TY - JOUR
T1 - Genetic predisposition to higher body fat yet lower cardiometabolic risk in children and adolescents
AU - Viitasalo, Anna
AU - Schnurr, Theresia Maria
AU - Pitkänen, Niina
AU - Hollensted, Mette
AU - Nielsen, Tenna R H
AU - Pahkala, Katja
AU - Lintu, Niina
AU - Lind, Mads Vendelbo
AU - Atalay, Mustafa
AU - Frithioff-Bøjsøe, Christine
AU - Fonvig, Cilius Esmann
AU - Grarup, Niels
AU - Kähönen, Mika
AU - Larnkjær, Anni
AU - Pedersen, Oluf Borbye
AU - Holm, Jens-Christian
AU - Michaelsen, Kim F.
AU - Lakka, Timo A
AU - Lehtimäki, Terho
AU - Raitakari, Olli
AU - Hansen, Torben
AU - Kilpeläinen, Tuomas Oskari
N1 - CURIS 2019 NEXS 228
PY - 2019
Y1 - 2019
N2 - Background: Most obese children show cardiometabolic impairments, such as insulin resistance, dyslipidemia, and hypertension. Yet some obese children retain a normal cardiometabolic profile. The mechanisms underlying this variability remain largely unknown. We examined whether genetic loci associated with increased insulin sensitivity and relatively higher fat storage on the hip than on the waist in adults are associated with a normal cardiometabolic profile despite higher adiposity in children.Methods: We constructed a genetic score using variants previously linked to increased insulin sensitivity and/or decreased waist-hip ratio adjusted for body mass index (BMI), and examined the associations of this genetic score with adiposity and cardiometabolic impairments in a meta-analysis of six cohorts, including 7391 European children aged 3-18 years.Results: The genetic score was significantly associated with increased degree of obesity (higher BMI-SDS beta = 0.009 SD/allele, SE = 0.003, P = 0.003; higher body fat mass beta = 0.009, SE = 0.004, P = 0.031), yet improved body fat distribution (lower WHRadjBMI beta = -0.014 SD/allele, SE = 0.006, P = 0.016), and favorable concentrations of blood lipids (higher HDL cholesterol: beta = 0.010 SD/allele, SE = 0.003, P = 0.002; lower triglycerides: beta = -0.011 SD/allele, SE = 0.003, P = 0.001) adjusted for age, sex, and puberty. No differences were detected between prepubertal and pubertal/postpubertal children. The genetic score predicted a normal cardiometabolic profile, defined by the presence of normal glucose and lipid concentrations, among obese children (OR = 1.07 CI 95% 1.01-1.13, P = 0.012, n = 536).Conclusions: Genetic predisposition to higher body fat yet lower cardiometabolic risk exerts its influence before puberty.
AB - Background: Most obese children show cardiometabolic impairments, such as insulin resistance, dyslipidemia, and hypertension. Yet some obese children retain a normal cardiometabolic profile. The mechanisms underlying this variability remain largely unknown. We examined whether genetic loci associated with increased insulin sensitivity and relatively higher fat storage on the hip than on the waist in adults are associated with a normal cardiometabolic profile despite higher adiposity in children.Methods: We constructed a genetic score using variants previously linked to increased insulin sensitivity and/or decreased waist-hip ratio adjusted for body mass index (BMI), and examined the associations of this genetic score with adiposity and cardiometabolic impairments in a meta-analysis of six cohorts, including 7391 European children aged 3-18 years.Results: The genetic score was significantly associated with increased degree of obesity (higher BMI-SDS beta = 0.009 SD/allele, SE = 0.003, P = 0.003; higher body fat mass beta = 0.009, SE = 0.004, P = 0.031), yet improved body fat distribution (lower WHRadjBMI beta = -0.014 SD/allele, SE = 0.006, P = 0.016), and favorable concentrations of blood lipids (higher HDL cholesterol: beta = 0.010 SD/allele, SE = 0.003, P = 0.002; lower triglycerides: beta = -0.011 SD/allele, SE = 0.003, P = 0.001) adjusted for age, sex, and puberty. No differences were detected between prepubertal and pubertal/postpubertal children. The genetic score predicted a normal cardiometabolic profile, defined by the presence of normal glucose and lipid concentrations, among obese children (OR = 1.07 CI 95% 1.01-1.13, P = 0.012, n = 536).Conclusions: Genetic predisposition to higher body fat yet lower cardiometabolic risk exerts its influence before puberty.
U2 - 10.1038/s41366-019-0414-0
DO - 10.1038/s41366-019-0414-0
M3 - Journal article
C2 - 31332278
VL - 43
SP - 2007
EP - 2016
JO - International Journal of Obesity
JF - International Journal of Obesity
SN - 0307-0565
ER -