FGF21 deficiency is associated with childhood obesity, insulin resistance and hypoadiponectinaemia: The BCAMS Study - 28/01/17

Doi : 10.1016/j.diabet.2016.12.003

G. Li ^a,^{^{1
These authors contributed equally to this work.}}, J. Yin ^a,^f,^{^{1
These authors contributed equally to this work.}}, J. Fu ^a, L. Li ^a, S.F.A. Grant ^b,^g,^h, C. Li ^b, M. Li ^c, J. Mi ^d, M. Li ^a,^b,^⁎ , S. Gao ^e,^⁎
^a Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing 100730, China
^b Division of Endocrinology, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
^c Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA 19104, USA
^d Department of Epidemiology, Capital Institute of Pediatrics, Beijing 100020, China
^e Department of Endocrinology, Chaoyang Hospital, Capital Medical University, Beijing 100043, China
^f Department of Endocrinology, First Affiliated Hospital, Shanxi Medical University, Shanxi 030001, China
^g Division of Human Genetics, The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA
^h Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

^⁎Corresponding author at: Ming Li, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.^⁎⁎Corresponding author at: Department of Endocrinology, Chaoyang Hospital, Capital Medical University, Beijing 100043, China.

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Saturday 28 January 2017

Abstract

Objective

Fibroblast growth factor 21 (FGF21) exerts beneficial effects on metabolic homoeostasis and has been reported to be regulated by adiponectin, leptin and resistin. However, while an association between increased circulating FGF21 and metabolic disorders has been reported in adults, paediatric-specific data are lacking.

Design and methods

This study investigated the relationship between FGF21 levels and obesity, insulin resistance (IR), the metabolic syndrome (MetS) and adipokines (adiponectin, leptin and resistin) in a cohort of 3231 Chinese youngsters aged 6–18.

Results

There were gender- and puberty-related differences in FGF21 levels. Unexpectedly, FGF21 levels were decreased in children with obesity, and negatively correlated with insulin, HOMA-IR and leptin levels after adjusting for age, gender, puberty and lifestyle factors. Moreover, multiple regression analyses showed that serum FGF21 positively predicted adiponectin levels while resistin positively predicted FGF21 levels independent of BMI (P<0.05). Children in the lowest FGF21 quintile were more likely to have IR (OR: 1.85, 95% CI: 1.41–2.42; P=0.002) and MetS (OR: 1.62, 95% CI: 1.14–2.28; P=0.007) than those in the highest quintile. Further adjusting for BMI and/or the three adipokines modified the association of FGF21 with MetS (P>0.10) but not with IR (P<0.01).

Conclusion

Although the associations between adiponectin, leptin, resistin and metabolic abnormalities in our paediatric population were similar to those in adults, correlations of FGF21 levels with obesity, IR and MetS were the inverse of those found in adults. Our present findings suggest that FGF21 deficiency, rather than resistance, contribute to IR and hypoadiponectinaemia independently of obesity in young people.

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Keywords : Adipokines, Children, Fibroblast growth factor 21, Insulin resistance, Obesity, Metabolic syndrome

Abbreviations : FGF21, IR, T2D, CVD, MetS, BMI, WC, SBP, DBP, TG, TC, HDL-C, LDL-C, HOMA-IR