{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T14:35:38Z","timestamp":1793111738540,"version":"4.5.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Laboratoires Fournier SA, Dijon, France"},{"name":"The University of Sydney","id":[{"id":"https:\/\/ror.org\/0384j8v12","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims\/hypothesis<\/jats:title>\n                    <jats:p>Metabolic risk in type 2 diabetes is not fully captured by standard clinical measures. Use of NMR-based metabolomic indices may enhance risk prediction, but their role in individuals with type 2 diabetes is unresolved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed data from 9550 adults with type 2 diabetes who were followed for 5 years in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. The composite index MVX (metabolic vulnerability), and its components IVX (inflammation vulnerability index) and MMX (metabolic malnutrition index), were derived from baseline plasma NMR. Associations with mortality and non-fatal events were assessed using Cox models adjusted for clinical variables and treatment allocation. Predictive performance was assessed using C statistics and variable contribution analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All three indices were associated with total mortality. Participants in the highest MVX quintile (Q5) had an over fourfold greater unadjusted mortality risk, and more than double the risk after adjustment (HR 2.31; 95% CI 1.71, 3.12). Each standard deviation increase in MVX showed a 75% higher mortality risk (95% CI 62, 89;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.001). MVX was associated with cardiovascular and cancer mortality separately, and independently predicted non-fatal cardiovascular events and new incident cancer. MMX and IVX showed weaker and less consistent associations. MVX improved risk model discrimination (C\u00a0statistic 0.725 to 0.737;\n                      <jats:italic>p<\/jats:italic>\n                      =0.0003) and outperformed prior CVD history as a predictor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>MVX independently predicts total and cardiovascular mortality in type 2 diabetes, offering prognostic value beyond traditional risk factors. The absolute event rates reflect the treatment standards of the FIELD recruitment period (1997\u20132000), prior to widespread use of several contemporary cardioprotective therapies. The results support further investigation of the clinical utility of MVX for determination of personalised risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-026-06848-6","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:23:13Z","timestamp":1789647793000},"page":"3533-3547","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Indices of obesity, malnutrition and inflammation are strong predictors of mortality in adults with type 2 diabetes: the FIELD study"],"prefix":"10.1007","volume":"69","author":[{"given":"Anthony C.","family":"Keech","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel L.","family":"O\u2019Connell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej S.","family":"Januszewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Dalton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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The assistance of the staff of Medfiles (Finland) and DataPharm (Australia) is gratefully acknowledged, as is the Australian Institute of Health and Welfare for providing assistance with searching of the National Death Index. We are indebted to J.-C. Ansquer (Laboratoires Fournier SA, Dijon, France), who died on 3 December 2023, for his enthusiastic support and scientific insights throughout the FIELD study. We thank Labcorp (Morrisville, NC, USA) for their support in performing the multimarker assays used to derive the MMX, IVX and MVX indices. We also thank the many adults with type 2 diabetes who participated in the FIELD trial.","order":1,"name":"Ethics","label":"Acknowledgements","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"De-identified participant data and relevant study variables supporting the findings of this study may be made available for academic use upon reasonable request, subject to the limitations of participant consent and approval by representatives of the FIELD trial steering committee. Requests should be directed to the corresponding author. Approved researchers will be required to enter into a data access agreement with the National Health and Medical Research Council Clinical Trials Centre, University of Sydney. Because of participant consent and governance restrictions, the full dataset cannot be deposited in a public repository.","order":2,"name":"Ethics","label":"Data availability","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"Open Access funding enabled and organized by CAUL and its Member Institutions. The FIELD study was supported by a grant from Laboratoires Fournier SA, Dijon, France, and was coordinated independently by the National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia, overseen by the study management committee. The study was also supported by the National Health and Medical Research Council, Australia, through a unit grant, a project grant, and fellowships to ACK and RJS.","order":3,"name":"Ethics","label":"Funding","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"ACK reports receiving grants from the National Health and Medical Research Council, research support from Abbott, AbbVie, Amgen, Mylan, Aspen and Viatris, serving on an advisory committee for Viatris, receiving speaker honoraria from Novartis, Pfizer and Sanofi, and serving on a data safety monitoring board for Kowa. RJS reports receiving grants from the National Health and Medical Research Council, research support from Bayer, Bristol Myers Squibb, MSD, Amgen and Roche, and consulting fees from Fivephusion. DRS reports receiving grants from Regeneron, Amgen, Arrowhead, Ionis, Novartis and MSD, consulting fees from Amgen and Novartis, participation on advisory boards for the LIPID, FIELD and NOMAD studies, and serving as Clinical Committee Chair of the Australian Atherosclerosis Society. AJJ reports receiving grants from the National Health and Medical Research Council. JDO reports being a co-inventor on a patent (US11156621B2) owned by Labcorp relating to multivariable metabolic vulnerability index evaluations. The remaining authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","label":"Authors\u2019 relationships and activities","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"ACK, RJS, DRS, M-RT, RSS and JDB contributed to the FIELD study conception. ACK, RLO, ASJ, AJJ and JDO contributed to the design of this work. ACK, LL, RJS, DRS, M-RT, RSS, JDB and JDO contributed to data acquisition. ACK, RLO, ASJ and CD contributed to data analysis. ACK, RLO, CD, RJS, DRS, AJJ and JDO contributed to data interpretation. ACK, RLO, ASJ, AJJ and JDO drafted the manuscript. All authors critically reviewed and edited the manuscript, and approved the final version for submission. ACK, RLO and CD verified the data and had access to the raw data. ACK and JDO are the guarantors of this work, and, as such, had full access to the data and take responsibility for the integrity of the data and the accuracy of the data analysis.","order":5,"name":"Ethics","label":"Contribution statement","group":{"name":"EthicsHeading","label":"Ethics"}}]}}