Uchida Taisuke, Ueno Hiroaki, Konagata Ayaka, Taniguchi Norifumi, Kogo Fumiko, Nagatomo Yuma, Shimizu Koichiro, Yamaguchi Hideki, Shimoda Kazuya
Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
Diabetes Ther. 2023 Mar;14(3):569-579. doi: 10.1007/s13300-023-01370-z. Epub 2023 Feb 3.
Endothelial dysfunction is a risk factor for cardiovascular disease in patients with diabetes. We hypothesized that imeglimin, a novel oral hypoglycemic agent, would improve endothelial function.
In this study, imeglimin was administered to patients with type 2 diabetes and HbA1c ≥ 6.5% who were not receiving insulin therapy. A meal tolerance test (592 kcal, glucose 75.0 g, fat 28.5 g) was performed before and 3 months after administration, and endothelial function, blood glucose, insulin, glucagon, and triglycerides were evaluated. Endothelial function was assessed by flow-mediated dilation (FMD).
Twelve patients (50% male) with a median age of 55.5 years old (interquartile range [IQR] 51.3-66.0) were enrolled. Fasting FMD did not differ before or 3 months after imeglimin administration (from 6.1 [3.9-8.5] to 6.6 [3.9-9.0], p = 0.092), but 2 h postprandial FMD was significantly improved 3 months after imeglimin administration (from 2.3 [1.9-3.4] to 2.9 [2.4-4.7], p = 0.013). In terms of the glucose profile, imeglimin administration significantly improved HbA1c (from 7.2 ± 0.6% to 6.9 ± 0.6%, p = 0.007), fasting glucose (from 138 ± 19 mg/dL to 128 ± 20 mg/dL, p = 0.020), and 2 h postprandial glucose (from 251 ± 47 mg/dL to 215 ± 68 mg/dL, p = 0.035). The change in 2 h postprandial FMD between before and 3 months after imeglimin administration (Δ2 h postprandial FMD) was negatively correlated with Δ2 h postprandial glucose (r = - 0.653, p = 0.021) in a univariate correlation coefficient analysis. Both patients with and without decreased postprandial glucose 3 months after imeglimin administration had improved postprandial FMD.
In this small study, imeglimin administration improved 2 h postprandial FMD. Both glycemic control-dependent and -independent mechanisms might contribute to improved endothelial function.
This research was registered in the University Hospital Medical Information Network (UMIN, UMIN000046311).
内皮功能障碍是糖尿病患者心血管疾病的危险因素。我们推测新型口服降糖药依美格列明可改善内皮功能。
在本研究中，将依美格列明给予未接受胰岛素治疗、2型糖尿病且糖化血红蛋白（HbA1c）≥6.5%的患者。在给药前和给药3个月后进行了一次糖耐量试验（592千卡，葡萄糖75.0克，脂肪28.5克），并评估了内皮功能、血糖、胰岛素、胰高血糖素和甘油三酯。通过血流介导的血管舒张（FMD）评估内皮功能。
纳入了12例患者（50%为男性），中位年龄为55.5岁（四分位间距[IQR]51.3 - 66.0）。依美格列明给药前和给药3个月后的空腹FMD无差异（从6.1[3.9 - 8.5]至6.6[3.9 - 9.0]，p = 0.092），但依美格列明给药3个月后餐后2小时FMD显著改善（从2.3[1.9 - 3.4]至2.9[2.4 - 4.7]，p = 0.013）。在血糖谱方面，依美格列明给药显著改善了HbA1c（从7.2±0.6%至6.9±0.6%，p = 0.007）、空腹血糖（从138±19mg/dL至128±20mg/dL，p = 0.020）和餐后2小时血糖（从251±47mg/dL至215±68mg/dL，p = 0.035）。在单变量相关系数分析中，依美格列明给药前和给药3个月后餐后2小时FMD的变化（Δ餐后2小时FMD）与Δ餐后2小时血糖呈负相关（r = - 0.653，p = 0.021）。依美格列明给药3个月后餐后血糖降低和未降低的患者餐后FMD均有改善。
在这项小型研究中，依美格列明给药改善了餐后2小时FMD。血糖控制依赖和非依赖机制可能都有助于改善内皮功能。
本研究已在大学医院医学信息网络（UMIN，UMIN000046311）注册。
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