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Changes in Gastrointestinal Hormone Responses, Insulin Sensitivity, and Beta-Cell Function Within 2 Weeks After Gastric Bypass in Non-diabetic Subjects

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Abstract

Background

Roux-en-Y gastric bypass (RYGB) surgery causes profound changes in secretion of gastrointestinal hormones and glucose metabolism. We present a detailed analysis of the early hormone changes after RYGB in response to three different oral test meals designed to provide this information without causing side effects (such as dumping).

Methods

We examined eight obese non-diabetic patients before and within 2 weeks after RYGB. On separate days, oral glucose tolerance tests (25 or 50 g glucose dissolved in 200 mL of water) and a liquid mixed meal test (200 mL 300 kcal) were performed. We measured fasting and postprandial glucose, insulin, C-peptide, glucagon, total and intact glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), peptide YY3-36 (PYY), cholecystokinin (CCK), total and active ghrelin, gastrin, somatostatin, pancreatic polypeptide (PP), amylin, leptin, free fatty acids (FFA), and registered postprandial dumping. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance.

Results

Fasting glucose, insulin, ghrelin, and PYY were significantly decreased and FFA was elevated postoperatively. Insulin sensitivity increased after surgery. The postprandial response increased for C-peptide, GLP-1, GLP-2, PYY, CCK, and glucagon (in response to the mixed meal) and decreased for total and active ghrelin, leptin, and gastrin, but were unchanged for GIP, amylin, PP, and somatostatin after surgery. Dumping symptoms did not differ before and after the operation or between the tests.

Conclusions

Within 2 weeks after RYGB, we found an increase in insulin secretion and insulin sensitivity. Responses of appetite-regulating intestinal hormones changed dramatically, all in the direction of reducing hunger.

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References

  1. Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009;122:248–56.

    Article  PubMed  Google Scholar 

  2. Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995;222:339–50.

    Article  PubMed  CAS  Google Scholar 

  3. Cummings DE, Weigle DS, Frayo RS, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med. 2002;346:1623–30.

    Article  PubMed  Google Scholar 

  4. Korner J, Bessler M, Inabnet W, et al. Exaggerated glucagon-like peptide-1 and blunted glucose-dependent insulinotropic peptide secretion are associated with Roux-en-Y gastric bypass but not adjustable gastric banding. Surg Obes Relat Dis. 2007;3:597–601.

    Article  PubMed  Google Scholar 

  5. le Roux CW, Aylwin SJ, Batterham RL, et al. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg. 2006;243:108–14.

    Article  PubMed  Google Scholar 

  6. Schauer PR, Burguera B, Ikramuddin S, et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus. Ann Surg. 2003;238:467–84.

    PubMed  Google Scholar 

  7. Beckman LM, Beckman TR, Sibley SD, et al. Changes in gastrointestinal hormones and leptin after Roux-en-Y gastric bypass surgery. JPEN J Parenter Enteral Nutr. 2011;35:169–80.

    Article  PubMed  CAS  Google Scholar 

  8. Campos GM, Rabl C, Peeva S, et al. Improvement in peripheral glucose uptake after gastric bypass surgery is observed only after substantial weight loss has occurred and correlates with the magnitude of weight lost. J Gastrointest Surg. 2010;14:15–23.

    Article  PubMed  Google Scholar 

  9. Falken Y, Hellstrom PM, Holst JJ, et al. Changes in glucose homeostasis after Roux-en-Y gastric bypass surgery for obesity at day three, two months, and one year after surgery: role of gut peptides. J Clin Endocrinol Metab. 2011;96(7):2227–35.

    Article  PubMed  CAS  Google Scholar 

  10. Isbell JM, Tamboli RA, Hansen EN, et al. The importance of caloric restriction in the early improvements in insulin sensitivity after Roux-en-Y gastric bypass surgery. Diabetes Care. 2010;33:1438–42.

    Article  PubMed  CAS  Google Scholar 

  11. le Roux CW, Welbourn R, Werling M, et al. Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass. Ann Surg. 2007;246:780–5.

    Article  PubMed  Google Scholar 

  12. Umeda LM, Silva EA, Carneiro G, et al. Early improvement in glycemic control after bariatric surgery and its relationships with insulin, GLP-1, and glucagon secretion in type 2 diabetic patients. Obes Surg. 2011;21(7):896–901.

    Article  PubMed  Google Scholar 

  13. Vilsboll T, Krarup T, Sonne J, et al. Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab. 2003;88:2706–13.

    Article  PubMed  CAS  Google Scholar 

  14. Herrmann C, Goke R, Richter G, et al. Glucagon-like peptide-1 and glucose-dependent insulin-releasing polypeptide plasma levels in response to nutrients. Digestion. 1995;56:117–26.

    Article  PubMed  CAS  Google Scholar 

  15. Elliott RM, Morgan LM, Tredger JA, et al. Glucagon-like peptide-1 (7–36)amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: acute post-prandial and 24-h secretion patterns. J Endocrinol. 1993;138:159–66.

    Article  PubMed  CAS  Google Scholar 

  16. Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87:1409–39.

    Article  PubMed  CAS  Google Scholar 

  17. Rijkelijkhuizen JM, McQuarrie K, Girman CJ, et al. Effects of meal size and composition on incretin, alpha-cell, and beta-cell responses. Metabolism. 2010;59:502–11.

    Article  PubMed  CAS  Google Scholar 

  18. Carr RD, Larsen MO, Winzell MS, et al. Incretin and islet hormonal responses to fat and protein ingestion in healthy men. Am J Physiol Endocrinol Metab. 2008;295:E779–84.

    Article  PubMed  CAS  Google Scholar 

  19. Lindgren O, Carr R, Holst J, et al. Dissociated incretin hormone response to protein versus fat ingestion in obese subjects. Diabetes Obes Metab. 2011;13(9):863–5.

    Article  PubMed  CAS  Google Scholar 

  20. Deitel M. The change in the dumping syndrome concept. Obes Surg. 2008;18:1622–4.

    Article  PubMed  Google Scholar 

  21. Tack J, Arts J, Caenepeel P, et al. Pathophysiology, diagnosis and management of postoperative dumping syndrome. Nat Rev Gastroenterol Hepatol. 2009;6:583–90.

    Article  PubMed  Google Scholar 

  22. Tokunaga M, Hiki N, Ohyama S, et al. Effects of reconstruction methods on a patient's quality of life after a proximal gastrectomy: subjective symptoms evaluation using questionnaire survey. Langenbecks Arch Surg. 2009;394:637–41.

    Article  PubMed  Google Scholar 

  23. Orskov C, Rabenhoj L, Wettergren A, et al. Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide I in humans. Diabetes. 1994;43:535–9.

    Article  PubMed  CAS  Google Scholar 

  24. Wilken M, Larsen FS, Buckley D, et al. New highly specific immunoassays for glucagon-like peptide 1 (GLP-1). Diabetologia. 1999;42(1):A196.

    Google Scholar 

  25. Krarup T, Madsbad S, Moody AJ, et al. Diminished immunoreactive gastric inhibitory polypeptide response to a meal in newly diagnosed type I (insulin-dependent) diabetics. J Clin Endocrinol Metab. 1983;56:1306–12.

    Article  PubMed  CAS  Google Scholar 

  26. Krarup T, Holst JJ. The heterogeneity of gastric inhibitory polypeptide in porcine and human gastrointestinal mucosa evaluated with five different antisera. Regul Pept. 1984;9:35–46.

    Article  PubMed  CAS  Google Scholar 

  27. Orskov C, Jeppesen J, Madsbad S, et al. Proglucagon products in plasma of noninsulin-dependent diabetics and nondiabetic controls in the fasting state and after oral glucose and intravenous arginine. J Clin Invest. 1991;87:415–23.

    Article  PubMed  CAS  Google Scholar 

  28. Hartmann B, Johnsen AH, Orskov C, et al. Structure, measurement, and secretion of human glucagon-like peptide-2. Peptides. 2000;21:73–80.

    Article  PubMed  CAS  Google Scholar 

  29. Hilsted L, Holst JJ. On the accuracy of radioimmunological determination of somatostatin in plasma. Regul Pept. 1982;4:13–31.

    Article  PubMed  CAS  Google Scholar 

  30. Rehfeld JF, Stadil F, Rubin B. Production and evaluation of antibodies for the radioimmunoassay of gastrin. Scand J Clin Lab Invest. 1972;30:221–32.

    Article  PubMed  CAS  Google Scholar 

  31. Rehfeld JF. Gastrins in serum. A review of gastrin radioimmunoanalysis and the discovery of gastrin heterogeneity in serum. Scand J Gastroenterol. 1973;8:577–83.

    PubMed  CAS  Google Scholar 

  32. Rehfeld JF. Accurate measurement of cholecystokinin in plasma. Clin Chem. 1998;44:991–1001.

    PubMed  CAS  Google Scholar 

  33. Rehfeld JF, Sun G, Christensen T, et al. The predominant cholecystokinin in human plasma and intestine is cholecystokinin-33. J Clin Endocrinol Metab. 2001;86:251–8.

    Article  PubMed  CAS  Google Scholar 

  34. Borg CM, le Roux CW, Ghatei MA, et al. Progressive rise in gut hormone levels after Roux-en-Y gastric bypass suggests gut adaptation and explains altered satiety. Br J Surg. 2006;93:210–5.

    Article  PubMed  CAS  Google Scholar 

  35. Lin E, Phillips LS, Ziegler TR, et al. Increases in adiponectin predict improved liver, but not peripheral, insulin sensitivity in severely obese women during weight loss. Diabetes. 2007;56:735–42.

    Article  PubMed  CAS  Google Scholar 

  36. Turner RC, Holman RR. Insulin rather than glucose homoeostasis in the pathophysiology of diabetes. Lancet. 1976;1:1272–4.

    Article  PubMed  CAS  Google Scholar 

  37. Camastra S, Gastaldelli A, Mari A et al. Early and longer term effects of gastric bypass surgery on tissue-specific insulin sensitivity and beta cell function in morbidly obese patients with and without type 2 diabetes. Diabetologia. 2011;54(8):2093–102.

    Google Scholar 

  38. Henry RR, Scheaffer L, Olefsky JM. Glycemic effects of intensive caloric restriction and isocaloric refeeding in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1985;61:917–25.

    Article  PubMed  CAS  Google Scholar 

  39. Czupryniak L, Pawlowski M, Szymanski D, et al. Plasma glucose after stomach or jejunum glucose infusion in Roux-en-Y gastric bypass patients—a possible implication for early satiety mechanism. Exp Clin Endocrinol Diabetes. 2011;119:186–9.

    Article  PubMed  CAS  Google Scholar 

  40. Rodieux F, Giusti V, D'Alessio DA, et al. Effects of gastric bypass and gastric banding on glucose kinetics and gut hormone release. Obesity (Silver Spring). 2008;16:298–305.

    Article  CAS  Google Scholar 

  41. Dirksen C, Hansen DL, Madsbad S et al. Postprandial diabetic glucose tolerance is normalized by gastric bypass feeding as opposed to gastric feeding and is associated with exaggerated GLP-1 secretion: a case report. Diabetes Care. 2010;33(2):375–7

    Google Scholar 

  42. Kashyap SR, Daud S, Kelly KR, et al. Acute effects of gastric bypass versus gastric restrictive surgery on beta-cell function and insulinotropic hormones in severely obese patients with type 2 diabetes. Int J Obes (Lond). 2010;34:462–71.

    Article  CAS  Google Scholar 

  43. Laferrere B, Heshka S, Wang K, et al. Incretin levels and effect are markedly enhanced 1 month after Roux-en-Y gastric bypass surgery in obese patients with type 2 diabetes. Diabetes Care. 2007;30:1709–16.

    Article  PubMed  CAS  Google Scholar 

  44. Cummings DE, Overduin J, Foster-Schubert KE. Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution. J Clin Endocrinol Metab. 2004;89:2608–15.

    Article  PubMed  CAS  Google Scholar 

  45. Morinigo R, Moize V, Musri M, et al. Glucagon-like peptide-1, peptide YY, hunger, and satiety after gastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab. 2006;91:1735–40.

    Article  PubMed  CAS  Google Scholar 

  46. Rehfeld JF. Incretin physiology beyond glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide: cholecystokinin and gastrin peptides. Acta Physiol (Oxf). 2011;201:405–11.

    Article  CAS  Google Scholar 

  47. Laferrere B, Teixeira J, McGinty J, et al. Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin Endocrinol Metab. 2008;93:2479–85.

    Article  PubMed  CAS  Google Scholar 

  48. Laferrere B, Swerdlow N, Bawa B, et al. Rise of oxyntomodulin in response to oral glucose after gastric bypass surgery in patients with type 2 diabetes. J Clin Endocrinol Metab. 2010;95:4072–6.

    Article  PubMed  CAS  Google Scholar 

  49. Balkan B, Li X. Portal GLP-1 administration in rats augments the insulin response to glucose via neuronal mechanisms. Am J Physiol Regul Integr Comp Physiol. 2000;279:R1449–54.

    PubMed  CAS  Google Scholar 

  50. Nishizawa M, Nakabayashi H, Uchida K, et al. The hepatic vagal nerve is receptive to incretin hormone glucagon-like peptide-1, but not to glucose-dependent insulinotropic polypeptide, in the portal vein. J Auton Nerv Syst. 1996;61:149–54.

    Article  PubMed  CAS  Google Scholar 

  51. Schwartz TW, Rehfeld JF, Stadil F, et al. Pancreatic-polypeptide response to food in duodenal-ulcer patients before and after vagotomy. Lancet. 1976;1:1102–5.

    Article  PubMed  CAS  Google Scholar 

  52. Bloom SR, Polak JM. Gut hormones. Adv Clin Chem. 1980;21:177–244.

    Article  PubMed  CAS  Google Scholar 

  53. Holst JJ. Postprandial insulin secretion after gastric bypass surgery: the role of glucagon-like Peptide 1. Diabetes. 2011;60:2203–5.

    Article  PubMed  CAS  Google Scholar 

  54. Batterham RL, Cohen MA, Ellis SM, et al. Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med. 2003;349:941–8.

    Article  PubMed  CAS  Google Scholar 

  55. Murphy KG, Bloom SR. Gut hormones and the regulation of energy homeostasis. Nature. 2006;444:854–9.

    Article  PubMed  CAS  Google Scholar 

  56. Beckman LM, Beckman TR, Earthman CP. Changes in gastrointestinal hormones and leptin after Roux-en-Y gastric bypass procedure: a review. J Am Diet Assoc. 2010;110:571–84.

    Article  PubMed  CAS  Google Scholar 

  57. de Heer J, Pedersen J, Orskov C. The alpha cell expresses glucagon-like peptide-2 receptors and glucagon-like peptide-2 stimulates glucagon secretion from the rat pancreas. Diabetologia. 2007;50:2135–42.

    Article  PubMed  Google Scholar 

  58. Meier JJ, Nauck MA, Pott A, et al. Glucagon-like peptide 2 stimulates glucagon secretion, enhances lipid absorption, and inhibits gastric acid secretion in humans. Gastroenterology. 2006;130:44–54.

    Article  PubMed  CAS  Google Scholar 

  59. Broglio F, Arvat E, Benso A, et al. Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. J Clin Endocrinol Metab. 2001;86:5083–6.

    Article  PubMed  CAS  Google Scholar 

  60. Cummings DE. Ghrelin and the short- and long-term regulation of appetite and body weight. Physiol Behav. 2006;89:71–84.

    Article  PubMed  CAS  Google Scholar 

  61. Korner J, Bessler M, Cirilo LJ, et al. Effects of Roux-en-Y gastric bypass surgery on fasting and postprandial concentrations of plasma ghrelin, peptide YY, and insulin. J Clin Endocrinol Metab. 2005;90:359–65.

    Article  PubMed  CAS  Google Scholar 

  62. Korner J, Inabnet W, Conwell IM, et al. Differential effects of gastric bypass and banding on circulating gut hormone and leptin levels. Obesity (Silver Spring). 2006;14:1553–61.

    Article  CAS  Google Scholar 

  63. Morinigo R, Vidal J, Lacy AM, et al. Circulating peptide YY, weight loss, and glucose homeostasis after gastric bypass surgery in morbidly obese subjects. Ann Surg. 2008;247:270–5.

    Article  PubMed  Google Scholar 

  64. Martins C, Kjelstrup L, Mostad IL, et al. Impact of sustained weight loss achieved through Roux-en-Y gastric bypass or a lifestyle intervention on ghrelin, obestatin, and ghrelin/obestatin ratio in morbidly obese patients. Obes Surg. 2011;21:751–8.

    Article  PubMed  Google Scholar 

  65. Sundbom M, Holdstock C, Engstrom BE, et al. Early changes in ghrelin following Roux-en-Y gastric bypass: influence of vagal nerve functionality? Obes Surg. 2007;17:304–10.

    Article  PubMed  Google Scholar 

  66. Moran TH. Cholecystokinin and satiety: current perspectives. Nutrition. 2000;16:858–65.

    Article  PubMed  CAS  Google Scholar 

  67. Tadross JA, le Roux CW. The mechanisms of weight loss after bariatric surgery. Int J Obes (Lond). 2009;33 Suppl 1:S28–32.

    Article  Google Scholar 

  68. Kellum JM, Kuemmerle JF, O'Dorisio TM, et al. Gastrointestinal hormone responses to meals before and after gastric bypass and vertical banded gastroplasty. Ann Surg. 1990;211:763–70.

    Article  PubMed  CAS  Google Scholar 

  69. Rubino F, Gagner M, Gentileschi P, et al. The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism. Ann Surg. 2004;240:236–42.

    Article  PubMed  Google Scholar 

  70. Schrumpf E, Giercksky KE, Nygaard K, et al. Gastrin secretion before and after gastric bypass surgery for morbid obesity. Scand J Gastroenterol. 1981;16:721–5.

    Article  PubMed  CAS  Google Scholar 

  71. Schrumpf E, Bergan A, Djoseland O, et al. The effect of gastric bypass operation on glucose tolerance in obesity. Scand J Gastroenterol Suppl. 1985;107:24–31.

    Article  PubMed  CAS  Google Scholar 

  72. Padoin AV, Galvao NM, Moretto M, et al. Obese patients with type 2 diabetes submitted to banded gastric bypass: greater incidence of dumping syndrome. Obes Surg. 2009;19:1481–4.

    Article  PubMed  Google Scholar 

  73. Thorell A, Nygren J, Ljungqvist O. Insulin resistance: a marker of surgical stress. Curr Opin Clin Nutr Metab Care. 1999;2:69–78.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors are indebted to the patients for their willingness to participate in this study. The authors also appreciate the technical assistance of Alis Andersen and Sussi Polmann (Hvidovre University Hospital, Copenhagen, Denmark), Lene Albak and Sofie Pilgaard (Department of Biomedical Sciences, the Panum Institute, University of Copenhagen, Denmark), Alice Lieth and Rikke Kröncke (Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark), and Gitte Kølander Hansen and Vibeke Nielsen (Novo Nordisk, Måløv, Denmark).

Conflicts of Interest

BSW and TRC are employed at Novo Nordisk and NBJ and SHJ are receiving funds to cover one third of their scholarships from Novo Nordisk. No other potential conflicts of interest relevant to this article were declared by any of the authors: SHJ, SCO, CD, NBJ, KNB, UK, DW, TA, LSN, LEH, JFR, BSW, TRC, DLH, JJH, and SM.

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Jacobsen, S.H., Olesen, S.C., Dirksen, C. et al. Changes in Gastrointestinal Hormone Responses, Insulin Sensitivity, and Beta-Cell Function Within 2 Weeks After Gastric Bypass in Non-diabetic Subjects. OBES SURG 22, 1084–1096 (2012). https://doi.org/10.1007/s11695-012-0621-4

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