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Reappraising the stereotypes of diabetes in the modern diabetogenic environment

Nature Reviews Endocrinology volume 5, pages 483–489 (2009)Cite this article

Abstract

The prevailing concentration of blood glucose is a result of the integrated regulation of insulin secretion and insulin action. Nevertheless, the classic stereotypes of diabetes are dichotomous: type 1 diabetes mellitus (T1DM) is attributed to impaired insulin secretion, and type 2 diabetes mellitus (T2DM) is primarily attributed to impaired insulin action (insulin resistance). The available evidence indicates that this view is overly simplistic. Impaired insulin secretion (β-cell dysfunction) is also a feature of T2DM, and insulin resistance is also a risk factor for the development of T1DM. Moreover, with the increasing incidence of T2DM and T1DM in both developed and developing countries, attributed to environmental factors, the existence of 'hybrid' diabetes types that have clinical and pathogenetic features of both conditions is becoming clearly evident. A common thread across the spectrum of diabetes might be the activation of innate immunological and inflammatory pathways by a proinflammatory environment, which leads to β-cell dysfunction in T2DM, insulin resistance in both T2DM and T1DM, and enhanced adaptive immunity that kills β cells in T1DM. Embracing a holistic view of the diabetes syndrome will help us to understand the environmental basis for the epidemic of diabetes and improve preventative strategies.

Key Points

  • The incidences of both type 1 and type 2 diabetes mellitus have increased over the past half century in the developed world

  • Insulin deficiency and insulin resistance occur in both type 1 and type 2 diabetes

  • Environmental factors, including high-calorie and proinflammatory diets, sedentary lifestyles in sanitized indoor environments and vitamin D insufficiency amongst others, have contributed to the diabetes epidemic

  • Activation of innate immune responses by factors in the modern environment, in association with weight gain, might be a common mechanism that promotes all forms of diabetes

  • Clinicians and scientists must advocate public health policies that target the obesity–diabetes epidemic

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Figure 1: Gene–environment interactions that promote inflammatory mechanisms of diabetes.

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Acknowledgements

This work was funded by Program (516700) and Infrastructure (361646) grants from the National Health and Medical Research Council of Australia (NHMRC), a Victorian State Government Operational Infrastructure Support Grant, the Diabetes Australia Research Trust (DART) and the Royal Australian College of Physicians Research Foundation. J. M. Wentworth is a Doherty Fellow, and L. C. Harrison is a Senior Principal Research Fellow, of the NHMRC.

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  1. Autoimmunity & Transplantation Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, VIC, Australia

    John M. Wentworth, Spiros Fourlanos & Leonard C. Harrison

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  1. John M. Wentworth
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Correspondence to Leonard C. Harrison.

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Wentworth, J., Fourlanos, S. & Harrison, L. Reappraising the stereotypes of diabetes in the modern diabetogenic environment. Nat Rev Endocrinol 5, 483–489 (2009). https://doi.org/10.1038/nrendo.2009.149

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