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

Abstract

Sphingolipids are linked to the pathogenesis of type 2 diabetes (T2D). To test the hypothesis that plasma sphingolipid profiles predict incident prediabetes. A case-control study nested in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study, a 5-year follow-up study. Academic health center. Normoglycemic adults enrolled in the POP-ABC study. Assessments included OGTT, insulin sensitivity and insulin secretion. Participants with incident prediabetes were matched in age, sex, and ethnicity with non-progressors. We assayed 58 sphingolipid species (ceramides, monohexosyl ceramides, sphingomyelins, and sphingosine) using LC/tandem mass spectrometry in baseline plasma levels from participants and determined association with prediabetes risk. The primary outcome was progression from normoglycemia to prediabetes, defined as impaired fasting glucose or impaired glucose tolerance. The mean age of participants (N = 140; 50% Black, 50% female) was 48.1 ± 8.69 y, BMI 30.1 ± 5.78 kg/m2, fasting plasma glucose (FPG) 92.7 ± 5.84 mg/dl, and two-hour plasma glucose (2hrPG) 121 ± 23.3 mg/dl. Of the 58 sphingolipid species assayed, higher ratios of sphingomyelin C26:0/C26:1 (OR 2.73 [95% CI 1.172-4.408], P = 0.015) and ceramide C18:0/C18:1 (OR 1.236 [95% CI 1.042-1.466], P = 0.015) in baseline plasma specimens were significantly associated with progression to prediabetes during the 5-year follow-up period, after adjustments for age, race, sex, BMI, FPG, 2hPG, insulin sensitivity, and insulin secretion. We conclude that the saturated-to-monounsaturated ratios of long-chain ceramide C18:0/C18:1 and very-long-chain sphingomyelin C26:0/C26:1 are potential biomarkers of prediabetes risk among individuals with parental history of T2D.