Effect of metformin on Wnt5a in individuals new-onset type 2 diabetes with different body mass indexes: The evidences from the real word research.

Aim: Metformin is a first-line therapy for the treatment of Type 2 diabetes mellitus (T2DM), due to its inhibition of hepatic gluconeogenesis. Wingless family member 5a (Wnt5a) was significantly decreased in newly diagnosed T2DM patients and regulates secretion of ß cells through the Wnt/calcium signalling cascades. This study aims to investigate how metformin works on glucose-lowering effects in diabetes and whether the mechanism underlying it is associated with Wnt5a. Methods: A total of 144 participants were enrolled in this study. Serum Wnt5a levels were measured by an enzyme-linked immunosorbent assay (ELISA). The demographic and clinical parameters were evaluated in normal weight, overweight and obese new-onset T2DM subjects grouped. Results: Wnt5a was increased in overweight T2DM patients and obese T2DM patients compared with the levels in normal Body Mass Index (BMI) T2DM. The level of Wnt5a gradually increased after 3 and 6 months of metformin treatment. Among the three groups, the most significant improvement in blood glucose was observed in the obese type 2 diabetic patients, and the improvement showed a significant correlation with Wnt5a protein after patients received metformin treatment. Pearson correlation showed that there was a significant relationship between △2hOGTT and Wnt5a. After further adjusting for sex and age, a significant association existed only between Wnt5a and 2-h oral glucose tolerance test(2hOGTT), and this association was negative. Conclusion: Our results indicate that Wnt5a may play a role in the mechanism by which metformin improves blood glucose in patients with type 2 diabetes.