Checkpoint inhibitor treatment induces an increase in HbA1c in nondiabetic patients

Melanoma Res. 2019 Jun;29(3):328-332. doi: 10.1097/CMR.0000000000000585.

Abstract

Immunotherapy greatly improves clinical outcomes in treated patients with cancer. However, the long-lasting immune response and long duration of therapy could induce long-term adverse effects owing to the chronic inflammation induced. Type 2 diabetes is now recognized as an inflammatory disease. In addition, immunotherapy is concerned with increase in the production of tumor necrosis factor-α, interleukin-2, and interferon-γ, which are involved in the inflammatory process. Based on these observations, we hypothesized that anti-programmed cell death-1 (anti-PD-1) and/or anticytotoxic T-lymphocyte-associated protein-4 therapy could contribute to type 2 diabetes genesis in treated patients. Therefore, to evaluate this hypothesis, we studied HbA1c levels during follow-up in patients treated with anti-PD-1 and/or anticytotoxic T-lymphocyte-associated protein-4 therapy. A prospective and observational study was performed in an oncodermatology department (Saint-Louis Hospital, Paris, France) from March 2015 to February 2017. Sixty-two patients meeting the inclusion criteria were enrolled. Forty-three patients had paired HbA1c measurements during their follow-up period and were analyzed. The median follow-up was 3 months. We noted an increase in HbA1c levels from 5.3% [interquartile range (IQR): 5.1-5.5; range: 4.5-6.2) to 5.45% (IQR: 5.2-5.7; range: 4.7-6.2; P=0.037). This observation was confirmed in the subgroup of patients who did not receive concomitant glucocorticoids; their median HbA1c levels increased from 5.3% (IQR: 5.1-5.5; range: 4.7-6.2) to 5.5% (IQR: 5.2-5.7; range: 4.7-6.3; P=0.025). Variables such as age, BMI, and sex were not associated with the HbA1c level increase, but a tendency toward rising HbA1c levels was observed in treatments longer than 12 months. This study demonstrates that treatment with anti-PD-1 antibodies may impair glucose metabolism, as measured by increasing HbA1c levels.

Publication types

  • Clinical Trial
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / adverse effects
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / diagnosis*
  • Cardiovascular Diseases / etiology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / etiology
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin / analysis*
  • Humans
  • Immunotherapy / adverse effects*
  • Ipilimumab / adverse effects*
  • Male
  • Melanoma
  • Middle Aged
  • Nivolumab / adverse effects*
  • Prognosis
  • Prospective Studies
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Survival Rate

Substances

  • Antineoplastic Agents, Immunological
  • Glycated Hemoglobin A
  • Ipilimumab
  • hemoglobin A1c protein, human
  • Nivolumab