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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 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 (??=?0.109?±?0.050 (SE); p?=?2.73?×?10-2), fasting plasma glucose (??=?0.010?±?0.005 mmol/l; p?=?2.51?×?10-2) and systolic BP SD score (??=?0.026?±?0.012; p?=?3.32?×?10-2) as well as lower HDL-cholesterol (??=?-0.008?±?0.003 mmol/l; p?=?1.23?×?10-3), total fat-mass percentage (??=?-0.143?±?0.054%; p?=?9.15?×?10-3) and fat-mass percentage in the legs (??=?-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 (??=?-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.

SUBMITTER: Graae AS

PROVIDER: S-EPMC6061152 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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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 obese.

Graae Anne-Sofie AS Hollensted Mette M Kloppenborg Julie T JT Mahendran Yuvaraj Y Schnurr Theresia M TM Appel Emil Vincent R EVR Rask Johanne J Nielsen Tenna R H TRH Johansen Mia Ø MØ Linneberg Allan A Jørgensen Marit E ME Grarup Niels N Kadarmideen Haja N HN Holst Birgitte B Pedersen Oluf O Holm Jens-Christian JC Hansen Torben T

Diabetologia 20180531 8

<h4>Aims/hypothesis</h4>A genetic risk score (GRS) consisting of 53 insulin resistance variants (GRS<sub>53</sub>) was recently demonstrated to associate with insulin resistance in adults. We speculated that the GRS<sub>53</sub> 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 alter ...[more]

PMID: 29855666

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Project description:BackgroundFat mass (FM) in overweight/obese subjects has a primary role in determining low-grade chronic inflammation and, in turn, insulin resistance (IR) and ectopic lipid storage within the liver. Obesity, aging, and FM influence the growth hormone/insulin-like growth factor (IGF)-I axis, and chronic inflammation might reduce IGF-I signaling. Altered IGF-I axis is frequently observed in patients with Hepatic steatosis (HS). We tested the hypothesis that FM, or spleen volume and C-reactive protein (CRP)--all indexes of chronic inflammation--could affect the IGF-I axis status in overweight/obese, independently of HS.MethodsThe study population included 48 overweight/obese women (age 41 ± 13 years; BMI: 35.8 ± 5.8 kg/m2; range: 25.3-53.7), who underwent assessment of fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance (HOMA), cholesterol and triglycerides, HDL-cholesterol, transaminases, high-sensitive CRP, uric acid, IGF-I, IGF binding protein (BP)-1, IGFBP-3, and IGF-I/IGFBP-3 ratio. Standard deviation score of IGF-I according to age (zSDS) were also calculated. FM was determined by bioelectrical impedance analysis. HS severity grading (score 0-4 according liver hyperechogenicity) and spleen longitudinal diameter (SLD) were evaluated by ultrasound.ResultsMetabolic syndrome (MS) and HS were present in 33% and 85% of subjects, respectively. MS prevalence was 43% in subjects with increased SLD. IGF-I values, but not IGF-I zSDS, and IGF-I/IGFBP-3 ratio were significantly lower, while FM%, FPI, HOMA, ALT, CRP, were significantly higher in patients with severe HS than in those with mild HS. IGF-I zSDS (r = -0.42, r = -0.54, respectively; p < 0.05), and IGFBP-1 (r = -0.38, r = -0.42, respectively; p < 0.05) correlated negatively with HS severity and FM%. IGF-I/IGFBP-3 ratio correlated negatively with CRP, HS severity, and SLD (r = -0.30, r = -0.33, r = -0.43, respectively; p < 0.05). At multivariate analysis the best determinants of IGF-I were FM% (β = -0.49; p = 0.001) and IGFBP-1 (β = -0.32; p = 0.05), while SLD was in the IGF-I/IGFBP-3 ratio (β = -0.43; p = 0.004).ConclusionsThe present study suggests that lower IGF-I status in our study population is associated with higher FM, SLD, CRP and more severe HS.

Dataset Information

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.

Publications

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.

Similar Datasets

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