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- Title
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.
- Authors
Thankamony, Ajay; Jensen, Rikke Beck; O'Connell, Susan M; Day, Felix; Kirk, Jeremy; Donaldson, Malcolm; Ivarsson, Sten A; Söder, Olle; Roche, Edna; Hoey, Hilary; Ong, Ken K; Dunger, David B; Juul, Anders
- Abstract
<bold>Background: </bold>Genetic susceptibility to insulin resistance is associated with lower adiposity in adults. Insulin resistance, and therefore adiposity, may alter sensitivity to 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).<bold>Methods: </bold>In 89 short prepubertal SGA children (age, 6.2 ± 1.6 y; 55 boys) treated with GH for 1 year in a multicenter study, body fat percentage was estimated at baseline and 1 year using dual-energy x-ray absorptiometry. The main outcome measures were treatment-related changes in height, IGF-1 standard deviation score, insulin sensitivity, insulin secretion, and disposition index. Combined multiallele gene scores based on single nucleotide polymorphisms with known associations with lower insulin sensitivity (gene scores for insulin resistance [GS-InRes]) and insulin secretion (gene scores for insulin secretion [GS-InSec]) were analyzed for their relationships with adiposity.<bold>Results: </bold>Mean percentage body fat at baseline was low compared to normative data (P = .045) and decreased even further on GH treatment (baseline vs 1-year z-scores, -0.26 ± 1.2 vs -1.23 ± 1.54; P < .0001). Baseline percentage body fat was positively associated with IGF-1 responses (p-trends = .042), first-year height gains (B [95% confidence interval], 0.61 cm/y [0.28,0.95]; P < .0001), insulin secretion at baseline (p-trends = .020) and 1 year (p-trends = .004), and disposition index at 1 year (p-trends = .024). GS-InRes was inversely associated with body mass index (-0.13 SD score per allele [-0.26, -0.01]; P = .040), body fat (-0.49% per allele [-0.97, -0.007]; P = .047), and limb fat (-0.81% per allele [-1.62, 0.00]; P = .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 = .001) and a higher trunk-limb fat ratio at 1 year (0.04 per allele [0.01, 0.08]; P = .008). GS-InSec was positively associated with truncal fat (0.36% per allele [0.09, 0.63]; P = .009).<bold>Conclusions: </bold>Adiposity in SGA children has favorable effects on GH sensitivity and glucose metabolism. The associations with multiallele scores support a causal role of insulin resistance in linking lesser body fat to reduced sensitivity to exogenous GH.
- Subjects
RECOMBINANT proteins; HUMAN growth hormone; GLUCOSE metabolism; ADIPOSE tissues; BIRTH size; BODY composition; HUMAN body composition; DIAGNOSIS; DIGESTIVE organs; GENETICS; INSULIN; INSULIN resistance; ISLANDS of Langerhans; RESEARCH funding; SOMATOMEDIN; STATURE; TREATMENT effectiveness; PHOTON absorptiometry; GENOTYPES; THERAPEUTICS
- Publication
Journal of Clinical Endocrinology & Metabolism, 2016, Vol 101, Issue 1, p131
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2015-3019