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Background: Optimization of nutritional status is recommended in patients with cystic fibrosis (CF) given the association between lower body mass index (BMI) and poor clinical outcomes. However, higher BMI and body fat correlate with glucose impairment and higher leptin levels in the general population. Differences in body composition and leptin levels between the categories of glucose tolerance were assessed in youth with CF and healthy controls., Methods: In a cross-sectional study, 59 adolescents and young adults with CF and 15 healthy controls matched by age and gender, underwent body composition analysis using dual energy X-ray absorptiometry (DXA) and a 2-hour oral glucose tolerance test (OGTT). Measures of insulin sensitivity, β-cell insulin secretion and fasting leptin levels were obtained., Results: Of the participants with CF, 62% were classified as abnormal glucose tolerant and 22% with cystic fibrosis related diabetes (CFRD). Patients with CFRD had a lower fat mass index (FMI) z-score, wt z-score and leptin levels compared to the control group (-1.86 vs. - 0.59, p=0.01; -1.86 vs 0.44, p=<0.001 and 7.9 vs vs. 27.7 µg/L, p=0.01). Leptin correlated positively with FMI z-score, BMI, weight z-score and indices of insulin secretion. FMI z-score correlated positively with higher insulin resistance (HOMA-IR), and lower insulin sensitivity (Matsuda index) (r=0.31; p =0.01 and r=-0.29; p=0.02, respectively) in the CF group., Conclusions: This study shows that despite new therapeutic strategies, youth with CF have lower body fat, weight z-score and leptin levels, particularly in subjects with early onset CFRD., Competing Interests: Declaration of Competing Interest No potential conflicts of interest relevant to this article were reported by any of the authors, (Copyright © 2021 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)