Abstract: FR-PO0931
Lower Plasma Long-Chain Ceramides Are Independently Associated with Incident Albuminuria in Youth-Onset Type 2 Diabetes
Session Information
- Pediatric Nephrology: Genetic Diseases, Development, Neonatal Nephrology, Glomerular Diseases, and More
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1800 Pediatric Nephrology
Authors
- Miller, Kristen, University of Washington, Seattle, Washington, United States
- Zhang, Guanshi, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Ragi, Nagarjunachary, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- D'Antonio, Matteo, University of Washington, Seattle, Washington, United States
- Weissenkampen, James Dylan, University of Washington, Seattle, Washington, United States
- Choi, Ye Ji, University of Washington, Seattle, Washington, United States
- Ramesh, Shivani, University of Washington, Seattle, Washington, United States
- Leidholt, Savanah L., University of Washington, Seattle, Washington, United States
- El ghormli, Laure K., The George Washington University Milken Institute School of Public Health, Washington, District of Columbia, United States
- de Boer, Ian, University of Washington, Seattle, Washington, United States
- Nelson, Robert G., University of Washington, Seattle, Washington, United States
- Layton, Anita T., University of Waterloo, Waterloo, Ontario, Canada
- Waikar, Sushrut S., Boston Medical Center, Boston, Massachusetts, United States
- Heerspink, Hiddo Jan L., University Medical Center Groningen, Groningen, Netherlands
- White, Neil H., Washington University in St Louis, St. Louis, Missouri, United States
- Tommerdahl, Kalie L., University of Washington, Seattle, Washington, United States
- Laffel, Lori M., Joslin Diabetes and Endocrinology Research Center, Boston, Massachusetts, United States
- Shah, Amy Sanghavi, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
- Drews, Kimberly L., Louisiana State University Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States
- Ryder, Justin R., Ann and Robert H Lurie Children's Hospital of Chicago Foundation, Chicago, Illinois, United States
- Gubitosi-Klug, Rose, University Hospitals Rainbow Babies & Children's Hospital, Cleveland, Ohio, United States
- Bjornstad, Petter, University of Washington, Seattle, Washington, United States
- Sharma, Kumar, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Pyle, Laura, University of Washington, Seattle, Washington, United States
Background
Approximately 50% of people with youth-onset type 2 diabetes (Y-T2D) develop diabetic kidney disease (DKD) by young adulthood, increasing the risk of kidney failure and premature death. The direction of association between ceramides and DKD varies by chain length and tissue compartment, yet data are limited in Y-T2D. We assessed whether baseline plasma ceramides are associated with development of albuminuria in Y-T2D.
Methods
We measured 6 plasma ceramides in 379 newly diagnosed participants in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study, using a Thermo Vanquish LC system coupled to an Orbitrap mass spectrometer. Urine albumin-to-creatinine ratio (UACR) was measured annually for up to 15 years. Incident albuminuria was defined as UACR ≥30 mg/g on ≥2 of 3 consecutive measures. We evaluated whether baseline plasma ceramides were associated with time to incident albuminuria in Cox proportional hazards models adjusted for sex, HbA1c, triglycerides, systolic blood pressure, and estimated insulin sensitivity. P-values were FDR-corrected for multiple comparisons and p<0.05 was considered significant.
Results
Participants were predominantly female (63%) and on average 14±2 years old. Of the 379 participants, 160 (42%) developed albuminuria at a median of 13 years from enrollment. Three ceramides were independently associated with albuminuria and all were long-chain and very-long-chain ceramides: C24(d18:1/24:0) (hazard ratio, HR: 0.74 per 1 SD [95% CI: 0.64, 0.87]; Figure 1), C16(d18:1/16:0) (HR: 0.75 [0.63, 0.90]), and C22(d18:1/22:0) (HR: 0.76 [0.64, 0.90]). Lower baseline plasma ceramide concentrations were associated with higher hazard of albuminuria.
Conclusion
Lower baseline plasma concentrations of 3 long-chain and very-long-chain ceramides were associated with development of albuminuria in Y-T2D. Plasma ceramides are biomarker candidates for early detection of DKD in this high-risk population and warrant further study.
Funding
- NIDDK Support