Sugiyama Seigo, Jinnouchi Hideaki, Kurinami Noboru, Hieshima Kunio, Yoshida Akira, Jinnouchi Katsunori, Nishimura Hiroyuki, Suzuki Tomoko, Miyamoto Fumio, Kajiwara Keizo, Jinnouchi Tomio
Diabetes Care Center, Jinnouchi Hospital, Japan.
Cardiovascular Division, Diabetes Care Center, Jinnouchi Hospital, Japan.
Intern Med. 2018 Aug 1;57(15):2147-2156. doi: 10.2169/internalmedicine.0701-17. Epub 2018 Mar 30.
Objective Sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce cardiovascular events and decrease the body fat mass in patients with type 2 diabetes mellitus (T2DM). We examined whether or not the SGLT2-inhibitor dapagliflozin can improve the endothelial function associated with a reduction in abdominal fat mass. Methods We prospectively recruited patients with uncontrolled [hemoglobin A1c (HbA1c) >7.0%] T2DM who were not being treated by SGLT2 inhibitors. Patients were treated with add-on dapagliflozin (5 mg/day) or non-SGLT2 inhibitor medicines for 6 months to improve their HbA1c. We measured the peripheral microvascular endothelial function as assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT) and calculated the natural logarithmic transformed value of the RH-PAT index (LnRHI). We then investigated changes in the LnRHI and abdominal fat area using computed tomography (CT). Results The subjects were 54 patients with uncontrolled T2DM (72.2% men) with a mean HbA1c of 8.1%. The HbA1c was significantly decreased in both groups, with no significant difference between the groups. Dapagliflozin treatment, but not non-SGLT2 inhibitor treatment, significantly increased the LnRHI. The changes in the LnRHI were significantly greater in the dapagliflozin group than in the non-SGLT2 inhibitor group. Dapagliflozin treatment, but not non-SGLT2 inhibitor treatment, significantly decreased the abdominal visceral fat area, subcutaneous fat area (SFA), and total fat area (TFA) as assessed by CT and significantly increased the plasma adiponectin levels. The percentage changes in the LnRHI were significantly correlated with changes in the SFA, TFA, systolic blood pressure, and adiponectin. Conclusion Add-on treatment with dapagliflozin significantly improves the glycemic control and endothelial function associated with a reduction in the abdominal fat mass in patients with uncontrolled T2DM.
目的 钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂可降低2型糖尿病（T2DM）患者的心血管事件发生率并减少体脂量。我们研究了SGLT2抑制剂达格列净是否能改善与腹部脂肪量减少相关的内皮功能。方法 我们前瞻性招募了未使用SGLT2抑制剂治疗且糖化血红蛋白（HbA1c）>7.0%的血糖控制不佳的T2DM患者。患者接受加用达格列净（5毫克/天）或非SGLT2抑制剂药物治疗6个月以改善其HbA1c。我们通过反应性充血外周动脉张力测定法（RH-PAT）评估外周微血管内皮功能，并计算RH-PAT指数的自然对数转换值（LnRHI）。然后我们使用计算机断层扫描（CT）研究LnRHI和腹部脂肪面积的变化。结果 受试者为54例血糖控制不佳的T2DM患者（72.2%为男性），平均HbA1c为8.1%。两组患者的HbA1c均显著降低，组间无显著差异。达格列净治疗可显著增加LnRHI，但非SGLT2抑制剂治疗无此作用。达格列净组LnRHI的变化显著大于非SGLT2抑制剂组。达格列净治疗可显著降低CT评估的腹部内脏脂肪面积、皮下脂肪面积（SFA）和总脂肪面积（TFA），并显著提高血浆脂联素水平。LnRHI的百分比变化与SFA、TFA、收缩压和脂联素的变化显著相关。结论 加用达格列净治疗可显著改善血糖控制不佳的T2DM患者的血糖控制及与腹部脂肪量减少相关的内皮功能。
