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Aims <p>Limited studies explored the association between ceramides and the risk of type 2 diabetes mellitus (T2DM). We aimed to investigated whether plasma ceramides and their ratios to Cer(d18:1/16:0) would be associated with T2DM in Chinese adult residents.</p> Methods <p>This investigation was designed as a matched case-control study nested within a community-based longitudinal cohort in Suzhou, China. Plasma concentrations of eight ceramides (C16–C24) were measured quantitatively in 234 cases and 468 matched controls using high-throughput targeted lipidomics. Conditional logistic regression models were used to estimate odds ratios (ORs). We assessed the improvements in risk discrimination by net reclassification improvement (NRI) and integrated discrimination improvement (IDI).</p> Results <p>Seven ceramides (d18:1/16:0, d18:1/18:0, d18:1/20:0, d18:1/22:0, d18:1/22:1, d18:1/24:0, d18:1/24:1) were positively associated with incident T2DM. Among them, Cer(d18:1/24:0) showed the strongest association with increased T2DM risk (OR = 2.17 (95% CI: 1.29,3.66, <i>P</i>-trend &lt; 0.05). Additionally, the ratios of Cer(d18:1/18:0)/Cer(d18:1/16:0) and Cer(d18:1/20:0)/Cer(d18:1/16:0) were significantly associated with T2DM risk, and adjusted ORs for the highest vs. lowest quartiles were 2.11 (95% CI: 1.27,3.51), and 1.69 (95% CI: 1.04,2.76), respectively (all <i>P</i>-trend &lt; 0.05). The addition of individual ceramides or ceramide ratios to conventional risk factors significantly improved the discrimination and risk reclassification (all <i>P</i> &lt; 0.05).</p> Conclusions <p>Distinct plasma ceramides are associated with the T2DM risk and Cer(d18:1/24:0) serves as the strongest predictive marker. Moreover, the ratios of Cer(d18:1/18:0)/Cer(d18:1/16:0) and Cer(d18:1/20:0)/Cer(d18:1/16:0) are also particularly robust independent predictors of incident T2DM. Ceramides and their ratios can be used to identify high-risk patients with T2DM, providing targets for the primary and secondary prevention of T2DM.</p>

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Targeted metabolomics identifies associations of plasma ceramides and their ratios with incident type 2 diabetes mellitus

  • 期刊论文

  • 发表日期：

    2026年8月4日

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  • Chuyi Ruan,
  • Yihui Sheng,
  • Ruyu Xue,
  • Hong Huang,
  • Shaoyan Zhang

摘要

Aims

Limited studies explored the association between ceramides and the risk of type 2 diabetes mellitus (T2DM). We aimed to investigated whether plasma ceramides and their ratios to Cer(d18:1/16:0) would be associated with T2DM in Chinese adult residents.

Methods

This investigation was designed as a matched case-control study nested within a community-based longitudinal cohort in Suzhou, China. Plasma concentrations of eight ceramides (C16–C24) were measured quantitatively in 234 cases and 468 matched controls using high-throughput targeted lipidomics. Conditional logistic regression models were used to estimate odds ratios (ORs). We assessed the improvements in risk discrimination by net reclassification improvement (NRI) and integrated discrimination improvement (IDI).

Results

Seven ceramides (d18:1/16:0, d18:1/18:0, d18:1/20:0, d18:1/22:0, d18:1/22:1, d18:1/24:0, d18:1/24:1) were positively associated with incident T2DM. Among them, Cer(d18:1/24:0) showed the strongest association with increased T2DM risk (OR = 2.17 (95% CI: 1.29,3.66, P-trend < 0.05). Additionally, the ratios of Cer(d18:1/18:0)/Cer(d18:1/16:0) and Cer(d18:1/20:0)/Cer(d18:1/16:0) were significantly associated with T2DM risk, and adjusted ORs for the highest vs. lowest quartiles were 2.11 (95% CI: 1.27,3.51), and 1.69 (95% CI: 1.04,2.76), respectively (all P-trend < 0.05). The addition of individual ceramides or ceramide ratios to conventional risk factors significantly improved the discrimination and risk reclassification (all P < 0.05).

Conclusions

Distinct plasma ceramides are associated with the T2DM risk and Cer(d18:1/24:0) serves as the strongest predictive marker. Moreover, the ratios of Cer(d18:1/18:0)/Cer(d18:1/16:0) and Cer(d18:1/20:0)/Cer(d18:1/16:0) are also particularly robust independent predictors of incident T2DM. Ceramides and their ratios can be used to identify high-risk patients with T2DM, providing targets for the primary and secondary prevention of T2DM.