Baseline leptin and leptin reduction predict improvements in metabolic variables and long-term fat loss in obese children and adolescents: a prospective study of an inpatient weight-loss program

BACKGROUND: It is unclear whether high plasma leptin in obese individuals represents leptin resistance or whether individuals with marked reductions in leptin concentrations in response to weight loss may be at greater risk of regaining weight. Moreover, whether changes in leptin predict metabolic improvements during weight loss is uncertain. OBJECTIVE: The objective was to prospectively examine associations between plasma leptin, body fat, and weight and metabolic risk factors in obese children during weight loss. DESIGN: In obese children and adolescents [n = 203; mean age: 14.1 y, >98th body mass index (BMI) percentile for age and sex] participating in a 2-mo inpatient weight-loss program, we measured changes in body composition (by dual-energy X-ray absorptiometry), plasma leptin, insulin, and lipids. After discharge, anthropometric measures and plasma leptin were remeasured at 6 (n = 139) and 12 (n = 100) mo. RESULTS: During the 2-mo program, mean (±SD) weight and fat loss were 13.9 ± 4.0 kg and 9.2 ± 2.5 kg, respectively; and mean plasma leptin decreased by 76%. Weight and fat loss were sustained, and no significant differences in BMI-SD score (SDS) or body composition were found between 12 and 2 mo. Baseline leptin was a negative predictor for percentage fat loss at 2, 6, and 12 mo (P < 0.05). The percentage change in leptin during the 2-mo intervention positively correlated with the relative change in fasting insulin, the relative change in LDL cholesterol at 2 mo, percentage fat loss, and change in BMI-SDS at 2 and 6 mo (P < 0.02). CONCLUSIONS: Even in obese children with strongly elevated baseline leptin, large leptin reductions that predict short- and long-term loss of body fat and improvements in lipids and insulin sensitivity can be achieved. Thus, increased plasma leptin in obese children may not necessarily reflect leptin resistance; many children appear to remain leptin sensitive at this age.