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Susceptibility to type 2 diabetes mellitus—from genes to prevention

Nature Reviews Endocrinology volume 10, pages 198–205 (2014)Cite this article

Subjects

Key Points

  • Over the past few years, more than 65 genetic loci associated with type 2 diabetes mellitus (T2DM) have been discovered that reveal novel biologic pathways

  • Clinical T2DM prediction models are improved by the addition of information about genetic risk variants

  • Genetic risk scores that aggregate risk variants can predict incident T2DM in populations of diverse ethnic background and age range

  • Lifestyle interventions targeting moderate weight loss lower the risk of T2DM, independent of the genetic burden, and might have increased benefit among individuals at high genetic risk

Abstract

Knowledge of the genetics of type 2 diabetes mellitus (T2DM) has evolved tremendously over the past few years. Following advances in technology and analytical approaches, collaborative case–control genome-wide association studies have revealed up to 65 loci credibly associated with T2DM. Prospective population studies have demonstrated that aggregated genetic risk scores, so-called because they sum the genetic risk attributed to each locus, can predict incident T2DM among individuals of various age ranges and diverse ethnic backgrounds. With each set of T2DM loci discovered, increasing the number of loci in these scores has improved their predictive ability, although a prediction plateau may already have been reached. The current literature shows that intensive lifestyle interventions are effective for preventing T2DM at any level of genetic risk and might be particularly efficacious among individuals with high genetic susceptibility. By contrast, counselling to inform patients about their personal T2DM genetic risk profiles does not seem to improve motivation or attitudes that lead to positive lifestyle behaviour changes. Future studies should investigate the role of genetics for both T2DM prediction and prevention in young populations in the hope of reducing disease burden for future generations.

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Figure 1: Cumulative number of T2DM loci discovered and T2DM risk per risk allele, by year, since 2000.
Figure 2: Prediction of T2DM in the Framingham Offspring Study adding genetic risk scores to a clinical prediction model.
Figure 3: Net NRI values of adding genetic risk scores to clinical prediction models according to the age at baseline.
Figure 4: Outcome of intensive lifestyle intervention in the Diabetes Prevention Program.

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Author information

Authors and Affiliations

  1. Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, 50 Staniford Street, 9th floor, Boston, 02114, MA, USA

    Marie-France Hivert

  2. Section of General Internal Medicine, VA Boston Healthcare System, Harvard Medical School, 50 Staniford Street, 9th floor, Boston, 02114, MA, USA

    Jason L. Vassy

  3. General Medicine Division, Massachusetts General Hospital, Harvard Medical School, 50 Staniford Street, 9th floor, Boston, 02114, MA, USA

    James B. Meigs

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  1. Marie-France Hivert
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All authors researched the data for the article and provided a substantial contribution to discussions of the content. M.-F.H. and J.L.V. contributed equally to writing the article. J.B.M. reviewed and edited the manuscript before submission.

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Correspondence to Marie-France Hivert.

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Hivert, MF., Vassy, J. & Meigs, J. Susceptibility to type 2 diabetes mellitus—from genes to prevention. Nat Rev Endocrinol 10, 198–205 (2014). https://doi.org/10.1038/nrendo.2014.11

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