Indices of obesity, malnutrition and inflammation are strong predictors of mortality in adults with type 2 diabetes: the FIELD study
8 affiliations
- 1National Health and Medical Research Council Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW Australia
- 2Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, NSW Australia
- 3Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW Australia
- 4Department of Medicine, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
- 5Christchurch Hospital and NZ Clinical Research Ltd, Christchurch, New Zealand
- 6Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
- 7Diabetes and Vascular Medicine, Baker Heart and Diabetes Institute, Melbourne, VIC Australia
- 8School of Medicine, University of North Carolina, Chapel Hill, NC USA
Abstract
Aims/hypothesis: 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.
Methods: 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.
Results: 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; p<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 statistic 0.725 to 0.737; p=0.0003) and outperformed prior CVD history as a predictor.
Conclusions/interpretation: 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 (1997–2000), 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.
Graphical Abstract:
Supplementary Information: The online version contains peer-reviewed but unedited supplementary material available at https://doi.org/10.1007/s00125-026-06848-6.
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BibTeX
@article{keech2026indices,
title = {{Indices of obesity, malnutrition and inflammation are strong predictors of mortality in adults with type 2 diabetes: the FIELD study}},
author = {Anthony C. Keech and Rachel L. O’Connell and Andrzej S. Januszewski and Liping Li and Chris Dalton and R. John Simes and David R. Sullivan and Marja-Ritta Taskinen and Russell S. Scott and James D. Best and Alicia J. Jenkins and James D. Otvos},
journal = {Diabetologia},
year = {2026},
month = sep,
doi = {10.1007/s00125-026-06848-6},
url = {https://doi.org/10.1007/s00125-026-06848-6},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Indices of obesity, malnutrition and inflammation are strong predictors of mortality in adults with type 2 diabetes: the FIELD study
AU - Anthony C. Keech
AU - Rachel L. O’Connell
AU - Andrzej S. Januszewski
AU - Liping Li
AU - Chris Dalton
AU - R. John Simes
AU - David R. Sullivan
AU - Marja-Ritta Taskinen
AU - Russell S. Scott
AU - James D. Best
AU - Alicia J. Jenkins
AU - James D. Otvos
PY - 2026
DA - 2026/09/17
JO - Diabetologia
DO - 10.1007/s00125-026-06848-6
UR - https://doi.org/10.1007/s00125-026-06848-6
AB - Aims/hypothesis: 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. Methods: 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. Results: 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; p<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 statistic 0.725 to 0.737; p=0.0003) and outperformed prior CVD history as a predictor. Conclusions/interpretation: 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 (1997–2000), 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. Graphical Abstract: Supplementary Information: The online version contains peer-reviewed but unedited supplementary material available at https://doi.org/10.1007/s00125-026-06848-6.
SN - 0012-186X
SN - 1432-0428
ER -