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 Diabetes Prevention Trial-Type 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 < 1 year were excluded due to the potential confounding effects of aging, obesity, and insulin resistance on uridine homeostasis. Twenty-three 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 = .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 < .001). The receiver operating characteristic curve indicates that baseline fasting uridine demonstrates discriminatory performance for T1D (area under the curve = 0.773). Mixed-effects modeling identifies a significant time × group interaction, with group-specific uridine dynamics evident prior to T1D onset in humans. CONCLUSION: Our findings suggest that fasting uridine changes precede T1D onset and may serve as an early biomarker.