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Promises and pitfalls of beta cell–replacement therapies

Nature Metabolism volume 3, pages 1036–1037 (2021)Cite this article

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Diabetes therapeutic approaches continue to expand and to be refined. As the field moves toward more intensive insulin- and cell-based therapies, care must be taken to mimic healthy physiological insulin dynamics and avoid hyperinsulinemia, with its deleterious downstream complications.

The goal of any treatment for diabetes mellitus is achieving optimal glycaemic control with the consequent aim of decreasing the disease complications that result from glycaemic volatility, chronic hyperglycaemia and other metabolic perturbations. This objective is true for both type 1 diabetes (T1D), a result of the autoimmune destruction of a substantial proportion of beta cells, and type 2 diabetes (T2D), which occurs when insufficient functional beta cells are present to meet the body’s demands. The current clinical standard of care is provision of exogenous insulin for all patients with T1D as well as for an increasing number of patients with T2D. The discovery of insulin in 1921 saved millions of lives over the past 100 years, and at present no viable alternatives to exogenous insulin therapy are available for most patients with T1D and advanced T2D. The benefits of exogenous insulin are many, but it is not a cure, and this treatment regimen requires multiple daily injections or pump-mediated infusion, as well as close monitoring of blood glucose levels. Despite improved delivery and monitoring, exogenous insulin has not eliminated complications of diabetes, such as cardiovascular disease, diabetic nephropathy, retinopathy and neuropathy. Unfortunately, insulin therapy itself causes insulin resistance and weight gain1,2; therefore, any new diabetes therapy must balance the essential effects of insulin with its counterproductive consequences.

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Fig. 1: Progress and future challenges in the development of stem cell–derived beta-like cells for the treatment of diabetes and prevention of long-term complications.

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Acknowledgements

We thank many colleagues, including J. Kushner, F. Lynn and T. Kieffer, for illuminating discussions on this topic over the years. We thank all of the authors whose work has inspired us.

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  1. Life Sciences Institute, Diabetes Research Group, University of British Columbia, Vancouver, British Columbia, Canada

    Jelena Kolic & James D. Johnson

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  1. Jelena Kolic
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  2. James D. Johnson
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J.K. and J.D.J. cowrote the manuscript.

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Correspondence to James D. Johnson.

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Peer review information Nature Metabolism thanks the anonymous reviewers for their contribution to the peer review of this work.

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Kolic, J., Johnson, J.D. Promises and pitfalls of beta cell–replacement therapies. Nat Metab 3, 1036–1037 (2021). https://doi.org/10.1038/s42255-021-00433-4

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