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An individual participant data meta-analysis on metabolomics profiles for obesity and insulin resistance in European children.

ABSTRACT: Childhood obesity prevalence is rising in countries worldwide. A variety of etiologic factors contribute to childhood obesity but little is known about underlying biochemical mechanisms. We performed an individual participant meta-analysis including 1,020 pre-pubertal children from three European studies and investigated the associations of 285 metabolites measured by LC/MS-MS with BMI z-score, height, weight, HOMA, and lipoprotein concentrations. Seventeen metabolites were significantly associated with BMI z-score. Sphingomyelin (SM) 32:2 showed the strongest association with BMI z-score (P?=?4.68?×?10-23) and was also closely related to weight, and less strongly to height and LDL, but not to HOMA. Mass spectrometric analyses identified SM 32:2 as myristic acid containing SM d18:2/14:0. Thirty-five metabolites were significantly associated to HOMA index. Alanine showed the strongest positive association with HOMA (P?=?9.77?×?10-16), while acylcarnitines and non-esterified fatty acids were negatively associated with HOMA. SM d18:2/14:0 is a powerful marker for molecular changes in childhood obesity. Tracing back the origin of SM 32:2 to dietary source in combination with genetic predisposition will path the way for early intervention programs. Metabolic profiling might facilitate risk prediction and personalized interventions in overweight children.

SUBMITTER: Hellmuth C

PROVIDER: S-EPMC6433919 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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An individual participant data meta-analysis on metabolomics profiles for obesity and insulin resistance in European children.

Hellmuth Christian C Kirchberg Franca F FF Brandt Stephanie S Moß Anja A Walter Viola V Rothenbacher Dietrich D Brenner Hermann H Grote Veit V Gruszfeld Dariusz D Socha Piotr P Closa-Monasterolo Ricardo R Escribano Joaquin J Luque Veronica V Verduci Elvira E Mariani Benedetta B Langhendries Jean-Paul JP Poncelet Pascale P Heinrich Joachim J Lehmann Irina I Standl Marie M Uhl Olaf O Koletzko Berthold B Thiering Elisabeth E Wabitsch Martin M

Scientific reports 20190325 1

Childhood obesity prevalence is rising in countries worldwide. A variety of etiologic factors contribute to childhood obesity but little is known about underlying biochemical mechanisms. We performed an individual participant meta-analysis including 1,020 pre-pubertal children from three European studies and investigated the associations of 285 metabolites measured by LC/MS-MS with BMI z-score, height, weight, HOMA, and lipoprotein concentrations. Seventeen metabolites were significantly associa ...[more]

PMID: 30911015

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Project description:BACKGROUND:Short sleep duration has been suggested to lead to insulin resistance both directly by altering glucose metabolism and indirectly through obesity. This study aims to investigate associations between nocturnal sleep duration and insulin resistance considering abdominal obesity as a mediator. METHODS:We analysed data of 3 900 children aged 2-15 years participating in the second (2009/10) and third (2013/14) examination wave of the European IDEFICS/I.Family study (hereafter referred to as baseline and follow-up). Information on nocturnal sleep duration was collected by questionnaires and age-standardised (SLEEP z-score). The homeostasis model assessment (HOMA) was calculated from fasting insulin and fasting glucose obtained from blood samples; waist circumference (WAIST) was measured with an inelastic tape. HOMA and WAIST were used as indicators for insulin resistance and abdominal obesity, respectively, and transformed to age- and sex-specific z-scores. Cross-sectional and longitudinal associations between SLEEP z-score and HOMA z-score were investigated based on a path model considering WAIST z-score as a mediator adjusting for relevant confounders. RESULTS:Cross-sectionally, baseline SLEEP z-score was negatively associated with baseline WAIST z-score (unstandardised effect estimate -0.120, 95% confidence interval [-0.167; -0.073]). We observed no direct effect of baseline SLEEP z-score on baseline HOMA z-score but a negative indirect effect through baseline WAIST z-score (-0.042 [-0.058; -0.025]). Longitudinally, there was no direct effect of baseline SLEEP z-score on HOMA z-score at follow-up but a negative indirect effect through both baseline WAIST z-score and WAIST z-score at follow-up (-0.028 [-0.040; -0.016]). CONCLUSIONS:Our results do not support the hypothesis of an association between short sleep duration and insulin resistance independent of abdominal obesity. However, longer sleep duration may exert short and long term beneficial effects on insulin resistance through its beneficial effects on abdominal obesity.

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Dataset Information

An individual participant data meta-analysis on metabolomics profiles for obesity and insulin resistance in European children.

Publications

An individual participant data meta-analysis on metabolomics profiles for obesity and insulin resistance in European children.

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