Insulin Resistance and Hypertension

Insulin resistance refers to the reduction in insulin-mediated glucose uptake in insulin-sensitive tissues, specifically in skeletal muscle. As a compensatory response, hyperinsulinemia ensues to maintain normal blood glucose levels. In epidemiological studies, fasting insulin level is commonly used as a surrogate marker of insulin resistance. In normoglycemic subjects, fasting insulin correlated well with whole-body glucose uptake ( r =−0.68) as measured by the “gold standard” euglycemic hyperinsulinemic clamp method, although the correlation was lower in individuals with impaired glucose tolerance or type 2 diabetes mellitus.1 Although fasting insulin is a reasonable measure of insulin resistance, it is potentially confounded by variability in insulin secretion. Thus, the indexes derived from fasting insulin and glucose, such as the Homeostasis Model Assessment (HOMA),2 the Quantitative Insulin Sensitivity Check Index (QUICKI),3 and the insulin sensitivity index (ISI) developed by Gutt and coworkers,4 have been more widely used to assess insulin resistance in clinical and population-based studies.See p 1719 Although the role of insulin resistance in the pathophysiology of type 2 diabetes mellitus is well accepted, the relationship between insulin resistance and blood pressure remains controversial. Nearly 40 years ago, Welborn and colleagues5 observed that nondiabetic patients with essential hypertension had significantly higher plasma insulin concentrations than did normotensive individuals. This positive relationship has been confirmed in several longitudinal studies, but the results are not entirely consistent. In some studies, the association between hyperinsulinemia and incident hypertension disappeared after adjustment for body mass index (BMI), suggesting that the association is confounded or mediated through obesity. Therefore, the causal role of insulin resistance/compensatory hyperinsulinemia in the development of hypertension continues to be debated.As reported in this issue of Circulation , Arnlov and colleagues6 investigated the relationship between insulin sensitivity, using ISI, and the 4-year incidence of hypertension and blood …