Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Metabolic surgery: the role of the gastrointestinal tract in diabetes mellitus

Nature Reviews Endocrinology volume 6, pages 102–109 (2010)Cite this article

Subjects

Abstract

Several conventional methods of bariatric surgery can induce long-term remission of type 2 diabetes mellitus (T2DM); novel gastrointestinal surgical procedures are reported to have similar effects. These procedures also dramatically improve other metabolic conditions, including hyperlipidemia and hypertension, in both obese and nonobese patients. Several studies have provided evidence that these metabolic effects are not simply the results of drastic weight loss and decreased caloric intake but might be attributable, in part, to endocrine changes resulting from surgical manipulation of the gastrointestinal tract. In this Review, we provide an overview of the clinical evidence that demonstrates the effects of such interventions—termed metabolic surgery—on T2DM and discuss the implications for future research. In light of the evidence presented here, we speculate that the gastrointestinal tract might have a role in the pathophysiology of T2DM and obesity.

Key Points

  • Conventional and novel bariatric surgeries induce long-term remission of type 2 diabetes mellitus (T2DM) and dramatically improve other metabolic conditions, including hyperlipidemia and hypertension

  • Animal studies and clinical investigations show that the effects of surgery on T2DM might be partly explained by endocrine changes that result from surgical manipulation of the gastrointestinal tract

  • Current BMI-based criteria for patient selection are not sufficiently inclusive to define indications for surgical treatment and evaluation of the risk profile of patients with T2DM

  • Randomized, controlled trials that compare surgery with medical treatment should aim to define the role of surgery in the management of T2DM and identify new criteria for selection

  • Research into the mechanisms of action of metabolic surgery represents an extraordinary opportunity to improve our understanding of the pathophysiology of T2DM and ultimately improve its treatment

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Conventional bariatric operations.
Figure 2: Novel methods of metabolic surgery.
Figure 3: Hypothetical role of nutrient-stimulated GI dysfunction in T2DM.

Similar content being viewed by others

References

  1. Buchwald, H. et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 292, 1724–1737 (2004).

    Article  CAS  PubMed  Google Scholar 

  2. Cohen, R., Pinheiro, J. S., Correa, J. L. & Schiavon, C. A. Laparoscopic Roux-en-Y gastric bypass for BMI <35 kg/m2: a tailored approach. Surg. Obes. Relat. Dis. 2, 401–404 (2006).

    Article  PubMed  Google Scholar 

  3. Lee, W. J. et al. Effect of laparoscopic mini-gastric bypass for type 2 diabetes mellitus: comparison of BMI >35 and <35 kg/m2. J. Gastrointest. Surg. 12, 945–952 (2008).

    Article  PubMed  Google Scholar 

  4. O'Brien, P. E. et al. Treatment of mild to moderate obesity with laparoscopic adjustable gastric banding or an intensive medical program: a randomized trial. Ann. Intern. Med. 144, 625–633 (2006).

    Article  PubMed  Google Scholar 

  5. Suter, M., Calmes, J. M., Paroz, A. Romy, A. & Giusti, V. Results of Roux-en-Y gastric bypass in morbidly obese vs super obese patients: similar body weight loss, correction of comorbidities, and improvement of quality of life. Arch. Surg. 144, 312–318 (2009).

    Article  PubMed  Google Scholar 

  6. Thaler, J. P. & Cummings, D. E. Hormonal and metabolic mechanisms of diabetes remission after gastrointestinal surgery. Endocrinology 150, 2518–2525 (2009).

    Article  CAS  PubMed  Google Scholar 

  7. Sjöström, L. et al. Swedish Obese Subjects Study Scientific Group. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N. Engl. J. Med. 351, 2683–2693 (2004).

    Article  PubMed  Google Scholar 

  8. Dixon, J. B. et al. Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial. JAMA 299, 316–323 (2008).

    CAS  PubMed  Google Scholar 

  9. Pories, W. J. et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann. Surg. 222, 339–350 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Schauer, P. R. et al. Effect of laparoscopic Roux-en-Y gastric bypass on type 2 diabetes mellitus. Ann. Surg. 238, 467–484 (2003).

    PubMed  PubMed Central  Google Scholar 

  11. Scopinaro, N. Biliopancreatic diversion: mechanisms of action and long-term results. Obes. Surg. 16, 683–689 (2006).

    Article  PubMed  Google Scholar 

  12. Vidal, J. et al. Type 2 diabetes mellitus and the metabolic syndrome following sleeve gastrectomy in severely obese subjects. Obes. Surg. 18, 1077–1082 (2008).

    Article  CAS  PubMed  Google Scholar 

  13. Gan, S. S., Talbot, M. L. & Jorgensen, J. O. Efficacy of surgery in the management of obesity-related type 2 diabetes mellitus. ANZ J. Surg. 77, 958–962 (2007).

    Article  PubMed  Google Scholar 

  14. Chiellini, C., Rubino, F., Castagneto, M., Nanni, G. & Mingrone, G. The effect of bilio-pancreatic diversion on type 2 diabetes in patients with BMI <35 kg/m2. Diabetologia 52, 1027–1030 (2009).

    Article  CAS  PubMed  Google Scholar 

  15. Noya, G. et al. Biliopancreatic diversion preserving the stomach and pylorus in the treatment of hypercholesterolemia and diabetes type II: results in the first 10 cases. Obes. Surg. 8, 67–72 (1998).

    Article  CAS  PubMed  Google Scholar 

  16. Scopinaro, N., Marinari, G. M., Camerini, G. B., Papadia, F. S. & Adami, G. F. Specific effects of biliopancreatic diversion on the major components of metabolic syndrome: a long-term follow-up study. Diabetes Care 28, 2406–2411 (2005).

    Article  PubMed  Google Scholar 

  17. Cohen, R. V., Schiavon, C. A., Pinheiro, J. S., Correa, J. L. & Rubino, F. Duodenal–jejunal bypass for the treatment of type 2 diabetes in patients with body mass index of 22–34 kg/m2: a report of 2 cases. Surg. Obes. Relat. Dis. 3, 195–197 (2007).

    Article  PubMed  Google Scholar 

  18. Ramos, A. C. et al. Laparoscopic duodenal–jejunal exclusion in the treatment of type 2 diabetes mellitus in patients with BMI <30 kg/m² (LBMI). Obes. Surg. 19, 307–312 (2009).

    Article  PubMed  Google Scholar 

  19. Ferzli, G. S. et al. Clinical improvement after duodenojejunal bypass for non obese type 2 diabetes despite minimal improvement in glycemic homeostasis. World J. Surg. 33, 972–979 (2009).

    Article  CAS  PubMed  Google Scholar 

  20. DePaula, A. L. et al. Laparoscopic treatment of type 2 diabetes mellitus for patients with a body mass index less than 35. Surg. Endosc. 22, 706–716 (2008).

    Article  CAS  PubMed  Google Scholar 

  21. DePaula, A. L., Macedo, A. L., Mota, B. R. & Schraibman, V. Laparoscopic ileal interposition associated to a diverted sleeve gastrectomy is an effective operation for the treatment of type 2 diabetes mellitus patients with BMI 21–29. Surg. Endosc. 23, 1313–1320 (2009).

    Article  CAS  PubMed  Google Scholar 

  22. Aguirre, V., Stylopoulos, N., Grinbaum, R. & Kaplan, L. M. An endoluminal sleeve induces substantial weight loss and normalizes glucose homeostasis in rats with diet-induced obesity. Obesity 16, 2585–2592 (2008).

    Article  CAS  PubMed  Google Scholar 

  23. Rodriguez-Grunert, L. et al. First human experience with endoscopically delivered and retrieved duodenal–jejunal bypass sleeve. Surg. Obes. Relat. Dis. 4, 55–59 (2008).

    Article  PubMed  Google Scholar 

  24. MacDonald, K. G. Jr et al. The gastric bypass operation reduces the progression and mortality of non-insulin-dependent diabetes mellitus. J. Gastrointest. Surg. 1, 213–220 (1997).

    Article  PubMed  Google Scholar 

  25. Flum, D. R. & Dellinger, E. P. Impact of gastric bypass operation on survival: a population-based analysis. J. Am. Coll. Surg. 199, 543–551 (2004).

    Article  PubMed  Google Scholar 

  26. Christou, N. V. et al. Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients. Ann. Surg. 240, 416–423 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Sowemimo, O. A. et al. Natural history of morbid obesity without surgical intervention. Surg. Obes. Relat. Dis. 3, 73–77 (2007).

    Article  PubMed  Google Scholar 

  28. Peeters, A. et al. Substantial intentional weight loss and mortality in the severely obese. Ann. Surg. 246, 1028–1033 (2007).

    Article  PubMed  Google Scholar 

  29. Perry, C. D., Hutter, M. M., Smith, D. B., Newhouse, J. P. & McNeil, B. J. Survival and changes in comorbidities after bariatric surgery. Ann. Surg. 247, 21–27 (2008).

    Article  PubMed  Google Scholar 

  30. Adams, T. D. et al. Long-term mortality after gastric bypass surgery. N. Engl. J. Med. 357, 753–761 (2007).

    Article  CAS  PubMed  Google Scholar 

  31. Sjöström, L. et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N. Engl. J. Med. 357, 741–752 (2007).

    Article  PubMed  Google Scholar 

  32. Buchwald, H., Estok, R., Fahrbach, K., Bane, D. & Sledge, I. Trends in mortality in bariatric surgery: a systematic review and meta-analysis. Surgery 142, 621–632 (2007).

    Article  PubMed  Google Scholar 

  33. Wittgrove, A. C. & Clark, G. W. Laparoscopic gastric bypass, Roux-en-Y 500 patients: technique and results, with 3–60 month follow-up. Obes. Surg. 10, 233–239 (2000).

    Article  CAS  PubMed  Google Scholar 

  34. Morínigo, R. et al. GLP-1 and changes in glucose tolerance following gastric bypass surgery in morbidly obese subjects. Obes. Surg. 16, 1594–1601 (2006).

    Article  PubMed  Google Scholar 

  35. Wickremesekera, K., Miller, G., Naotunne, T. D., Knowles, G. & Stubbs, R. S. Loss of insulin resistance after Roux-en-Y gastric bypass surgery: a time course study. Obes. Surg. 15, 474–481 (2005).

    Article  PubMed  Google Scholar 

  36. Pontiroli, A. E. et al. Laparoscopic gastric banding prevents type 2 diabetes and arterial hypertension and induces their remission in morbid obesity: a 4-year case-controlled study. Diabetes Care 28, 2703–2709 (2005).

    Article  PubMed  Google Scholar 

  37. LABS Consortium. Perioperative safety in the longitudinal assessment of bariatric surgery. N. Engl. J. Med. 361, 445–454 (2009).

  38. Khuri, S. F. et al. Comparison of surgical outcomes between teaching and non-teaching hospitals in the Department of Veterans Affairs. Ann. Surg. 234, 370–382 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Encinosa, W. E., Bernard, D. M., Du, D. & Steiner, C. A. Recent improvements in bariatric surgery outcomes. Med. Care 47, 531–535 (2009).

    Article  PubMed  Google Scholar 

  40. Nguyen, N. T., Hinojosa, M., Fayad, C., Varela, E. & Wilson, S. E. Use and outcomes of laparoscopic versus open gastric bypass at academic and medical centers. J. Am. Coll. Surg. 205, 248–255 (2007).

    Article  PubMed  Google Scholar 

  41. Han, S. H. et al. Improved outcomes using a systematic and evidence based approach to the laparoscopic Roux-en-Y gastric bypass in a single academic institution. Am. Surg. 73, 955–958 (2007).

    PubMed  Google Scholar 

  42. Mari, A. et al. Restoration of normal glucose tolerance in severely obese patients after bilio-pancreatic diversion: role of insulin sensitivity and beta cell function. Diabetologia 49, 2136–2143 (2006).

    Article  CAS  PubMed  Google Scholar 

  43. Patti, M. E. et al. Severe hypoglycaemia post-gastric bypass requiring partial pancreatectomy: evidence for inappropriate insulin secretion and pancreatic islet hyperplasia. Diabetologia 48, 2236–2240 (2005).

    Article  CAS  PubMed  Google Scholar 

  44. Polyzogopoulou, E. V., Kalfarentzos, F., Vagenakis, A. G. & Alexandrides, T. K. Restoration of euglycemia and normal acute insulin response to glucose in obese subjects with type 2 diabetes following bariatric surgery. Diabetes 52, 1098–1103 (2003).

    Article  CAS  PubMed  Google Scholar 

  45. Laferrère, B. 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. 93, 2479–2485 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  46. 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. 239, 1–11 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Kindel, T. L., Yoder, S. M., Seeley, R. J., D'Alessio, D. A. & Tso, P. Duodenal–jejunal exclusion improves glucose tolerance in the diabetic, Goto-Kakizaki rat by a GLP-1 receptor-mediated mechanism. J. Gastrointest. Surg. 13, 1762–1772 (2009).

    Article  PubMed  Google Scholar 

  48. Pacheco, D. et al. The effects of duodenal–jejunal exclusion on hormonal regulation of glucose metabolism in Goto-Kakizaki rats. Am. J. Surg. 194, 221–224 (2007).

    Article  CAS  PubMed  Google Scholar 

  49. Wang, T. T. 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. 247, 968–975 (2008).

    Article  PubMed  Google Scholar 

  50. Troy, S. et al. Intestinal gluconeogenesis is a key factor for early metabolic changes after gastric bypass but not after gastric lap-band in mice. Cell. Metab. 8, 201–211 (2008).

    Article  CAS  PubMed  Google Scholar 

  51. Strader, A. D., Clausen, T. R., Goodin, S. Z. & Wendt, D. Ileal interposition improves glucose tolerance in low dose streptozotocin-treated diabetic and euglycemic rats. Obes. Surg. 19, 96–104 (2009).

    Article  PubMed  Google Scholar 

  52. Pattou, F. et al. Restoration of beta cell function after bariatric surgery in type 2 diabetes patients: A prospective controlled study comparing gastric banding and gastric bypass. Obes. Surg. 17, 1041–1043 (2007).

    Google Scholar 

  53. Pattou, F. et al. Catering of insulin secretion after a gastric bypass in type 2 diabetes is independent from weight loss and correlated to the increase of GLP. Diabetes Metab. 34, A23 (2008).

    Article  Google Scholar 

  54. Cummings, D. E., Overduin, J., Foster-Schubert, K. E. & Carlson, M. J. Role of the bypassed proximal intestine in the anti-diabetic effects of bariatric surgery. Surg. Obes. Relat. Dis. 3, 109–115 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Moo, T. A. & Rubino, F. Gastrointestinal surgery as treatment for type 2 diabetes. Curr. Opin. Endocrinol. Diabetes Obes. 15, 153–158 (2008).

    Article  PubMed  Google Scholar 

  56. Damholt, A. B., Buchan, A. M. & Kofod, H. Glucagon-like-peptide-1 secretion from canine L-cells is increased by glucose-dependent-insulinotropic peptide but unaffected by glucose. Endocrinology 139, 2085–2091 (1998).

    Article  CAS  PubMed  Google Scholar 

  57. Rubino, F. et al. The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism. Ann. Surg. 2, 236–242 (2004).

    Article  Google Scholar 

  58. le Roux, C. W. et al. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann. Surg. 243, 108–114 (2006).

    Article  PubMed  Google Scholar 

  59. le Roux, C. W. et al. Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass. Ann. Surg. 246, 780–785 (2007).

    Article  PubMed  Google Scholar 

  60. Korner, J. et al. Differential effects of gastric bypass and banding on circulating gut hormone and leptin levels. Obesity 14, 1553–1561 (2006).

    Article  CAS  PubMed  Google Scholar 

  61. Korner, J. 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. 90, 359–365 (2005).

    Article  CAS  PubMed  Google Scholar 

  62. Cummings, D. E. et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N. Engl. J. Med. 346, 1623–1630 (2002).

    Article  PubMed  Google Scholar 

  63. Laferrère, B. 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 30, 1709–1716 (2007).

    Article  PubMed  Google Scholar 

  64. NIH Conference. Gastrointestinal surgery for severe obesity. Consensus Development Conference Panel. Ann. Intern. Med. 115, 956–961 (1991).

  65. Pasarica, M. & Dhurandhar, N. V. Infectobesity: obesity of infectious origin. Adv. Food Nutr. Res. 52, 61–102 (2007).

    Article  CAS  PubMed  Google Scholar 

  66. Burcelin, R., Luche, E., Serino, M. & Amar, J. The gut microbiota ecology: a new opportunity for the treatment of metabolic diseases? Front. Biosci. 14, 5107–5117 (2009).

    Article  CAS  Google Scholar 

  67. Lovshin, J. A. & Drucker, D. J. Incretin-based therapies for type 2 diabetes mellitus. Nat. Rev. Endocrinol. 5, 262–269 (2009).

    Article  CAS  PubMed  Google Scholar 

  68. Rubino, F. Is type 2 diabetes an operable intestinal disease? A provocative yet reasonable hypothesis. Diabetes Care. 31 (Suppl. 2), S290–S296 (2008).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Section of Gastrointestinal Metabolic Surgery, Weill Cornell Medical College/New York Presbyterian Hospital, 525 East 68th Street, P-714, New York, 10065, NY, USA

    Francesco Rubino & Federica del Genio

  2. Department of Public Health, Weill Cornell Medical College/New York Presbyterian Hospital, 525 East 68th Street, P-714, New York, 10065, NY, USA

    Sarah L. R'bibo & Madhu Mazumdar

  3. Department of Biochemistry, Weill Cornell Medical College/New York Presbyterian Hospital, 525 East 68th Street, P-714, New York, 10065, NY, USA

    Timothy E. McGraw

Authors
  1. Francesco Rubino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarah L. R'bibo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Federica del Genio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Madhu Mazumdar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Timothy E. McGraw
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francesco Rubino.

Ethics declarations

Competing interests

Francesco Rubino declares associations with the following companies: Covidien (speakers bureau), Ethicon Endo-Surgery (speakers bureau), GI Dynamics (consultant), NGM Biopharmaceuticals (consultant) and Roche (research support).

Timothy E. McGraw declares associations with the following companies: Hoffman-La Roche (research support) and Sanofi Aventis (research support).

Sarah L. R'Bibo, Federica del Genio and Madhu Mazumdar declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rubino, F., R'bibo, S., del Genio, F. et al. Metabolic surgery: the role of the gastrointestinal tract in diabetes mellitus. Nat Rev Endocrinol 6, 102–109 (2010). https://doi.org/10.1038/nrendo.2009.268

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrendo.2009.268

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing