The Early Effect of the Roux-en-Y Gastric Bypass on Hormones Involved in Body Weight Regulation and Glucose Metabolism

Abstract

Objective: To evaluate the early effect of Roux-en-Y (RYGB) gastric bypass on hormones involved in body weight regulation and glucose metabolism. Significant Background Data: The RYGB is an effective bariatric procedure for which the mechanism of action has not been elucidated yet. Reports of hormonal changes after RYGB suggest a possible endocrine effect of the operation; however, it is unknown whether these changes are the cause or rather the effect of surgically induced weight loss. We speculated that if the mechanism of action of the RYGB involves an endocrine effect, then hormonal changes should occur early after surgery, prior to substantial body weight changes. Methods: Ten patients with a mean preoperative body mass index (BMI) of 46.2 kg/m 2 (40 -53 kg/m 2 ) underwent laparoscopic RYGB. Six patients had type 2 diabetes treated by oral hypoglycemic agents. Preoperatively and 3 weeks following surgery, all patients were tested for fasting glucose, insulin, glucagon, insulinlike growth factor 1 (IGF-1), leptin, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), adrenocorticotropic hormone (ACTH), corticosterone, and neuropeptide Y (NPY). Results: Changes in mean BMI were rather minimal (43.2 kg/m 2 ; P ϭ not significant), but there was a significant decrease in blood glucose (P ϭ 0.005), insulin (P ϭ 0.02), IGF-1 (P Ͻ 0.05), leptin (P ϭ 0.001), and an increase in ACTH levels (P ϭ 0.01). The other hormones were not significantly changed by surgery. All the 6 diabetic patients had normal glucose and insulin levels and did not require medications after surgery. The RYGB reduced GIP levels in diabetic patients (P Ͻ 0.01), whereas no changes in GIP levels were found in nondiabetics. Conclusions: Roux-en-Y gastric bypass determines considerable hormonal changes before significant BMI changes take place. These results support the hypothesis of an endocrine effect as the possible mechanism of action of RYGB. S urgery represents the most effective therapeutic modality for morbid obesity.1,2 Interestingly, the Roux-en-Y gastric bypass (RYGB), a procedure that includes the creation of a small proximal gastric pouch and the bypass of the duodenum and proximal jejunum from the transit of food, not only determines permanent reduction of excess body weight, but also induces resolution of type 2 diabetes mellitus in more than 80% of morbidly obese patients. 3Body weight is the result of complex physiologic mechanisms that control food intake and energy expenditure. Regulation of body weight involves several systems such as the adipose tissue, 4 the hypothalamus, 5 and the adrenal glands, 6 which are linked by neural and hormonal signals. Recent investigations have identified several key molecules that regulate food intake, including ghrelin, neuropeptide Y (NPY), 7 and melanocortins 8 and have focused on the relationship between obesity and leptin levels. The effectiveness of gastric bypass in inducing remarkable weight loss and control of diabetes represents an "experimental mod...

Early administration of the glucose-dependent insulinotropic polypeptide receptor antagonist (Pro3)GIP prevents the development of diabetes and related metabolic abnormalities associated with genetically inherited obesity in ob/ob mice

“…Although the above conclusions are necessarily based on experimental studies in animal models, there are strong parallels with recent studies in humans undergoing surgical bypass for treatment of gross obesity and associated diabetes [46][47][48][49]. The similarity with our results of GIP receptor blockage in ob/ob mice suggest that GIP is key in this type of surgery and links obesity to insulin resistance and diabetes in man.…”

Circadian rhythms of GIP and GLP1 in glucose-tolerant and in type 2 diabetic patients after biliopancreatic diversion

“…Although a diverse anatomical modification of the small intestine takes place in the Roux-en-Y gastric bypass (RYGB), in which the stomach is anastomosed with the jejunum a few centimetres after Treitz's ligament, the effects of BPD and RYGB in terms of GIP suppression in diabetic patients seem to be comparable. After gastric bypass, Rubino et al [10] found that GIP decreased to normal levels in diabetic patients, whereas it increased slightly but not significantly in obese non-diabetic patients. This similarity might depend on the distribution of GIPsecreting K cells, which are present in both the duodenum and the jejunum [27].…”

“…Relatively few data are available concerning the effect of bariatric surgery on incretin secretion [10][11][12][13][14][15] and, at least to our knowledge, no data exist regarding the response of incretin to multiple meals.…”

Restoration of normal glucose tolerance in severely obese patients after bilio-pancreatic diversion: role of insulin sensitivity and beta cell function

“…[24]). However, these hormones do not seem likely candidates, as there is no evidence that they can cause drastic changes in insulin sensitivity such as observed in this study.…”