PREDIABETES is a term used to describe a state characterized by higher than normal blood glucose levels but yet to reach diabetic levels [1], which is usually related to impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG). Prediabetes has become a growing global problem. Data from USA indicate that the prevalence of IFG is about 26% and that of IGT is about 15% in the adult population based on oral glucose tolerance test (OGTT) Abstract. One of human GLP-1 analogues, liraglutide has been approved as adjuvant therapy to oral medication in T2DM. It was also shown to prevent diabetes in obese subjects and rats. However, it is unknown whether liraglutide can effectively mitigate the effects of prediabetes. We therefore investigate this by treating 12-weeks old Otsuka-Long-Evans-Tokushima fatty (OLETF) rats with liraglutide 50, 100, and 200 μg/kg, respectively twice a day for 12 weeks. Eight Long-EvansTokushima-Otsuka (LETO) rats with saline injection served as normal controls. Body weight, food intake, lipid profiles, inflammatory markers (fibrinogen, Hs-CRP, IL-6, TNFα, and PAI-1), glycemic metabolism and insulin sensitivity, and apoptotic factors (Bcl-2 and Bax) expression were monitored. We found that 12-week old OLETF rats had significantly increased body weight, food intake, serum levels of lipid profiles, inflammatory markers, and insulin compared to LETO rats. FPG level was significantly increased but still lower than 7mmol/L without impaired glucose tolerance (IGT). After 12 weeks, vehicle-treated OLETF rats had further deterioration in IFG, IGT, insulin resistance, lipid profiles, and inflammatory state. Pancreatic islets were hypertrophic with distorted structure, scarring, and inflammatory cell infiltration. However, in the three liraglutide-treated groups, IFG, IGT, the increased lipid profiles and inflammatory markers were reversed. Insulin resistance was similar to the level before the treatment. Moreover, liraglutide restored the islet structure, up-regulated Bcl-2 expression and down-regulated Bax expression. It indicated that liraglutide could suppress diabetes onset in OLETF rats with prediabetes, probably by reserving β cell function via regulating apoptotic factors as well as ameliorating lipid metabolism and inflammatory reactions.

The prevalence of type 2 diabetes mellitus (T2DM) is increasing every year. Medications are currently the most common therapy for T2DM. However, these medications have certain adverse effects. In order to find safe and effective ways to improve this disease, researchers have discovered that some natural products can decrease blood sugar. Flavonoids are one of the most essential low molecular weight phenolic chemicals in the plant world, which widely exist in plant roots, stems, leaves, flowers, and fruits. They possess a variety of biological activities, including organ protection, hypoglycemic, lipid-lowering, anti-oxidative and anti-inflammatory effects. Some natural flavonoids ameliorate T2DM and its complications through anti-oxidation, anti-inflammatory action, glucose and lipid metabolism regulation, insulin resistance management, etc. Hence, this review aims at demonstrating the potential benefits of flavonoids in T2DM and its complications. This laid the foundation for the development of novel hypoglycemic medications from flavonoids.