ArticleThe Journal of clinical endocrinology and metabolism2025
Inflammation and Prediction of Death in Type 2 Diabetes. Evidence of an Intertwined Link With Tryptophan Metabolism.
Article in The Journal of clinical endocrinology and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Acylcarnitines and prediction of renal function decline in type 2 diabetes.BMJ open diabetes research & care · 2026Article
- Indole-3-propionic acid enhances glycolytic myofiber formation in piglets through PI3K-mTOR activation and gut microbiota-driven tryptophan metabolic alteration.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Inflammation and Prediction of Death in Type 2 Diabetes. Evidence of an Intertwined Link With Tryptophan Metabolism.The Journal of clinical endocrinology and metabolism · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors.
Funding
Abstract
contextThe role of inflammation in shaping death risk in diabetes is still unclear.
objectiveTo study whether inflammation is associated with and helps predict mortality risk in patients with type 2 diabetes. To explore the intertwined link between inflammation and tryptophan metabolism on death risk.
methodsThere were 2 prospective cohorts: the aggregate Gargano Mortality Study (1731 individuals; 872 all-cause deaths) as the discovery sample, and the Foggia Mortality Study (490 individuals; 256 deaths) as validation sample. Twenty-seven inflammatory markers were measured. Causal mediation analysis and in vitro studies were carried out to explore the link between inflammatory markers and the kynurenine to tryptophan ratio (KTR) in shaping mortality risk.
resultsUsing multivariable stepwise Cox regression analysis, interleukin (IL)-4, IL-6, IL-8, IL-13, RANTES, and interferon gamma-induced protein-10 (IP-10) were independently associated with death. An inflammation score (I score) comprising these 6 molecules is strongly associated with death in both the discovery and the validation cohorts HR (95% CI) 2.13 (1.91-2.37) and 2.20 (1.79-2.72), respectively. The I score improved discrimination and reclassification measures (all P < .01) of 2 mortality prediction models based on clinical variables. The causal mediation analysis showed that 28% of the KTR effect on mortality was mediated by IP-10. Studies in cultured endothelial cells showed that 5-methoxy-tryptophan, an anti-inflammatory metabolite derived from tryptophan, reduces the expression of IP-10, thus providing a functional basis for the observed causal mediation.
conclusionAdding the I score to clinical prediction models may help identify individuals who are at greater risk of death. Deeply addressing the intertwined relationship between low-grade inflammation and imbalanced tryptophan metabolism in shaping mortality risk may help discover new therapies targeting patients characterized by these abnormalities.
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