Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro Cuore, Rome, Italy.
UOC di Medicina Nucleare, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro Cuore, Rome, Italy.
Cardiovasc Diabetol. 2023 Dec 19;22(1):349. doi: 10.1186/s12933-023-02091-0.
We recently demonstrated that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) leads to an increase in myocardial flow reserve in patients with type 2 diabetes (T2D) with stable coronary artery disease (CAD). The mechanism by which this occurs is, however, unclear. One of the risk factors for cardiovascular disease is inflammation of epicardial adipose tissue (EAT). Since the latter is often increased in type 2 diabetes patients, it could play a role in coronary microvascular dysfunction. It is also well known that SGLT-2i modify adipose tissue metabolism. We aimed to investigate the effects of the SGLT-2i dapagliflozin on metabolism and visceral and subcutaneous adipose tissue thickness in T2D patients with stable coronary artery disease and to verify whether these changes could explain observed changes in myocardial flow.
We performed a single-center, prospective, randomized, double-blind, controlled clinical trial with 14 T2D patients randomized 1:1 to SGLT-2i dapagliflozin (10 mg daily) or placebo. The thickness of visceral (epicardial, mediastinal, perirenal) and subcutaneous adipose tissue and glucose uptake were assessed at baseline and 4 weeks after treatment initiation by 2-deoxy-2-[F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography during hyperinsulinemic euglycemic clamp.
The two groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, BMI, renal and heart function). Dapagliflozin treatment significantly reduced EAT thickness by 19% (p = 0.03). There was a significant 21.6% reduction in EAT glucose uptake during euglycemic hyperinsulinemic clamp in the dapagliflozin group compared with the placebo group (p = 0.014). There were no significant effects on adipose tissue thickness/metabolism in the other depots explored.
SGLT-2 inhibition selectively reduces EAT thickness and EAT glucose uptake in T2D patients, suggesting a reduction of EAT inflammation. This could explain the observed increase in myocardial flow reserve, providing new insights into SGLT-2i cardiovascular benefits.
我们最近的研究表明，钠-葡萄糖共转运蛋白 2 抑制剂（SGLT-2i）治疗可增加 2 型糖尿病（T2D）合并稳定型冠状动脉疾病（CAD）患者的心肌血流储备。然而，其发生机制尚不清楚。心血管疾病的一个危险因素是心外膜脂肪组织（EAT）的炎症。由于后者在 2 型糖尿病患者中常增加，因此可能在冠状动脉微血管功能障碍中发挥作用。众所周知，SGLT-2i 可改变脂肪组织代谢。我们旨在研究 SGLT-2i 达格列净对 T2D 合并稳定型冠状动脉疾病患者代谢和内脏及皮下脂肪组织厚度的影响，并验证这些变化是否可以解释观察到的心肌血流变化。
我们进行了一项单中心、前瞻性、随机、双盲、对照临床试验，纳入了 14 名 T2D 患者，按 1:1 比例随机分为 SGLT-2i 达格列净（每日 10mg）或安慰剂组。在开始治疗后 4 周，通过正电子发射断层扫描/计算机断层扫描 2-脱氧-2-[F]氟-D-葡萄糖进行高胰岛素正葡萄糖钳夹，评估内脏（心外膜、纵隔、肾周）和皮下脂肪组织的厚度和葡萄糖摄取。
两组患者的基线特征（年龄、糖尿病病程、HbA1c、BMI、肾功能和心功能）匹配良好。达格列净治疗可使 EAT 厚度显著降低 19%（p=0.03）。达格列净组在高胰岛素正葡萄糖钳夹期间 EAT 葡萄糖摄取量较安慰剂组显著降低 21.6%（p=0.014）。在其他研究的脂肪组织厚度/代谢方面，无显著影响。
SGLT-2 抑制可选择性降低 T2D 患者的 EAT 厚度和 EAT 葡萄糖摄取，提示 EAT 炎症减少。这可以解释观察到的心肌血流储备增加，为 SGLT-2i 的心血管获益提供了新的见解。
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