OBJECTIVE: Leptin, the product of the ob gene, is present in higher concentrations in blood of obese subjects than of lean subjects. There is scarce information on the role of leptin in the pathogenesis of human obesity and little is known about leptin serum levels in obese children. DESIGN, SUBJECTS AND MEASUREMENTS: To evaluate the in¯uences of age, sex, pubertal development and weight excess on serum leptin levels, we have studied 390 obese subjects (OS) and 320 normal weight subjects (NWS) aged 5±16 y. Fasting insulin concentrations were assayed in NWS, and an oral glucose tolerance test was carried out in OS and total insulin area under the curve (TIA) was calculated. RESULTS: Log-transformed values of leptin serum concentrations appeared to be distributed according to an acceptable Gaussian pattern. As observed in adults, serum leptin concentrations in children and adolescents were also increased (4±5 times) in OS as compared to NWS. In both males and females, subdivided according to pubertal stages, serum leptin varied signi®cantly in stage IV±V as compared to the lower stages, with a reduction in males and an increase in females. On comparing the two sexes, greater serum leptin concentrations were observed in females of both NWS and OS. A signi®cant linear correlation was found in both groups, subdivided according to sex and pubertal stage, between log values of serum leptin and standard deviation scores (SDS) of body mass index (BMI), and logtransformed relative body weight (RBW). Using partial correlation analysis in subjects subdivided according to sex and pubertal stages, log values of serum leptin and fasting insulin values, adjusted by age and SDS of BMI, correlated signi®cantly with a weaker correlation in males than in females. In OS, the leptin concentrations correlated better with TIA than with fasting insulin. A weight reduction program (WRP) was carried out in 141 OS and signi®cant reductions of serum leptin and fasting insulin were observed, showing a reduction of RBW. There was a correlation between the reduction of RBW and of serum leptin, but not of fasting insulin. No variation was found in non-responsive OS. RBW reduction correlated with leptin, but not with insulin (fasting and TIA), evaluated before the therapeutic program started. CONCLUSION: As observed in adults, obese children and adolescents have higher serum leptin concentrations. However, several conditions should be taken into account when evaluating leptin concentrations in children. There are differences, independent of BMI, relative to pubertal stage and sex, females having greater leptin concentrations than males. There is evidence of a possible role for leptin in the effectiveness of a weight reduction program in OS.

BackgroundThe aim of this study was to investigate sex differences and associations of high molecular weight (HMW) adiponectin, leptin and proinflammatory adipokines, individually or in combinations, with adiposity and insulin resistance (IR) measures in prepubertal childhood.MethodologyWe studied 305 prepubertal children (boys/girls: 144/161; Tanner stage 1; age: 5-13 yr), included in a cohort of 44,231 adolescents who participated in an extensive Italian school-based survey. According to Cole's criteria, 105 individuals were lean (L; boys/girls: 59/46), 60 overweight (OW; boys/girls: 32/28) and 140 obese (OB; boys/girls: 70/70). Measurements comprised total and HMW adiponectin, leptin, as well as a panel of proinflammatory adipokines/chemokines associated with diabetes risk.Principal FindingsLeptin-, and the leptin-to-HMW adiponectin ratio (L/HMW)-, increased progressively (p<0.0001) from L to OW to OB boys and girls. When compared with L peers, OW and OB girls exhibited lower (p<0.001) HMW adiponectin levels, while in boys the HMW multimers did not differ significantly across the BMI-stratified groups. OB girls displayed higher (p<0.05) IL-8, IL-18, monocyte chemoattractant protein-1 (MCP-1) and soluble intercellular adhesion molecule-1 levels (sICAM-1) than L girls, whereas increased macrophage migration inhibitory factor (MIF) concentrations in OB vs OW boys were seen. HMW adiponectin (negatively), leptin or inflammatory markers (positively) correlated with adiposity and IR measures. In multivariate models, leptin represented a strong and independent determinant of HOMA-IR (R2 0.378; p<0.01). Adjustment for age, BMIz-score, lipids and inflammatory mediators abolished the association between leptin and HOMA-IR in boys, while in girls leptin remained still a significant predictor of IR (R2 0.513; p<0.01). Finally, in both sexes, the joint effect of the L/HMW did not improve the prediction of basal IR as compared with leptin levels alone, which were mainly explained by the BMIz-score. ConclusionsIn prepubertal children, leptin emerges as a sex-independent discrimination marker of adiposity degree and as a useful, sex-associated predictor of the systemic insulin resistance.

Circulating concentrations of adipocytokines are abnormal in Type 1 diabetic children, although the direction of change differs by cytokine. Pubertal development, in addition to insulin treatment and glycaemic control, also influences the concentrations.

The associations found between both ghrelin and galanin with adiposity indices could be considered as an indirect signal of involvement of the two peptides in the development of the nutritional status of the IDDM adolescents. The reduction in both forms of ghrelin could be involved in the development of the body mass increase of IDDM subjects with opposite effects, either influencing insulin sensitivity or exerting a compensatory restraint of feeding.

Objective: To examine the hypothesis of an influence of leptin on growth factors and on biochemical markers of bone turnover of prepubertal overweight children. Design and Methods: 395 prepubertal children, 6–13 years of age, were selected and the relationships between circulating serum levels of leptin and insulin-like growth factor I (IGF-I), insulin growth factor binding protein-3 (IGFBP-3) and some biochemical markers of bone turnover (osteocalcin, OC; carboxyterminal propeptide of type I procollagen, PICP, and carboxyterminal propeptide of type I collagen, ICTP) were analyzed. The subjects were subdivided into normal weight (NW, n = 163) and weight excess (WE, n = 232) subjects. Results and Conclusions: Significant differences between the two groups were found for leptin (p < 0.01), IGF-I (p < 0.01) and IGFBP-3 (p < 0.01), with higher values in WEs, and for OC (p < 0.01) with higher values in NWs. A significant reduction of leptin (p < 0.01) and IGFBP-3 (p < 0.01) serum values and an increase of those of OC (p < 0.01) and PICP (p < 0.05), but not of ICTP, were registered in 103 WEs who showed a drop in weight excess during a weight-excess reduction program. No variations were observed in 26 non-responsive subjects. In a multivariate analysis in which leptin, corrected by BMI and sex, was the independent variable, a significant negative correlation was found with PICP (β = –0.235, p < 0.01), IGF-I (β = –0.180, p < 0.01) and height velocity (β = –0.155, p < 0.01). There was no correlation with OC, ICTP and IGFBP-3. The results demonstrate that nutritional status and leptin levels are involved in the regulation of growth factors and biochemical markers of bone formation.