Plasma Sphingolipid Profile of Healthy Black and White Adults Differs Based on Their Parental History of Type 2 Diabetes

Abstract

Abstract Context Ceramides and sphingolipids have been linked to type 2 diabetes (T2D). The Ceramides and Sphingolipids as Predictors of Incident Dysglycemia (CASPID) study is designed to determine the association of plasma sphingolipids with the pathophysiology of human T2D. Objective A comparison of plasma sphingolipids profiles in Black and White adults with (FH+) and without (FH−) family history of T2D. Design We recruited 100 Black and White FH− (54 Black, 46 White) and 140 FH+ (75 Black, 65 White) adults. Fasting plasma levels of 58 sphingolipid species, including 18 each from 3 major classes (ceramides, monohexosylceramides, and sphingomyelins, all with 18:1 sphingoid base) and 4 long-chain sphingoid base–containing species, were measured by liquid chromatography/mass spectrometry. Results Sphingomyelin was the most abundant sphingolipid in plasma (89% in FH−), and was significantly elevated in FH+ subjects (93%). Ceramides and monohexosylceramides comprised 5% and 6% of total sphingolipids in the plasma of FH− subjects, and were reduced significantly in FH+ subjects (3% and 4%, respectively). In FH+ subjects, most ceramide and monohexosylceramide species were decreased but sphingomyelin species were increased. The level of C18:1 species of all 3 classes was elevated in FH+ subjects. Conclusion Elevated levels of sphingomyelin, the major sphingolipids of plasma, and oleic acid–containing sphingolipids in healthy FH+ subjects compared with healthy FH− subjects may reflect heritable elements linking sphingolipids and the development of T2D.