Elevated Serum Growth Differentiation Factor 15 Levels as a Potential Biomarker of the Efficacy of Imeglimin in Individuals With Type 2 Diabetes Mellitus: An Exploratory Study.

IF 1.6 Q2 MEDICINE, GENERAL & INTERNAL Journal of clinical medicine research Pub Date : 2024-10-01 Epub Date: 2024-10-30 DOI:10.14740/jocmr6031
Naoki Wada, Takaaki Murakami, Muhammad Fauzi, Kentaro Sakaki, Shinobu Oshima, Yoshihito Shimada, Kanae Asai, Ayako Oshima, Satoko Nomura, Erina Joo, Michiko Mori, Ryoko Fujiwara, Kenichiro Shide, Keiko Wada, Daisuke Yabe, Nobuya Inagaki, Norio Harada
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Abstract

Background: The aim of the present study was to conduct a prospective observational study to explore the effects of imeglimin on systemic energy metabolism/body composition and to identify potential mitochondria-related biomarkers of the efficacy of the drug in clinical settings.

Methods: In this prospective observational study, 16 participants with type 2 diabetes mellitus in the diabetes clinic of Kyoto University Hospital were enrolled. Individuals were started on imeglimin as monotherapy or add-on therapy.

Results: After 3 months under imeglimin treatment, there was no significant change in basal metabolism or body composition. However, serum levels of growth differentiation factor 15 (GDF15) were higher while those of serum fibroblast growth factor 21 and urine 8-hydroxy-2'-deoxyguanosine were not changed. Additional in vitro examination revealed that imeglimin induces GDF15 protein release from human hepatocytes.

Conclusions: Three-month imeglimin treatment increased serum GDF15 levels in clinical type 2 diabetes mellitus patients along with little change in basal metabolism or body composition, suggesting GDF15 as a potential marker for the efficacy of imeglimin.

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血清生长分化因子 15 水平升高作为 2 型糖尿病患者服用伊美格列明疗效的潜在生物标志物:一项探索性研究
研究背景本研究旨在开展一项前瞻性观察研究,探讨伊迈格列明对全身能量代谢/身体成分的影响,并确定该药物在临床环境中疗效的潜在线粒体相关生物标志物:在这项前瞻性观察研究中,16 名 2 型糖尿病患者在京都大学医院糖尿病诊所接受了治疗。结果:接受伊迈格列明单药治疗或附加治疗 3 个月后,患者的血糖水平明显下降:结果:接受伊麦格列明治疗 3 个月后,基础代谢和身体成分没有明显变化。然而,血清中生长分化因子 15(GDF15)的水平升高了,而血清中成纤维细胞生长因子 21 和尿液中 8-羟基-2'-脱氧鸟苷的水平没有变化。其他体外检查显示,伊麦角林能诱导人肝细胞释放 GDF15 蛋白:结论:为期三个月的伊麦格列明治疗可提高临床 2 型糖尿病患者的血清 GDF15 水平,而基础代谢或身体成分变化不大,这表明 GDF15 是伊麦格列明疗效的潜在标志物。
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