Effects of various gastrointestinal procedures on β-cell function in obesity and type 2 diabetes.

Bariatric surgery is a gastrointestinal procedure that has emerged as the most effective treatment for weight loss. Roux-en-Y gastric bypass and sleeve gastrectomy are the main procedures currently performed. However, the benefits of bariatric surgery extend beyond weight loss. In fact, improvements in β-cell function occur before clinically meaningful weight loss and contribute to type 2 diabetes mellitus (T2D) remission. Herein, we discuss evidence supporting the efficacy of bariatric surgery for weight loss and improved insulin secretion in patients with and without T2D. The exact mechanism by which bariatric surgery elicits a favorable change in β-cell function remains unclear, but a leading hypothesis is that rerouted nutrient flow to the gut alters enteroendocrine hormone production (e.g., glucagon-like polypeptide 1, polypeptide tyrosine-tyrosine, ghrelin), gut microbiome metabolites (e.g., lipopolysaccharides, short-chain fatty acids), and circulating bile acid changes that favor appetite suppression, metabolic rate, and insulin action. We also highlight the role of adipose-derived factors (e.g., pancreatic fat content, adiponectin) that may have an effect on β-cell function, as well as discuss the clinical determinants of diabetes remission (e.g., age and T2D duration). Taken together, the acute improvements seen with bariatric surgery are weight-independent and likely related to incretin-mediated effects on postprandial glucose metabolism and insulin sensitivity. Over longer periods of time, increases in bile acids, reductions in pancreatic lipid content, and elevated adiponectin levels may also contribute to reduced disease risk. As a result, the gut appears to be a novel target for favorably preventing and treating obesity-related metabolic disorders.