Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
Integrated Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA.
Diabetes Care. 2024 Nov 1;47(11):2024-2032. doi: 10.2337/dc24-0859.
Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are effective procedures to treat and manage type 2 diabetes (T2D). However, the underlying metabolic adaptations that mediate improvements in glucose homeostasis remain largely elusive. The purpose of this study was to identify metabolic signatures associated with biochemical resolution of T2D after medical therapy (MT) or bariatric surgery.
Plasma samples from 90 patients (age 49.9 ± 7.6 years; 57.7% female) randomly assigned to MT (n = 30), RYGB (n = 30), or SG (n = 30) were retrospectively subjected to untargeted metabolomic analysis using ultra performance liquid chromatography with tandem mass spectrometry at baseline and 24 months of treatment. Phenotypic importance was determined by supervised machine learning. Associations between change in glucose homeostasis and circulating metabolites were assessed using a linear mixed effects model.
The circulating metabolome was dramatically remodeled after SG and RYGB, with largely overlapping signatures after MT. Compared with MT, SG and RYGB profoundly enhanced the concentration of metabolites associated with lipid and amino acid signaling, while limiting xenobiotic metabolites, a function of decreased medication use. Random forest analysis revealed 2-hydroxydecanoate as having selective importance to RYGB and as the most distinguishing feature between MT, SG, and RYGB. To this end, change in 2-hydroxydecanoate correlated with reductions in fasting glucose after RYGB but not SG or MT.
We identified a novel metabolomic fingerprint characterizing the longer-term adaptations to MT, RYGB, and SG. Notably, the metabolomic profiles of RYGB and SG procedures were distinct, indicating equivalent weight loss may be achieved by divergent effects on metabolism.
Roux-en-Y 胃旁路术（RYGB）和袖状胃切除术（SG）是治疗和管理 2 型糖尿病（T2D）的有效方法。然而，介导葡萄糖稳态改善的潜在代谢适应仍很大程度上难以捉摸。本研究的目的是确定与 T2D 患者经药物治疗（MT）或减肥手术治疗后生化缓解相关的代谢特征。
从随机分配到 MT（n=30）、RYGB（n=30）或 SG（n=30）的 90 名患者（年龄 49.9±7.6 岁；57.7%为女性）的血浆样本中，采用超高效液相色谱-串联质谱法在基线和治疗 24 个月时进行非靶向代谢组学分析。通过有监督的机器学习确定表型重要性。使用线性混合效应模型评估葡萄糖稳态变化与循环代谢物之间的相关性。
SG 和 RYGB 后循环代谢组发生了显著重塑，与 MT 后基本重叠的特征。与 MT 相比，SG 和 RYGB 显著增强了与脂质和氨基酸信号相关的代谢物浓度，同时限制了外源性代谢物，这是药物使用减少的功能。随机森林分析显示，2-羟基癸酸对 RYGB 具有选择性重要性，是 MT、SG 和 RYGB 之间最具区分性的特征。为此，2-羟基癸酸的变化与 RYGB 后空腹血糖的降低相关，但与 SG 或 MT 无关。
我们确定了一种新的代谢组学特征，可用于描述 MT、RYGB 和 SG 的长期适应。值得注意的是，RYGB 和 SG 手术的代谢谱不同，这表明通过对代谢的不同影响可能达到等效的减重效果。
