Systems Signature Reveals Unique Remission-path of Diabetes Generated by Gastric Bypass Surgery

Gastric bypass surgery (GBP) emerging as a powerful tool for treatment of obesity has been applied for remission of diabetes. However, the GBP global molecular effects on diabetes remission independent of weight loss remain largely unknown. We profiled plasma metabolites and proteins of 10 normoglycemic obese (NO) and 9 diabetic obese (DO) patients at 1-week, 3-months and 1-year stages after Roux-en-Y gastric bypass (RYGB) as well pre-RYGB stage, by which 146 proteins and 128 metabolites were detected from both NO and DO groups at all four stages. By analyzing a set of bi-molecular associations among the corresponding network of the subjects with our newly developed computational method, we defined the representing physiological states (called the edge-states, in contrast to the traditional node-states) and the related molecular networks of NO and DO patients, respectively. The PCA results and hubnetworks of NO subjects were significantly different from those of DO patients; particularly, the hub-network rearrangement of both groups differentially went through after RYGB. In conclusion, by developing network-based systems signatures rather than relying on individual molecules, we for the first time reveal that RYGB generates a unique recovering-path for diabetes remission independent of weight loss.