Percentiles of fasting serum insulin, glucose, HbA1c and HOMA-IR in pre-pubertal normal weight European children from the IDEFICS cohort

OBJECTIVES: The aim of this study is to present age-and sex-specific reference values of insulin, glucose, glycosylated haemoglobin (HbA1c) and the homeostasis model assessment to quantify insulin resistance (HOMA-IR) for pre-pubertal children. METHODS: The reference population consists of 7074 normal weight 3- to 10.9-year-old pre-pubertal children from eight European countries who participated in at least one wave of the IDEFICS ('identification and prevention of dietary-and lifestyle-induced health effects in children and infants') surveys (2007-2010) and for whom standardised laboratory measurements were obtained. Percentile curves of insulin (measured by an electrochemiluminescence immunoassay), glucose, HbA1c and HOMA-IR were calculated as a function of age stratified by sex using the general additive model for location scale and shape (GAMLSS) method. RESULTS: Levels of insulin, fasting glucose and HOMA-IR continuously show an increasing trend with age, whereas HbA1c shows an upward trend only beyond the age of 8 years. Insulin and HOMA-IR values are higher in girls of all age groups, whereas glucose values are slightly higher in boys. Median serum levels of insulin range from 17.4 and 13.2 pmol l(-1) in 3-< 3.5-year-old girls and boys, respectively, to 53.5 and 43.0 pmol l(-1) in 10.5-< 11-year-old girls and boys. Median values of glucose are 4.3 and 4.5 mmol l(-1) in the youngest age group and 49.3 and 50.6 mmol l(-1) in the oldest girls and boys. For HOMA-IR, median values range from 0.5 and 0.4 in 3-< 3.5-year-old girls and boys to 1.7 and 1.4 in 10.5-< 11-year-old girls and boys, respectively. CONCLUSIONS: Our study provides the first standardised reference values for an international European children's population and provides the, up to now, largest data set of healthy pre-pubertal children to model reference percentiles for markers of insulin resistance. Our cohort shows higher values of Hb1Ac as compared with a single Swedish study while our percentiles for the other glucose metabolic markers are in good accordance with previous studies

Analysis of the contribution of <it>FTO</it>, <it>NPC1, ENPP1, NEGR1, GNPDA2</it> and <it>MC4R</it> genes to obesity in Mexican children

<p>Abstract</p> <p>Background</p> <p>Recent genome wide association studies (GWAS) and previous positional linkage studies have identified more than 50 single nucleotide polymorphisms (SNPs) associated with obesity, mostly in Europeans. We aimed to assess the contribution of some of these SNPs to obesity risk and to the variation of related metabolic traits, in Mexican children.</p> <p>Methods</p> <p>The association of six European obesity-related SNPs in or near <it>FTO, NPC1, ENPP1, NEGR1, GNPDA2</it> and <it>MC4R</it> genes with risk of obesity was tested in 1,463 school-aged Mexican children (<it>N</it>_{<it>cases</it>} = 514; <it>N</it>_{<it>controls</it>} = 949). We also assessed effects of these SNPs on the variation of body mass index (BMI), fasting serum insulin levels, fasting plasma glucose levels, total cholesterol and triglyceride levels, in a subset of 1,171 nonobese Mexican children.</p> <p>Results</p> <p>We found a significant effect of <it>GNPDA2</it> rs10938397 on risk of obesity (odds ratio [OR] = 1.30; <it>P</it> = 1.34 × 10^-3). Furthermore, we found nominal associations between obesity risk or BMI variation and the following SNPs: <it>ENPP1</it> rs7754561, <it>MC4R</it> rs17782313 and <it>NEGR1</it> rs2815752. Importantly, the at-risk alleles of both <it>MC4R</it> rs17782313 and <it>NPC1</it> rs1805081 showed significant effect on increased fasting glucose levels (β = 0.36 mmol/L; <it>P</it> = 1.47 × 10^-3) and decreased fasting serum insulin levels (β = −0.10 μU/mL; <it>P</it> = 1.21 × 10^-3), respectively.</p> <p>Conclusion</p> <p>Our present results suggest that some obesity-associated SNPs previously reported in Europeans also associate with risk of obesity, or metabolic quantitative traits, in Mexican children. Importantly, we found new associations between <it>MC4R</it> and fasting glucose levels, and between <it>NPC1</it> and fasting insulin levels.</p