An adult-based insulin resistance genetic risk score associates with insulin resistance, metabolic traits and altered fat distribution in Danish children and adolescents who are overweight or obese

Anne-Sofie Graae, Mette Hollensted, Julie T Kloppenborg, Yuvaraj Mahendran, Theresia M Schnurr, Emil Vincent R Appel, Johanne Rask, Tenna R H Nielsen, Mia Ø Johansen, Allan Linneberg, Marit E Jørgensen, Niels Grarup, Haja N Kadarmideen, Birgitte Holst, Oluf Pedersen, Jens-Christian Holm, Torben Hansen*

*Corresponding author for this work

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    Abstract

    A genetic risk score (GRS) consisting of 53 insulin resistance variants (GRS53) was recently demonstrated to associate with insulin resistance in adults. We speculated that the GRS53 might already associate with insulin resistance during childhood, and we therefore aimed to investigate this in populations of Danish children and adolescents. Furthermore, we aimed to address whether the GRS associates with components of the metabolic syndrome and altered body composition in children and adolescents. We examined a total of 689 children and adolescents who were overweight or obese and 675 children and adolescents from a population-based study. Anthropometric data, dual-energy x-ray absorptiometry scans, BP, fasting plasma glucose, fasting serum insulin and fasting plasma lipid measurements were obtained, and HOMA-IR was calculated. The GRS53 was examined for association with metabolic traits in children by linear regressions using an additive genetic model. In overweight/obese children and adolescents, the GRS53 associated with higher HOMA-IR (β = 0.109 ± 0.050 (SE); p = 2.73 × 10-2), fasting plasma glucose (β = 0.010 ± 0.005 mmol/l; p = 2.51 × 10-2) and systolic BP SD score (β = 0.026 ± 0.012; p = 3.32 × 10-2) as well as lower HDL-cholesterol (β = -0.008 ± 0.003 mmol/l; p = 1.23 × 10-3), total fat-mass percentage (β = -0.143 ± 0.054%; p = 9.15 × 10-3) and fat-mass percentage in the legs (β = -0.197 ± 0.055%; p = 4.09 × 10-4). In the population-based sample of children, the GRS53 only associated with lower HDL-cholesterol concentrations (β = -0.007 ± 0.003 mmol/l; p = 1.79 × 10-2). An adult-based GRS comprising 53 insulin resistance susceptibility SNPs associates with insulin resistance, markers of the metabolic syndrome and altered fat distribution in a sample of Danish children and adolescents who were overweight or obese.
    Original languageEnglish
    JournalDiabetologia
    Volume61
    Issue number8
    Pages (from-to)1769-1779
    Number of pages11
    ISSN0012-186X
    DOIs
    Publication statusPublished - 2018

    Bibliographical note

    This article is distributed under the terms of the Creative Commons At tribution 4.0 International License (http:/ /creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

    Keywords

    • Epidemiology
    • Genetic association
    • Genetic risk score
    • Genetics
    • Insulin resistance
    • Insulin sensitivity
    • Obesity
    • Paediatric obesity
    • Weight regulation

    Cite this

    Graae, A-S., Hollensted, M., Kloppenborg, J. T., Mahendran, Y., Schnurr, T. M., Appel, E. V. R., Rask, J., Nielsen, T. R. H., Johansen, M. Ø., Linneberg, A., Jørgensen, M. E., Grarup, N., Kadarmideen, H. N., Holst, B., Pedersen, O., Holm, J-C., & Hansen, T. (2018). An adult-based insulin resistance genetic risk score associates with insulin resistance, metabolic traits and altered fat distribution in Danish children and adolescents who are overweight or obese. Diabetologia, 61(8), 1769-1779. https://doi.org/10.1007/s00125-018-4640-0