Mechanism of Metabolic Advantages After Bariatric Surgery

The acute glucose-lowering effect of certain bariatric procedures—before any significant weight loss has occurred—has been known for decades (1). In a comprehensive meta-analysis by Buchwald et al. (2), type 2 diabetes remission rates after the most common bariatric procedure, Roux-en-Y gastric bypass (RYGB), were reported to be 80%. Applying the 2009 consensus criteria for the definition of diabetes remission has been reported to show complete remission of diabetes in “only” 41% of 160 RYGB-treated obese patients with type 2 diabetes (3). Importantly, bariatric surgery seems to improve several components of the metabolic syndrome, and type 2 diabetes–specific mortality rates have been demonstrated to be up to 90% lower in RYGB-treated subjects compared with nontreated control subjects (2,4). In comparison with medical therapy alone, recent clinical trials have shown that RYGB or biliopancreatic diversion resulted in better glucose control (5), RYGB achieved glycemic control in significantly more patients (6), and sleeve gastrectomy resolved the diabetic state more effectively (7). Thus, it is well established that bariatric procedures improve glycemic control or even resolve the type 2 diabetic state. However, the mechanisms by which these operations bring about their glucose-lowering effects remain much debated. Obviously, the body weight–lowering effect of these operations contributes to the long-term improvements in glucose metabolism (primarily via increased hepatic and peripheral insulin sensitivity [8]), but it is striking that amelioration of hyperglycemia after bariatric surgery occurs within days of the surgery, pointing to immediate, weight loss–independent mechanisms possibly related to surgery-induced changes in food intake (caloric restriction), gastrointestinal (GI) anatomy, or transit of nutrients. The predominant hypotheses on the physiological background for the metabolic advantages (specifically, the glucose-lowering effects) after bariatric surgery include changed release of GI hormones (increased secretion of hormones with antidiabetes properties and reduced secretion of “diabetogenic” hormones) and surgery-induced …