Obesity Surgery

, Volume 27, Issue 8, pp 2090–2098 | Cite as

Common Channel Length in Bypass Surgery Does Not Impact T2DM in Diabetic Zucker Rats

  • Claudia Laessle
  • Sven Michelmichel
  • Goran Marjanovic
  • Simon Kuesters
  • Gabriel Seifert
  • Ulrich T. Hopt
  • Jodok Matthias Fink
Original Contributions



Metabolic surgery is known to impact glucose tolerance but the exact mechanism is still unclear. Based on recently-published data, especially the role of the hindgut may require redefinition.


Either a loop duodeno-jejunostomy (DJOS) with exclusion of one third of total intestinal length, a loop duodeno-ileostomy (DiOS, exclusion of two thirds), or SHAM operation was performed in 9-week-old Zucker diabetic fatty rats. One, 3, and 6 months after surgery, an oral glucose tolerance test (OGTT) and glucose-stimulated hormone analyses were conducted. Body weight was documented weekly.


DJOS and DiOS animals showed significantly better glucose control in all OGTTs than the SHAM group (two-way ANOVA p < 0.0001). Body weight developed largely parallel in both intervention groups; SHAM animals had gained significantly less weight after 6 months (Mann-Whitney DJOS/DiOS vs. SHAM p < 0.05, DJOS vs. DiOS p > 0.05). Operative interventions had no impact on GLP-1 and GIP levels at any time point (Mann-Whitney p > 0.05 for all). DJOS/DiOS operations could preserve insulin production up to 6 months, while there was already a sharp decline of insulin levels in the SHAM group (Mann-Whitney: DJOS/DiOS vs. SHAM p < 0.05 for all time points). Additionally, insulin sensitivity was improved significantly 1 month postoperative in both intervention groups compared to SHAM (Mann-Whitney DJOS/DiOS vs. SHAM p < 0.05).


The data of the current study demonstrate a sharp amelioration of glucose control after duodenal exclusion with unchanged levels of GLP-1 and GIP. Direct or delayed hindgut stimulation had no impact on glucose control in our model.


Duodeno-enterostomy Type 2 diabetes mellitus Obesity surgery Metabolic surgery 



The authors thank Silke Hempel for the outstanding work in assistance with ELISA measurements. Also, we thank Dieter Hauschke for his advice in statistical questions. Moreover, we thank Claudia Bravo and Monika Kolterjahn for the excellent work with animal care.

Compliance with Ethical Standards

All animal experimental protocols were approved by the local Animal Welfare Committee under the auspices of the responsible regional commission. All applicable institutional and national guidelines for the care and use of animals were followed.

Grant Information


Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    WHO | Obesity and overweight [Internet]. WHO. [cited 2016 Apr 19]. Available from:
  2. 2.
    WHO | Diabetes [Internet]. WHO. [cited 2016 Apr 19]. Available from:
  3. 3.
    Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3(11):e442.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Ribaric G, Buchwald JN, McGlennon TW. Diabetes and weight in comparative studies of bariatric surgery vs conventional medical therapy: a systematic review and meta-analysis. Obes Surg. 2014;24(3):437–55.CrossRefPubMedGoogle Scholar
  5. 5.
    Maggard-Gibbons M, Maglione M, Livhits M, et al. Bariatric surgery for weight loss and glycemic control in nonmorbidly obese adults with diabetes: a systematic review. JAMA. 2013;309(21):2250.CrossRefPubMedGoogle Scholar
  6. 6.
    Lee W-J, Hur KY, Lakadawala M, et al. Gastrointestinal metabolic surgery for the treatment of diabetic patients: a multi-institutional international study. J Gastrointest Surg. 2012;16(1):45–52.CrossRefPubMedGoogle Scholar
  7. 7.
    Mingrone G, Panunzi S, De Gaetano A, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012;366(17):1577–85.CrossRefPubMedGoogle Scholar
  8. 8.
    Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2012;55(6):1577–96.CrossRefPubMedGoogle Scholar
  9. 9.
    DePaula AL, Macedo ALV, Schraibman V, et al. Hormonal evaluation following laparoscopic treatment of type 2 diabetes mellitus patients with BMI 20–34. Surg Endosc. 2009;23(8):1724–32.CrossRefPubMedGoogle Scholar
  10. 10.
    Horwitz D, Saunders JK, Ude-Welcome A, Marie Schmidt A, Dunn V, Leon Pachter H, et al. Three-year follow-up comparing metabolic surgery versus medical weight management in patients with type 2 diabetes and BMI 30–35. The role of sRAGE biomarker as predictor of satisfactory outcomes. Surg Obes Relat Dis [Internet]. 2016 Jan [cited 2016 May 9]; Available from:
  11. 11.
    Scopinaro N, Camerini G, Papadia F, Andraghetti G, Cordera R, Adami GF. Long-term clinical and functional impact of biliopancreatic diversion on type 2 diabetes in morbidly and non–morbidly obese patients. Surg Obes Relat Dis [Internet]. 2015; Available from:
  12. 12.
    The American Diabetes Association’s “Standards of Medical Care in Diabetes.” Diabetes Care. 2015;38(Supplement_1):S1–2.Google Scholar
  13. 13.
    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(3):339–52.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Cummings DE, Cohen RV. Bariatric/metabolic surgery to treat type 2 diabetes in patients with a BMI & lt; 35 kg/m 2. Diabetes Care. 2016;39(6):924–33.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Schauer PR, Mingrone G, Ikramuddin S, et al. Clinical outcomes of metabolic surgery: efficacy of glycemic control, weight loss, and remission of diabetes. Diabetes Care. 2016;39(6):902–11.CrossRefPubMedGoogle Scholar
  16. 16.
    Nauck MA. Unraveling the science of incretin biology. Am J Med. 2009;122(6):S3–10.CrossRefPubMedGoogle Scholar
  17. 17.
    Rubino F, Gagner M. Potential of surgery for curing type 2 diabetes mellitus. Ann Surg. 2002;236(5):554–9.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Reimann F. Molecular mechanisms underlying nutrient detection by incretin-secreting cells. Int Dairy J. 2010;20(4):236–42.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Drucker DJ. The biology of incretin hormones. Cell Metab. 2006;3(3):153–65.CrossRefPubMedGoogle Scholar
  20. 20.
    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(2):236–42.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    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(5):741–9.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Li P, Zhu L, Wang G, Yang X, Yi B, Zhu S. The role of foregut exclusion in the deterioration of glucose and lipid metabolism induced by a high-fat diet. Diabetes Res Clin Pract [Internet]. 2016 Jan [cited 2016 Apr 19]; Available from:
  23. 23.
    Chai J, Zhang G, Liu S, et al. Exclusion of the distal ileum cannot reverse the anti-diabetic effects of duodenal-jejunal bypass surgery. Obes Surg. 2016;26(2):261–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Ren Z-Q, Zhang P-B, Zhang X-Z, et al. Duodenal-jejunal exclusion improves insulin resistance in type 2 diabetic rats by upregulating the hepatic insulin signaling pathway. Nutrition. 2015;31(5):733–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Castagneto M, Mingrone G. The effect of gastrointestinal surgery on insulin resistance and insulin secretion. Curr Atheroscler Rep. 2012;14(6):624–30.CrossRefPubMedGoogle Scholar
  26. 26.
    Hedberg J, Sundström J, Sundbom M. Duodenal switch versus Roux-en-Y gastric bypass for morbid obesity: systematic review and meta-analysis of weight results, diabetes resolution and early complications in single-centre comparisons. Obes Rev. 2014;15(7):555–63.CrossRefPubMedGoogle Scholar
  27. 27.
    Currò G, Centorrino T, Cogliandolo A, et al. A clinical and nutritional comparison of biliopancreatic diversion performed with different common and alimentary channel lengths. Obes Surg. 2015;25(1):45–9.CrossRefPubMedGoogle Scholar
  28. 28.
    De Luca M, Angrisani L, Himpens J, et al. Indications for surgery for obesity and weight-related diseases: position statements from the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO). Obes Surg. 2016;26(8):1659–96.CrossRefPubMedGoogle Scholar
  29. 29.
    Sánchez-Pernaute A, Herrera MAR, Pérez-Aguirre ME, et al. Single anastomosis duodeno–ileal bypass with sleeve gastrectomy (SADI-S). One to Three-Year Follow-up Obes Surg. 2010;20(12):1720–6.PubMedGoogle Scholar
  30. 30.
    Marjanovic G, Holzner P, Kulemann B, et al. Pitfalls and technical aspects during the research of intestinal anastomotic healing in rats. Eur Surg Res. 2010;45(3–4):314–20.CrossRefPubMedGoogle Scholar
  31. 31.
    Karcz WK, Kuesters S, Marjanovic G, et al. Duodeno-enteral omega switches—more physiological techniques in metabolic surgery. Videosurgery Miniinvasive Tech. 2013;4:273–9.CrossRefGoogle Scholar
  32. 32.
    Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9.CrossRefPubMedGoogle Scholar
  33. 33.
    Katz A, Nambi SS, Mather K, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000;85(7):2402–10.CrossRefPubMedGoogle Scholar
  34. 34.
    Pacheco D, de Luis DA, Romero A, et al. The effects of duodenal-jejunal exclusion on hormonal regulation of glucose metabolism in Goto-Kakizaki rats. Am J Surg. 2007;194(2):221–4.CrossRefPubMedGoogle Scholar
  35. 35.
    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):1–11.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Kindel TL, Yoder SM, Seeley RJ, et al. Duodenal-jejunal exclusion improves glucose tolerance in the diabetic, Goto-Kakizaki rat by a GLP-1 receptor-mediated mechanism. J Gastrointest Surg. 2009;13(10):1762–72.CrossRefPubMedGoogle Scholar
  37. 37.
    Chambers AP, Jessen L, Ryan KK, et al. Wilson–Pérez HE, Stefater MA, et al. weight-independent changes in blood glucose homeostasis after gastric bypass or vertical sleeve gastrectomy in rats. Gastroenterology. 2011;141(3):950–8.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Abegg K, Corteville C, Docherty NG, et al. Effect of bariatric surgery combined with medical therapy versus intensive medical therapy or calorie restriction and weight loss on glycemic control in Zucker diabetic fatty rats. Am J Physiol - Regul Integr Comp Physiol. 2015;308(4):R321–9.Google Scholar
  39. 39.
    Grueneberger JM, Karcz-Socha I, Sawczyn T, et al. Systematic ileal transposition in Zucker rats shows advantage for long segment distal transposition. Surgery. 2014;155(1):165–72.Google Scholar
  40. 40.
    Brethauer SA, Aminian A, Romero-Talamás H, Batayyah E, Mackey J, Kennedy L, et al. Can diabetes be surgically cured? Long-term metabolic effects of bariatric surgery in obese patients with type 2 diabetes mellitus: Ann Surg. 2013:1.Google Scholar
  41. 41.
    Shimabukuro M, Zhou Y-T, Levi M, et al. Fatty acid-induced β cell apoptosis: a link between obesity and diabetes. Proc Natl Acad Sci. 1998;95(5):2498–502.Google Scholar
  42. 42.
    Insulin Values for Obese Male ZDF Rats Fed IR Purina 5008 (Portage, MI and Kingston, NY - September 2005) [Internet]. Available from:
  43. 43.
    Weight chart for obese male ZDf rats fed IR Purina 5008 (Portage, MI and Kingstone, NY-September 2005)[Internet]. Available from:
  44. 44.
    Gumbs AA, Modlin IM, Ballantyne GH. Changes in insulin resistance following bariatric surgery: role of caloric restriction and weight loss. Obes Surg. 2005;15(4):462–73.Google Scholar
  45. 45.
    Liu Y, Zhou Y, Wang Y, et al. Roux-en-Y gastric bypass-induced improvement of glucose tolerance and insulin resistance in type 2 diabetic rats are mediated by glucagon-like peptide-1. Obes Surg. 2011;21(9):1424–31.Google Scholar
  46. 46.
    Salinari S, le Roux CW, Bertuzzi A, et al. Duodenal-jejunal bypass and jejunectomy improve insulin sensitivity in Goto-Kakizaki diabetic rats without changes in incretins or insulin secretion. Diabetes. 2014;63(3):1069–78.Google Scholar
  47. 47.
    Zhou X, Qian B, Ji N, Lui C, Liu Z, Li B, et al. Pancreatic hyperplasia after gastric bypass surgery in a GK rat model of non-obese type 2 diabetes. J Endocrinol. 2016;228:13–23.Google Scholar
  48. 48.
    Speck M, Cho YM, Asadi A, et al. Duodenal-jejunal bypass protects GK rats from -cell loss and aggravation of hyperglycemia and increases enteroendocrine cells coexpressing GIP and GLP-1. AJP Endocrinol Metab. 2011;300(5):E923–32.Google Scholar
  49. 49.
    Kindel TL, Yoder SM, D’Alessio DA, et al. The effect of duodenal–jejunal bypass on glucose-dependent insulinotropic polypeptide secretion in Wistar rats. Obes Surg. 2010;20(6):768–75.Google Scholar
  50. 50.
    Mingrone G, Castagneto-Gissey L. Mechanisms of early improvement/resolution of type 2 diabetes after bariatric surgery. Diabetes Metab. 2009;35(6):518–23.Google Scholar
  51. 51.
    Zander M, Madsbad S, Madsen JL, et al. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and β-cell function in type 2 diabetes: a parallel-group study. Lancet. 2002;359(9309):824–30.CrossRefPubMedGoogle Scholar
  52. 52.
    Perfetti R, Hui H. The role of GLP-1 in the life and death of pancreatic beta cells. Horm Metab Res. 2004;36(11/12):804–10.CrossRefPubMedGoogle Scholar
  53. 53.
    Buchwald H, Menchaca HJ, Michalek VN, et al. Ileal effect on blood glucose, HbA1c, and GLP-1 in Goto-Kakizaki rats. Obes Surg. 2014;24(11):1954–60.CrossRefPubMedGoogle Scholar
  54. 54.
    Seyfried F, Bueter M, Spliethoff K, et al. Roux-en Y gastric bypass is superior to duodeno-jejunal bypass in improving glycaemic control in Zucker diabetic fatty rats. Obes Surg. 2014;24(11):1888–95.CrossRefPubMedGoogle Scholar
  55. 55.
    Flynn CR, Albaugh VL, Cai S, et al. Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery. Nat Commun. 2015;6:7715.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Kohli R, Setchell KD, Kirby M, et al. A surgical model in male obese rats uncovers protective effects of bile acids post-bariatric surgery. Endocrinology. 2013;154(7):2341–51.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Angrisani L, Santonicola A, Iovino P, et al. Bariatric surgery worldwide 2013. Obes Surg. 2015;25(10):1822–32.CrossRefPubMedGoogle Scholar
  58. 58.
    Topart P, Becouarn G, Delarue J. Weight loss and nutritional outcomes 10 years after biliopancreatic diversion with duodenal switch. Obes Surg [Internet]. 2017 Jan 4 [cited 2017 Jan 14]; Available from:
  59. 59.
    Hedberg J, Sundbom M. superior Weight loss and lower HbA1c 3 years after duodenal switch compared with Roux-en-Y gastric bypass—a randomized controlled trial. Surg Obes Relat Dis 2012;8(3):338–343.Google Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Claudia Laessle
    • 1
  • Sven Michelmichel
    • 1
  • Goran Marjanovic
    • 1
  • Simon Kuesters
    • 1
  • Gabriel Seifert
    • 1
  • Ulrich T. Hopt
    • 1
  • Jodok Matthias Fink
    • 1
  1. 1.Department of General and Visceral SurgeryAlbert-Ludwigs-UniversityFreiburgGermany

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