Plasma kynurenine pathway metabolites in association with diabetes: A cross-sectional study

Abnormalities of the kynurenine pathway of tryptophan catabolism have been linked with an increased risk of cardiovascular disease. However, the association between kynurenine pathway metabolism and diabetes remains unclear.

We conducted a secondary analysis of the baseline data of 796 adults from the Prospective Follow-up Study on Cardiovascular Morbidity and Mortality in China (PFS-CMMC). Plasma kynurenine pathway metabolites, including tryptophan, kynurenine, kynurenic acid (KA), 3-hydroxykynurenine (3-HK), anthranilic acid (AA), 3-hydroxyanthranilic acid (3-HAA), xanthurenic acid (XA), 2-ketoadipic acid (2-KAA), and nicotinamide, were measured by ultrahigh performance liquid chromatography tandem mass spectrometry. Unconditional logistic regression analyses were used to calculate odds ratios (ORs) and their 95 % confidence intervals (CIs).

After adjustment for all confounders, three metabolites were positively associated with increased odds of diabetes. The OR (95 % CI) for the highest compared with the lowest quartile was 2.07 (1.16, 3.78) for 3-HAA, 3.56 (1.93, 6.83) for 2-KAA, and 1.82 (1.01, 3.35) for nicotinamide (all P trend <0.05). In contrast, participants in the fourth quartile of tryptophan levels had reduced odds of diabetes when compared to those in the first quartile (OR: 0.39, 95 % CI: 0.21, 0.72; P trend = 0.007). No significant associations were observed for plasma kynurenine, KA, 3-HK, AA, or XA.

Increased plasma 3-HAA, 2-KAA, and nicotinamide were associated with higher odds of diabetes, whereas higher levels of tryptophan were associated with lower odds of diabetes in the community-dwelling population. Our findings suggest that the kynurenine pathway metabolites may be involved in the pathophysiology of diabetes.