in-depth analysis of 6596 proteins (SomaScan 7K) in 374 baseline plasma samples from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study to identify multi-protein signatures associated with the onset of albuminuria (urine albumin-to-creatinine ratio [UACR] ≥30 mg/g), a rapid decline in estimated glomerular filtration rate (eGFR) [annual eGFR decline >3 mL/min/1.73m2 and/or ≥3.3% at two consecutive visits], and hyperfiltration (≥135 mL/min/1.73m2 at two consecutive visits). Elastic net Cox regression with 10-fold cross-validation was applied to the top 100 proteins (ranked by p-value) to identify multi-protein signatures of time to development of DKD outcomes. Results: Participants in the TODAY study (14±2 years old, 63% female, 7±6 months diabetes duration) experienced high rates of early DKD: 43% developed albuminuria, 48% hyperfiltration, and 16% rapid eGFR decline. Increased levels of seven and three proteins were predictive of shorter time to develop albuminuria and rapid eGFR decline, respectively; 118 proteins predicted time to development of hyperfiltration. Elastic net Cox proportional hazards model identified multi-protein signatures of time to incident early DKD with concordance for models with clinical covariates and selected proteins between 0.81 and 0.96, while the concordance for models with clinical covariates only was between 0.56 and 0.63. Conclusions: Our research sheds new light on proteomic changes early in the course of youth-onset type 2 diabetes that associate with DKD. Proteomic analyses identified promising risk factors that predict DKD risk in youth with type 2 diabetes and could deepen our understanding of DKD mechanisms and potential interventions. Copyright © 2024 by the American Society of Nephrology...

中文翻译：

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蛋白质组学分析揭示了与 2 型糖尿病青少年早期糖尿病肾病相关的多蛋白特征


对青少年和青少年 2 型糖尿病治疗方案 （TODAY） 研究的 374 份基线血浆样本中的 6596 种蛋白质 （SomaScan 7K） 进行深入分析，以确定与白蛋白尿发作相关的多蛋白特征（尿白蛋白与肌酐比值 [UACR] ≥30 mg/g），估计肾小球滤过率 （eGFR） 快速下降 [年平均 eGFR 下降 >3 mL/min/1.73m2 和/或 ≥连续两次就诊 3.3%]，以及 和高滤（连续两次就诊 ≥135 mL/min/1.73m2）。将具有 10 倍交叉验证的弹性网 Cox 回归应用于前 100 种蛋白质（按 p 值排名），以确定 DKD 结果发展时间的多蛋白质特征。结果： TODAY 研究的参与者 （14±2 岁，63% 女性，糖尿病病程 7±6 个月）的早期 DKD 发生率高：43% 发生白蛋白尿，48% 发生高滤过，16% 的 eGFR 快速下降。7 和 3 蛋白水平升高分别预示着发生白蛋白尿的时间更短和 eGFR 快速下降;118 个蛋白质预测了高滤过发展的时间。弹性网 Cox 比例风险模型确定了发生早期 DKD 的时间的多蛋白特征，具有临床协变量和选定蛋白质的模型在 0.81 和 0.96 之间是一致的，而只有临床协变量的模型的一致性在 0.56 和 0.63 之间。结论： 我们的研究为与 DKD 相关的青年发病 2 型糖尿病早期的蛋白质组学变化提供了新的思路。蛋白质组学分析确定了预测 2 型糖尿病青年 DKD 风险的有希望的风险因素，并可能加深我们对 DKD 机制和潜在干预措施的理解。美国肾脏病学会版权所有 © 2024...