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Therapies to Preserve β-Cell Function in Type 1 Diabetes

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Abstract

In spite of modern techniques, the burden for patients with type 1 diabetes mellitus will not disappear, and type 1 diabetes will remain a life-threatening disease causing severe complications and increased mortality. We have to learn of ways to stop the destructive process, preserve residual insulin secretion or even improve the disease via β-cell regeneration. This will give a milder disease, a more stable metabolism, simpler treatment and perhaps even cure. Therapies based on single drugs have not shown sufficient efficacy; however, there are several treatments with encouraging efficacy and no apparent, or rather mild, adverse events. As the disease process is heterogeneous, treatments have to be chosen to fit relevant subgroups of patients, and step by step efficacy can possibly be improved by the use of combination therapies. Thus immunosuppressive therapies like anti-CD3 and anti-CD20 monoclonal antibodies might be combined with fusion proteins such as etanercept [tumor necrosis factor (TNF)-α inhibitor] and/or abatacept (CTLA4-Ig) early after onset to stop the destructive process, supported by β-cell protective agents. The effect may be prolonged by using autoantigen therapy [glutamate decarboxylase (GAD) proinsulin], and by adding agents facilitating β-cell regeneration [e.g. glucagon-like peptide-1 (GLP-1)] there should be a good chance to make the disease milder, perhaps leading to cure in some patients.

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Acknowledgments

In addition to the author, the Linköping Diabetes Immune Intervention study group consists of Assistant Professor Rosaura Casas, a number of postdoctoral researchers (currently Sri Elluru, Hugo Barcenilla, Saubashya Sur, Betatriz Iglesias) and PhD students including Linda Åkerman.

We are grateful to excellent technical assistance from Ingela Johansson and Gosia Smolinska, and from research nurses Eva Isacson and AnnMarie Sandström. All pediatricians involved in our studies are also gratefully acknowledged.

Our studies on immune intervention have been generously supported by Barndiabetesfonden (Swedish Child Diabetes Foundation), Swedish Research Council, Research Council of Southeast Sweden (FORSS), and the mechanistic studies are supported by the Juvenile Diabetes Research Foundation (JDFR).

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  1. Division of Pediatrics, Department of Clinical and Experimental Medicine, Linköping University, 58185, Linköping, Sweden

    Johnny Ludvigsson

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Correspondence to Johnny Ludvigsson.

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Diamyd Medical sponsored the phase II/III GAD trials and has also given unrestricted financial support for the investigator-initiated mechanistic studies connected to these trials. Honoraria for lectures have been received from NovoNordisk, Lilly and Sanofi Aventis., and as a member of Advisory Boards of LifeScan and DebioPharm.

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Ludvigsson, J. Therapies to Preserve β-Cell Function in Type 1 Diabetes. Drugs 76, 169–185 (2016). https://doi.org/10.1007/s40265-015-0511-x

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