{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:57:22Z","timestamp":1793372242926,"version":"4.5.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca corrente"],"award-info":[{"award-number":["Ricerca corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca corrente"],"award-info":[{"award-number":["Ricerca corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca corrente"],"award-info":[{"award-number":["Ricerca corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca corrente"],"award-info":[{"award-number":["Ricerca corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca corrente"],"award-info":[{"award-number":["Ricerca corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca corrente"],"award-info":[{"award-number":["Ricerca corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca corrente"],"award-info":[{"award-number":["Ricerca corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca corrente"],"award-info":[{"award-number":["Ricerca corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca corrente"],"award-info":[{"award-number":["Ricerca corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca corrente"],"award-info":[{"award-number":["Ricerca corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca corrente"],"award-info":[{"award-number":["Ricerca corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca corrente"],"award-info":[{"award-number":["Ricerca corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca corrente"],"award-info":[{"award-number":["Ricerca corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cardiovasc Diabetol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Type 2 diabetes (T2D) is a chronic metabolic disorder associated with aging, systemic inflammation, and increased long-term mortality. Identifying prognostic biomarkers may improve risk stratification and guide personalized interventions. This study aimed to evaluate the long-term prognostic value of circulating biomarkers related to inflammation, metabolic stress, and organ damage in individuals with T2D.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective study was conducted on a cohort of 478 individuals with T2D, followed for a median of 16.1\u00a0years. Ten circulating biomarkers (IL-6, IL-10, CD163, CXCL9, CCL22, GDF15, IL-33, FGF21, Follistatin, and neurofilament light chain [NfL]) were quantified using an automated immunoassay platform. Kaplan\u2013Meier survival analysis and Cox proportional hazards models were used to assess their prognostic significance for all-cause mortality. A biomarker-based scoring model was developed by integrating independent predictors of mortality. Predictive performance was evaluated in comparison with the RECODe equation, a validated risk model for diabetes complications and mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Deceased individuals exhibited significantly higher levels of IL-6, IL-10, CXCL9, FGF21, NfL, and GDF15. Biomarker levels correlated with both microvascular and macrovascular complications, particularly neuropathy, nephropathy, retinopathy, and major adverse cardiovascular events (MACE). In multivariable Cox regression analysis, four biomarkers emerged as independent predictors of mortality: CXCL9 (HR per 1 SD increase 1.19, 95% CI 1.05\u20131.36,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006), GDF15 (HR 1.16, 95% CI 1.02\u20131.33,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.032), NfL (HR 1.25, 95% CI 1.09\u20131.43,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001), and FGF21 (HR 1.20, 95% CI 1.04\u20131.37,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009). A composite biomarker score (range: 4\u201312) stratified individuals into distinct risk categories, with each 1-point increase in the score associated with a 55% higher mortality risk (HR 1.53, 95% CI 1.35\u20131.74,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). The biomarker score remained independently predictive after adjusting for clinical covariates and significantly improved individual-level risk classification beyond the RECODe model, as demonstrated by net reclassification and discrimination improvement metrics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that inflammatory and metabolic stress-related biomarkers independently predict long-term mortality in T2D. The biomarker-based scoring model enhances risk stratification and improves the prognostic performance of existing clinical tools, such as the RECODe equation, potentially informing targeted clinical interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12933-025-02830-5","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T08:42:59Z","timestamp":1751964179000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A scoring model integrating CXCL9, GDF15, FGF21, and NfL, predicts long-term mortality in type 2 diabetes: a retrospective study"],"prefix":"10.1186","volume":"24","author":[{"given":"Matilde","family":"Sbriscia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Caccese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Marchegiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rina","family":"Recchioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Matacchione","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Giordani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Francini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Salvioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Conte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Landolfo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Rita","family":"Bonfigli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Turchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacopo","family":"Sabbatinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Olivieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Giuliani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"issue":"3","key":"2830_CR1","doi-asserted-by":"publisher","DOI":"10.1002\/hsr2.2004","volume":"7","author":"MJ Hossain","year":"2024","unstructured":"Hossain MJ, Al-Mamun M, Islam MR. Diabetes mellitus, the fastest growing global public health concern: early detection should be focused. Health Sci Rep. 2024;7(3): e2004.","journal-title":"Health Sci Rep"},{"issue":"39","key":"2830_CR2","doi-asserted-by":"publisher","first-page":"4043","DOI":"10.1093\/eurheartj\/ehad192","volume":"44","author":"N Marx","year":"2023","unstructured":"Marx N, Federici M, Schutt K, Muller-Wieland D, Ajjan RA, Antunes MJ, et al. 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J. 2023;44(39):4043\u2013140.","journal-title":"Eur Heart J"},{"key":"2830_CR3","doi-asserted-by":"crossref","unstructured":"Emerging Risk Factors C. Life expectancy associated with different ages at diagnosis of type 2 diabetes in high-income countries: 23 million person-years of observation. Lancet Diabetes Endocrinol. 2023;11(10):731\u201342.","DOI":"10.1016\/S2213-8587(23)00223-1"},{"issue":"1","key":"2830_CR4","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1186\/s12872-023-03638-5","volume":"23","author":"C Chen","year":"2023","unstructured":"Chen C, Chen Y, Gao Q, Wei Q. Association of systemic immune inflammatory index with all-cause and cause-specific mortality among individuals with type 2 diabetes. BMC Cardiovasc Disord. 2023;23(1):596.","journal-title":"BMC Cardiovasc Disord"},{"issue":"9","key":"2830_CR5","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.1111\/dom.14081","volume":"22","author":"F Prattichizzo","year":"2020","unstructured":"Prattichizzo F, Giuliani A, Sabbatinelli J, Matacchione G, Ramini D, Bonfigli AR, et al. Prevalence of residual inflammatory risk and associated clinical variables in patients with type 2 diabetes. Diabetes Obes Metab. 2020;22(9):1696\u2013700.","journal-title":"Diabetes Obes Metab"},{"key":"2830_CR6","doi-asserted-by":"publisher","first-page":"1294819","DOI":"10.3389\/fendo.2024.1294819","volume":"15","author":"X An","year":"2024","unstructured":"An X, Zhang Y, Sun W, Kang X, Ji H, Sun Y, et al. Early effective intervention can significantly reduce all-cause mortality in prediabetic patients: a systematic review and meta-analysis based on high-quality clinical studies. Front Endocrinol (Lausanne). 2024;15:1294819.","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"12","key":"2830_CR7","doi-asserted-by":"publisher","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","volume":"25","author":"D Furman","year":"2019","unstructured":"Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, et al. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019;25(12):1822\u201332.","journal-title":"Nat Med"},{"issue":"3","key":"2830_CR8","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.2337\/db12-1625","volume":"63","author":"G Lowe","year":"2014","unstructured":"Lowe G, Woodward M, Hillis G, Rumley A, Li Q, Harrap S, et al. 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. Diabetes. 2014;63(3):1115\u201323.","journal-title":"Diabetes"},{"key":"2830_CR9","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.atherosclerosis.2016.04.015","volume":"250","author":"GW Landman","year":"2016","unstructured":"Landman GW, Kleefstra N, Groenier KH, Bakker SJ, Groeneveld GH, Bilo HJ, et al. Inflammation biomarkers and mortality prediction in patients with type 2 diabetes (ZODIAC-27). Atherosclerosis. 2016;250:46\u201351.","journal-title":"Atherosclerosis"},{"issue":"5","key":"2830_CR10","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.2337\/dc19-2489","volume":"43","author":"MG Scarale","year":"2020","unstructured":"Scarale MG, Copetti M, Garofolo M, Fontana A, Salvemini L, De Cosmo S, et al. The synergic association of hs-CRP and serum amyloid P component in predicting all-cause mortality in patients with type 2 diabetes. Diabetes Care. 2020;43(5):1025\u201332.","journal-title":"Diabetes Care"},{"key":"2830_CR11","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.cyto.2019.02.005","volume":"117","author":"R Tian","year":"2019","unstructured":"Tian R, Tian M, Wang L, Qian H, Zhang S, Pang H, et al. C-reactive protein for predicting cardiovascular and all-cause mortality in type 2 diabetic patients: a meta-analysis. Cytokine. 2019;117:59\u201364.","journal-title":"Cytokine"},{"issue":"1","key":"2830_CR12","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/s12933-024-02207-0","volume":"23","author":"MG Rolver","year":"2024","unstructured":"Rolver MG, Emanuelsson F, Nordestgaard BG, Benn M. Contributions of elevated CRP, hyperglycaemia, and type 2 diabetes to cardiovascular risk in the general population: observational and Mendelian randomization studies. Cardiovasc Diabetol. 2024;23(1):165.","journal-title":"Cardiovasc Diabetol"},{"issue":"2","key":"2830_CR13","doi-asserted-by":"publisher","first-page":"E411","DOI":"10.1152\/ajpendo.00166.2019","volume":"317","author":"S Aparicio-Siegmund","year":"2019","unstructured":"Aparicio-Siegmund S, Garbers Y, Flynn CM, Waetzig GH, Gouni-Berthold I, Krone W, et al. The IL-6-neutralizing sIL-6R-sgp130 buffer system is disturbed in patients with type 2 diabetes. Am J Physiol Endocrinol Metab. 2019;317(2):E411\u201320.","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2830_CR14","doi-asserted-by":"publisher","first-page":"430","DOI":"10.3389\/fimmu.2018.00430","volume":"9","author":"L Badimon","year":"2018","unstructured":"Badimon L, Pena E, Arderiu G, Padro T, Slevin M, Vilahur G, et al. C-reactive protein in atherothrombosis and angiogenesis. Front Immunol. 2018;9:430.","journal-title":"Front Immunol"},{"key":"2830_CR15","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1038\/s43587-021-00082-y","volume":"1","author":"N Sayed","year":"2021","unstructured":"Sayed N, Huang Y, Nguyen K, Krejciova-Rajaniemi Z, Grawe AP, Gao T, et al. An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging. Nat Aging. 2021;1:598\u2013615.","journal-title":"Nat Aging"},{"issue":"6","key":"2830_CR16","doi-asserted-by":"publisher","first-page":"784","DOI":"10.2337\/dc16-2175","volume":"40","author":"A Bidadkosh","year":"2017","unstructured":"Bidadkosh A, Lambooy SPH, Heerspink HJ, Pena MJ, Henning RH, Buikema H, et al. Predictive properties of biomarkers GDF-15, NTproBNP, and hs-TnT for morbidity and mortality in patients with type 2 diabetes with nephropathy. Diabetes Care. 2017;40(6):784\u201392.","journal-title":"Diabetes Care"},{"issue":"1","key":"2830_CR17","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1186\/s12902-024-01713-2","volume":"24","author":"C Wang","year":"2024","unstructured":"Wang C, Wang S, Wang Y. The association between joint serum neurofilament light chain and type 2 diabetes with all-cause and cardiovascular mortality in US adults: a longitudinal study of NHANES. BMC Endocr Disord. 2024;24(1):186.","journal-title":"BMC Endocr Disord"},{"issue":"32","key":"2830_CR18","doi-asserted-by":"publisher","first-page":"50835","DOI":"10.18632\/oncotarget.10615","volume":"7","author":"AR Bonfigli","year":"2016","unstructured":"Bonfigli AR, Spazzafumo L, Prattichizzo F, Bonafe M, Mensa E, Micolucci L, et al. Leukocyte telomere length and mortality risk in patients with type 2 diabetes. Oncotarget. 2016;7(32):50835\u201344.","journal-title":"Oncotarget"},{"key":"2830_CR19","doi-asserted-by":"crossref","unstructured":"Association AD. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes\u20142019. Diabetes Care. 2018;42(Supplement_1):S13\u2013S28.","DOI":"10.2337\/dc19-S002"},{"issue":"10","key":"2830_CR20","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1016\/S2213-8587(17)30221-8","volume":"5","author":"S Basu","year":"2017","unstructured":"Basu S, Sussman JB, Berkowitz SA, Hayward RA, Yudkin JS. Development and validation of risk equations for complications of type 2 diabetes (RECODe) using individual participant data from randomised trials. Lancet Diabetes Endocrinol. 2017;5(10):788\u201398.","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2830_CR21","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.cmpb.2019.05.023","volume":"177","author":"M Og\u0142uszka","year":"2019","unstructured":"Og\u0142uszka M, Orzechowska M, J\u0119droszka D, Witas P, Bednarek AK. Evaluate Cutpoints: adaptable continuous data distribution system for determining survival in Kaplan-Meier estimator. Comput Methods Programs Biomed. 2019;177:133\u20139.","journal-title":"Comput Methods Programs Biomed"},{"issue":"6","key":"2830_CR22","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.2337\/db22-0095","volume":"71","author":"MG Scarale","year":"2022","unstructured":"Scarale MG, Mastroianno M, Prehn C, Copetti M, Salvemini L, Adamski J, et al. Circulating metabolites associate with and improve the prediction of all-cause mortality in type 2 diabetes. Diabetes. 2022;71(6):1363\u201370.","journal-title":"Diabetes"},{"key":"2830_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2024.111575","volume":"209","author":"J Zhang","year":"2024","unstructured":"Zhang J, Fan X, Xu Y, Wang K, Xu T, Han T, et al. Association between inflammatory biomarkers and mortality in individuals with type 2 diabetes: NHANES 2005\u20132018. Diabetes Res Clin Pract. 2024;209: 111575.","journal-title":"Diabetes Res Clin Pract"},{"key":"2830_CR24","doi-asserted-by":"crossref","unstructured":"Sabbatinelli J, Castiglione S, Macr\u00ec F, Giuliani A, Ramini D, Vinci MC, et al. Circulating levels of AGEs and soluble RAGE isoforms are associated with all-cause mortality and development of cardiovascular complications in type 2 diabetes: a retrospective cohort study. Cardiovasc Diabetol. 2022;21(1).","DOI":"10.1186\/s12933-022-01535-3"},{"issue":"1","key":"2830_CR25","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1186\/s12933-022-01616-3","volume":"21","author":"J Sabbatinelli","year":"2022","unstructured":"Sabbatinelli J, Giuliani A, Bonfigli AR, Ramini D, Matacchione G, Campolucci C, et al. Prognostic value of soluble ST2, high-sensitivity cardiac troponin, and NT-proBNP in type 2 diabetes: a 15-year retrospective study. Cardiovasc Diabetol. 2022;21(1):180.","journal-title":"Cardiovasc Diabetol"},{"issue":"1","key":"2830_CR26","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1186\/s12933-024-02351-7","volume":"23","author":"J Sabbatinelli","year":"2024","unstructured":"Sabbatinelli J, Giuliani A, Kwiatkowska KM, Matacchione G, Belloni A, Ramini D, et al. DNA Methylation-derived biological age and long-term mortality risk in subjects with type 2 diabetes. Cardiovasc Diabetol. 2024;23(1):250.","journal-title":"Cardiovasc Diabetol"},{"issue":"9","key":"2830_CR27","doi-asserted-by":"publisher","first-page":"2830","DOI":"10.2337\/dc12-1906","volume":"36","author":"S De Cosmo","year":"2013","unstructured":"De Cosmo S, Copetti M, Lamacchia O, Fontana A, Massa M, Morini E, et al. Development and validation of a predicting model of all-cause mortality in patients with type 2 diabetes. Diabetes Care. 2013;36(9):2830\u20135.","journal-title":"Diabetes Care"},{"issue":"1","key":"2830_CR28","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s12933-025-02683-y","volume":"24","author":"BF Di Giacomo","year":"2025","unstructured":"Di Giacomo BF, Bosco G, Di Marco M, Scilletta S, Miano N, Musmeci M, et al. Evaluation of glycemic status and subclinical atherosclerosis in familial hypercholesterolemia subjects with or without LDL receptor mutation. Cardiovasc Diabetol. 2025;24(1):126.","journal-title":"Cardiovasc Diabetol"},{"key":"2830_CR29","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.ejim.2024.12.002","volume":"132","author":"G Bosco","year":"2025","unstructured":"Bosco G, Di Giacomo BF, Di Marco M, Scilletta S, Miano N, Capuccio S, et al. Evaluations of metabolic and innate immunity profiles in subjects with familial hypercholesterolemia with or without subclinical atherosclerosis. Eur J Intern Med. 2025;132:118\u201326.","journal-title":"Eur J Intern Med"},{"key":"2830_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101569","volume":"75","author":"M Conte","year":"2022","unstructured":"Conte M, Giuliani C, Chiariello A, Iannuzzi V, Franceschi C, Salvioli S. GDF15, an emerging key player in human aging. Ageing Res Rev. 2022;75: 101569.","journal-title":"Ageing Res Rev"},{"issue":"10","key":"2830_CR31","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1038\/s41574-021-00529-7","volume":"17","author":"D Wang","year":"2021","unstructured":"Wang D, Day EA, Townsend LK, Djordjevic D, Jorgensen SB, Steinberg GR. GDF15: emerging biology and therapeutic applications for obesity and cardiometabolic disease. Nat Rev Endocrinol. 2021;17(10):592\u2013607.","journal-title":"Nat Rev Endocrinol"},{"issue":"7796","key":"2830_CR32","doi-asserted-by":"publisher","first-page":"E24","DOI":"10.1038\/s41586-020-2031-4","volume":"578","author":"AP Coll","year":"2020","unstructured":"Coll AP, Chen M, Taskar P, Rimmington D, Patel S, Tadross JA, et al. Publisher Correction: GDF15 mediates the effects of metformin on body weight and energy balance. Nature. 2020;578(7796):E24.","journal-title":"Nature"},{"issue":"11","key":"2830_CR33","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1016\/j.tem.2022.08.004","volume":"33","author":"D Aguilar-Recarte","year":"2022","unstructured":"Aguilar-Recarte D, Barroso E, Palomer X, Wahli W, Vazquez-Carrera M. Knocking on GDF15\u2019s door for the treatment of type 2 diabetes mellitus. Trends Endocrinol Metab. 2022;33(11):741\u201354.","journal-title":"Trends Endocrinol Metab"},{"issue":"6","key":"2830_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2022.101380","volume":"48","author":"X Qian","year":"2022","unstructured":"Qian X, He S, Shen X, Shi N, Gong Q, An Y, et al. Circulating levels of GDF-15 for predicting cardiovascular and cancer morbidity and mortality in type 2 diabetes: findings from Da Qing IGT and Diabetes Study. Diabetes Metab. 2022;48(6): 101380.","journal-title":"Diabetes Metab"},{"issue":"1","key":"2830_CR35","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1161\/ATVBAHA.110.213512","volume":"31","author":"MP Bonaca","year":"2011","unstructured":"Bonaca MP, Morrow DA, Braunwald E, Cannon CP, Jiang S, Breher S, et al. Growth differentiation factor-15 and risk of recurrent events in patients stabilized after acute coronary syndrome: observations from PROVE IT-TIMI 22. Arterioscler Thromb Vasc Biol. 2011;31(1):203\u201310.","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"11","key":"2830_CR36","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/s41574-020-0386-0","volume":"16","author":"L Geng","year":"2020","unstructured":"Geng L, Lam KSL, Xu A. The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic. Nat Rev Endocrinol. 2020;16(11):654\u201367.","journal-title":"Nat Rev Endocrinol"},{"issue":"6","key":"2830_CR37","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1210\/clinem\/dgac729","volume":"108","author":"A Post","year":"2023","unstructured":"Post A, Dam WA, Sokooti S, Groothof D, Gloerich J, van Gool AJ, et al. Circulating FGF21 concentration, fasting plasma glucose, and the risk of type 2 diabetes: results from the PREVEND study. J Clin Endocrinol Metab. 2023;108(6):1387\u201393.","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2830_CR38","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1186\/s12902-023-01426-y","volume":"23","author":"L You","year":"2023","unstructured":"You L, Hong X, Wu H, Liang D, Li F, Zheng D, et al. The association of FGF-21 with the risk of newly diagnosed type-2 diabetes mellitus: a cross-sectional study in Southern China. BMC Endocr Disord. 2023;23(1):188.","journal-title":"BMC Endocr Disord"},{"issue":"19","key":"2830_CR39","doi-asserted-by":"publisher","first-page":"12673","DOI":"10.18632\/aging.206114","volume":"16","author":"G Handzlik","year":"2024","unstructured":"Handzlik G, Owczarek AJ, Wiecek A, Mossakowska M, Zdrojewski T, Chudek A, et al. Fibroblast growth factor 21 inversely correlates with survival in elderly population\u2014the results of the Polsenior2 study. Aging (Albany NY). 2024;16(19):12673\u201384.","journal-title":"Aging (Albany NY)"},{"key":"2830_CR40","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2024.117799","volume":"555","author":"WJ Tucker","year":"2024","unstructured":"Tucker WJ, Tucker B, Januszewski AS, Jenkins AJ, Keech AC, Kestenbaum BR, et al. Association of circulating fibroblast growth factor 21 levels with all-cause and cardiovascular mortality: the multi-ethnic study of atherosclerosis. Clin Chim Acta. 2024;555: 117799.","journal-title":"Clin Chim Acta"},{"issue":"3","key":"2830_CR41","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.jdiacomp.2007.12.001","volume":"23","author":"M Higurashi","year":"2009","unstructured":"Higurashi M, Ohya Y, Joh K, Muraguchi M, Nishimura M, Terawaki H, et al. Increased urinary levels of CXCL5, CXCL8 and CXCL9 in patients with type 2 diabetic nephropathy. J Diabetes Complications. 2009;23(3):178\u201384.","journal-title":"J Diabetes Complications"},{"key":"2830_CR42","doi-asserted-by":"publisher","first-page":"35","DOI":"10.11606\/S1518-8787.2019053000855","volume":"53","author":"JSC Amorim","year":"2019","unstructured":"Amorim JSC, Torres KCL, Teixeira-Carvalho A, Martins-Filho OA, Lima-Costa MF, Peixoto SV. Inflammatory markers and occurrence of falls: Bambui cohort study of aging. Rev Saude Publica. 2019;53:35.","journal-title":"Rev Saude Publica"},{"issue":"10","key":"2830_CR43","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.1002\/jbmr.4646","volume":"37","author":"QT Phan","year":"2022","unstructured":"Phan QT, Chua KY, Jin A, Winkler C, Koh WP. CXCL9 predicts the risk of osteoporotic hip fracture in a prospective cohort of Chinese men-a matched case-control study. J Bone Miner Res. 2022;37(10):1843\u20139.","journal-title":"J Bone Miner Res"},{"issue":"3","key":"2830_CR44","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1007\/s00125-022-05846-8","volume":"66","author":"H Maalmi","year":"2023","unstructured":"Maalmi H, Strom A, Petrera A, Hauck SM, Strassburger K, Kuss O, et al. Serum neurofilament light chain: a novel biomarker for early diabetic sensorimotor polyneuropathy. Diabetologia. 2023;66(3):579\u201389.","journal-title":"Diabetologia"},{"issue":"1","key":"2830_CR45","doi-asserted-by":"publisher","first-page":"15612","DOI":"10.1038\/s41598-024-66444-9","volume":"14","author":"AS Kim","year":"2024","unstructured":"Kim AS, Lee JM. The limited role of serum neurofilament light chain in predicting pain severity of patients with diabetic polyneuropathy. Sci Rep. 2024;14(1):15612.","journal-title":"Sci Rep"},{"issue":"6","key":"2830_CR46","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/S2213-8587(20)30118-2","volume":"8","author":"V Srikanth","year":"2020","unstructured":"Srikanth V, Sinclair AJ, Hill-Briggs F, Moran C, Biessels GJ. Type 2 diabetes and cognitive dysfunction-towards effective management of both comorbidities. Lancet Diabetes Endocrinol. 2020;8(6):535\u201345.","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"12","key":"2830_CR47","doi-asserted-by":"publisher","first-page":"e2246","DOI":"10.1210\/clinem\/dgae102","volume":"109","author":"Y Cai","year":"2024","unstructured":"Cai Y, Wei Q, Wang S, Lu X. All-cause mortality differentials by diabetes status and serum neurofilament light-chain levels in US general adults. J Clin Endocrinol Metab. 2024;109(12):e2246\u201354.","journal-title":"J Clin Endocrinol Metab"},{"key":"2830_CR48","doi-asserted-by":"crossref","unstructured":"Marchegiani F, Recchioni R, Marcheselli F, Di Rosa M, Sabbatinelli J, Matacchione G, et al. Association of admission serum levels of neurofilament light chain and in-hospital mortality in geriatric patients with COVID-19. J Neurol. 2022.","DOI":"10.1007\/s00415-022-11373-8"}],"container-title":["Cardiovascular Diabetology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12933-025-02830-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12933-025-02830-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12933-025-02830-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T09:16:47Z","timestamp":1752139007000},"score":1,"resource":{"primary":{"URL":"https:\/\/cardiab.biomedcentral.com\/articles\/10.1186\/s12933-025-02830-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,8]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2830"],"URL":"https:\/\/doi.org\/10.1186\/s12933-025-02830-5","relation":{},"ISSN":["1475-2840"],"issn-type":[{"value":"1475-2840","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,8]]},"assertion":[{"value":"30 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study received approval from the Institutional Review Board of IRCCS INRCA hospital (Approval No. 34\/CdB\/03). Written informed consent was obtained from all participants in compliance with the principles outlined in the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"270"}}