https://www.selleckchem.com/products/ide397-gsk-4362676.html s not associated with increased depression. Tsukushi, a newly identified hepatokine, has been recently characterized as a potent modifier in lipid metabolism and energy homeostasis, but the role of Tsukushi in diabetes remains almost unknown. We detected for the first time the increased serum Tsukushi levels in newly diagnosed type 2 diabetes, exploring the relationship between Tsukushi and various metabolic parameters. A total of 172 participants were recruited, including 86 patients with newly diagnosed type 2 diabetes and 86 subjects with normal glucose tolerance according to oral glucose tolerance test. Serum Tsukushi was measured by ELISA. The insulin resistance, pancreas β-cell function and insulin sensitivity were determined by homeostasis model assessment (HOMA-IR, HOMA-β), Stumvoll insulin sensitivity index (ISI ) and Stumvoll metabolic clearance rate (MCR ). Serum Tsukushi was significantly higher in type 2 diabetes than in normal glucose tolerance [1.22(0.86,1.74) vs 0.8(0.5,1.38) ng/mL; P<0.001]. Multiple regression analysis showed that BMI, 2-h post-OGTT glucose and TC were independently related factors influencing Tsukushi. Logistic regression analyses demonstrated that Tsukushi was associated with higher risk of type 2 diabetes independently. Circulating Tsukushi levels significantly increase in patients with type 2 diabetes, which suggest that Tsukushi may play a role in type 2 diabetes pathogenesis. Circulating Tsukushi levels significantly increase in patients with type 2 diabetes, which suggest that Tsukushi may play a role in type 2 diabetes pathogenesis. Although metformin has been reported to affect the gut microbiome, the mechanism has not been fully determined. We explained the potential underlying mechanisms of metformin through a multiomics approach. An open-label and single-arm clinical trial involving 20 healthy Korean was conducted. Serum glucose and insulin concentrations were