Scholarlink

Aims/hypothesis <p>The heterogeneity of autoimmune diabetes may be associated with variable metabolic alterations. Our aim was to investigate differences in the metabolomic and lipidomic profile of autoimmune diseases and to identify pathways linked to beta cell damage. To this end, we compared latent autoimmune diabetes in adults (LADA) and type 1 diabetes, also comparing them with rheumatoid arthritis (RA), a related autoimmune condition, and healthy control participants.</p> Methods <p>Metabolomic and lipidomic analyses were performed for 136 individuals (49 with LADA, 44 with type 1 diabetes, 29 with RA and 14 control participants). Omics of pancreatic islets from healthy donors were also evaluated after in vitro treatment with proinflammatory cytokines.</p> Results <p>LADA and type 1 diabetes differed from RA in terms of lipidomics and metabolomics. Phosphatidylethanolamines, ceramides, lysophosphatidylcholine and several metabolites at the entry sites of the tricarboxylic acid cycle were higher in type 1 diabetes compared with LADA. In pancreatic islets treated with proinflammatory cytokines, tryptophan concentration was reduced by 80%, indicating the activation of tryptophan metabolism in response to the inflammatory stimulus. In people with autoimmune disorders, kynurenine/tryptophan ratio (Kyn/Trp), a marker of tryptophan pathway activation, was higher than in the control group (Kyn/Trp ratio in control group, median [25th–75th percentile]: 0.014 [0.012–0.019]), with a progressive decline from RA (0.027 [0.022–0.032]) to LADA (0.021 [0.018–0.024]) and then to type 1 diabetes (0.018 [0.014–0.022]), ANCOVA <i>p</i>&lt;0.0001. In LADA, Kyn/Trp was directly associated with fasting C-peptide levels in the multivariate regression model accounting for confounders (<i>p</i>=0.038).</p> Conclusions/interpretation <p>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.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Metabolomic profile differs between LADA and type 1 diabetes identifying tryptophan metabolism as a pathway involved in the heterogeneity of autoimmune diabetes

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月26日

查看全文
  • Ernesto Maddaloni,
  • Samantha Pezzica,
  • Rocco Amendolara,
  • Silvia Sabatini,
  • Gabriele Mocciaro,
  • Guido Sebastiani,
  • Luca D’Onofrio,
  • Fabrizia Carli,
  • Marta Tesi,
  • Mara Suleiman,
  • Luca Navarini,
  • Laura Nigi,
  • Caterina Formichi,
  • Marta Vomero,
  • Marco Minerba,
  • Piero Marchetti,
  • Francesco Dotta,
  • Raffaella Buzzetti,
  • Amalia Gastaldelli

摘要

Aims/hypothesis

The heterogeneity of autoimmune diabetes may be associated with variable metabolic alterations. Our aim was to investigate differences in the metabolomic and lipidomic profile of autoimmune diseases and to identify pathways linked to beta cell damage. To this end, we compared latent autoimmune diabetes in adults (LADA) and type 1 diabetes, also comparing them with rheumatoid arthritis (RA), a related autoimmune condition, and healthy control participants.

Methods

Metabolomic and lipidomic analyses were performed for 136 individuals (49 with LADA, 44 with type 1 diabetes, 29 with RA and 14 control participants). Omics of pancreatic islets from healthy donors were also evaluated after in vitro treatment with proinflammatory cytokines.

Results

LADA and type 1 diabetes differed from RA in terms of lipidomics and metabolomics. Phosphatidylethanolamines, ceramides, lysophosphatidylcholine and several metabolites at the entry sites of the tricarboxylic acid cycle were higher in type 1 diabetes compared with LADA. In pancreatic islets treated with proinflammatory cytokines, tryptophan concentration was reduced by 80%, indicating the activation of tryptophan metabolism in response to the inflammatory stimulus. In people with autoimmune disorders, kynurenine/tryptophan ratio (Kyn/Trp), a marker of tryptophan pathway activation, was higher than in the control group (Kyn/Trp ratio in control group, median [25th–75th percentile]: 0.014 [0.012–0.019]), with a progressive decline from RA (0.027 [0.022–0.032]) to LADA (0.021 [0.018–0.024]) and then to type 1 diabetes (0.018 [0.014–0.022]), ANCOVA p<0.0001. In LADA, Kyn/Trp was directly associated with fasting C-peptide levels in the multivariate regression model accounting for confounders (p=0.038).

Conclusions/interpretation

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.

Graphical Abstract