Associations of plasma sphingolipids with measures of insulin sensitivity, ß-cell function, and incident diabetes in Japanese Americans.

ABSTRACT

BACKGROUND AND AIMS: To prospectively investigate associations of plasma sphingolipids with insulin sensitivity, ß-cell function, and incident diabetes in the Japanese American Community Diabetes Study. METHODS AND RESULTS: 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), ß-cell function (oral disposition index DIo) and with incident diabetes over 5 years follow-up. Concentrations of four species (Ceramide C160, C180, C200, and C220) 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 C180 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 C180 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 %). CONCLUSION: Plasma Ceramide C180 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 C180 could be a potential biomarker for identifying those at risk of developing diabetes.