Soluble urokinase plasminogen activator receptor and interleukin-6 improves prediction of all-cause mortality and major adverse cardiovascular events in Type 1 diabetes

IF 9.2 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine Pub Date : 2025-07-07 DOI:10.1111/joim.20108

Hashmat Sayed Zohori Bahrami, Peter Godsk Jørgensen, Jens Dahlgaard Hove, Ulrik Dixen, Line Jee Hartmann Rasmussen, Jesper Eugen-Olsen, Peter Rossing, Magnus T. Jensen

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引用次数: 0

Abstract

Background

Type 1 diabetes (T1D) increases premature mortality risk, with cardiovascular disease being the leading cause. Chronic inflammation may play a role. Associations between inflammatory biomarkers and mortality are not well-known in T1D.

Methods

We evaluated a prospective clinical cohort with T1D without known cardiovascular disease. The inflammatory biomarkers soluble-urokinase-plasminogen-activator-receptor (suPAR) and interleukin-6 (IL-6) were measured. Patients were stratified by elevated/low suPAR or IL-6, or simultaneously elevated suPAR and IL-6. Primary and secondary endpoints were all-cause mortality and major adverse cardiovascular events (MACE), respectively. Cox models were adjusted for 10 Steno T1 Risk Engine variables and inflammatory biomarkers. Net reclassification improvement (NRI) and C-statistics were calculated.

Results

Among 962 participants (52% male, median age 50, median follow-up 13.1 years), mortality was higher in patients with elevated inflammation: 31% for elevated versus 9% for low suPAR; 30% for elevated versus 11% for low IL-6; and 50% for simultaneously elevated suPAR and IL-6 versus 5% for low suPAR and IL-6. In fully adjusted models, elevated inflammation was associated with mortality (hazard ratios [95% confidence intervals]: suPAR 2.0 [1.4–3.0, p < 0.001], IL-6 1.8 [1.3–2.6; p = 0.001], and combined 4.0 [2.3–7.2, p < 0.001]) and MACE (suPAR 1.9 [1.4–2.6, p < 0.001], IL-6 1.4 [1.0–1.8, p = 0.034], and combined 2.6 [1.7–4.1, p < 0.001]). Adding suPAR, IL-6, and their combination to the Steno T1 Risk Engine improved NRI for mortality by 61%, 53%, and 84%, respectively, whereas C-statistics improved from 0.808 to 0.829, 0.826, and 0.881, respectively.

Conclusions

suPAR, IL-6, and especially their combination independently predicts all-cause mortality and MACE in T1D without known cardiovascular disease.

Abstract Image

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可溶性尿激酶纤溶酶原激活物受体和白介素-6改善1型糖尿病全因死亡率和主要不良心血管事件的预测

背景：1型糖尿病（T1D）增加过早死亡风险，心血管疾病是主要原因。慢性炎症可能起作用。炎症生物标志物与T1D患者死亡率之间的关系尚不清楚。方法：我们评估了一个没有已知心血管疾病的T1D患者的前瞻性临床队列。检测炎症生物标志物可溶性尿激酶-纤溶酶原激活物受体（suPAR）和白细胞介素-6 （IL-6）。根据suPAR或IL-6升高/降低或suPAR和IL-6同时升高对患者进行分层。主要终点和次要终点分别是全因死亡率和主要不良心血管事件（MACE）。Cox模型根据10个Steno T1风险引擎变量和炎症生物标志物进行调整。计算净重分类改善（NRI）和c -统计量。结果：在962名参与者中（52%为男性，中位年龄50岁，中位随访13.1年），炎症升高患者的死亡率更高：suPAR升高患者为31%，低suPAR患者为9%；IL-6升高30%，低11%；同时升高的suPAR和IL-6为50%，低suPAR和IL-6为5%。在完全调整的模型中，炎症升高与死亡率相关（危险比[95%置信区间]:suPAR 2.0 [1.4-3.0, p]）。结论：suPAR、IL-6，尤其是它们的联合独立预测无已知心血管疾病的T1D患者的全因死亡率和MACE。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Internal Medicine 医学-医学：内科

CiteScore

22.00

自引率

0.90%

发文量

176

审稿时长

4-8 weeks

期刊介绍： JIM – The Journal of Internal Medicine, in continuous publication since 1863, is an international, peer-reviewed scientific journal. It publishes original work in clinical science, spanning from bench to bedside, encompassing a wide range of internal medicine and its subspecialties. JIM showcases original articles, reviews, brief reports, and research letters in the field of internal medicine.