Mechanism of metabolic surgery for the treatment of Type 2 Diabetes Mellitus (T2DM)

Abstract

After metabolic surgery, patients with type 2 diabetes (T2DM) typically experience a rapid improvement in glycemic control before any significant weight loss occurs. Furthermore, a significant proportion of patients are able to achieve long-term T2DM remission and improvement in β-cell function. While historically believed to be related to weight loss and caloric restriction, multiple weight loss independent mechanisms have been identified to contribute to the long-term glycemic effects induced by metabolic surgery. There are changes in bile acid metabolism, the gut microbiome, incretins, and other gut hormones after surgery that are implicated. It is also becoming increasingly evident that adipose tissue, specifically visceral adipose tissue, is implicated in the pathogenesis of insulin resistance (IR) and T2DM through inflammatory changes involving the host immune system. Therefore, metabolic surgery may exert its effects by reducing the inflammatory response through reduction of adipose. While these mechanisms may seem discrete, there is a significant cross-talk between all these factors that contributes to the regulation of glucose homeostasis. Together, this leads to reduced gluconeogenesis, improved glucose tissue uptake, reduced IR, and improved β-cell function after metabolic surgery.