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 Johansen; Allan Linneberg; Marit E. Jørgensen; Niels Grarup; Haja N. Kadarmideen; Birgitte Holst; Oluf Pedersen; Jens-Christian Holm; Torben Hansen

doi:10.1007/s00125-018-4640-0

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 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

Department of Clinical Medicine

5 Citations (Scopus)

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Abstract

Aims/hypothesis: 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. Methods: 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. Results: 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). Conclusions/interpretation: 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 language	English
Journal	Diabetologia
Volume	61
Issue number	8
Pages (from-to)	1769-1779
ISSN	0012-186X
DOIs	https://doi.org/10.1007/s00125-018-4640-0
Publication status	Published - Aug 2018

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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 obeseFinal published version, 756 KBLicence: CC BY

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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., 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

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. / Graae, Anne Sofie; Hollensted, Mette; Kloppenborg, Julie T. et al.
In: Diabetologia, Vol. 61, No. 8, 08.2018, p. 1769-1779.

Research output: Contribution to journal › Journal article › Research › peer-review

Graae, AS, Hollensted, M, Kloppenborg, JT, Mahendran, Y, Schnurr, TM, Appel, EVR, Rask, J, Nielsen, TRH, Johansen, M, Linneberg, A, Jørgensen, ME, Grarup, N, Kadarmideen, HN, 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, vol. 61, no. 8, pp. 1769-1779. https://doi.org/10.1007/s00125-018-4640-0

@article{e8f3bfb6ebf74734b8ad7afe93d8e23a,

title = "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",

abstract = "Aims/hypothesis: 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. Methods: 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. Results: 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). Conclusions/interpretation: 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.",

keywords = "Epidemiology, Genetic association, Genetic risk score, Genetics, Insulin resistance, Insulin sensitivity, Obesity, Paediatric obesity, Weight regulation",

author = "Graae, {Anne Sofie} and Mette Hollensted and Kloppenborg, {Julie T.} and Yuvaraj Mahendran and Schnurr, {Theresia M.} and Appel, {Emil Vincent R.} and Johanne Rask and Nielsen, {Tenna R.H.} and Mia Johansen and Allan Linneberg and J{\o}rgensen, {Marit E.} and Niels Grarup and Kadarmideen, {Haja N.} and Birgitte Holst and Oluf Pedersen and Jens-Christian Holm and Torben Hansen",

year = "2018",

month = aug,

doi = "10.1007/s00125-018-4640-0",

language = "English",

volume = "61",

pages = "1769--1779",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer",

number = "8",

}

TY - JOUR

T1 - 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

AU - Graae, Anne Sofie

AU - Hollensted, Mette

AU - Kloppenborg, Julie T.

AU - Mahendran, Yuvaraj

AU - Schnurr, Theresia M.

AU - Appel, Emil Vincent R.

AU - Rask, Johanne

AU - Nielsen, Tenna R.H.

AU - Johansen, Mia

AU - Linneberg, Allan

AU - Jørgensen, Marit E.

AU - Grarup, Niels

AU - Kadarmideen, Haja N.

AU - Holst, Birgitte

AU - Pedersen, Oluf

AU - Holm, Jens-Christian

AU - Hansen, Torben

PY - 2018/8

Y1 - 2018/8

N2 - Aims/hypothesis: 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. Methods: 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. Results: 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). Conclusions/interpretation: 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.

AB - Aims/hypothesis: 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. Methods: 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. Results: 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). Conclusions/interpretation: 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.

KW - Epidemiology

KW - Genetic association

KW - Genetic risk score

KW - Genetics

KW - Insulin resistance

KW - Insulin sensitivity

KW - Obesity

KW - Paediatric obesity

KW - Weight regulation

U2 - 10.1007/s00125-018-4640-0

DO - 10.1007/s00125-018-4640-0

M3 - Journal article

C2 - 29855666

AN - SCOPUS:85047897958

SN - 0012-186X

VL - 61

SP - 1769

EP - 1779

JO - Diabetologia

JF - Diabetologia

IS - 8

ER -

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

Abstract

Keywords

UN SDGs

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