Abstract: PO0735
Urinary Sphingolipids in Youth-Onset Diabetes
Session Information
- Diabetic Kidney Disease: Clinical
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 602 Diabetic Kidney Disease: Clinical
Authors
- Nehus, Edward, Marshall University, Huntington, West Virginia, United States
- Mitsnefes, Mark, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
Background
Sphingolipid metabolism is altered in diabetes has been implicated as a mediator of diabetic kidney disease (DKD). The purpose of this study was to evaluate urinary sphingolipids as an early marker of kidney injury in youth with type 1 (T1) and type 2 diabetes (T2DM).
Methods
A comprehensive panel of urinary sphingolipids, including sphingomyelin (SM), glucosylceramide (GC), ceramide (Cer), and lactoslyceramide (LC) species, was performed in patients with youth-onset diabetes from the Treatment Options for Diabetes in Youth (TODAY) cohort. Sphingolipid levels, normalized to urine creatinine, were compared in 57 youth with T1DM, 59 with T2DM, and 44 healthy control subjects. The association of sphingolipids with early markers of DKD (albumin-to-creatinine [ACR] ratio and estimated glomerular filtration rate [eGFR]) was evaluated.
Results
The median age (IQR) of youth with diabetes was 22.2 years (19.9, 23.6) and the median duration of diabetes was 9.3 (8.5, 10.2) years. Urinary sphingolipid concentrations in youth with and without DKD (ACR ≥ 30) were significantly elevated compared to healthy subjects (all p<0.001). There were no significant differences between youth with type 1 and type 2 diabetes. All sphingolipid species were positively correlated with eGFR (all p < 0.001) and negatively with albumin-to-creatinine ratio (p < 0.001 for SM, Cer, GC; p = 0.0015 for LC). In multivariable analysis that adjusted for BMI and HgbA1c, all urinary sphingolipid species remained significantly associated with eGFR (all p < 0.01). SM, GC, and Cer species remained independently associated with ACR (all p < 0.05).
Conclusion
Urinary sphingolipids are elevated in youth with diabetes and correlate with eGFR and albuminuria. Urinary sphingolipids may therefore represent an early marker of DKD.