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Heterogeneity in glucose response curves during an oral glucose tolerance test and associated cardiometabolic risk

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Abstract

We aimed to examine heterogeneity in glucose response curves during an oral glucose tolerance test with multiple measurements and to compare cardiometabolic risk profiles between identified glucose response curve groups. We analyzed data from 1,267 individuals without diabetes from five studies in Denmark, the Netherlands and the USA. Each study included between 5 and 11 measurements at different time points during a 2-h oral glucose tolerance test, resulting in 9,602 plasma glucose measurements. Latent class trajectories with a cubic specification for time were fitted to identify different patterns of plasma glucose change during the oral glucose tolerance test. Cardiometabolic risk factor profiles were compared between the identified groups. Using latent class trajectory analysis, five glucose response curves were identified. Despite similar fasting and 2-h values, glucose peaks and peak times varied greatly between groups, ranging from 7–12 mmol/L, and 35–70 min. The group with the lowest and earliest plasma glucose peak had the lowest estimated cardiovascular risk, while the group with the most delayed plasma glucose peak and the highest 2-h value had the highest estimated risk. One group, with normal fasting and 2-h values, exhibited an unusual profile, with the highest glucose peak and the highest proportion of smokers and men. The heterogeneity in glucose response curves and the distinct cardiometabolic risk profiles may reflect different underlying physiologies. Our results warrant more detailed studies to identify the source of the heterogeneity across the different phenotypes and whether these differences play a role in the development of type 2 diabetes and cardiovascular disease.

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Acknowledgments

A.H., R.K.S. and D.R.W. are supported by the Danish Diabetes Academy. The Danish Diabetes Academy is funded by the Novo Nordisk Foundation.

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Authors and Affiliations

  1. Department of Public Health, Section of Epidemiology, Aarhus University, Aarhus, Denmark

    Adam Hulman & Daniel R. Witte

  2. Danish Diabetes Academy, Odense, Denmark

    Adam Hulman, Rebecca K. Simmons & Daniel R. Witte

  3. Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary

    Adam Hulman

  4. Department of Public Health, Section of General Practice, Aarhus University, Aarhus, Denmark

    Rebecca K. Simmons

  5. MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK

    Rebecca K. Simmons

  6. Steno Diabetes Center, Gentofte, Denmark

    Dorte Vistisen & Kristine Færch

  7. 1st Department of Medicine, Semmelweis University Faculty of Medicine, Budapest, Hungary

    Adam G. Tabák

  8. Department of Epidemiology and Public Health, University College London, London, UK

    Adam G. Tabák

  9. Department of Biostatistics and Epidemiology, VU Medical Center, Amsterdam, Netherlands

    Jacqueline M. Dekker, Marjan Alssema, Femke Rutters & Anitra D. M. Koopman

  10. EMGO+ Institute for Health and Care Research, VU Medical Center, Amsterdam, Netherlands

    Jacqueline M. Dekker, Femke Rutters & Anitra D. M. Koopman

  11. Unilever Research and Development, Vlaardingen, Netherlands

    Marjan Alssema

  12. School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Edgbaston, UK

    Thomas P. J. Solomon

  13. Institute for Metabolism and Systems Research, University of Birmingham, Edgbaston, UK

    Thomas P. J. Solomon

  14. Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA

    John P. Kirwan

  15. Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Torben Hansen, Anna Jonsson, Anette Prior Gjesing, Oluf Pedersen & Thorkild I. A. Sørensen

  16. Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark

    Hans Eiberg

  17. Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark

    Arne Astrup

  18. Institute of Preventive Medicine, Frederiksberg and Bispebjerg University Hospital, The Capital Region, Copenhagen, Denmark

    Thorkild I. A. Sørensen

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  1. Adam Hulman
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Correspondence to Adam Hulman.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Hulman, A., Simmons, R.K., Vistisen, D. et al. Heterogeneity in glucose response curves during an oral glucose tolerance test and associated cardiometabolic risk. Endocrine 55, 427–434 (2017). https://doi.org/10.1007/s12020-016-1126-z

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