Insulin resistance: the link between obesity and cardiovascular disease.

There seems to be general agreement that the prevalence of obesity is increasing in the United States and that we are in the midst of an obesity epidemic. The disease-related implications of this epidemic have received an enormous amount of publicity in the popular media, but public awareness of the untoward effects of excess weight has not led to an effective approach to dealing with the dilemma. The gravity of the problem is accentuated in light of the report that only approximately 50% of physicians polled provided weight loss counseling. Given the importance of excess adiposity as increasing the risk of CVD, 2DM, and hypertension and the combination of an increase in the prevalence of overweight/obesity and a health care system unprepared to deal with this situation, it is essential that considerable thought be given as to how to best address this dilemma. In this context, it must be emphasized that CVD, 2DM, and hypertension are characterized by resistance to insulin-mediated glucose disposal and that insulin resistance and the compensatory hyperinsulinemia associated with insulin resistance have been shown to be independent predictors of all three clinical syndromes. It has also been apparent for many years that overweight/obese individuals tend to be insulin resistant and become more insulin sensitive with weight loss.25 In light of these observations, it seems reasonable to suggest that insulin resistance is the link between overweight/obesity and the adverse clinical syndromes related to excess adiposity. The evidence summarized in this review shows that the more overweight an individual, the more likely he or she is insulin resistant and at increased risk to develop all the abnormalities associated with this defect in insulin action. Not all overweight/obese individuals are insulin resistant, however, any more than all insulin resistant individuals are overweight/obese. More important, there is compelling evidence that CVD risk factors are present to a significantly greater degree in the subset of overweight/obese individuals that is also insulin resistant. Not surprisingly,we have also demonstrated that an improvement in CVD risk factors with weight loss occurs to a significantly greater degree in those overweight/obese individuals who are also insulin resistant at baseline. In view of the ineffectiveness of current clinical approaches to weight loss, it seems necessary to recognize that not all overweight/obese individuals are at equal risk to develop CVD and that it is clinically useful to identify those at highest risk. The simplest way to achieve this task seems to be focusing on the CVD risk factors that are highly associated with insulin resistance/hyperinsulinemia. If this is done, then intense efforts at weight control can be brought to bear on those who not only need it the most but also have the most to gain by losing weight.