Introduction & Objective: This study aims to explore the effects of metabolic bariatric surgery (MBS) on plasma proteins linked to diabetic kidney disease and hypertension in youth with type 2 diabetes (T2D). Methods: We measured 7604 proteins in 326 plasma samples from severely obese youth, both with and without T2D, in the Teen-LABS study, examining pre- and post-MBS changes (6 month, 1, 2-, 3-, 4-, and 5-year follow-up). This analysis focused on proteins identified in the TODAY cohort as predictors of severe albuminuria (ACR ≥300 mg/g) and hypertension (SBP≥130/80 mm Hg), in youth with T2D (n=374), using Cox proportional hazard models adjusted for age, sex, HbA1c, log-transformed triglycerides and estimated insulin sensitivity. A mixed model evaluated proteomic changes post-MBS, maintaining a 5% false discovery rate with reported q-values. Results: In Teen-LABS, several proteins associated with a higher risk of severe albuminuria and hypertension in TODAY showed notable post-surgical downregulation. Higher pigment epithelium-derived factor (PEDF) at baseline predicted onset to severe albuminuria (HR: 1.63, 95% CI 1.12, 2.37, per 1 SD increment) and hypertension (HR: 1.41, 95% CI 1.22, 1.63, per 1 SD increment) over 15 years in TODAY after multivariable adjustments. In Teen-LABS, PEDF decreased post-MBS compared to baseline at 6 months follow-up (logFC: -0.30, q-value=1.24x10-31), year 1 (logFC: -0.28, q-value=2.35x10-29), year 2 (logFC: -0.32, q-value=1.85x10-34), year 3 (logFC: -0.28, q-value=6.95x10-29), year 4 (logFC: -0.30, q-value=4.13x10-28) and year 5 (logFC: -0.30, q-value=2.78x10-26). Conclusion: These analyses show durable attenuation of plasma PEDF after MBS, a protein strongly associated with risk of severe albuminuria and hypertension in youth with T2D. PEDF is implicated in endothelial dysfunction and vascular damage through impaired angiogenesis and endothelial repair mechanisms. Disclosure P. Narongkiatikhun: None. Y. Choi: None. N. Nguyen: None. K. Nash: None. K.L. Tommerdahl: None. M. Kretzler: Research Support; Boehringer-Ingelheim, Certa, Traveere Pharmaceuticals, Maze Therapeutics, Roche Pharmaceuticals, AstraZeneca, Novo Nordisk, Moderna, Inc., Chinook Therapeutics Inc., angion, Lilly Diabetes, Renalytix, Gilead Sciences, Inc., Regeneron Pharmaceuticals Inc., Janssen Pharmaceuticals, Inc. T. Inge: Consultant; Medtronic, Eli Lilly and Company, Brainstorm Therapeutics. Stock/Shareholder; Standard Bariatrics. Consultant; Teleflex. J.R. Ryder: None. L. Pyle: None. P. Bjornstad: Consultant; AstraZeneca, Boehringer-Ingelheim. Advisory Panel; Lilly Diabetes, Novo Nordisk, Bayer Inc., Horizon Therapeutics plc. Funding National Institutes of Health

中文翻译：

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1135-P：色素上皮衍生因子、糖尿病肾病和高血压——破译青少年代谢性减肥手术的蛋白质组学反应


简介和目的：本研究旨在探讨代谢减肥手术 (MBS) 对 2 型糖尿病 (T2D) 青年患者血浆蛋白与糖尿病肾病和高血压相关的影响。方法：在 Teen-LABS 研究中，我们测量了患有和不患有 T2D 的严重肥胖青少年的 326 份血浆样本中的 7604 种蛋白质，检查 MBS 前后的变化（6 个月、1、2-、3-、4- ，以及 5 年随访）。该分析重点关注在 TODAY 队列中使用 Cox 比例风险模型确定的蛋白质，这些蛋白质是 T2D 青少年 (n=374) 中严重蛋白尿 (ACR ≥300 mg/g) 和高血压 (SBP≥130/80 mm Hg) 的预测因子根据年龄、性别、HbA1c、对数转换甘油三酯和估计的胰岛素敏感性进行调整。混合模型评估了 MBS 后的蛋白质组变化，报告的 q 值保持 5% 的错误发现率。结果：在 Teen-LABS 中，几种与今日严重蛋白尿和高血压风险较高相关的蛋白质在手术后表现出显着的下调。基线时较高的色素上皮衍生因子 (PEDF) 预测出现严重白蛋白尿（HR：1.63，95% CI 1.12，2.37，每 1 SD 增量）和高血压（HR：1.41，95% CI 1.22，1.63，每 1 SD）经过多变量调整后，今天的增长率已超过 15 年。在 Teen-LABS 中，MBS 治疗后第 1 年（logFC：-0.30，q 值=1.24x10-31）时，PEDF 与基线相比有所下降（logFC：-0.30，q 值=2.35x10-31）（logFC：-0.28，q 值=2.35x10- 29)，第 2 年（logFC：-0.32，q 值=1.85x10-34），第 3 年（logFC：-0.28，q 值=6.95x10-29），第 4 年（logFC：-0.30，q 值） =4.13x10-28）和第 5 年（logFC：-0.30，q 值=2.78x10-26）。结论：这些分析显示，MBS 后血浆 PEDF 持续减弱，这是一种与青少年 T2D 患者严重蛋白尿和高血压风险密切相关的蛋白质。 PEDF 通过血管生成和内皮修复机制受损而导致内皮功能障碍和血管损伤。披露 P. Narongkiatikhun：无。崔永元：没有。 N. Nguyen：没有。 K·纳什：没有。 K.L.托默达尔：没有。 M. Kretzler：研究支持；勃林格殷格翰、Certa、Traveere Pharmaceuticals、Maze Therapeutics、罗氏制药、阿斯利康、诺和诺德、Moderna, Inc.、Chinook Therapeutics Inc.、angion、礼来糖尿病、Renalytix、吉利德科学公司、Regeneron Pharmaceuticals Inc.、杨森制药, Inc. T. Inge：顾问；美敦力、礼来公司、Brainstorm Therapeutics。股票/股东；标准减肥治疗。顾问;泰利福。 J.R.莱德：没有。 L.派尔：没有。 P. Bjornstad：顾问；阿斯利康、勃林格殷格翰。顾问小组；礼来糖尿病公司、诺和诺德公司、拜耳公司、Horizo​​n Therapeutics plc。 资助国立卫生研究院