Changes of insulin sensitivity and secretion after bariatric/metabolic surgery

Abstract

Type 2 diabetes (T2D) is classically characterized by failure of pancreatic β-cell function and insulin secretion to compensate for a prevailing level of insulin resistance, typically associated with visceral obesity. Although this is usually a chronic, progressive disease in which delay of end-organ complications is the primary therapeutic goal for medical and behavioral approaches, several types of bariatric surgery, especially those that include intestinal bypass components, exert powerful antidiabetes effects to yield remission of T2D in most cases. It has become increasingly clear that in addition to the known benefits of acute caloric restriction and chronic weight loss to ameliorate T2D, bariatric/metabolic operations also engage a variety of weight-independent mechanisms to improve glucose homeostasis, enhancing insulin sensitivity and secretion to varying degrees depending on the specific operation. In this paper, we review the effects of Roux-en-Y gastric bypass, biliopancreatic diversion, and vertical sleeve gastrectomy on the primary determinants of glucose homeostasis: insulin sensitivity, insulin secretion, and, to the lesser extent that it is known, insulin-independent glucose disposal. A full understanding of these effects should help optimize surgical and device-based designs to provide maximal antidiabetes impact, and it holds the promise to identify targets for possible novel diabetes pharmacotherapeutics. These insights also contribute to the conceptual rationale for use of bariatric operations as "metabolic surgery," employed primarily to treat T2D, including among patients not obese enough to qualify for surgery based on traditional criteria related to high body mass index.