Obesity Epidemiology

388 EPIDEMIOLOGIC STUDIES OF DETERMINANTS OF OBESITYweight maintenance or even weight loss may reflect the fact that initially obese subjectstend to gain less weight than those who are initially lean. Thus, the relationshipbetween baseline insulin resistance and weight gain during follow-up can be confoundedby baseline weight. Although many studies have adjusted for baseline weight, residualconfounding remains a concern. In several studies, the relationship between insulin sensitivityand weight gain became nonsignificant after adjusting for baseline weight. Third,measurements of insulin resistance differ across studies. Several studies used euglycemicclamp, the gold standard for measurement of insulin resistance, but most used homeostasismodel assessment (HOMA) insulin resistance index or fasting insulin, which is agood surrogate measure of insulin resistance in nondiabetic populations, but its validityin diabetic populations and in children and the elderly is less established. Finally, moststudies assessed insulin resistance only once at baseline. Longitudinal studies are neededto examine whether change in insulin resistance predicts subsequent weight change.LeptinLeptin, one of the first identified adipocyte-secreted hormones, 48 stimulates energyexpenditure and reduces appetite, thus decreasing food intake. In ob/ob mice, leptin deficiencycaused by mutations of the ob gene leads to hyperphagia and extreme obesity,while administration of recombinant leptin reduced body weight and obesity. 48-50 Unlikemice, overweight and obese humans typically have elevated leptin levels. 51,52 Resistanceto leptin’s activity, which is analogous to insulin resistance, is thought to be a mechanismunderlying the direct relationship between obesity and plasma leptin levels. 53In cross-sectional studies, plasma leptin levels have been strongly associated withBMI and measures of fat distribution (e.g., skinfold and waist circumference). 54-56 Severalprospective cohort studies have evaluated the relationship between plasma leptin concentrationsand subsequent weight change. Ravussin et al. 57 measured fasting plasma leptinconcentrations in two groups of weight-matched nondiabetic Pima Indians followed forapproximately 3 years. After adjusting for initial percent body fat, low leptin concentrationsat baseline were associated with greater weight gain.As in studies on other metabolic predictors of obesity in Pima Indians, initial resultson low leptin and weight gain have not been consistently replicated in other populations.Lindroos et al. 58 found that during a 4-year follow-up, high baseline leptin levelspredicted less weight gain (or more weight loss) in women without an obese parent.Among those with at least one obese parent, it had no predictive capability. In an 8-yearstudy, Folsom et al. 59 reported no relationship between initial leptin levels and weightchange in a biracial sample (whites and blacks) (P = .47). However, there was a strongcorrelation between increases in leptin levels and body weight over time (r = .62). Similarly,in the Mauritius Non-communicable Disease Study, Hodge et al. 60 found no differencein 5-year changes in BMI, WHR, or waist circumference among men with low,normal, or high leptin levels at baseline. Among women, the largest increase in WHRwas found in the low leptin group. In the Rancho Bernardo cohort, 61 there was a positiveassociation between leptin levels and attained body weight, but leptin levels did notpredict subsequent weight change. In the Mexico City Diabetes Study, 62 baseline leptinlevels did not predict weight gain during 3.25 years of follow-up in nondiabetic subjects.In addition, relatively low leptin levels did not appear to predict 4-year weight regainafter weight loss in postmenopausal women. 63 Furthermore, Niskanen et al. 64 reportedthat baseline leptin levels did not predict response to weight loss intervention in obesemen and women.