Bariatric surgery and type 2 diabetes: are there weight loss-independent therapeutic effects of upper gastrointestinal bypass?

Type 2 diabetes (T2D) is a major worldwide public health concern. Despite a large armamentarium of T2D medications, a large proportion of patients fail to achieve recommended treatment goals for glycemic control. Weight loss has profound beneficial effects on the metabolic abnormalities involved in the pathogenesis of T2D. Accordingly, bariatric surgery, which is the most effective available weight loss therapy, is also the most effective therapy for treating patients with T2D. Surgical procedures that bypass the upper gastrointestinal (UGI) tract are particularly effective in achieving partial and even complete remission of T2D, suggesting that UGI bypass has weight loss-independent effects on glycemic control. Although a number of hypotheses (e.g. a role for multiorgan insulin sensitivity, β-cell function, incretin response, the gut microbiome, bile acid metabolism, intestinal glucose metabolism and browning of adipose tissue) have been proposed to explain the potential unique effects of UGI tract bypass surgery, none has yet been adequately evaluated to determine therapeutic importance in patients with T2D. Here, we review the efficacy of UGI bypass surgery in treating T2D and the mechanisms that have been proposed to explain its potential weight loss-independent therapeutic effects.