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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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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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, <i>p</i> < 0.001], IL-6 1.8 [1.3–2.6; <i>p </i>= 0.001], and combined 4.0 [2.3–7.2, <i>p</i> < 0.001]) and MACE (suPAR 1.9 [1.4–2.6, <i>p</i> < 0.001], IL-6 1.4 [1.0–1.8, <i>p </i>= 0.034], and combined 2.6 [1.7–4.1, <i>p</i> < 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.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>suPAR, IL-6, and especially their combination independently predicts all-cause mortality and MACE in T1D without known cardiovascular disease.</p>\n </section>\n </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 3","pages":"188-199"},"PeriodicalIF":9.2000,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20108","citationCount":"0","resultStr":"{\"title\":\"Soluble urokinase plasminogen activator receptor and interleukin-6 improves prediction of all-cause mortality and major adverse cardiovascular events in Type 1 diabetes\",\"authors\":\"Hashmat Sayed Zohori Bahrami, Peter Godsk Jørgensen, Jens Dahlgaard Hove, Ulrik Dixen, Line Jee Hartmann Rasmussen, Jesper Eugen-Olsen, Peter Rossing, Magnus T. Jensen\",\"doi\":\"10.1111/joim.20108\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>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, <i>p</i> < 0.001], IL-6 1.8 [1.3–2.6; <i>p </i>= 0.001], and combined 4.0 [2.3–7.2, <i>p</i> < 0.001]) and MACE (suPAR 1.9 [1.4–2.6, <i>p</i> < 0.001], IL-6 1.4 [1.0–1.8, <i>p </i>= 0.034], and combined 2.6 [1.7–4.1, <i>p</i> < 0.001]). 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Soluble urokinase plasminogen activator receptor and interleukin-6 improves prediction of all-cause mortality and major adverse cardiovascular events in Type 1 diabetes
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.
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.
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