Abstract
Type 1 diabetes (T1D) is an autoimmune disease characterized by the selective destruction of pancreatic β-cells. Although successful islet transplantation provides a promising treatment, high cost, lack of donor organs, immune-mediated destruction of transplanted islets, and side effects from immunosuppressive drugs greatly limit its uses. Therefore, the search for novel and cost-effective agents that can prevent or ameliorate T1D is extremely important to decrease the burden of T1D. In this study, we discovered that epicatechin (EC, 0.5% in drinking water), a flavonol primarily in cocoa, effectively prevented T1D in nonobese diabetic (NOD) mice. At 32 weeks of age, 66.7% of control mice had overt diabetes, whereas only 16.6% of EC-treated mice became diabetic. Consistently, EC mice had significantly higher plasma insulin levels but lower glycosylated hemoglobin concentrations compared to control mice. EC had no significant effects on food or water intake and body weight gain in NOD mice, suggesting that EC's effect was not due to alterations in these variables. Treatment with EC elevates circulating anti-inflammatory cytokine interleukin-10 levels, ameliorates pancreatic insulitis, and improves pancreatic islet mass. These findings demonstrate that EC may be a novel, plant-derived compound capable of preventing T1D by modulating immune function and thereby preserving islet mass.