Inflammation and Prediction of Death in Type 2 Diabetes. Evidence of an Intertwined Link With Tryptophan Metabolism
An erratum to this article was published (J Clin Endocrinol Metab, 22 Apr 2025 ↗)
Authors' conclusion
Adding 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.
Study context
- Population
- Patients with T2D; 2 prospective cohorts2 cohorts
- Participants
- 1,731 vs 490
- Exposure
- Gargano Mortality Study vs Foggia Mortality Study
- Gargano Mortality Studyn = 1,731
- Foggia Mortality Studyn = 490
- Outcome
- All-cause mortality
Methodological detailsdiscovery and validation cohorts, causal mediation analysis, in vitro studies
- Discovery and validation cohorts
- Causal mediation analysis
- In vitro studies
Main finding
As reported in the abstract
Death per inflammation score (I score: IL-4, IL-6, IL-8, IL-13, RANTES, IP-10)
| Group | Value | HR |
|---|---|---|
| Gargano Mortality Study | 872 events | 2.13 (95% CI 1.91-2.37) |
| Foggia Mortality Study | 256 events | 2.20 (95% CI 1.79-2.72) |
Value
Gargano Mortality Study872 events
Foggia Mortality Study256 events
HR
Gargano Mortality Study2.13 (95% CI 1.91-2.37)
Foggia Mortality Study2.20 (95% CI 1.79-2.72)
Observational data: associations, not effects.
Further findings
Added prediction of I score to 2 clinical mortality models
- I score improved discrimination and reclassification measures
- all P < .01
Mediation of kynurenine to tryptophan ratio (KTR) effect on mortality
- Share of KTR effect on mortality mediated by IP-10
- 28%
- In cultured endothelial cells, 5-methoxy-tryptophan reduces IP-10 expression
- Causal mediation analysis
Original publication
Inflammation and Prediction of Death in Type 2 Diabetes. Evidence of an Intertwined Link With Tryptophan Metabolism. J Clin Endocrinol Metab. Published 28 August 2024. doi:10.
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