Restoration of Euglycemia After Duodenal Bypass Surgery

Questions: 1. What is the most commonly used restrictive bariatric procedure worldwide?2. What is the difference between Roux-en-Y gastric bypass and sleeve gastrotectomy?3. Why the secretion of gut hormone in adjustable gastric banding (AGB) is mainly considered to be due to weight loss?4. What is the possible role for GLP-1 in bariatric surgery?5. Which experiments support the hypothesis that GLP-1 is directly involved in improvement of glycemia in gastric bypass in animal and humans?6. Explain why reduction in ghrelin secretion in bariatric surgery would be beneficial on glucose homeostasis?7. Explain why improvement seen in diabetes in some type of bariatric surgery is independent of weight loss?8. What did you find most interesting or difficult? Answers: 1. The most commonly used restrictive bariatric procedure worldwide is adjustable gastric banding (AGB). 2. In the Roux-en-Y gastric bypass (RYGB) surgery a major part of the stomach, duodenum and 40 cm of the jejunum are bypassed whereas the sleeve gastrotectomy involves the removal of 75% of the stomach, thr removed part includes the hormone secreting gastric fundus.3. The gastrointestinal tract remains intact as a result of the AGB surgery and continues to secrete gut hormones. However, the reduced intake capacity of the diabetic patient causes weight loss and leads to better glucose homeostasis and the improved glucose levels are independent of change in gut hormone secretion levels.4. The secretion of GLP-1 which is low in obese patients shoots up by six times after bariatric surgery. An incretin hormone, GLP-1 signals satiety and stimulates secretion of insulin. It suppresses glucagon secretion and retards gastric emptying. The increased levels of GLP-1 therefore improve glucos e homeostasis in patients who have undergone bariatric surgery. However, the levels of GLP-1 are not raised in adjustable banding surgery as opposed to bariatric procedures which involve removal of parts of the GI tract.5. A set of experiments performed on rats and humans supports the hypothesis that GLP-1 is directly involved in improvement of glucose homeostasis in gastric bypass treated subjects.Exendin 9 - 39 amide (Ex-9) has been used to study the physiological activity of GLP-1. Ex-9 is known to block GLP-1 activity by binding to its receptors. GLP-1 action causing release of post prandial insulin gets blocked without any impact on other hormones required for insulin secretion. Diabetic rats that were treated with a duodenal-jejunal bypass (an RYGB-like surgical procedure) exhibited improved glucose homeostasis in comparison with sham-operated rats.Ex-9 has been used in humans to check whether high secretion of insulin in RYGB treated patients can be attributed to GLP-1 induced secretion of insulin from beta cells causing post-surgical hypoglycemia. Administration of Ex-9 resulted in a 33% fall in insulin secretion.6. The removal of gastric fundus during bariatric surgery causes reduction in ghrelin secretion. This hormone is known to stimulate appetite. It inhibits insulin secretion through a mechanism yet to be clearly understood. Ghrelin suppresses adiponectin a hormone that plays a role in insulin sensitization and causes stimulation of counter regulatory hormones. Ghrelin secretion is affected by the vagus nerve which is severed during bariatric procedures on purpose. The secretion of ghrelin continues after the procedure during which the vagus nerve remains intact.7. Improvement in glucose homeostasis has been seen in diabetics who have been treated with bariatric surgery irrespective of weight loss. The sudden rise in GLP-1 post bariatric procedures that reduce ghrelin secretion leads to greater satiety and insulin secretion. The duodenal bypass may cause higher levels of gut hormones to be released which directly improve insulin sensitivity.Secretion of diabetogenic gut secretions is reduced. Alterations in bile acids and gut microflora can improve glucose homeostasis.8. The role of GLP-1 in achieving glucose homeostasis in patients treated with bariatric surgery is the most interesting and that bypass surgeries may be bypassed in future. References: Jiao, J., Bae, E. J., Bandopadhyay, G., Oliver, J., Marathe, C., Chen, M., Hsu, J.-Y., Chen, Y., Tian, H., Olefsky, J. M., and Saberi, M. (2013). Restoration of euglycemia after duodenal bypass surgery is reliant on central and peripheral inputs in Zucker fa/fa rats. Diabetes. 62: 1074-83.Vetter, M. L., Ritter, S., Wadden, T. A., and Sarwer, D. B. (2012). Comparison of bariatric surgical procedures for diabetes remission: efficiency and mechanisms. Diabetes Spectrum. 25(4):200-10. Doi:10.2337/diaspect.25.4.200.