2형당뇨병 환자에서 SGLT2 억제제 치료에 따른 혈장·소변 대사체 및 체성분 변화: 전향적 임상연구 = A prospective clinical trial to analyze changes in Metabolites and Body composition following use of SGLT2 inhibitor in patients with type 2 diabetes

다국어 초록 (Multilingual Abstract)

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors provide early and robust cardiorenal protection, yet the earliest metabolic responses underlying these benefits remain unclear. This study investigated early metabolic reprogramming after SGLT2 inhibition using integrated plasma and urine metabolomics with detailed body-composition profiling.
Methods: In this prospective, single-arm study, ten adults with type 2 diabetes were assessed at baseline and at 1, 3, and 6 months after initiating SGLT2 inhibitor therapy. Longitudinal metabolomic profiling using UHPLC–HRMS was combined with dual-energy X-ray absorptiometry, bioimpedance measurements, and clinical and biochemical parameters. Multivariate models, absolute quantification, pathway enrichment, network topology, and ROC analyses were performed.
Results: Urinary kynurenic acid, indoxyl sulfate, and suberic acid increased significantly, indicating activation of the tryptophan–kynurenine pathway, modulation of gut-derived indole metabolism, and enhanced peroxisomal fatty-acid oxidation. In plasma, L-tyrosine, LysoPC(16:1), and uric acid decreased, while L-octanoylcarnitine increased, reflecting shifts toward fatty-acid–based energy use, altered aromatic amino-acid turnover, phospholipid remodeling, and reduced tubular urate reabsorption. Notably, the reduction in LysoPC(16:1), together with choline-centered network centrality, suggested early rewiring of glycerophospholipid metabolism as a potential upstream mechanism linking membrane remodeling to improved insulin sensitivity. Clinically, body weight and BMI declined modestly, relative skeletal muscle mass decreased despite preserved absolute muscle mass and strength, and HOMA-IR improved significantly without major lipid changes.
Conclusions: SGLT2 inhibition induces rapid, coordinated metabolic remodeling across amino-acid, lipid, glycerophospholipid, and renal excretory pathways before substantial changes in regional adiposity. The prominence of the LysoPC–choline axis highlights membrane phospholipid remodeling as a candidate early mediator of improved metabolic flexibility and insulin sensitivity. These metabolite trajectories provide mechanistic insight into upstream drug effects and may serve as early biomarkers of therapeutic response in type 2 diabetes.

목차 (Table of Contents)

• 제1장 서론 1
• 제2장 연구 방법 3
• 제3장 결과 11
• 제4장 고찰 15
• 제5장 참고문헌 23
• 제6장 표 29
• 제7창 그림 34