Longitudinal Dynamics of Fasting Plasma Uridine in the Preclinical Stage of Type 1 Diabetes

Abstract Context Elevated blood uridine levels have been reported in children with newly diagnosed Type 1 diabetes (T1D), however, their relevance to disease onset remains unclear. Objective To explore whether changes in plasma uridine are associated with the development of T1D in at-risk individuals. Methods Pre- and post-T1D-onset oral glucose tolerance test plasma samples from 45 cases and matched controls in the DPT-1 trial were examined for uridine concentrations using LC-MS/MS. Cases with age > 21, BMI >25, HbA1c > 5.7%, or interval from screening to T1D diagnosis < 1year were excluded due to the potential confounding effects of aging, obesity, and insulin resistance on uridine homeostasis. 23 matched case-control pairs were used to evaluate associations between uridine levels and T1D risk. Results Individuals who later developed T1D (cases) exhibited an increase in plasma uridine around the onset of T1D (5.03 ± 0.86 µM before and 6.10 ± 1.40 µM after T1D diagnosis, p = 0.001), whereas individuals who did not develop T1D (controls) showed a decrease (6.20 ± 1.32 µM at visit 1 and 5.20 ± 1.33 µM at visit 2, p < 0.001). The receiver operating characteristic curve indicates that baseline fasting uridine demonstrates discriminatory performance for T1D (AUC = 0.773). Mixed effects modeling identifies a significant time × group interaction, with group-specific uridine dynamics evident prior to T1D onset in humans. Conclusions Our findings suggest that fasting uridine changes precede T1D onset and may serve as an early biomarker.