Longitudinal changes in pancreatic and adipocyte hormones following Roux-en-Y gastric bypass surgery.

AIMS/HYPOTHESIS: Bariatric surgery is an effective treatment for severe obesity, as in addition to dramatic weight loss, co-morbidities such as type 2 diabetes are frequently resolved. Although altered gastrointestinal peptide hormone secretion and its relationship with post-surgical improvements in insulin sensitivity has been studied, much less is known about long-term changes in pancreatic and adipose tissue-derived hormones. Our objective was to conduct a comprehensive longitudinal investigation of the endocrine changes following Roux-en-Y gastric bypass surgery (RYGBP), focusing on pancreatic and adipocyte hormones and systemic markers of inflammation. METHODS: Nineteen severely obese women (BMI 45.6 +/- 1.6 kg/m(2)) were studied prior to RYGBP, and at 1, 3, 6, and 12 months after RYGBP. Body composition was assessed before surgery and at 1 and 12 months. RESULTS: Pre-surgical adiposity was correlated with circulating adipocyte hormones (leptin, visfatin) and inflammatory molecules (IL-6, high sensitivity C-reactive protein [hsCRP], monocyte chemoattractant protein-1). As expected, RYGBP reduced fat mass and fasting insulin and glucose concentrations. In addition, reductions of fasting pancreatic polypeptide (PP) and glucagon concentrations were observed at 1 and 3 months, respectively. In the 12 months following RYGBP, concentrations of most adipocyte hormones (leptin, acylation-stimulating hormone and visfatin, but not retinol-binding hormone-4) and inflammatory molecules (IL-6, hsCRP and soluble intracellular adhesion molecule-1) were significantly reduced. Reductions of insulin resistance (measured by homeostasis model assessment of insulin resistance) were independently associated with changes of glucagon, visfatin and PP. Pre-surgical HMW adiponectin concentrations independently predicted losses of body weight and fat mass. CONCLUSIONS/INTERPRETATION: These results suggest that pancreatic and adipocyte hormones may contribute to the long-term resolution of insulin resistance after RYGBP.

Circulating concentrations of high-molecular-weight adiponectin are increased following Roux-en-Y gastric bypass surgery.

AIMS/HYPOTHESIS: In addition to weight loss, bariatric surgery for severe obesity dramatically alleviates insulin resistance. In this study, we investigated whether circulating concentrations of the high-molecular-weight (HMW) form of adiponectin are increased following gastric bypass surgery. The HMW form is implicated as the multimer responsible for adiponectin's hepatic insulin-sensitising actions. SUBJECTS AND METHODS: We studied 19 women who were undergoing Roux-en-Y gastric bypass surgery. Studies were conducted prior to, and 1 and 12 months after surgery. RESULTS: One month after surgery, total plasma adiponectin concentrations were unchanged. Nevertheless, increases in both HMW (by 40+/-15%, p=0.006) and the proportion of adiponectin in the HMW form (from 40+/-2 to 50+/-2%, p<0.0001) were observed. At 12 months, total and HMW adiponectin concentrations were increased by 58+/-8% and 118+/-21%, respectively (both p<0.001). The majority (80%) of the increase of total adiponectin was due to an increase of the HMW form. After adjustment for covariates, increases of HMW and total adiponectin at 12 months were correlated with the decrease of fat mass (HMW, p=0.0076; total, p=0.0302). In subjects with improved insulin sensitivity at 12 months after surgery (n=18), the increase of HMW, but not that of total adiponectin, predicted the relative decrease of insulin resistance (HMW: p=0.0044; total: p=0.0775, after adjustment for covariates). CONCLUSIONS/INTERPRETATION: These data suggest that the reduction of fat mass following gastric bypass surgery is an important determinant of the increase of HMW adiponectin concentrations, which in turn is associated with and may contribute to the resulting improvement of insulin sensitivity.