Objective: Ceramides (CER) and sphingolipids (SPL) have been linked to type 2 Diabetes (T2D) . Here we compared plasma SPL profiles in Black and White adults without a family history of T2D (FH−) vs. those with parental T2D (FH+) .
Methods: We studied 240 healthy subjects: 140 FH+ (70 B, 70 W) and 100 FH− (50 B, 50 W) . Assessments included OGTT, insulin sensitivity (Si-clamp) and insulin secretion (AIRg) . Liquid chromatography/mass spectrometry was used to assay fasting plasma levels of 54 SPL species (18 each from 3 major classes: CER, monohexosyl ceramide {MHC}, and sphingomyelins {SM}) . We compared mole percent composition of SPL species within each class in FH+ and FH− groups.
Results: The subjects’ mean (SD) age was 43.1 + 12.0 y, BMI 29.4 + 6.21, fasting glucose 91.4 + 6.90 mg/dl and 2-hr plasma glucose (2hPG) 123 + 26.3 mg/dl. Total levels of SPL, CER, MHC and SM did not differ by race or sex, and correlated with 2hPG and AIRg but not age, BMI, FPG or Si-clamp. FH+ and FH− adults were concordant for 37 of 54 SPL and discordant for 17 species. Compared with FH−, the FH+ subjects had higher molar abundance of 8 CER, 4 MHC and 2 SM, but lower values for C24:0 Cer, C24:0 MHC, and C26:0 MHC (Table 1) .
Conclusion: Plasma SPL species correlate with glucose tolerance, are altered by parental T2D history, and may reflect heritable elements linking SPL and glucose metabolism.
N. Mandal: None. J. Y. Wan: None. F. B. Stentz: None. E. Nyenwe: None. A. A. Patel: None. S. Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Sanofi.
National Institutes of Health (5R01DK128129)
