Obesity Epidemiology

METABOLIC AND HORMONAL PREDICTORS OF OBESITY 389Several prospective studies have identified a positive association between baselineleptin levels and subsequent weight gain. Among Japanese-Americans, Chessler et al. 65found a positive association between leptin levels and increased body weight, BMI, andbody fat after adjusting for baseline adiposity, age, and fasting insulin. In the HealthProfessionals’ Follow-up Study, 66 higher baseline leptin levels predicted 4-year weightgain among overweight men but not among normal-weight men. In a Dutch study with6.8 years of follow-up, van Rossum et al. 67 compared baseline leptin in 259 subjectswho had gained substantial weight (an average of 12.6 kg) to baseline leptin in 277 subjectswith stable weight. Those who gained weight had significantly elevated leptin levelscompared with weight maintainers.Several studies have also suggested that higher plasma leptin levels predict futureweight gain in children. Savoye et al. 68 measured baseline fasting leptin levels in a biracialcohort of 68 obese children aged 7 to 18 years. After adjusting for baseline BMI, Tannerstage, years of follow-up, and fasting insulin, there was a positive association betweenhigher leptin levels and a greater increase in BMI Z-scores in girls (P = .006) (but notboys) during 2.5 years of follow-up. Johnson et al. 69 studied the relationship betweeninitial leptin levels and body fat mass in 85 children (42 white, 43 African American)and found a positive association between initial leptin levels and increase in body fatmass (measured by dual energy x-ray absorptiometry [DXA]) over time, suggestingthat higher leptin levels may promote fat gain in children. These results could also implythat children on a trajectory towards obesity have already developed leptin resistance.In contrast to earlier findings that relatively low leptin levels predicted future weightgain in Pima Indian adults, most subsequent studies found either no relationship betweenleptin and weight gain or that higher leptin levels predicted increased weight gain inadults and children. There is little evidence that leptin levels predict response to weightloss interventions. Although leptin is known to have a strong cross-sectional relationshipwith obesity and to play a critical role in energy homeostasis, it does not appear to havea major role in predicting future weight trajectories.AdiponectinAdiponectin (also known as APM1) is a protein synthesized and secreted exclusively byadipose tissue. 70,71 In humans, adiponectin is one of the most abundant plasma proteins,with a concentration of about 5-10 µg/mL. 72 These levels are reduced in obese adults,but increase with weight loss. 73 Adiponectin is inversely correlated with fasting glucose,insulin, and insulin resistance independent of BMI. 72 Several studies have reported thatsubjects with lower adiponectin levels are more likely to develop type 2 diabetes independentof adiposity. 74-76Despite a clear relationship between adiponectin levels and improved insulinsensitivity, there is no evidence that low plasma adiponectin levels predict subsequentweight gain. Vozarova et al. 77 examined plasma adiponectin concentrations and weightchange in 219 nondiabetic Pima Indians and found no significant association betweenplasma adiponectin concentrations at baseline and changes in weight or BMI duringthe follow-up. Similarly, the Rancho Bernardo cohort 61 showed no relationship betweenbaseline adiponectin levels and subsequent changes in body weight in men or women 60to 91 years of age. These results suggest that low adiponectin levels are a consequence ofobesity rather than a cause. They also suggest that the beneficial effects of adiponectinon risk of type 2 diabetes may be mediated through mechanisms that are independentof body weight.