著者

Jun Tanimura Hiromi Nakagawa Takeo Tanaka Akihiro Kikuchi Sachie Osada Yoshiaki Tanaka Kumpei Tokuyama Toshinari Takamura

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.66, no.7, pp.615-620, 2019 (Released:2019-07-28)

参考文献数

11

被引用文献数

9 11

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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.

著者

Yasuaki Wada Kazuya Murata Takeo Tanaka Yoshio Nose Chikage Kihara Kosuke Uchida Shinichi Okuda Takehisa Susa Yukari Kishida Masunori Matsuzaki

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.76, no.3, pp.675-681, 2012 (Released:2012-02-24)

参考文献数

24

被引用文献数

24 28

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Background: The time interval between the onset of early transmitral flow velocity (E) and that of early diastolic mitral annular velocity (e') (TE-e') is a good predictor of elevated left ventricular (LV) filling pressure in patients with sinus rhythm. Although the evaluation of LV filling pressure using E/e' has been challenging in atrial fibrillation (AF), the usefulness of TE-e' is unknown. Methods and Results: E and e' were simultaneously recorded using dual Doppler echocardiography in 45 AF patients (30 men; mean age, 69±9 years). E/e' and TE-e' were calculated and compared with the pulmonary capillary wedge pressure (PCWP), which was measured invasively. E/e' and TE/e' correlated with PCWP (E/e', r=0.57, P<0.001; TE-e', r=0.77, P<0.001). Using receiver operating characteristic analysis, the optimal cut-off for TE-e' was 34ms (sensitivity, 95%; specificity, 88%) and that for E/e' was 14.6 (sensitivity, 50%; specificity, 84%) in order to predict >12-mmHg PCWP. When the combined cut-offs of TE-e' >34ms and E/e' >14.6 were used, the sensitivity and specificity of predicting elevated PCWP were improved to 100% and 88%, respectively. Conclusions: In AF patients, the simultaneous recording of E and e' using dual Doppler echocardiography and the analysis of TE-e', in addition to E/e', improved the accuracy of evaluation of LV filling pressure. (Circ J 2012; 76: 675-681)