Adiposity in children born small for gestational age is associated with β-cell function, genetic variants for insulin resistance and response to growth hormone treatment
Jensen, Rikke Beck
O’Connell, Susan M
Journal of Clinical Endocrinology & Metabolism
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Thankamony, A., Jensen, R. B., O’Connell, S. M., Day, F., Kirk, J., Donaldson, M., Ivarsson, S., et al. (2015). Adiposity in children born small for gestational age is associated with β-cell function, genetic variants for insulin resistance and response to growth hormone treatment. Journal of Clinical Endocrinology & Metabolism, 101 131-142. https://doi.org/10.1210/jc.2015-3019
Background: Genetic susceptibility to insulin resistance is associated with lower adiposity in adults. Insulin resistance, and therefore adiposity, may alter sensitivity to Growth Hormone (GH). We aimed to determine the relationship between adiposity, genetic susceptibility to insulin resistance or insulin secretion, and response to GH treatment in short children born small for gestational age (SGA). Methods: In 89 (55 boys) short prepubertal SGA children (age, 6.2±1.6years) treated with GH for one year in a multicentre study, body fat percentage was estimated at baseline and 1-year using DXA. The main outcome measures were treatment-related changes in height, IGF-1 standard deviation scores (SDS), insulin sensitivity, insulin secretion and disposition index. Combined multiallele gene scores based on single nucleotide polymorphisms with known associations with lower insulin sensitivity (GS-InRes) and insulin secretion (GS-InsSec) were analysed for their relationships with adiposity. Results: Mean percentage body fat at baseline was low compared to normative data (p=0.045), and decreased even further on GH treatment (baseline vs 1-year z-scores, -0.26±1.2 vs -1.23±1.54; p<0.0001). Baseline percentage body fat was positively associated with IGF-1 responses (p-trends=0.042), first-year height gains (B[95%CI]:0.61cm/year [0.28,0.95]; p<0.0001), insulin secretion at baseline (p-trends=0.020) and at 1-year (p-trends=0.004), and disposition index at 1-year (p-trends=0.024). GS-InRes was inversely associated with BMI (-0.13 SDS per-allele [-0.26,-0.01]; p=0.040), body fat (-0.49% per-allele [-0.97,-0.007]; p=0.047), and limb fat (-0.81% per-allele [-1.62,0.00]; p=0.049) at baseline. During GH treatment, GS-InRes was related to a lesser decline in trunk fat (0.38% per-allele [0.16,0.59]; p=0.001) and a higher trunk-limb fat ratio at 1-year (0.04 per-allele [0.01,0.08]; p=0.008). GS-InSec was positively associated with truncal fat (0.36% per-allele [0.09,0.63]; p=0.009). Conclusions: A diposity in SGA children has favourable effects on GH sensitivity and glucose metabolism. The associations with multiallele scores support a causal role of insulin resistance in linking lower body fat to reduced sensitivity to exogenous GH.
This study was funded by research grants from the Danish Council for Independent Research/Medical Sciences and Novo Nordisk A/S. The research work was also supported by International Center for Research and Research Training in Endocrine Disrupting Effects on Male Reproduction and Child Health (EDMaRC), Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Denmark.
EC FP7 CP (305485)
Medical Research Council (MC_U106179472)
External DOI: https://doi.org/10.1210/jc.2015-3019
This record's URL: https://www.repository.cam.ac.uk/handle/1810/252677