Background Leucine-rich alpha-2 glycoprotein 1 (LRG1) is a circulating protein in the transforming growth factor-beta superfamily. We sought to study whether LRG1 might predict risk for all-cause and cause-specific mortality in individuals with type 2 diabetes. Methods 2012 outpatients with type 2 diabetes were followed for a median of 7.2 years and 188 death events were identified. Association of LRG1 with risk for mortality was assessed by multivariable Cox regression models. Results Participants with a higher concentration of LRG1 had an increased risk for all-cause mortality [HR (95% CI), 1.76 (1.03–3.01), 1.75 (1.03–2.98), and 4.37 (2.72–7.02) for quartiles 2, 3, and 4, respectively, compared to quartile 1]. The association remained significant after adjustment for known cardio-renal risk factors including estimated glomerular filtration rate and albuminuria [adjusted HR 2.76 (1.66–4.59), quartile 4 versus 1]. As a continuous variable, a 1-SD increment in LRG1 was associated with 1.34 (1.14–1.57)-fold adjusted risk for all-cause mortality. High plasma LRG1 was independently associated with mortality attributable to cardiovascular disease, infection, and renal diseases. Adding LRG1 into a clinical variable-based model improved discrimination (c statistics from 0.828 to 0.842, P = 0.006) and reclassification (net reclassification improvement 0.47, 95% CI 0.28–0.67) for prediction of 5-year all-cause mortality. Conclusion Plasma LRG1 predicts risk for all-cause mortality and mortality attributable to cardiovascular disease, infection, and renal disease independent of known cardio-renal risk factors. It may be a potential novel biomarker to improve risk stratification in individuals with type 2 diabetes.

中文翻译：

---

血浆富含亮氨酸的 Alpha-2 糖蛋白 1 (LRG1) 与 2 型糖尿病患者全因和特定原因死亡率的关联

背景 富含亮氨酸的 alpha-2 糖蛋白 1 (LRG1) 是转化生长因子-β 超家族中的一种循环蛋白。我们试图研究 LRG1 是否可以预测 2 型糖尿病患者全因和特定原因死亡率的风险。方法 对 2012 例门诊 2 型糖尿病患者进行中位随访 7.2 年，共发现 188 例死亡事件。通过多变量 Cox 回归模型评估 LRG1 与死亡风险的关联。结果 LRG1 浓度较高的参与者全因死亡率的风险增加 [HR (95% CI)、1.76 (1.03–3.01)、1.75 (1.03–2.98) 和 4.37 (2.72–7.02) 四分位数 2， 3 和 4，分别与四分位数 1] 相比。在调整已知的心肾危险因素（包括估计的肾小球滤过率和白蛋白尿）后，这种关联仍然显着[调整后的 HR 2.76 (1.66–4.59)，四分位数 4 对 1]。作为一个连续变量，LRG1 增加 1-SD 与全因死亡率的 1.34（1.14-1.57）倍调整风险相关。高血浆 LRG1 与心血管疾病、感染和肾脏疾病导致的死亡率独立相关。将 LRG1 添加到基于临床变量的模型中可以改善辨别力（c 统计量从 0.828 到 0.842，P = 0.006）和重新分类（净重新分类改善 0.47，95% CI 0.28-0.67），以预测 5 年全因死亡率。结论 血浆 LRG1 可预测全因死亡率和心血管疾病、感染、和肾脏疾病，与已知的心肾危险因素无关。它可能是一种潜在的新型生物标志物，可改善 2 型糖尿病患者的风险分层。