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Clinical Studies and Practice

Overall and central obesity with insulin sensitivity and secretion in a Han Chinese population: a Mendelian randomization analysis

International Journal of Obesity volume 40, pages 1736–1741 (2016)Cite this article

Subjects

Abstract

Background/Objectives:

Clinical heterogeneity exists in overall obesity and obesity in terms of susceptibility to type 2 diabetes, but the relationship is vulnerable to be confounded by traditional risk factors in epidemiological studies. We aimed to characterize the impact of obesity in insulin secretion and sensitivity by using Mendelian randomization (MR) approach with genetic variants.

Subjects/Methods:

We first constructed two genetic risk scores based on 38 established loci for body mass index (BMI; a surrogate of overall obesity) and 13 waist-to-hip ratio (WHR; a surrogate of central obesity) to assess the causal effects of BMI and WHR on several glycaemic-related traits in 2884 community-based Han Chinese individuals.

Results:

Both of BMI and WHR were observationally correlated with insulin secretion and sensitivity indices. The MR analysis demonstrated that a genetically determined 1 s.d. (3.35 kg m−2) higher BMI caused a unit of 178.18 pmol l−1 higher Stumvoll first-phase and 35.52 pmol l−1 higher Stumvoll second-phase insulin secretion (P=0.001 and 0.002, respectively), which were even independent of central obesity (P=0.019 and 0.039, respectively). In contrast, a genetically determined 1 s.d. higher WHR (a change of 0.002 in WHR) caused a unit of 1.21 higher homeostasis model assessment of insulin resistance and 18.40 lower Gutt index (representing the insulin sensitivity) (P=0.048 and 0.028, respectively). No substantial heterogeneity existed between the observed associations and the genetic estimated associations (P for difference >0.05).

Conclusions:

We provide new causal evidence that the impact of obesity on insulin secretion and sensitivity could vary between overall obesity and central obesity in Han Chinese populations and also identify the extent to which overall obesity affects compensatory insulin secretion and central obesity inversely links to insulin sensitivity.

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Acknowledgements

This work is supported by 973 Program of China (2013CB530606), program from National Natural Science Foundation of China grants (81322010, 81300619 and 81570713), The Shanghai Jiaotong Medical/Engineering Foundation (YG2014MS18), National Program for Support of Top-notch Young Professionals and grants from the State Key Laboratory of Medical Genomics, Youth research project of Shanghai Municipal Health Bureau (20134Y048). We thank all the research volunteers and cooperative workers for their participation.

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Author notes

  1. T Wang, X Ma and T Tang: These authors contributed equally to this work.

Authors and Affiliations

  1. Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

    T Wang, X Ma, D Peng, R Zhang, M Chen, J Yan, S Wang, D Yan, Z He, F Jiang, Y Bao, C Hu & W Jia

  2. Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China

    T Tang & X Cheng

  3. National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China

    L Jin & Z Liu

  4. Institute for Metabolic Diseases, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital South Campus, Shanghai, China

    C Hu

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  1. T Wang
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  16. C Hu
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Corresponding authors

Correspondence to C Hu or W Jia.

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Supplementary Information accompanies this paper on International Journal of Obesity website

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Wang, T., Ma, X., Tang, T. et al. Overall and central obesity with insulin sensitivity and secretion in a Han Chinese population: a Mendelian randomization analysis. Int J Obes 40, 1736–1741 (2016). https://doi.org/10.1038/ijo.2016.155

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