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Int J Obes (Lond). 2019 Jul 22. doi: 10.1038/s41366-019-0414-0. [Epub ahead of print]

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

Author information

1
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. anna.viitasalo@uef.fi.
2
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
3
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
4
The Children's Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark.
5
Department of Pediatrics, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
6
Paavo Nurmi Centre, Sports and Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku, Turku, Finland.
7
Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
8
Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
9
The Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.
10
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland.
11
Faculty of Medicine and Health Technology, Finnish Cardiovascular Research Center, Tampere University, Tampere, Finland.
12
University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark.
13
Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
14
Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
15
Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
16
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.

Abstract

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.

PMID:
31332278
DOI:
10.1038/s41366-019-0414-0

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