Metabolomic Signatures Link Tea Consumption to Lower Incidence of Macrovascular and Microvascular Complications in Type 2 Diabetes: A Prospective Cohort Study

<strong>Background</strong><strong>: </strong>The association between tea consumption and complications of type 2 diabetes (T2D) remains inconsistent, with limited insights into underlying mechanisms. We aimed to identify tea-related metabolomic signatures and explore associations with risks of T2D complications. <strong>Methods:</strong> We included 26,472 T2D participants from the UK Biobank. Tea consumption was assessed via food frequency questionnaire. Using UK Biobank baseline plasma metabolomics data from 247,967 participants, we developed a tea-related metabolomic signature via elastic net regression. Cox regression models were used to evaluated associations among tea consumption, the metabolomic signature, and T2D complications. Mediation analyses were utilized to assess the contribution of different domains of tea-related metabolomic signatures in explaining the association between tea intake and T2D complications. <strong>Results:</strong> Compared with non-drinkers, moderate tea consumption (specifically 2-3 cups/day) was associated with the lowest risks of microvascular (HR=0.888, 95% CI: 0.823-0.958) and macrovascular complications (HR=0.921, 95% CI: 0.858-0.989). Tea-related metabolomic signature demonstrated a nonlinear association with both micro- and macrovascular complications. Participants in the third quartile of tea-related metabolomic signatures exhibited the lowest risks of diabetic nephropathy (HR=0.824, 95% CI: 0.704-0.964), diabetic retinopathy (HR=0.644, 95% CI: 0.564-0.736), diabetic neuropathy (HR=0.675, 95% CI: 0.530-0.859), cerebrovascular disease (HR=0.779, 95% CI: 0.644-0.942), and peripheral vascular disease (HR=0.580, 95% CI: 0.443-0.759). The glycolysis-related signature was identified as a key contributor in the mediation analyses. <strong>Conclusions:</strong> Moderate tea consumption of 2-3 cups per day is associated with the lowest risks of T2D complications, partially mediated by tea-related metabolomic signatures. These findings highlight novel insights and suggest potential dietary strategies for T2D management.