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. 2024 Jun;39(6):1875-1883.
doi: 10.1007/s00467-023-06257-6. Epub 2024 Jan 3.

Urinary sphingolipids in adolescents and young adults with youth-onset diabetes

Edward J Nehus  1 , Nicole M Sheanon  2   3 , Wujuan Zhang  3   4 , Santica M Marcovina  5 , Kenneth D R Setchell  3   4 , Mark M Mitsnefes  3   6
Affiliations

Urinary sphingolipids in adolescents and young adults with youth-onset diabetes

Edward J Nehus et al. Pediatr Nephrol. 2024 Jun.

Abstract

Background: This study evaluated urinary sphingolipids as a marker of diabetic kidney disease (DKD) in adolescents and young adults with youth-onset type 1 and type 2 diabetes.

Methods: A comprehensive panel of urinary sphingolipids, including sphingomyelin (SM), glucosylceramide (GC), ceramide (Cer), and lactosylceramide (LC) species, was performed in patients with youth-onset diabetes from the SEARCH for Diabetes in Youth cohort. Sphingolipid levels, normalized to urine creatinine, were compared in 57 adolescents and young adults with type 1 diabetes, 59 with type 2 diabetes, and 44 healthy controls. The association of sphingolipids with albumin-to-creatinine (ACR) ratio and estimated glomerular filtration rate (eGFR) was evaluated.

Results: The median age (interquartile range [IQR]) of participants was 23.1 years (20.9, 24.9) and the median duration of diabetes was 9.3 (8.5, 10.2) years. Urinary sphingolipid concentrations in patients with and without DKD (ACR ≥ 30 mg/g) were significantly elevated compared to healthy controls. There were no significant differences in sphingolipid levels between participants with type 1 and type 2 diabetes. In multivariable analysis, many sphingolipid species were positively correlated with ACR. Most significant associations were evident for the following species: C18 SM, C24:1 SM, C24:1 GC, and C24:1 Cer (all p < 0.001). Sphingolipid levels were not associated with eGFR. However, several interaction terms (diabetes type*sphingolipid) were significant, indicating diabetes type may modify the association of sphingolipids with eGFR.

Conclusion: Urinary sphingolipids are elevated in adolescents and young adults with youth-onset diabetes and correlate with ACR. Urinary sphingolipids may therefore represent an early biomarker of DKD.

Keywords: Diabetic kidney disease; Pediatrics; Sphingolipids; Youth-onset diabetes.

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