Type 2 diabetes increases the risk of death. To address this problem, biomarkers of novel pathogenic pathways capable of identifying high-risk patients must be identified. For a study, researchers examined the link between serum metabolites and all-cause mortality in type 2 diabetes, as well as whether the associated metabolites mediate the effect of inflammation on mortality risk and improve ENFORCE (EstimatioN oF mORtality risk in type 2 diabetic patients) and RECODe (Risk Equation for Complications Of Type 2 Diabetes), two well-known all-cause mortality prediction models in diabetes. 856 people (279 all-cause fatalities) were studied in two cohorts. Investigators analyzed serum metabolites (n=188) and pro-and anti-inflammatory cytokines (n=7).
Hexanoylcarnitine, kynurenine, and tryptophan were substantially and independently related to mortality in the pooled analysis (hazard ratio [HR] 1.60 [95% CI 1.43–1.80]; 1.53 [1.37–1.71]; and 0.71 [0.62–0.80] per 1 SD). The kynurenine-to-tryptophan ratio (KTR), a proxy for indoleamine-2,3-dioxygenase, converts tryptophan to kynurenine and contributes to a pro-inflammatory state, mediated 42% of the important link between antiatherogenic interleukin (IL) 13 and mortality. The addition of the three metabolites enhanced both mortality prediction models’ discrimination and reclassification (both P<0.01). Hexanoylcarnitine, tryptophan, and kynurenine are linked to and enhance the prognosis of all-cause mortality in type 2 diabetes. More research was needed to determine if KTR-lowering therapies lessen the risk of mortality, particularly in individuals with low IL-13.
