Targeting inflammation in the treatment of type 2 diabetes: time to start

Key Points

  • Inflammation has an important role in the pathogenesis of type 2 diabetes and associated complications.

  • Clinical studies have demonstrated that interleukin-1 (IL-1) antagonists, salsalate and tumour necrosis factor (TNF) antagonists improve glucose metabolism.

  • Anti-inflammatory drugs may have disease-modifying and long-lasting effects.

  • Future genetic and biomarker studies may profile responders to a specific anti-inflammatory treatment.

  • Combining or sequentially using multiple anti-inflammatory drugs may provide a tailored solution for treating patients with type 2 diabetes.

Abstract

The role of inflammation in the pathogenesis of type 2 diabetes and associated complications is now well established. Several conditions that are driven by inflammatory processes are also associated with diabetes, including rheumatoid arthritis, gout, psoriasis and Crohn's disease, and various anti-inflammatory drugs have been approved or are in late stages of development for the treatment of these conditions. This Review discusses the rationale for the use of some of these anti-inflammatory treatments in patients with diabetes and what we could expect from their use. Future immunomodulatory treatments may not target a specific disease, but could instead act on a dysfunctional pathway that causes several conditions associated with the metabolic syndrome.

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Figure 1: The development of type 2 diabetes.
Figure 2: Islet inflammation in type 2 diabetes.
Figure 3: Storage of excessive nutrients in adipose tissues leads to an inflammatory response and insulin resistance.

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Acknowledgements

The author wishes to thank his scientific collaborators who have contributed so much to these studies, in particular K. Maedler, M. Faulenbach, C. M. Larsen, D. M. Schumann, J. Ehses, H. Ellingsgaard, C. Cavelti-Weder, K. Timper, M. Böni-Schnetzler, P. A. Halban, T. Mandrup Poulsen and C. A. Dinarello.

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Correspondence to Marc Y. Donath.

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M.Y.D. is listed as the inventor on a patent (WO6709) filed in 2003 for the use of an interleukin-1 receptor antagonist for the treatment of, or prophylaxis against, type 2 diabetes.

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Donath, M. Targeting inflammation in the treatment of type 2 diabetes: time to start. Nat Rev Drug Discov 13, 465–476 (2014). https://doi.org/10.1038/nrd4275

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