{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:47:33Z","timestamp":1793393253292,"version":"4.5.0"},"reference-count":50,"publisher":"The Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministero dell\u2019Istruzione dell\u2019Universit\u00e0"},{"name":"Ministero dell\u2019Universit\u00e0"},{"name":"Heal Italia"},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RF-2013-02356459"],"award-info":[{"award-number":["RF-2013-02356459"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["PNRR-MAD-2022-12375970"],"award-info":[{"award-number":["PNRR-MAD-2022-12375970"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ricerca corrente"},{"name":"European Health Data & Evidence Network"},{"DOI":"10.13039\/501100010767","name":"Innovative Medicines Initiative 2 Joint Undertaking","doi-asserted-by":"publisher","award":["806968"],"award-info":[{"award-number":["806968"]}],"id":[{"id":"10.13039\/501100010767","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program"},{"DOI":"10.13039\/100013322","name":"EFPIA","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>The role of inflammation in shaping death risk in diabetes is still unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To study whether inflammation is associated with and helps predict mortality risk in patients with type 2 diabetes. To explore the intertwined link between inflammation and tryptophan metabolism on death risk.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>There were 2 prospective cohorts: the aggregate Gargano Mortality Study (1731 individuals; 872 all-cause deaths) as the discovery sample, and the Foggia Mortality Study (490 individuals; 256 deaths) as validation sample. Twenty-seven inflammatory markers were measured. Causal mediation analysis and in vitro studies were carried out to explore the link between inflammatory markers and the kynurenine to tryptophan ratio (KTR) in shaping mortality risk.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Using multivariable stepwise Cox regression analysis, interleukin (IL)-4, IL-6, IL-8, IL-13, RANTES, and interferon gamma\u2013induced protein-10 (IP-10) were independently associated with death. An inflammation score (I score) comprising these 6 molecules is strongly associated with death in both the discovery and the validation cohorts HR (95% CI) 2.13 (1.91-2.37) and 2.20 (1.79-2.72), respectively. The I score improved discrimination and reclassification measures (all P &amp;lt; .01) of 2 mortality prediction models based on clinical variables. The causal mediation analysis showed that 28% of the KTR effect on mortality was mediated by IP-10. Studies in cultured endothelial cells showed that 5-methoxy-tryptophan, an anti-inflammatory metabolite derived from tryptophan, reduces the expression of IP-10, thus providing a functional basis for the observed causal mediation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Adding the I score to clinical prediction models may help identify individuals who are at greater risk of death. Deeply addressing the intertwined relationship between low-grade inflammation and imbalanced tryptophan metabolism in shaping mortality risk may help discover new therapies targeting patients characterized by these abnormalities.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae593","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T14:03:11Z","timestamp":1724853791000},"page":"e1323-e1333","source":"Crossref","is-referenced-by-count":5,"title":["Inflammation and Prediction of Death in Type 2 Diabetes. Evidence of an Intertwined Link With Tryptophan Metabolism"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7438-8955","authenticated-orcid":false,"given":"Claudia","family":"Menzaghi","sequence":"first","affiliation":[{"name":"Research Unit of Diabetes and Endocrine Diseases, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico \u201cCasa Sollievo della Sofferenza,\u201d 71013 San Giovanni Rotondo ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Marucci","sequence":"additional","affiliation":[{"name":"Research Unit of Diabetes and Endocrine Diseases, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico \u201cCasa Sollievo della Sofferenza,\u201d 71013 San Giovanni Rotondo ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3218-1646","authenticated-orcid":false,"given":"Mario","family":"Mastroianno","sequence":"additional","affiliation":[{"name":"Scientific Direction, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico \u201cCasa Sollievo della Sofferenza,\u201d 71013 San Giovanni Rotondo ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Di Ciaccia","sequence":"additional","affiliation":[{"name":"Research Unit of Diabetes and Endocrine Diseases, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico \u201cCasa Sollievo della Sofferenza,\u201d 71013 San Giovanni Rotondo ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Pia","family":"Armillotta","sequence":"additional","affiliation":[{"name":"Research Unit of Diabetes and Endocrine Diseases, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico \u201cCasa Sollievo della Sofferenza,\u201d 71013 San Giovanni Rotondo ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1274-4715","authenticated-orcid":false,"given":"Cornelia","family":"Prehn","sequence":"additional","affiliation":[{"name":"Metabolomics and Proteomics Core, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health , 85764 Neuherberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Salvemini","sequence":"additional","affiliation":[{"name":"Research Unit of Diabetes and Endocrine Diseases, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico \u201cCasa Sollievo della Sofferenza,\u201d 71013 San Giovanni Rotondo ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Mangiacotti","sequence":"additional","affiliation":[{"name":"Research Unit of Diabetes and Endocrine Diseases, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico \u201cCasa Sollievo della Sofferenza,\u201d 71013 San Giovanni Rotondo ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9259-0199","authenticated-orcid":false,"given":"Jerzy","family":"Adamski","sequence":"additional","affiliation":[{"name":"Institute of Experimental Genetics, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health , 85764 Neuherberg ,","place":["Germany"]},{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore , Singapore 117597 ,","place":["Singapore"]},{"name":"Institute of Biochemistry, Faculty of Medicine, University of Ljubljana , 1000 Ljubljana ,","place":["Slovenia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Fontana","sequence":"additional","affiliation":[{"name":"Biostatistics Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico \u201cCasa Sollievo della Sofferenza,\u201d 71013 San Giovanni Rotondo ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"De Cosmo","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico \u201cCasa Sollievo della Sofferenza,\u201d 71013 San Giovanni Rotondo ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9175-489X","authenticated-orcid":false,"given":"Olga","family":"Lamacchia","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medical and Surgical Sciences, University of Foggia , 71122 Foggia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Copetti","sequence":"additional","affiliation":[{"name":"Biostatistics Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico \u201cCasa Sollievo della Sofferenza,\u201d 71013 San Giovanni Rotondo ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1174-127X","authenticated-orcid":false,"given":"Vincenzo","family":"Trischitta","sequence":"additional","affiliation":[{"name":"Research Unit of Diabetes and Endocrine Diseases, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico \u201cCasa Sollievo della Sofferenza,\u201d 71013 San Giovanni Rotondo ,","place":["Italy"]},{"name":"Department of Experimental Medicine, Sapienza University of Rome , 00185 Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"issue":"10","key":"2025042208282438900_dgae593-B1","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S2213-8587(23)00223-1","article-title":"Life expectancy associated with different ages at diagnosis of type 2 diabetes in high-income countries: 23 million person-years of observation","volume":"11","author":"Emerging Risk Factors Collaboration","year":"2023","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"11","key":"2025042208282438900_dgae593-B2","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S2213-8587(22)00252-2","article-title":"Lifetime risk, life expectancy, and years of life lost to type 2 diabetes in 23 high-income jurisdictions: a multinational, population-based study","volume":"10","author":"Tomic","year":"2022","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"10397","key":"2025042208282438900_dgae593-B3","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0140-6736(23)01301-6","article-title":"Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the global burden of disease study 2021","volume":"402","author":"GBD 2021 Diabetes Collaborators","year":"2023","journal-title":"Lancet"},{"issue":"11","key":"2025042208282438900_dgae593-B4","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1007\/s00125-016-4065-6","article-title":"Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial","volume":"59","author":"G\u00e6de","year":"2016","journal-title":"Diabetologia"},{"issue":"5","key":"2025042208282438900_dgae593-B5","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.numecd.2018.02.009","article-title":"Attending diabetes clinics is associated with a lower all-cause mortality. a meta-analysis of observational studies performed in Italy","volume":"28","author":"Bonora","year":"2018","journal-title":"Nutr Metab Cardiovasc Dis"},{"issue":"1","key":"2025042208282438900_dgae593-B6","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s41512-018-0037-2","article-title":"Quantifying the added value of new biomarkers: how and how not","volume":"2","author":"Cook","year":"2018","journal-title":"Diagn Progn Res"},{"issue":"1","key":"2025042208282438900_dgae593-B7","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/s41392-023-01399-3","article-title":"Small molecule metabolites: discovery of biomarkers and therapeutic targets","volume":"8","author":"Qiu","year":"2023","journal-title":"Signal Transduct Target Ther"},{"issue":"12","key":"2025042208282438900_dgae593-B8","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic inflammation in the etiology of disease across the life span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat Med"},{"key":"2025042208282438900_dgae593-B9","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.atherosclerosis.2016.04.015","article-title":"Inflammation biomarkers and mortality prediction in patients with type 2 diabetes (ZODIAC-27)","volume":"250","author":"Landman","year":"2016","journal-title":"Atherosclerosis"},{"issue":"3","key":"2025042208282438900_dgae593-B10","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.2337\/db12-1625","article-title":"Circulating inflammatory markers and the risk of vascular complications and mortality in people with type 2 diabetes and cardiovascular disease or risk factors: the ADVANCE study","volume":"63","author":"Lowe","year":"2014","journal-title":"Diabetes"},{"issue":"5","key":"2025042208282438900_dgae593-B11","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.2337\/dc19-2489","article-title":"The synergic association of hs-CRP and serum amyloid P component in predicting all-cause mortality in patients with type 2 diabetes","volume":"43","author":"Scarale","year":"2020","journal-title":"Diabetes Care"},{"issue":"11","key":"2025042208282438900_dgae593-B12","doi-asserted-by":"crossref","first-page":"e4350","DOI":"10.1210\/clinem\/dgab472","article-title":"A serum resistin and multicytokine inflammatory pathway is linked with and helps predict all-cause death in diabetes","volume":"106","author":"Scarale","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"2025042208282438900_dgae593-B13","doi-asserted-by":"crossref","unstructured":"Menzaghi C, Marucci A, Mastroianno M, et al Inflammation and prediction of death in type 2 diabetes. Evidence of an intertwined link with tryptophan metabolism. Figshare. 10.6084\/m9.figshare.26404324figshare. Date of deposit 22 August 2024.","DOI":"10.1210\/clinem\/dgae593"},{"issue":"6","key":"2025042208282438900_dgae593-B14","doi-asserted-by":"crossref","first-page":"5742","DOI":"10.3390\/ijms24065742","article-title":"The tryptophan and kynurenine pathway involved in the development of immune-related diseases","volume":"24","author":"Tsuji","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"12","key":"2025042208282438900_dgae593-B15","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.2337\/dc23-1147","article-title":"Plasma tryptophan-kynurenine pathway metabolites and risk for progression to end-stage kidney disease in patients with type 2 diabetes","volume":"46","author":"Liu","year":"2023","journal-title":"Diabetes Care"},{"issue":"5","key":"2025042208282438900_dgae593-B16","doi-asserted-by":"crossref","first-page":"e003422","DOI":"10.1136\/bmjdrc-2023-003422","article-title":"Circulating metabolites improve the prediction of renal impairment in patients with type 2 diabetes","volume":"11","author":"Trischitta","year":"2023","journal-title":"BMJ Open Diabetes Res Care"},{"issue":"6","key":"2025042208282438900_dgae593-B17","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.2337\/db22-0095","article-title":"Circulating metabolites associate with and improve the prediction of all-cause mortality in type 2 diabetes","volume":"71","author":"Scarale","year":"2022","journal-title":"Diabetes"},{"issue":"Suppl 1","key":"2025042208282438900_dgae593-B18","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.2337\/diacare.27.2007.S15","article-title":"Standards of medical care in diabetes","volume":"27","author":"American Diabetes Association","year":"2004","journal-title":"Diabetes Care"},{"key":"2025042208282438900_dgae593-B19","doi-asserted-by":"crossref","first-page":"155044","DOI":"10.1016\/j.cyto.2020.155044","article-title":"Stability of 12 T-helper cell-associated cytokines in human serum under different pre-analytical conditions","volume":"129","author":"Stervbo","year":"2020","journal-title":"Cytokine"},{"issue":"1","key":"2025042208282438900_dgae593-B20","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1021\/acs.jproteome.7b00518","article-title":"Long-term stability of human plasma metabolites during storage at -80 \u00b0C","volume":"17","author":"Haid","year":"2018","journal-title":"J Proteome Res"},{"issue":"1","key":"2025042208282438900_dgae593-B21","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s11306-017-1312-x","article-title":"High-throughput extraction and quantification method for targeted metabolomics in murine tissues","volume":"14","author":"Zukunft","year":"2018","journal-title":"Metabolomics"},{"issue":"7","key":"2025042208282438900_dgae593-B22","doi-asserted-by":"crossref","first-page":"RESEARCH0034","DOI":"10.1186\/gb-2002-3-7-research0034","article-title":"Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes","volume":"3","author":"Vandesompele","year":"2002","journal-title":"Genome Biol"},{"issue":"1","key":"2025042208282438900_dgae593-B23","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1093\/bioinformatics\/btr597","article-title":"MissForest\u2013non-parametric missing value imputation for mixed-type data","volume":"28","author":"Stekhoven","year":"2012","journal-title":"Bioinformatics"},{"key":"2025042208282438900_dgae593-B24","first-page":"1","volume-title":"Classification and Regression Trees","author":"Leo","year":"1984"},{"issue":"9","key":"2025042208282438900_dgae593-B25","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.2337\/dc12-1906","article-title":"Development and validation of a predicting model of all-cause mortality in patients with type 2 diabetes","volume":"36","author":"De Cosmo","year":"2013","journal-title":"Diabetes Care"},{"issue":"10","key":"2025042208282438900_dgae593-B26","doi-asserted-by":"crossref","first-page":"4900","DOI":"10.1210\/jc.2019-00215","article-title":"Estimation of mortality risk in type 2 diabetic patients (ENFORCE): an inexpensive and parsimonious prediction model","volume":"104","author":"Copetti","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"issue":"10","key":"2025042208282438900_dgae593-B27","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/S2213-8587(17)30221-8","article-title":"Development and validation of risk equations for complications of type 2 diabetes (RECODe) using individual participant data from randomised trials","volume":"5","author":"Basu","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"3","key":"2025042208282438900_dgae593-B28","doi-asserted-by":"crossref","first-page":"586","DOI":"10.2337\/dc17-2002","article-title":"Validation of risk equations for complications of type 2 diabetes (RECODe) using individual participant data from diverse longitudinal cohorts in the U.S","volume":"41","author":"Basu","year":"2018","journal-title":"Diabetes Care"},{"issue":"14","key":"2025042208282438900_dgae593-B29","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1002\/sim.5647","article-title":"A unified inference procedure for a class of measures to assess improvement in risk prediction systems with survival data","volume":"32","author":"Uno","year":"2013","journal-title":"Stat Med"},{"issue":"2","key":"2025042208282438900_dgae593-B30","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/sim.2929","article-title":"Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond","volume":"27","author":"Pencina","year":"2008","journal-title":"Stat Med"},{"issue":"1","key":"2025042208282438900_dgae593-B31","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/sim.4085","article-title":"Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers","volume":"30","author":"Pencina","year":"2011","journal-title":"Stat Med"},{"issue":"4","key":"2025042208282438900_dgae593-B32","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1037\/a0020761","article-title":"A general approach to causal mediation analysis","volume":"15","author":"Imai","year":"2010","journal-title":"Psychol Methods"},{"issue":"1","key":"2025042208282438900_dgae593-B33","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1038\/s41467-019-09329-0","article-title":"Identification of serum metabolites associating with chronic kidney disease progression and anti-fibrotic effect of 5-methoxytryptophan","volume":"10","author":"Chen","year":"2019","journal-title":"Nat Commun"},{"issue":"2","key":"2025042208282438900_dgae593-B34","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1161\/CIRCRESAHA.116.308559","article-title":"Endothelium-derived 5-methoxytryptophan is a circulating anti-inflammatory molecule that blocks systemic inflammation","volume":"119","author":"Wang","year":"2016","journal-title":"Circ Res"},{"issue":"7","key":"2025042208282438900_dgae593-B35","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1161\/CIRCULATIONAHA.106.672402","article-title":"Use and misuse of the receiver operating characteristic curve in risk prediction","volume":"115","author":"Cook","year":"2007","journal-title":"Circulation"},{"issue":"25 Pt B","key":"2025042208282438900_dgae593-B36","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1016\/j.jacc.2013.11.005","article-title":"2013 ACC\/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology\/American Heart Association task force on practice guidelines","volume":"63","author":"Goff","year":"2014","journal-title":"J Am Coll Cardiol"},{"issue":"1","key":"2025042208282438900_dgae593-B37","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/1475-2840-9-62","article-title":"The ubiquitous interleukin-6: a time for reappraisal","volume":"9","author":"Fisman","year":"2010","journal-title":"Cardiovasc Diabetol"},{"issue":"6","key":"2025042208282438900_dgae593-B38","doi-asserted-by":"crossref","first-page":"e1000099","DOI":"10.1371\/journal.pmed.1000099","article-title":"Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events?","volume":"6","author":"Sattar","year":"2009","journal-title":"PLoS Med"},{"issue":"1","key":"2025042208282438900_dgae593-B39","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/1475-2840-12-126","article-title":"Interleukin-6 and activin A are independently associated with cardiovascular events and mortality in type 2 diabetes: the prospective asker and b\u00e6rum cardiovascular diabetes (ABCD) cohort study","volume":"12","author":"Ofstad","year":"2013","journal-title":"Cardiovasc Diabetol"},{"issue":"10","key":"2025042208282438900_dgae593-B40","doi-asserted-by":"crossref","first-page":"a016295","DOI":"10.1101\/cshperspect.a016295","article-title":"IL-6 in inflammation, immunity, and disease","volume":"6","author":"Tanaka","year":"2014","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"3","key":"2025042208282438900_dgae593-B41","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1093\/cvr\/cvp241","article-title":"Interleukin 8 and cardiovascular disease","volume":"84","author":"Apostolakis","year":"2009","journal-title":"Cardiovasc Res"},{"key":"2025042208282438900_dgae593-B42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2012.10.553","article-title":"IL-4 and IL-13 employ discrete signaling pathways for target gene expression in alternatively activated monocytes\/macrophages","volume":"54","author":"Bhattacharjee","year":"2013","journal-title":"Free Radic Biol Med"},{"issue":"5","key":"2025042208282438900_dgae593-B43","doi-asserted-by":"crossref","first-page":"H833","DOI":"10.1152\/ajpheart.00310.2022","article-title":"Interleukin 4\/13 signaling in cardiac regeneration and repair","volume":"323","author":"Bakhshian Nik","year":"2022","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"1","key":"2025042208282438900_dgae593-B44","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1080\/15321819.2011.601781","article-title":"Cytokine serum profile in a group of Sicilian nonagenarians","volume":"33","author":"Palmeri","year":"2012","journal-title":"J Immunoassay Immunochem"},{"key":"2025042208282438900_dgae593-B45","doi-asserted-by":"crossref","first-page":"154157","DOI":"10.1016\/j.cyto.2017.09.013","article-title":"Platelet-derived chemokines in inflammation and atherosclerosis","volume":"122","author":"Bakogiannis","year":"2019","journal-title":"Cytokine"},{"key":"2025042208282438900_dgae593-B46","doi-asserted-by":"crossref","first-page":"893106","DOI":"10.1155\/2014\/893106","article-title":"The multifaceted functions of CXCL10 in cardiovascular disease","volume":"2014","author":"van den Borne","year":"2014","journal-title":"Biomed Res Int"},{"key":"2025042208282438900_dgae593-B47","doi-asserted-by":"crossref","first-page":"1178646917691938","DOI":"10.1177\/1178646917691938","article-title":"Kynurenine pathway of tryptophan metabolism: regulatory and functional aspects","volume":"10","author":"Badawy","year":"2017","journal-title":"Int J Tryptophan Res"},{"key":"2025042208282438900_dgae593-B48","doi-asserted-by":"crossref","first-page":"154838","DOI":"10.1016\/j.metabol.2021.154838","article-title":"Current trends in epidemiology of cardiovascular disease and cardiovascular risk management in type 2 diabetes","volume":"123","author":"Yun","year":"2021","journal-title":"Metabolism"},{"issue":"1","key":"2025042208282438900_dgae593-B49","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s12933-022-01516-6","article-title":"Cardiovascular disease in type 2 diabetes mellitus: progress toward personalized management","volume":"21","author":"Ma","year":"2022","journal-title":"Cardiovasc Diabetol"},{"issue":"3","key":"2025042208282438900_dgae593-B50","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.ecl.2021.05.001","article-title":"The changing nature of mortality and morbidity in patients with diabetes","volume":"50","author":"Pearson-Stuttard","year":"2021","journal-title":"Endocrinol Metab Clin North Am"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgae593\/59182750\/dgae593.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/5\/e1323\/59182750\/dgae593.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/5\/e1323\/59182750\/dgae593.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T12:29:00Z","timestamp":1745324940000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/110\/5\/e1323\/7742937"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,28]]},"references-count":50,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,8,28]]},"published-print":{"date-parts":[[2025,4,22]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgae593","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,5]]},"published":{"date-parts":[[2024,8,28]]}}}