Circulating Metabolites Associate with and Improve the Prediction of All-Cause Mortality in Type 2 Diabetes
Two cohorts comprising 856 individuals (279 all-cause deaths) were analyzed. Serum metabolites (n=188) and pro- and anti-inflammatory cytokines (n=7) were measured.
In the pooled analysis, hexanoylcarnitine, kynurenine and tryptophan were significantly and independently associated with mortality (HRs, [95%CIs] 1.60, [1.43-1.80]; 1.53, [1.37-1.71]; 0.71, [0.62-0.80] per 1SD). The kynurenine/tryptophan ratio (KTR-a proxy of indoleamine-2,3-dioxygenase which degrades tryptophan to kynurenine and contribute to a pro-inflammatory status) mediated 42% of the significant association between the anti-atherogenic IL-13 and mortality. Adding the three metabolites improved discrimination and reclassification (all P<0.01) of both mortality prediction models.
In type 2 diabetes, hexanoylcarnitine, tryptophan and kynurenine are associated to and improve the prediction of all-cause mortality. Further studies are needed to investigate whether interventions aimed at reducing KTR, also reduce the risk of death especially in patients with low IL-13.