THE METABOLICALLY OBESE, NORMAL-WEIGHT INDIVIDUAL REVISITED

Nearby 20 years ago, it was suggested that individuals exist who are n ot obese on the basis of height and weight, but who, like people with overt obesity, are hyperinsulinemic, insulin-resistant, and predispose d to type 2 diabetes, hypertriglyceridemia, and premature coronary hea rt disease. Since then it has become increasingly clear that such meta bolically obese, normal-weight (MONW) individuals are very common in t he general population and that they probably represent one end of the spectrum of people with the insulin resistance syndrome. Available evi dence also suggests that MONW individuals could account for the higher prevalence of type 2 diabetes, cardiovascular disease and other disor ders in people with a BMI in the 20-27 kg/m(2) range who have gained m odest amounts of weight (2-10 kg of adipose mass) in adult life. Speci fic factors that appear to predispose MONW, as well as more obese indi viduals, to insulin resistance include central fat distribution, inact ivity, and a low Vo(2max). Because these factors are potentially rever sible and because insulin resistance may contribute to the pathogenesi s of many diseases, it is our premise that a compelling argument can b e made for identifying MONW individuals and treating them with diet, e xercise, and possibly pharmacological agents before these diseases bec ome overt, or at least early after their onset. One reason for doing s o is that disorders such as type 2 diabetes may be accompanied by irre versible consequences, e.g., ischemic heart disease and nephropathy, a t the time of diagnosis or shortly thereafter. Another is that MONW in dividuals in general should be younger and more amenable and responsiv e to diet and exercise therapy than are obese patients with establishe d disease. That long-term diet and exercise can work is suggested by t wo large studies in which, over 5-6 years, the incidence of diabetes w as diminished in nonobese and minimally obese patients with impaired g lucose tolerance. Based on these considerations and the emerging world wide epidemic of type 2 diabetes, we believe that studies to assess wh ether therapies aimed at young MONW individuals can prevent the develo pment of type 2 diabetes and other diseases, including perhaps obesity itself, are urgently needed.