Plasma Ceramides and Other Sphingolipids in Relation to Incident Prediabetes in a Longitudinal Biracial Cohort.

ABSTRACT

CONTEXT Sphingolipids are linked to the pathogenesis of type 2 diabetes. OBJECTIVE: To test the hypothesis that plasma sphingolipid profiles predict incident prediabetes. DESIGN: A case-control study nested in the Pathobiology of Prediabetes in a Biracial Cohort study, a 5-year follow-up study. SETTING: Academic health center. PARTICIPANTS: Normoglycemic adults enrolled in the Pathobiology of Prediabetes in a Biracial Cohort study. Assessments included oral glucose tolerance test, insulin sensitivity, and insulin secretion. Participants with incident prediabetes were matched in age, sex, and ethnicity with nonprogressors. INTERVENTIONS: We assayed 58 sphingolipid species (ceramides, monohexosyl ceramides, sphingomyelins, and sphingosine) using liquid chromatography/tandem mass spectrometry in baseline plasma levels from participants and determined association with prediabetes risk. MAIN OUTCOME MEASURE: The primary outcome was progression from normoglycemia to prediabetes, defined as impaired fasting glucose or impaired glucose tolerance. RESULTS: The mean age of participants (N = 140; 50% Black, 50% female) was 48.1 ± 8.69 years, body mass index 30.1 ± 5.78 kg/m2, fasting plasma glucose 92.7 ± 5.84 mg/dL, and 2-hour plasma glucose 121 ± 23.3 mg/dL. Of the 58 sphingolipid species assayed, higher ratios of sphingomyelin C260/C261 (OR, 2.73 [95% CI, 1.172-4.408], P = .015) and ceramide C180/C181 (OR, 1.236 [95% CI, 1.042-1.466], P = .015) in baseline plasma specimens were significantly associated with progression to prediabetes during the 5-year follow-up period, after adjustments for age, race, sex, body mass index, fasting plasma glucose, 2-hour plasma glucose, insulin sensitivity, and insulin secretion. CONCLUSION: We conclude that the saturated-to-monounsaturated ratios of long-chain ceramide C180/C181 and very-long-chain sphingomyelin C260/C261 are potential biomarkers of prediabetes risk among individuals with parental history of type 2 diabetes.