SGLT2 Inhibitor Dapagliflozin Increases Skeletal Muscle and Brain Fatty Acid Uptake in Individuals With Type 2 Diabetes: A Randomized Double-Blind Placebo-Controlled Positron Emission Tomography Study
Aino Latva-Rasku, Eleni Rebelos, Jouni Tuisku, Richard Aarnio, Achol Bhowmik, Helmi Keskinen, Sanna Laurila, Minna Lahesmaa-Hatting, Laura Pekkarinen, Henrik Isackson, Anna K. Kirjavainen, Jukka Koffert, Kerstin Heurling, Lauri Nummenmaa, Ele Ferrannini, Jonas Oldgren, Jan Oscarsson, Pirjo Nuutila
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引用次数: 0
Abstract
OBJECTIVE The aim of this study was to investigate the impact of the sodium–glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on tissue fatty acid (FA) uptake in the skeletal muscle, brain, small intestine, and subcutaneous and visceral adipose tissue of individuals with type 2 diabetes by using positron emission tomography (PET). RESEARCH DESIGN AND METHODS In a 6-week randomized double-blind placebo-controlled trial, 53 patients with type 2 diabetes treated with metformin received either 10 mg dapagliflozin or placebo daily. Tissue FA uptake was quantified at baseline and end of treatment with PET and the long-chain FA analog radiotracer 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid. Treatment effects were assessed using ANCOVA, and the results are reported as least square means and 95% CIs for the difference between groups. RESULTS A total of 38 patients (dapagliflozin n = 21; placebo n = 17) completed the study. After 6 weeks, skeletal muscle FA uptake was increased by dapagliflozin compared with placebo (1.0 [0.07, 2.0] μmol ⋅ 100 g−1 ⋅ min−1; P = 0.032), whereas uptake was not significantly changed in the small intestine or visceral or subcutaneous adipose tissue. Dapagliflozin treatment significantly increased whole-brain FA uptake (0.10 [0.02, 0.17] μmol ⋅ 100 g−1 ⋅ min−1; P = 0.01), an effect observed in both gray and white matter regions. CONCLUSIONS Six weeks of treatment with dapagliflozin increases skeletal muscle and brain FA uptake, partly driven by a rise in free FA availability. This finding is in accordance with previous indirect measurements showing enhanced FA metabolism in response to SGLT2 inhibition and extends the notion of a shift toward increased FA use to muscle and brain.
目的 本研究旨在通过正电子发射断层扫描(PET)研究钠-葡萄糖共转运体 2 (SGLT2) 抑制剂达帕格列净对 2 型糖尿病患者骨骼肌、大脑、小肠、皮下和内脏脂肪组织中组织脂肪酸 (FA) 摄取的影响。研究设计与方法 在一项为期 6 周的随机双盲安慰剂对照试验中,53 名接受二甲双胍治疗的 2 型糖尿病患者每天服用 10 毫克达帕格列净或安慰剂。在基线和治疗结束时,使用 PET 和长链 FA 类似物放射性示踪剂 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid 对组织 FA 摄取量进行量化。治疗效果采用方差分析进行评估,结果以最小平方均值和组间差异的 95% CI 报告。结果 共有 38 名患者(达帕格列净 n = 21;安慰剂 n = 17)完成了研究。6 周后,与安慰剂相比,达帕格列净增加了骨骼肌对 FA 的吸收(1.0 [0.07, 2.0] μmol⋅100 g-1 ⋅min-1; P = 0.032),而小肠、内脏或皮下脂肪组织对 FA 的吸收没有显著变化。达帕格列净治疗可显著增加全脑 FA 摄取量(0.10 [0.02, 0.17] μmol⋅100 g-1⋅min-1; P = 0.01),在灰质和白质区域均可观察到这种效应。结论 达帕格列净治疗六周可增加骨骼肌和大脑对 FA 的吸收,部分原因是游离 FA 的增加。这一发现与之前的间接测量结果一致,表明SGLT2抑制剂可促进脂肪酸代谢,并将脂肪酸使用增加的概念延伸至肌肉和大脑。
期刊介绍:
The journal's overarching mission can be captured by the simple word "Care," reflecting its commitment to enhancing patient well-being. Diabetes Care aims to support better patient care by addressing the comprehensive needs of healthcare professionals dedicated to managing diabetes.
Diabetes Care serves as a valuable resource for healthcare practitioners, aiming to advance knowledge, foster research, and improve diabetes management. The journal publishes original research across various categories, including Clinical Care, Education, Nutrition, Psychosocial Research, Epidemiology, Health Services Research, Emerging Treatments and Technologies, Pathophysiology, Complications, and Cardiovascular and Metabolic Risk. Additionally, Diabetes Care features ADA statements, consensus reports, review articles, letters to the editor, and health/medical news, appealing to a diverse audience of physicians, researchers, psychologists, educators, and other healthcare professionals.