Metabolomic profile differs between latent autoimmune diabetes in adults (LADA) and type 1 diabetes identifying tryptophan metabolism as a pathway involved in the heterogeneity of autoimmune diabetes
Authors' conclusion
Metabolomic and lipidomic profiles differ between LADA and type 1 diabetes and vs RA, providing new insights into the heterogeneity of autoimmune diabetes. Our results confirm the involvement of tryptophan metabolism in autoimmune disorders, suggesting that the impaired activation of this pathway of immune tolerance in LADA is less pronounced than in type 1 diabetes, consistent with its milder degree of beta cell loss.
Study context
- Population
- Individuals with LADA, T1D or rheumatoid arthritis (RA) and healthy controls; plus pancreatic islets from healthy donors treated in vitro with proinflammatory cytokines
- Participants
- 136 individuals
- Exposure
- LADA vs T1D vs RA vs healthy controls
- LADAn = 49
- T1Dn = 44
- RAn = 29
- Controln = 14reference
- Outcome
- Kyn/Trp ratio (marker of tryptophan pathway activation)
Methodological detailsmetabolomic and lipidomic analyses, in vitro pancreatic islet experiments
- Metabolomic and lipidomic analyses
- In vitro pancreatic islet experiments
Main finding
As reported in the abstract
Control
0.014
median · IQR 0.012–0.019
RA
0.027
median · IQR 0.022–0.032
LADA
0.021
median · IQR 0.018–0.024
T1D
0.018
median · IQR 0.014–0.022
ANCOVA p<0.0001
Observational data: associations, not effects.
Further findings
| Outcome | P value |
|---|---|
| Association of Kyn/Trp with fasting C-peptide in LADALADA vs Control | P = 0.038 |
Lipidomic and metabolomic profiles
- LADA and T1D differed from RA in lipidomics and metabolomics
- Phosphatidylethanolamines, ceramides, lysophosphatidylcholine and several metabolites at TCA cycle entry sites higher in T1D vs LADA
Tryptophan concentration in pancreatic islets treated with proinflammatory cytokines
- Tryptophan concentration reduced
- 80%
Original publication
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