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Nilotinib exacerbates diabetes mellitus by decreasing secretion of endogenous insulin

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Abstract

We report a 74-year-old female with chronic myelogenous leukemia (CML) in accelerated phase with pre-existing severe type 2 diabetes (T2D) and hemorrhagic gastric ulcers who was successfully treated with nilotinib. We first considered second-generation tyrosine kinase inhibitors for the treatment of this patient, as they elicit a superior response compared with imatinib. We next selected nilotinib, rather than dasatinib, since the increased risk of bleeding associated with dasatinib represented a greater risk of fatality than aggravation of T2D with nilotinib. After improvement of hemorrhagic gastric ulcers and T2D with exogenous insulin therapy, we began nilotinib administration; insulin dose was increased to maintain her glucose levels whereas urine C-peptide level decreased. Conversely, when nilotinib was discontinued due to liver dysfunction, the dosage of injected insulin was decreased and urine C-peptide levels increased. After re-starting nilotinib, the required dose of insulin gradually increased again, and urine C-peptide level decreased, indicating that nilotinib may have impaired secretion of endogenous insulin. The patient obtained a complete cytogenetic response after 3 months of nilotinib treatment. Her T2D has since been well controlled by insulin therapy. To our knowledge, this is the first report that nilotinib treatment for patients with severe T2D may induce a reversible decrease in endogenous insulin secretion, although the precise underlying mechanisms remain unknown. We highly recommend sufficient screening and early intervention with exogenous insulin therapy for diabetic CML patients who receive nilotinib.

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Acknowledgments

This work was supported, in part, by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology in Japan (23390254 & 24659462 to T.M.).

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Authors and Affiliations

  1. Department of Hematology, Harasanshin Hospital, Fukuoka, Japan

    Yoshikiyo Ito, Yong Chong & Tomohiko Kamimura

  2. Department of Endocrinology, Harasanshin Hospital, Fukuoka, Japan

    Toshinobu Maki

  3. Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Toshihiro Miyamoto & Koichi Akashi

Authors
  1. Yoshikiyo Ito
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  2. Toshihiro Miyamoto
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  3. Yong Chong
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  4. Toshinobu Maki
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  5. Koichi Akashi
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  6. Tomohiko Kamimura
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Correspondence to Toshihiro Miyamoto.

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Ito, Y., Miyamoto, T., Chong, Y. et al. Nilotinib exacerbates diabetes mellitus by decreasing secretion of endogenous insulin. Int J Hematol 97, 135–138 (2013). https://doi.org/10.1007/s12185-012-1222-7

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  • DOI: https://doi.org/10.1007/s12185-012-1222-7

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