Clinical nutrition (Edinburgh, Scotland) · 2025
Plasma kynurenine pathway metabolites in association with diabetes: A cross-sectional study.
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Mu Yingjun, Gu Zijian, Wang Qingyao, Wang Xudong, Zhu Jiayao, Huang Junyao, Huang Qiaoliang, Zuo Hui
Аннотация
BACKGROUND: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.