Genetic predisposition to higher body fat yet lower cardiometabolic risk in children and adolescents

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Anna Viitasalo, Theresia Maria Schnurr, Niina Pitkänen, Mette Hollensted, Tenna R H Nielsen, Katja Pahkala, Niina Lintu, Mads Vendelbo Lind, Mustafa Atalay, Christine Frithioff-Bøjsøe, Cilius Esmann Fonvig, Niels Grarup, Mika Kähönen, Anni Larnkjær, Oluf Borbye Pedersen, Jens-Christian Holm, Kim F. Michaelsen, Timo A Lakka, Terho Lehtimäki, Olli Raitakari & 2 andre Torben Hansen, Tuomas Oskari Kilpeläinen

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.

OriginalsprogEngelsk
TidsskriftInternational Journal of Obesity
ISSN0307-0565
DOI
StatusE-pub ahead of print - 22 jul. 2019

Bibliografisk note

CURIS 2019 NEXS 228

ID: 224898619