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Increased BMI in the normal range has a negative effect on cardiometabolic risk markers

PLOS

Increases in excess fat adversely affect multiple cardiometabolic risk markers even in lean young adults according to a new study published this week in PLOS Medicine. The study by Peter Würtz from the University of Oulu, Finland, and colleagues suggests that, even within the range of body-mass index (BMI) considered to be healthy, there is no threshold below which a BMI increase does not adversely affect the metabolic profile of an individual.

Adiposity, or having excess body fat, is a growing global threat to public health. Compared to people with a lean body weight, individuals with higher BMI have an elevated risk of developing life-shortening cardiometabolic diseases, such as diabetes, heart attack, and stroke. In their study Dr. Würtz and colleagues used a technique called Mendelian randomization to assess whether increases in BMI in 12,664 mostly non-obese adolescents and young adults causally affects multiple cardiometabolic risk markers (82 molecules measured in their blood at a single time point). The authors found that adiposity adversely influences not only cholesterol and blood sugar levels, but also causes many other metabolic abnormalities across different metabolic pathways.

In a further analysis in which the authors studied the change in BMI and cardiometabolic risk markers of 1,488 young adults over 6 years, the authors found that the cardiometabolic risk profile of an individual was highly responsive to weight change over time.

The authors conclude, "[t]he ideal body weight that healthy adults should strive to attain remains controversial... The present study suggests widespread adverse metabolic effects with any increase in BMI among young adults within the non-obese weight range. However, modest weight loss was accompanied by multiple favorable changes in the systemic metabolite profile. The causative effect of adiposity on multiple cardiometabolic risk markers across the metabolite profile highlights the importance of population-level weight reduction as a key target for comprehensive risk factor control among young adults."

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Research Article

Funding: This study was supported by the Academy of Finland (grant no. 137870, 139635, 250422,136895,263836, 134309, 117797, 41071, 266286, 104781, 120315, 129418), and the Responding to Public Health Challenges Research Programme of the Academy of Finland (129269, 129429, 126925, 121584, 124282, 129378), and the Center of Excellence in Complex Disease Genetics, the Sigrid Juselius Foundation, the Yrjo¨ Jahnsson Foundation, the Finnish Foundation for Cardiovascular Research, the Finnish Diabetes Research Foundation; Oulu, Helsinki, Kuopio, Tampere, and Turku University Central Hospital Medical Funds, Biocenter Oulu, the Novo Nordisk Foundation, the Emil Aaltonen Foundation, the Paavo Nurmi Foundation, the Jenny and Antti Wihuri Foundation, the Juho

Vainio Foundation, the Finnish Cultural Foundation, the Finnish Funding Agency for Technology and Innovation, Strategic Research Funding from the University of Oulu, the Social Insurance Institution of Finland, the UK National Institute of Health Research (NIHR) Biomedical Research Centre at Imperial College Health Care NHS Trust and Imperial College London, the Medical Research Council UK, the US National Heart, Lung, and Blood Institute (5R01HL087679), the US National Institute of Mental Health (1RL1MH083268), the European Network of Genomic and Genetic Epidemiology project, and the European Union Seventh Framework Programme (BiomarCaRE: HEALTH-F2-2011-278913 and EurHEALTHAgeing: 277849). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: PW, AJK, PS, and MAK are shareholders of Brainshake Ltd, a startup company offering NMR-based metabolite profiling. SB has received research funding from Abbott, Abbott Diagnostics, Bayer, Boehringer Ingelheim, SIEMENS, and Thermo Fisher. SB has received honoraria for lectures from Abbott, Abbott Diagnostics, Astra Zeneca, Bayer, Boehringer Ingelheim, Medtronic, Pfizer, Roche, SIEMENS Diagnostics, SIEMENS, Thermo Fisher, and as member of Advisory Boards and for consulting for Boehringer Ingelheim, Bayer, Novartis, Roche, and Thermo Fisher. GDS is a member of the Editorial Board of PLOS Medicine. All other authors declare that no competing interests exist.

Citation: Würtz P, Wang Q, Kangas AJ, Richmond RC, Skarp J, et al. (2014) Metabolic Signatures of Adiposity in Young Adults: Mendelian Randomization Analysis and Effects of Weight Change. PLoS Med 11(12): e1001765. doi:10.1371/journal.pmed.1001765

Author Affiliations:

University of Oulu, FINLAND
University of Helsinki, FINLAND
University of Eastern Finland, FINLAND
University of Bristol, UNITED KINGDOM
National Institute for Health and Welfare, FINLAND
University of Turku and Turku University Hospital, FINLAND
University of Tampere and Tampere University Hospital, FINLAND
University Heart Center Hamburg, GERMANY
Finnish Institute of Occupational Health, FINLAND
Central Finland Central Hospital, FINLAND
Imperial College London, UNITED KINGDOM
Helsinki University Central Hospital, FINLAND
Wellcome Trust Sanger Institute, UNITED KINGDOM

Contact:

Peter Würtz
University of Oulu
FINLAND
+358 504670900
peter.wurtz@computationalmedicine.fi
http://www.computationalmedicine.fi

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