (1988) to describe a common insulin resistance syn drome that was characterized by insulin resistance with compensatory hyperinsulinemia, hypertriglyceridemia, reduced circulating levels of high-density lipoprotein (HDL)-cholesterol and hypertension. An droid (upper body) obesity is frequently associated with this syndrome in what is often referred to as the deadly quartet of obesity, hypertriglyceridemia, hy pertension and insulin resistance/hyperinsulinemia, which together markedly increase the risk of coronary heart disease (CHD). Consideration of the CHD risk associated with obesity must be interpreted in light of the relationship between obesity and the other com ponents of the quartet. Indeed, the risk of obesity in dependent of insulin resistance, hypertriglyceridemia and hypertension appears to be quite low (BarrettConnor 1985, Kaplan 1989). However, the practical relevance of this observation is questionable because obesity frequently does result in the manifestation of all four members of the quartet. For example, hyper tension and insulin resistance are approximately three and two times as prevalent, respectively, in obese vs. nonobese populations (Van Itallie 1985). Hyperinsulinemia is frequently cited as the key metabolic derangement that links obesity to glucose intolerance, hypertension and hypertriglyceridemia (e.g., Kaplan 1989; Reaven 1988, Rocchini 1991). However, it is difficult to separate hyperinsulinemia secondary to insulin resistance from independent ef fects of the insulin resistance per se. Indeed, a growing body of evidence, discussed subsequently in this re view, suggests that lack of insulin action on the vasculature rather than hyperinsulinemia may be respon sible for the increases in peripheral vascular resistance and blood pressure characteristic of insulin-resistant states. Accordingly, it is instructive to consider the impact of both insulinopenic and hyperinsulinemic conditions on the risk of developing hypertension. Consequently, the next section will briefly examine the epidemiology of hypertension in both Type I and Type II diabetes.