Type 2 diabetes mellitus—an autoimmune disease?


Inflammation-induced inhibition of the insulin signalling pathway can lead to insulin resistance and contribute to the development of type 2 diabetes mellitus (T2DM). Obesity and insulin resistance are associated with a chronic but subclinical inflammatory process that impairs insulin action in most tissues and could also hamper pancreatic β-cell function. The involvement of monocytic cells and the profiles of the chemokines and cytokines induced by this inflammation suggest an innate immune response. However, emerging data indicate that elements of the adaptive immune system could also be involved. As activation of an adaptive response requires antigen specificity, some researchers have hypothesized that T2DM evolves from an innate immune response to an autoimmune condition. In this Perspectives article, we present the arguments for and against this hypothesis and discuss which mechanisms could be involved in a putative switch from innate immunity to autoimmunity.

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Figure 1: Putative pathways of progression from innate to adaptive immune responses in obesity and type 2 diabetes mellitus.


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The authors' research is supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (Brazil), the Communauté Française de Belgique—Actions de Recherche Concertées, and the European Union projects Naimit and BetaBat, in the Framework Programme 7 of the European Community. The authors are also grateful to Mark Peakman of King's College London, UK, and Bart Roep of Leiden University Medical Centre, The Netherlands, for helpful discussions.

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The authors contributed equally to all aspects of this article.

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Correspondence to Lício A. Velloso.

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Velloso, L., Eizirik, D. & Cnop, M. Type 2 diabetes mellitus—an autoimmune disease?. Nat Rev Endocrinol 9, 750–755 (2013). https://doi.org/10.1038/nrendo.2013.131

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