Objective To systematically evaluate the association between key metabolites of the tryptophan-kynurenine (TRP-KYN) pathway in type 2 diabetes mellitus (T2DM). Methods Observational studies on the correlation between T2DM and metabolites of the TRP-KYN metabolic pathway were retrieved from PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, CBM, and VIP databases from inception to June 25, 2025. Two reviewers independently performed literature screening, extracted data, and assessed the risk of bias in the included studies. Meta-analysis was performed using Stata 18.0 software, effect sizes were expressed as standardized mean differences (SMDs) with 95% confidence intervals, and heterogeneity was evaluated via the Q test and I2 statistic. Results A total of 28 observational studies were included, of which 13 provided sufficient data for meta-analysis. The meta-analysis results indicated that compared with healthy individuals, the levels of kynurenine (SMD = 0.237, 95% CI 0.036–0.437, P = 0.021), kynurenic acid (SMD = 0.393, 95% CI 0.084–0.702, P = 0.013), kynurenine/tryptophan ratio (SMD = 0.294, 95% CI 0.075–0.513, P = 0.008), 3-hydroxykynurenine (SMD = 0.235, 95% CI 0.051–0.418, P = 0.012), xanthurenic acid (SMD = 0.162, 95% CI 0.026–0.298, P = 0.019), and anthranilic acid (SMD = 0.264, 95% CI 0.121–0.406, P < 0.001) in the peripheral blood of T2DM patients were significantly increased. However, no significant difference was observed in TRP (SMD = -0.087, 95% CI − 0.402–0.228, P = 0.588) and 3-HAA (SMD = − 0.049, 95% CI − 0.641–0.544, P = 0.872) between T2DM patients and healthy individuals. Subgroup analysis revealed that when LC–MS/MS was consistently employed for sample detection, TRP levels in T2DM patients (SMD = -0.524, 95% CI -1.035–0.014, P = 0.044) were significantly lower than those in healthy individuals; KYN levels in T2DM patients from European and American populations were significantly elevated (SMD = 0.237, 95% CI 0.036–0.437, P = 0.025), whereas no significant difference in KYN was observed in the Asian population. Conclusion The TRP-KYN pathway is in an overactivated state in T2DM patients, suggesting that this pathway may serve as a potential intervention target for T2DM.

Dysregulation of the tryptophan-kynurenine pathway in type 2 diabetes: a systematic review and meta-analysis

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2026年5月30日

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Qiaoling Zheng,
Shuyun Fu,
Weinan Liu,
Liqun Yao,
Chen Qiu,
Diandian Zhang,
Yanling Dai

摘要

Objective

To systematically evaluate the association between key metabolites of the tryptophan-kynurenine (TRP-KYN) pathway in type 2 diabetes mellitus (T2DM).

Methods

Observational studies on the correlation between T2DM and metabolites of the TRP-KYN metabolic pathway were retrieved from PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, CBM, and VIP databases from inception to June 25, 2025. Two reviewers independently performed literature screening, extracted data, and assessed the risk of bias in the included studies. Meta-analysis was performed using Stata 18.0 software, effect sizes were expressed as standardized mean differences (SMDs) with 95% confidence intervals, and heterogeneity was evaluated via the Q test and I² statistic.

Results

A total of 28 observational studies were included, of which 13 provided sufficient data for meta-analysis. The meta-analysis results indicated that compared with healthy individuals, the levels of kynurenine (SMD = 0.237, 95% CI 0.036–0.437, P = 0.021), kynurenic acid (SMD = 0.393, 95% CI 0.084–0.702, P = 0.013), kynurenine/tryptophan ratio (SMD = 0.294, 95% CI 0.075–0.513, P = 0.008), 3-hydroxykynurenine (SMD = 0.235, 95% CI 0.051–0.418, P = 0.012), xanthurenic acid (SMD = 0.162, 95% CI 0.026–0.298, P = 0.019), and anthranilic acid (SMD = 0.264, 95% CI 0.121–0.406, P < 0.001) in the peripheral blood of T2DM patients were significantly increased. However, no significant difference was observed in TRP (SMD = -0.087, 95% CI − 0.402–0.228, P = 0.588) and 3-HAA (SMD = − 0.049, 95% CI − 0.641–0.544, P = 0.872) between T2DM patients and healthy individuals. Subgroup analysis revealed that when LC–MS/MS was consistently employed for sample detection, TRP levels in T2DM patients (SMD = -0.524, 95% CI -1.035–0.014, P = 0.044) were significantly lower than those in healthy individuals; KYN levels in T2DM patients from European and American populations were significantly elevated (SMD = 0.237, 95% CI 0.036–0.437, P = 0.025), whereas no significant difference in KYN was observed in the Asian population.

Conclusion

The TRP-KYN pathway is in an overactivated state in T2DM patients, suggesting that this pathway may serve as a potential intervention target for T2DM.