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Objective: Body mass index (BMI) was determined in a population of school students from three provinces of central Italy. Fasting serum leptin concentrations were assayed in a large number of subjects from the same area, to determine their distribution as plotted against the standard deviation score (z-score) of BMI., Design, Subjects and Measurements: Height and weight were recorded from 31170 subjects (16175 male and 14995 female), aged 3-18 y, to construct BMI charts of children and adolescents from central Italy. Percentiles and z-score were calculated using the LMS method of Cole. Serum leptin concentrations were assayed in 1929 subjects (996 male and 933 female) after overnight fasting., Results: BMI percentiles of central Italy were higher than those from standards of other European and USA populations. When plotted against the z-score of BMI, serum leptin values were distributed according to an exponential curve, showing a steep pattern and a wide distribution, as BMI values increased. The hypothesis of the existence of two subgroups, based on a different relation between leptin and BMI, was verified and a separation point between the two subgroups was identified using cluster analysis, discriminant analysis and a novel method developed by our group, hereafter referred to as 'regression clustering'. This method allows identification of the value of the independent variable (z-score of BMI) which can be taken as a separation point. This analysis provided the best results and indicated the following separation points: central Italy standard, z-score = 0.72 (76.4th percentile) for males and z-score = 0.69 (75.5th percentile) for females; French standard (the one suggested for a European population by the European Childhood Obesity Group, ECOG), z-score = 1.46 (92.8th percentile) for males and z-score = 1.96 (97.5th percentile) for females. Similar but variable results were obtained when the same analysis was performed on serum leptin concentration, subdivided according to pubertal development (stage I, stage II-III, stage IV-V)., Conclusions: Children and adolescents from central Italy had greater BMI percentiles when compared to other European populations. Fasting serum leptin concentrations showed a distribution pattern related to z-score, thus allowing to identification of two different subgroups. The z-scores of BMI, identified as separation points, indicated a trend to leptin production by adipocytes that could be taken as indicators of significant increases of fat mass. This study proposes criteria and a statistical approach that could be useful in the identification of BMI cut-off values when screening children and adolescents for overweight.