Samuel Dagogo-Jack, Peace Asuzu, Jim Wan, Richard Grambergs, Frankie Stentz, Nawajes Mandal
The Journal of Clinical Endocrinology & Metabolism, Volume 109, Issue 10, October 2024, Pages 2530–2540
https://doi.org/10.1210/clinem/dgae179
Sphingolipids are linked to the pathogenesis of type 2 diabetes.
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 study, a 5-year follow-up study.
Academic health center.
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.
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.
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 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 C26:0/C26:1 (OR, 2.73 [95% CI, 1.172–4.408], P = .015) and ceramide C18:0/C18:1 (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.
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 type 2 diabetes.
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