The clinical course and potential underlying mechanisms of everolimus-induced hyperglycemia
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- Tanimura Jun
- Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Ishikawa 920-8640, Japan
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- Nakagawa Hiromi
- Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Ishikawa 920-8640, Japan
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- Tanaka Takeo
- Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Ishikawa 920-8640, Japan
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- Kikuchi Akihiro
- Division of Endocrinology and Metabolism, Department of Homeostatic Regulation, National Institute for Physiological Sciences, National Institute of Natural Sciences, Aichi 444-8585, Japan
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- Osada Sachie
- Department of Hospital Pharmacy, Kanazawa University Hospital, Ishikawa 920-8641, Japan
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- Tanaka Yoshiaki
- International Institute for Integrative Sleep Medicine, University of Tsukuba, Ibaraki 305-8550, Japan
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- Tokuyama Kumpei
- International Institute for Integrative Sleep Medicine, University of Tsukuba, Ibaraki 305-8550, Japan
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- Takamura Toshinari
- Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Ishikawa 920-8640, Japan
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説明
<p>The mechanistic target of rapamycin (mTOR) inhibitor everolimus is an antitumor agent known to cause hyperglycemia. However, the clinical course of everolimus-induced hyperglycemia, its pathophysiological basis, and the treatment strategy are not clear. In this case series report, we present the clinical course of everolimus-induced hyperglycemia in four patients. Hyperglycemia occurred 3–8 weeks after the administration of everolimus irrespective of the body mass index (range, 21.3–29.1 kg/m2) or pre-existing diabetes. Insulin or insulin secretagogues were required for glycemic control in most of the patients. Of note, the hyperglycemia was reversible in all patients, and none of the patients required anti-diabetic agents to achieve adequate glycemic control after cessation of everolimus therapy. To investigate the underlying mechanism of everolimus-induced hyperglycemia, we assessed insulin secretion and sensitivity by 75 g oral glucose tolerance test, arginine challenge test, and/or hyperinsulinemic-euglycemic clamp study using stable isotope-labeled glucose tracer in two patients. Everolimus did not affect insulin sensitivity in the liver, skeletal muscle, or the adipose tissue. In contrast, everolimus impaired insulin secretion and thereby increased basal hepatic glucose production. These findings further our understanding of the role of mTOR in glucose homeostasis in humans and provide insights for treatment strategies against everolimus-induced hyperglycemia.</p>
収録刊行物
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- Endocrine Journal
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Endocrine Journal 66 (7), 615-620, 2019
一般社団法人 日本内分泌学会
