Response to Comment on Gastaldelli et al. Short-term Effects of Laparoscopic Adjustable Gastric Banding Versus Roux-en-Y Gastric Bypass. Diabetes Care 2016;39:1925-1931

We would like to thank Drs. Algahim and Taegtmeyer for their comments (1) on our article (2). We agree that in the long term a significant weight loss, such as that obtained after bariatric/metabolic surgery, can surely contribute to the improvement of insulin sensitivity. Nonetheless, although in our series both gastric banding and Roux-en-Y gastric bypass (RYGB) led to significant improvement in hepatic insulin sensitivity, endogenous glucose production, and lipolysis, only RYGB improved insulin sensitivity of adipose tissue and whole-body insulin-mediated glucose uptake independently of caloric intake (2). Thus, we believe that it is intestinal surgical manipulation with diversion of nutrients from the stomach and the proximal intestine, rather than the degree of weight loss, that drives the improvement of insulin sensitivity in obese subjects. The authors highlight the importance of changes in adipokines, in particular leptin, in the improvement of muscular insulin sensitivity observed after bariatric/metabolic surgery (1,3). Several studies observed lower serum levels of proinflammatory adipokines after bariatric surgery (3–5), but the improvement in insulin resistance and glycemic control after RYGB was observed even in patients who did not display a reduction in adipose tissue inflammation (6). The role of leptin in the insulin sensitivity of obesity remains controversial. Leptin is secreted mainly by subcutaneous adipose tissue, and it is involved in the starvation/feeding switch within the ventrobasal hypothalamus but also in the modulation of energy homeostasis (7). It is well ascertained that lipodystrophy patients, who display an almost complete lack of subcutaneous fat and severe leptin deficiency, have reduced hepatic and peripheral insulin sensitivity (7). The weight loss induced by dieting or gastrointestinal surgery, leading to reduction of fat mass and leptin secretion, is associated with improvement in insulin sensitivity; however, we cannot exclude the possibility that the association between reduced serum levels of leptin and improvement in insulin sensitivity may be merely due to the reduction in total body fat.