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The multifaceted nature of diabetes mellitus induced by checkpoint inhibitors

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Abstract

Immune checkpoint inhibitors (CPI) are increasingly being used in oncology, and many autoimmune side effects have been described. Diabetes mellitus (DM) has been reported in approximately 1% of subjects treated with programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors, alone or in association with CTLA-4 inhibitors. In the present mini-review, we aimed to describe different clinical pictures and pathophysiology associated with these forms of diabetes. Data on CPI-related DM was gathered from the largest case series in the literature and from our centre dedicated to immunotherapy complications (ImmuCare—Hospices Civils de Lyon). Most cases are acute autoimmune insulin-dependent diabetes which are similar to fulminant diabetes (extremely acute onset with concomitant near-normal HbA1c levels). Other cases, however, have a phenotype close to type 2 diabetes or appear as a decompensation of previously known type 2 diabetes. The occurrence of diabetes can also be a complication of autoimmune pancreatitis induced by CPI use. Finally, two cases of diabetes in a context of autoimmune lipoatrophy have recently been described. Regarding the wide variety of CPI-induced diabetes, the discovery of a glucose disorder under CPI should motivate specialised care for aetiological diagnosis and appropriate treatment.

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Abbreviations

AGL:

Autoimmune generalised lipodystrophy

BMI:

Body mass index

CPI:

Checkpoint inhibitors

CTLA-4:

Cytotoxic T-lymphocyte antigen 4

DM:

Diabetes mellitus

FD:

Fulminant diabetes

PD-1:

Programmed death 1

PD-L1:

Programmed death ligand 1

NASH:

Non-alcoholic steatohepatitis

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Acknowledgements

We thank Verena Landel (DRCI, Hospices Civils de Lyon) for help in manuscript preparation and English revisions.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Endocrinology and Diabetes, St. Joseph - St. Luc Hospital, Quai Claude Bernard, 69007, Lyon, France

    Lucien Marchand

  2. Department of Endocrinology and Diabetes, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre-Bénite, France

    Emmanuel Disse, Sophie Reffet, Julien Vouillarmet, Charles Thivolet & Christine Cugnet-Anceau

  3. CarMeN Laboratory (INSERM U1060, INRA U1235, Université Claude Bernard Lyon1, INSA-Lyon), Lyon 1 University, Oullins, France

    Emmanuel Disse & Charles Thivolet

  4. Department of Dermatology, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre-Bénite, France

    Stéphane Dalle

  5. ImmuCare (Immunology Cancer Research), Hospices Civils de Lyon, Lyon, France

    Stéphane Dalle & Christine Cugnet-Anceau

  6. Department of Immunology, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre-Bénite, France

    Nicole Fabien

Authors
  1. Lucien Marchand
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  2. Emmanuel Disse
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  3. Stéphane Dalle
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  6. Nicole Fabien
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  7. Charles Thivolet
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  8. Christine Cugnet-Anceau
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Contributions

LM and CCA contributed to the literature search and writing the manuscript. ED, SD, SR, NF, JV, and CT contributed to writing the manuscript and revising for intellectual content. All authors approved the final version.

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Correspondence to Lucien Marchand.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

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Informed consent was obtained from all patients for being included in the study.

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Marchand, L., Disse, E., Dalle, S. et al. The multifaceted nature of diabetes mellitus induced by checkpoint inhibitors. Acta Diabetol 56, 1239–1245 (2019). https://doi.org/10.1007/s00592-019-01402-w

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  • DOI: https://doi.org/10.1007/s00592-019-01402-w

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