The metabolically obese, normal-weight individual revisited.

Abstract

Nearly 20 years ago, it was suggested that individuals exist who are not obese on the basis of height and weight, but who, like people with overt obesity, are hyperinsulinemic, insulin-resistant, and predisposed to type 2 diabetes, hypertriglyceridemia, and premature coronary heart disease. Since then it has become increasingly clear that such metabolically obese, normal-weight (MONW) individuals are very common in the general population and that they probably represent one end of the spectrum of people with the insulin resistance syndrome. Available evidence also suggests that MONW individuals could account for the higher prevalence of type 2 diabetes, cardiovascular disease, and other disorders in people with a BMI in the 20-27 kg/m2 range who have gained modest amounts of weight (2-10 kg of adipose mass) in adult life. Specific factors that appear to predispose MONW, as well as more obese individuals, to insulin resistance include central fat distribution, inactivity, and a low VO2max. Because these factors are potentially reversible and because insulin resistance may contribute to the pathogenesis of many diseases, it is our premise that a compelling argument can be made for identifying MONW individuals and treating them with diet, exercise, and possibly pharmacological agents before these diseases become overt, or at least early after their onset. One reason for doing so is that disorders such as type 2 diabetes may be accompanied by irreversible consequences, e.g., ischemic heart disease and nephropathy, at the time of diagnosis or shortly thereafter. Another is that MONW individuals in general should be younger and more amenable and responsive to diet and exercise therapy than are obese patients with established disease. That long-term diet and exercise can work is suggested by two large studies in which, over 5-6 years, the incidence of diabetes was diminished in nonobese and minimally obese patients with impaired glucose tolerance. Based on these considerations and the emerging worldwide epidemic of type 2 diabetes, we believe that studies to assess whether therapies aimed at young MONW individuals can prevent the development of type 2 diabetes and other diseases, including perhaps obesity itself, are urgently needed.

The new definition of metabolic syndrome by the international diabetes federation is less likely to identify metabolically abnormal but non-obese individuals than the definition by the revised national cholesterol education program: The Korea NHANES Study

“…It may be hypothesized that, although the discrepant group did not show central obesity, they have metabolic abnormalities associated with these unfavorable lifestyles and that these may lead to the consequences of metabolic syndrome. Ruderman et al 28,29 insisted that metabolically obese, normal-weight individuals are also predisposed to type 2 diabetes, hypertriglyceridemia, and coronary heart disease like people with overt obesity; therefore, it is important to identify and treat these individuals before these diseases become overt. Insulin resistance can occur independently of obesity and apparently contributes to a high prevalence of type 2 diabetes and CVD.…”

Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction

“…It is at least plausible that obesity and the features of MetS arise in parallel from disruptions of insulin metabolism (possibly a consequence of high insulin due to chronic high dietary CHO). Also a high prevalence of so called metabolically obese-normal-weight individuals with MetS has long been known [18]. In any case, it is generally agreed that the first line of attack against MetS or frank diabetes should be reduction in body mass.…”

Is a nutritional therapeutic approach unsuitable for metabolically healthy but obese women?

“…The importance of these distinctive features is confirmed by the profile of metabolically obese but normal-weight women, who are characterised by a diametrically opposite profile. These women have a higher body fat content in spite of a normal BMI, and show the cluster of phenotypic risk factors associated with the insulin resistance syndrome [7,8].With respect to the clinical relevance of metabolically healthy but obese women, in this issue of Diabetologia, Karelis et al [9] report the original finding that these women may respond differently to an energy-restricted diet than insulin-resistant obese women. From an original population of 121 obese women recruited for a weight loss programme, the authors present data on two selected subgroups of women: those within the upper quartile (the metabolically healthy but obese postmenopausal women) and those within the lower quartile (insulin-resistant and 'at-risk' individuals) of insulin sensitivity values as assessed by means of the euglycaemic-hyperinsulinaemic clamp.…”

“…The importance of these distinctive features is confirmed by the profile of metabolically obese but normal-weight women, who are characterised by a diametrically opposite profile. These women have a higher body fat content in spite of a normal BMI, and show the cluster of phenotypic risk factors associated with the insulin resistance syndrome [7,8].…”