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

Abstract

Context Ceramides (Cer) and sphingolipids (SPL) have been linked to type 2 diabetes (T2D). The CASPID (Ceramides and Sphingolipids as Predictors of Incident Dysglycemia) is designed to determine the association of plasma SPL with the pathophysiology of human T2D. Objective A comparison of plasma sphingolipids profiles in Black and White adults with and without family history of T2D. Design We recruited 100 Black and White adults with no family history of T2D (FH-, n=100: 54 B, 46 W) and 140 with parental history of T2D (FH+, n=140: 75 B, 65 W). Fasting plasma levels of 58 sphingolipid species, including 18 each from 3 major classes such as Ceramide, monohexosylceramide, and sphingomyelins, all with 18:1 sphingoid base; and 4 long-chain sphingoid base containing species were measured using liquid chromatography/mass spectrometry (LC-MS/MS). Results We found sphingomyelin as the most abundant sphingolipid in plasma (89% in FH-), which was significantly elevated in subjects with parental history of T2D (93%). Ceramides and monohexosylceramide comprise 5% and 6% of total sphingolipids in the plasma of subjects without a family history of T2D, which was reduced significantly in subjects with parental history of T2D (3%, and 4%, respectively). Consequently, most ceramides and monohexosylceramide individual species were decreased in subjects with parental history of T2D, but sphingomyelin species were increased. C18:1 containing species of all three classes was elevated in subjects with parental history of T2D. Conclusions Elevated levels of sphingomyelin, the major sphingolipids of plasma, and oleic acid-containing sphingolipids in healthy subjects with parental T2D history compared to healthy subjects with no family history may reflect heritable elements linking sphingolipids and the development of type 2 diabetes.