Objective: Sphingolipids (SPL) are involved in the pathogenesis of diabetes. We examined plasma SPL levels in relation to glycemic markers in people without diabetes.
Methods: Plasma SPL levels{ceramides (Cer), monohexosylceramides (MHC), sphingomyelin (SM) and sphingosine (So)} were assayed using LC-MS/MS in healthy adults free of diabetes. Using OGTT, subjects were classified into those with normal fasting (FPG) and 2hPG (NFG-NGT), IFG, IGT, and IFG-IGT.
Results: The participants (N=520, 63% female; 48% Black, 52% White) had a mean age of 45.5 + 9.84 yr, BMI 32.4 + 7.24 kg/m2 and waist 101 + 17.0 cm; FPG was 99.8 + 10.5 mg/dl mg/dl, 2hPG 145+ 29.4 mg/dl, and HbA1c 5.80 + 0.53%. FPG and 2hPG correlated inversely with MHC and positively with other circulating SPL levels (Fig. 1), adjusted for age, sex, race, BMI and waist. Weaker correlations were seen with HbA1c (r 0.04-0.19, P=0.43-<0.001). Compared with NFG-NGT, subjects with IFG-IGT had lower MHC and 4-fold higher Cer C16:0/C18:0 (P<0.0001).
Conclusion: Higher levels of major SPL species, and lower MHC, are associated with upward glycemic drift within the nondiabetic range, suggesting a link between SPL metabolism and glucoregulation.
P. Asuzu: None. N. Feto: None. F.B. Stentz: None. J.Y. Wan: None. N. Mandal: None. S. Dagogo-Jack: Consultant; Merck Sharp & Dohme Corp., Medtronic, Bayer Inc. Stock/Shareholder; Aerami.
National Institute of Health (DK128129)
