The Korean Journal of Medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지
DOI QR코드

DOI QR Code

Mechanism of Weight Loss and Diabetes Remission after Bariatric/Metabolic Surgery

비만/대사 수술이 체중 감소와 당뇨병 관해를 일으키는 기전

  • Cho, Young Min (Department of Internal Medicine, Seoul National University College of Medicine)
  • 조영민 (서울대학교 의과대학 내과학교실)
  • Published : 2013.05.01
⟨ Previous Next ⟩

Abstract

The greatest achievement in the treatment of obesity and diabetes would be the development of bariatric/metabolic surgery. At the beginning, bariatric surgeries were developed to simply reduce body weight in morbidly obese subjects. Before long, it was discovered that diabetes and other metabolic complications of obesity could be placed in remission. The remission rate of diabetes after bariatric surgery is strikingly high and, in the case of Roux-en-Y gastric bypass surgery, diabetes remission commonly occurs immediately after the surgery, when significant weight loss does not take place. Therefore, the concept of bariatric surgery has evolved into metabolic surgery. Physiologic changes in gastrointestinal endocrine system following the anatomical changes made by bariatric/metabolic surgery are regarded as the major mechanisms of weight loss and diabetes remission. In this regard, the foregut and hindgut hypotheses were suggested as the mechanisms associated with diabetes remission. With the advent of sleeve gastrectomy, which does not bypass the foregut (duodenum and proximal jejunum) but increases the secretion of glucagon-like peptide-1, the foregut hypothesis is currently under attack. However, a single mechanism is not enough to explain the metabolic effect of bariatric/metabolic surgery. Further studies are warranted to elucidate the mechanisms of metabolic improvements after bariatric/metabolic surgery.

Keywords

References

  1. Eckel RH. Clinical practice: nonsurgical management of obesity in adults. N Engl J Med 2008;358:1941-1950. https://doi.org/10.1056/NEJMcp0801652
  2. Harris MI, Hadden WC, Knowler WC, Bennett PH. Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in U.S. population aged 20-74 yr. Diabetes 1987;36:523-534. https://doi.org/10.2337/diab.36.4.523
  3. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444:840-846. https://doi.org/10.1038/nature05482
  4. Unger RH, Scherer PE. Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity. Trends Endocrinol Metab 2010;21:345-352. https://doi.org/10.1016/j.tem.2010.01.009
  5. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403. https://doi.org/10.1056/NEJMoa012512
  6. Gregg EW, Chen H, Wagenknecht LE, et al. Association of an intensive lifestyle intervention with remission of type 2 diabetes. JAMA 2012;308:2489-2496. https://doi.org/10.1001/jama.2012.67929
  7. 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; 222:339-350. https://doi.org/10.1097/00000658-199509000-00011
  8. Sjostrom L, Lindroos AK, Peltonen M, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004;351:2683-2693. https://doi.org/10.1056/NEJMoa035622
  9. Carlsson LM, Peltonen M, Ahlin S, et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med 2012;367:695-704. https://doi.org/10.1056/NEJMoa1112082
  10. Sjostrom L, Peltonen M, Jacobson P, et al. Bariatric surgery and long-term cardiovascular events. JAMA 2012;307:56-65. https://doi.org/10.1001/jama.2011.1914
  11. Sjostrom L, Gummesson A, Sjostrom CD, et al. Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial. Lancet Oncol 2009;10:653- https://doi.org/10.1016/S1470-2045(09)70159-7
  12. Sjostrom L, Narbro K, Sjostrom CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007;357:741-752. https://doi.org/10.1056/NEJMoa066254
  13. Karlsson J, Taft C, Rydén A, Sjostrom L, Sullivan M. Ten-year trends in health-related quality of life after surgical and conventional treatment for severe obesity: the SOS Intervention Study. Int J Obes (Lond) 2007;31:1248-1261. https://doi.org/10.1038/sj.ijo.0803573
  14. Cho YM, Kieffer TJ. K-cells and glucose-dependent insulinotropic polypeptide in health and disease. Vitam Horm 2010;84:111-150. https://doi.org/10.1016/B978-0-12-381517-0.00004-7
  15. Cho YM, Merchant CE, Kieffer TJ. Targeting the glucagon receptor family for diabetes and obesity therapy. Pharmacol Ther 2012;135:247-278. https://doi.org/10.1016/j.pharmthera.2012.05.009
  16. 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; 211:763-770. https://doi.org/10.1097/00000658-199006000-00016
  17. Pappas TN. Physiological satiety implications of gastrointestinal antiobesity surgery. Am J Clin Nutr 1992;55(2 Suppl):571S-572S. https://doi.org/10.1093/ajcn/55.2.571s
  18. Hickey MS, Pories WJ, MacDonald KG Jr, et al. A new paradigm for type 2 diabetes mellitus: could it be a disease of the foregut? Ann Surg 1998;227:637-643. https://doi.org/10.1097/00000658-199805000-00004
  19. Stoeckli R, Chanda R, Langer I, Keller U. Changes of body weight and plasma ghrelin levels after gastric banding and gastric bypass. Obes Res 2004;12:346-350. https://doi.org/10.1038/oby.2004.43
  20. Mason EE, Ito C. Gastric bypass. Ann Surg 1969;170: 329-339. https://doi.org/10.1097/00000658-196909010-00003
  21. Cummings DE, Overduin J, Foster-Schubert KE. Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution. J Clin Endocrinol Metab 2004;89:2608-2615. https://doi.org/10.1210/jc.2004-0433
  22. Halmi KA, Mason E, Falk JR, Stunkard A. Appetitive behavior after gastric bypass for obesity. Int J Obes 1981; 5:457-464.
  23. Wickremesekera K, Miller G, Naotunne TD, Knowles G, Stubbs RS. Loss of insulin resistance after Roux-en-Y gastric bypass surgery: a time course study. Obes Surg 2005;15: 474-481. https://doi.org/10.1381/0960892053723402
  24. Dixon JB, O'Brien PE, Playfair J, et al. Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial. JAMA 2008;299:316-323.
  25. 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;33:1438-1442. https://doi.org/10.2337/dc09-2107
  26. Lingvay I, Guth E, Islam A, Livingston E. Rapid improvement of diabetes after gastric bypass surgery: is it the diet or surgery? Diabetes Care 2013 Mar 25 [Epub]. http://dx.doi. org/10.2337/dc12-2316.
  27. 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. https://doi.org/10.1007/s11605-009-1060-y
  28. Bradley D, Conte C, Mittendorfer B, et al. Gastric bypass and banding equally improve insulin sensitivity and ${\beta}$ cell function. J Clin Invest 2012;122:4667-4674. https://doi.org/10.1172/JCI64895
  29. Dirksen C, Jorgensen NB, Bojsen-Moller KN, et al. Mechanisms of improved glycaemic control after Roux-en-Y gastric bypass. Diabetologia 2012;55:1890-1901. https://doi.org/10.1007/s00125-012-2556-7
  30. 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;346:1623-1630. https://doi.org/10.1056/NEJMoa012908
  31. Thaler JP, Cummings DE. Minireview: hormonal and metabolic mechanisms of diabetes remission after gastrointestinal surgery. Endocrinology 2009;150:2518-2525. https://doi.org/10.1210/en.2009-0367
  32. Peterli R, Steinert RE, Woelnerhanssen B, et al. Metabolic and hormonal changes after laparoscopic Roux-en-lllY gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg 2012;22:740-748. https://doi.org/10.1007/s11695-012-0622-3
  33. Chambers AP, Kirchner H, Wilson-Perez HE, et al. The effects of vertical sleeve gastrectomy in rodents are ghrelin independent. Gastroenterology 2013;144:50-52. e5. https://doi.org/10.1053/j.gastro.2012.09.009
  34. Overduin J, Frayo RS, Grill HJ, Kaplan JM, Cummings DE. Role of the duodenum and macronutrient type in ghrelin regulation. Endocrinology 2005;146:845-850. https://doi.org/10.1210/en.2004-0609
  35. Rubino F. Is type 2 diabetes an operable intestinal disease? a provocative yet reasonable hypothesis. Diabetes Care 2008;31(Suppl 2):S290-296. https://doi.org/10.2337/dc08-s271
  36. Rubino F, Marescaux J. Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease. Ann Surg 2004;239:1-11. https://doi.org/10.1097/01.sla.0000102989.54824.fc
  37. Rubino F, Forgione A, Cummings DE, et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg 2006;244:741-749. https://doi.org/10.1097/01.sla.0000224726.61448.1b
  38. Speck M, Cho YM, Asadi A, Rubino F, Kieffer TJ. Duodenal-jejunal bypass protects GK rats from {beta}-cell loss and aggravation of hyperglycemia and increases enteroendocrine cells coexpressing GIP and GLP-1. Am J Physiol Endocrinol Metab 2011;300:E923-932. https://doi.org/10.1152/ajpendo.00422.2010
  39. 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;33:375-377. https://doi.org/10.2337/dc09-1374
  40. Aguirre V, Stylopoulos N, Grinbaum R, Kaplan LM. An endoluminal sleeve induces substantial weight loss and normalizes glucose homeostasis in rats with diet-induced obesity. Obesity (Silver Spring) 2008;16:2585-2592. https://doi.org/10.1038/oby.2008.502
  41. Milone L, Gagner M, Ueda K, Bardaro SJ, Ki-Young Y. Effect of a polyethylene endoluminal duodeno-jejunal tube (EDJT) on weight gain: a feasibility study in a porcine model. Obes Surg 2006;16:620-626. https://doi.org/10.1381/096089206776944977
  42. Rodriguez-Grunert L, Galvao Neto MP, Alamo M, Ramos AC, Baez PB, Tarnoff M. First human experience with endoscopically delivered and retrieved duodenal-jejunal bypass sleeve. Surg Obes Relat Dis 2008;4:55-59. https://doi.org/10.1016/j.soard.2007.07.012
  43. Klein S, Fabbrini E, Patterson BW, et al. Moderate effect of duodenal-jejunal bypass surgery on glucose homeostasis in patients with type 2 diabetes. Obesity (Silver Spring) 2012; 20:1266-1272. https://doi.org/10.1038/oby.2011.377
  44. Lee HC, Kim MK, Kwon HS, Kim E, Song KH. Early changes in incretin secretion after laparoscopic duodenaljejunal bypass surgery in type 2 diabetic patients. Obes Surg 2010;20:1530-1535. https://doi.org/10.1007/s11695-010-0248-2
  45. Ramos AC, Galvao Neto MP, de Souza YM, et al. Laparoscopic duodenal-jejunal exclusion in the treatment of type 2 diabetes mellitus in patients with BMI < 30 kg/$m^2$ (LBMI). Obes Surg 2009;19:307-312. https://doi.org/10.1007/s11695-008-9759-5
  46. Geloneze B, Geloneze SR, Chaim E, et al. Metabolic surgery for non-obese type 2 diabetes: incretins, adipocytokines, and insulin secretion/resistance changes in a 1-year interventional clinical controlled study. Ann Surg 2012; 256:72-78. https://doi.org/10.1097/SLA.0b013e3182592c62
  47. Kindel TL, Yoder SM, Seeley RJ, D'Alessio DA, Tso P. Duodenal-jejunal exclusion improves glucose tolerance in the diabetic, Goto-Kakizaki rat by a GLP-1 receptormediated mechanism. J Gastrointest Surg 2009;13:1762-1772. https://doi.org/10.1007/s11605-009-0912-9
  48. Breen DM, Rasmussen BA, Kokorovic A, Wang R, Cheung GW, Lam TK. Jejunal nutrient sensing is required for duodenal-jejunal bypass surgery to rapidly lower glucose concentrations in uncontrolled diabetes. Nat Med 2012;18: 950-955. https://doi.org/10.1038/nm.2745
  49. De Gordejuela AG, Pujol Gebelli J, Garcia NV, Alsina EF, Medayo LS, Masdevall Noguera C. Is sleeve gastrectomy as effective as gastric bypass for remission of type 2 diabetes in morbidly obese patients? Surg Obes Relat Dis 2011;7: 506-509. https://doi.org/10.1016/j.soard.2011.01.003
  50. Jimenez A, Casamitjana R, Flores L, et al. Long-term effects of sleeve gastrectomy and Roux-en-Y gastric bypass surgery on type 2 diabetes mellitus in morbidly obese subjects. Ann Surg 2012;256:1023-1029. https://doi.org/10.1097/SLA.0b013e318262ee6b
  51. Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med 2012;366:1567-1576. https://doi.org/10.1056/NEJMoa1200225
  52. Holst JJ. Glucagonlike peptide 1: a newly discovered gastrointestinal hormone. Gastroenterology 1994;107: 1848-1855. https://doi.org/10.1016/0016-5085(94)90831-1
  53. 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;95:4072-4076. https://doi.org/10.1210/jc.2009-2767
  54. Jimenez A, Casamitjana R, Viaplana-Masclans J, Lacy A, Vidal J. GLP-1 action and glucose tolerance in subjects with remission of type 2 diabetes mellitus after gastric bypass surgery. Diabetes Care 2013 Jan 28 [Epub]. http://dx.doi.org/10.2337/dc12-1535.
  55. Salinari S, Bertuzzi A, Asnaghi S, Guidone C, Manco M, Mingrone G. First-phase insulin secretion restoration and differential response to glucose load depending on the route of administration in type 2 diabetic subjects after bariatric surgery. Diabetes Care 2009;32:375-380. https://doi.org/10.2337/dc08-1314
  56. 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: 462-471. https://doi.org/10.1038/ijo.2009.254
  57. Romero F, Nicolau J, Flores L, et al. Comparable early changes in gastrointestinal hormones after sleeve gastrectomy and Roux-En-Y gastric bypass surgery for morbidly obese type 2 diabetic subjects. Surg Endosc 2012;26:2231-2239. https://doi.org/10.1007/s00464-012-2166-y
  58. Basso N, Capoccia D, Rizzello M, et al. First-phase insulin secretion, insulin sensitivity, ghrelin, GLP-1, and PYY changes 72 h after sleeve gastrectomy in obese diabetic patients: the gastric hypothesis. Surg Endosc 2011;25: 3540-3550. https://doi.org/10.1007/s00464-011-1755-5
  59. Shah S, Shah P, Todkar J, Gagner M, Sonar S, Solav S. Prospective controlled study of effect of laparoscopic sleeve gastrectomy on small bowel transit time and gastric emptying half-time in morbidly obese patients with type 2 diabetes mellitus. Surg Obes Relat Dis 2010;6:152-157. https://doi.org/10.1016/j.soard.2009.11.019
  60. Patriti A, Aisa MC, Annetti C, et al. How the hindgut can cure type 2 diabetes. Ileal transposition improves glucose metabolism and beta-cell function in Goto-kakizaki rats through an enhanced Proglucagon gene expression and L-cell number. Surgery 2007;142:74-85. https://doi.org/10.1016/j.surg.2007.03.001
  61. Strader AD, Vahl TP, Jandacek RJ, Woods SC, D'Alessio DA, Seeley RJ. Weight loss through ileal transposition is accompanied by increased ileal hormone secretion and synthesis in rats. Am J Physiol Endocrinol Metab 2005; 288:E447-453. https://doi.org/10.1152/ajpendo.00153.2004
  62. Wang TT, Hu SY, Gao HD, et al. Ileal transposition controls diabetes as well as modified duodenal jejunal bypass with better lipid lowering in a nonobese rat model of type II diabetes by increasing GLP-1. Ann Surg 2008;247:968-975. https://doi.org/10.1097/SLA.0b013e318172504d
  63. Culnan DM, Albaugh V, Sun M, Lynch CJ, Lang CH, Cooney RN. Ileal interposition improves glucose tolerance and insulin sensitivity in the obese Zucker rat. Am J Physiol Gastrointest Liver Physiol 2010;299:G751-760. https://doi.org/10.1152/ajpgi.00525.2009
  64. Ikezawa F, Shibata C, Kikuchi D, et al. Effects of ileal interposition on glucose metabolism in obese rats with diabetes. Surgery 2012;151:822-830. https://doi.org/10.1016/j.surg.2011.12.026
  65. Strader AD. Ileal transposition provides insight into the effectiveness of gastric bypass surgery. Physiol Behav 2006;88:277-282. https://doi.org/10.1016/j.physbeh.2006.05.034
  66. DePaula AL, Macedo AL, Rassi N, et al. Laparoscopic treatment of metabolic syndrome in patients with type 2 diabetes mellitus. Surg Endosc 2008;22:2670-2678. https://doi.org/10.1007/s00464-008-9808-0
  67. Kim MK, Lee HC, Lee SH, et al. The difference of glucostatic parameters according to the remission of diabetes after Roux-en-Y gastric bypass. Diabetes Metab Res Rev 2012;28:439-446. https://doi.org/10.1002/dmrr.2297
  68. Heo YS, Park JM, Kim YJ, et al. Bariatric surgery versus conventional therapy in obese Korea patients: a multicenter retrospective cohort study. J Korean Surg Soc 2012;83: 335-342. https://doi.org/10.4174/jkss.2012.83.6.335
  69. Jorgensen NB, Jacobsen SH, Dirksen C, et al. Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with Type 2 diabetes and normal glucose tolerance. Am J Physiol Endocrinol Metab 2012; 303:E122-131. https://doi.org/10.1152/ajpendo.00073.2012

Cited by

  1. Effect and Mechanisms of Diabetes Resolution According to the Range of Gastric Resection and the Length of Anastomosis in Animal Models: Implication for Gastric Cancer Surgery in Patients with Diabete vol.42, pp.4, 2018, https://doi.org/10.1007/s00268-017-4228-8
  2. Less Invasive Bariatric/Metabolic Procedures for Weight Reduction and Glucose Control vol.29, pp.2, 2013, https://doi.org/10.7570/jomes20019