biostudies-literatureBae JCNIDDK NIH HHSNCRR NIH HHSNHLBI NIH HHSNational Institutes of Health633-641https://www.ebi.ac.uk/biostudies/studies/S-EPMC10922320biostudies-literatureUnknown34(3)<h4>Background and aims</h4>To prospectively investigate associations of plasma sphingolipids with insulin sensitivity, β-cell function, and incident diabetes in the Japanese American Community Diabetes Study.<h4>Methods and results</h4>Baseline plasma samples from adults without diabetes (n = 349; mean age 56.7 years, 51 % men) were assayed for circulating ceramide and sphingomyelin species. Adjusted regression models examined cross-sectional and longitudinal associations with insulin sensitivity (HOMA2-%S), β-cell function (oral disposition index: DIo) and with incident diabetes over 5 years follow-up. Concentrations of four species (Ceramide C16:0, C18:0, C20:0, and C22:0) were inversely associated with HOMA2-%S at baseline (all P values < 0.05, Q values < 0.05) and change in HOMA2-%S over 5 years (all P values < 0.05, Q values < 0.05). No sphingolipids were associated with baseline or change in DIo. Of the four species associated with HOMA2-%S, only Ceramide C18:0 was significantly and positively associated with incident diabetes (RR/1SD 1.44, 95 % CI 1.10-1.80, P = 0.006, Q = 0.024). The association of plasma Ceramide C18:0 with the risk of diabetes was partially mediated by change in HOMA2-%S between baseline and 5 years (mediation proportion: 61.5 %, 95 % CI 21.1%-212.5 %).<h4>Conclusion</h4>Plasma Ceramide C18:0 was associated with higher risk of incident diabetes which was partially mediated through a decrease in insulin sensitivity between baseline and five years. Circulating Ceramide C18:0 could be a potential biomarker for identifying those at risk of developing diabetes.Nutrition, metabolism, and cardiovascular diseases : NMCDAssociations of plasma sphingolipids with measures of insulin sensitivity, β-cell function, and incident diabetes in Japanese Americans.PMC10922320HL-049293DK-017047RR-000037R01 DK031170M01 RR000037P30 DK017047K24 DK002654R01 HL049293DK-002654P30 DK035816DK-031170DK-035816Sitlani CMUtzschneider KMThomas MKBae JCWander PLFujimoto WYBoyko EJLemaitre RNFretts AMBui HHLeonetti DfalseAssociations of plasma sphingolipids with measures of insulin sensitivity, β-cell function, and incident diabetes in Japanese Americans.<h4>Background and aims</h4>To prospectively investigate associations of plasma sphingolipids with insulin sensitivity, β-cell function, and incident diabetes in the Japanese American Community Diabetes Study.<h4>Methods and results</h4>Baseline plasma samples from adults without diabetes (n = 349; mean age 56.7 years, 51 % men) were assayed for circulating ceramide and sphingomyelin species. Adjusted regression models examined cross-sectional and longitudinal associations with insulin sensitivity (HOMA2-%S), β-cell function (oral disposition index: DIo) and with incident diabetes over 5 years follow-up. Concentrations of four species (Ceramide C16:0, C18:0, C20:0, and C22:0) were inversely associated with HOMA2-%S at baseline (all P values < 0.05, Q values < 0.05) and change in HOMA2-%S over 5 years (all P values < 0.05, Q values < 0.05). No sphingolipids were associated with baseline or change in DIo. Of the four species associated with HOMA2-%S, only Ceramide C18:0 was significantly and positively associated with incident diabetes (RR/1SD 1.44, 95 % CI 1.10-1.80, P = 0.006, Q = 0.024). The association of plasma Ceramide C18:0 with the risk of diabetes was partially mediated by change in HOMA2-%S between baseline and 5 years (mediation proportion: 61.5 %, 95 % CI 21.1%-212.5 %).<h4>Conclusion</h4>Plasma Ceramide C18:0 was associated with higher risk of incident diabetes which was partially mediated through a decrease in insulin sensitivity between baseline and five years. Circulating Ceramide C18:0 could be a potential biomarker for identifying those at risk of developing diabetes.2024-01-01T00:00:00Z2024 Mar2025-04-18T13:31:19.489Z2025-04-06T23:20:14.987ZS-EPMC109223203816112410.1016/j.numecd.2023.10.026