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Life sciences · Journal article
Diabetologia · September 17, 2026
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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.