Skip to main content
Log in

Immune cell-mediated inflammation and the early improvements in glucose metabolism after gastric banding surgery

  • Article
  • Published:
Diabetologia Aims and scope Submit manuscript

Abstract

Aims/hypothesis

The contribution of immune cells to the inflammasome that characterises type 2 diabetes mellitus and obesity is under intense research scrutiny. We hypothesised that early changes in glucose metabolism following gastric banding surgery may relate to systemic inflammation, particularly cell-mediated immunity.

Methods

Obese participants (BMI 43.4 ± 4.9 kg/m2, n = 15) with diabetes or impaired glucose tolerance (IGT) underwent laparoscopic adjustable gastric banding surgery. Measurements taken before, and at 2 and 12 weeks after surgery included: fasting glucose, glucose levels 2 h after a 75 g oral load, glucose incremental AUC, oral glucose insulin sensitivity index (OGIS), circulating immune cell numbers and activation, and adipokine levels. Subcutaneous and visceral adipose tissue were collected at surgery, and macrophage number and activation measured.

Results

There were significant reductions in fasting and 2 h glucose, as well as improved OGIS at 2 and 12 weeks. At 12 weeks, 80% of the diabetic participants reverted to normal glucose tolerance or IGT, and all IGT participants had normalised glucose tolerance. The 12 week fall in fasting glucose was significantly related to baseline lymphocyte and T lymphocyte numbers, and to granulocyte activation, but also to the magnitude of the 12 week reduction in lymphocyte and T lymphocyte numbers and TNF-α levels. In a model that explained 75% of the variance in the change in fasting glucose, the 12 week change in T lymphocytes was independently associated with the 12 week fall in fasting glucose.

Conclusions/interpretation

Rapid improvements in glucose metabolism after gastric banding surgery are related to reductions in circulating pro-inflammatory immune cells, specifically T lymphocytes. The contribution of immune cell-mediated inflammation to glucose homeostasis in type 2 diabetes and its improvement after bariatric surgery require further investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

CRP:

C-reactive protein

IGT:

Impaired glucose tolerance

OGIS:

Oral glucose insulin sensitivity index

SAT:

Subcutaneous adipose tissue

VAT:

Visceral adipose tissue

References

  1. Adams TD, Davidson LE, Litwin SE et al (2012) Health benefits of gastric bypass surgery after 6 years. J Am Med Assoc 308:1122–1131

    Article  CAS  Google Scholar 

  2. Adams TD, Gress RE, Smith SC et al (2007) Long-term mortality after gastric bypass surgery. N Engl J Med 357:753–761

    Article  PubMed  CAS  Google Scholar 

  3. Adams TD, Pendleton RC, Strong MB et al (2010) Health outcomes of gastric bypass patients compared to nonsurgical, nonintervened severely obese. Obesity (Silver Spring) 18:121–130

    Article  Google Scholar 

  4. Iaconelli A, Panunzi S, de Gaetano A et al (2011) Effects of bilio-pancreatic diversion on diabetic complications: a 10-year follow-up. Diabetes Care 34:561–567

    Article  PubMed  CAS  Google Scholar 

  5. Lee WJ, Hur KY, Lakadawala M, Kasama K, Wong SK, Lee YC (2012) Gastrointestinal metabolic surgery for the treatment of diabetic patients: a multi-institutional international study. J Gastrointest Surg 16:45–51, discussion 51–52

    Google Scholar 

  6. Leslie DB, Dorman RB, Serrot FJ et al (2012) Efficacy of the Roux-en-Y gastric bypass compared to medically managed controls in meeting the American Diabetes Association composite end point goals for management of type 2 diabetes mellitus. Obes Surg 22:367–374

    Article  PubMed  Google Scholar 

  7. Pontiroli AE, Folli F, Paganelli M et al (2005) 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

    Article  PubMed  Google Scholar 

  8. Scopinaro N, Adami GF, Papadia FS et al (2011) The effects of biliopancreatic diversion on type 2 diabetes mellitus in patients with mild obesity (BMI 30-35 kg/m2) and simple overweight (BMI 25-30 kg/m2): a prospective controlled study. Obes Surg 21:880–888

    Article  PubMed  Google Scholar 

  9. Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L (2004) XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 27:155–161

    Article  PubMed  CAS  Google Scholar 

  10. Sjostrom L, Narbro K, Sjostrom CD et al (2007) Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 357:741–752

    Article  PubMed  Google Scholar 

  11. Schauer PR, Kashyap SR, Wolski K et al (2012) Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med 366:1567–1576

    Article  PubMed  CAS  Google Scholar 

  12. Dixon JB, O’Brien PE, Playfair J et al (2008) Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial. J Am Med Assoc 299:316–323

    Article  CAS  Google Scholar 

  13. Mingrone G, Panunzi S, de Gaetano A et al (2012) Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med 366:1577–1585

    Article  PubMed  CAS  Google Scholar 

  14. Lee WJ, Chong K, Ser KH et al (2011) Gastric bypass vs sleeve gastrectomy for type 2 diabetes mellitus: a randomized controlled trial. Arch Surg 146:143–148

    Article  PubMed  Google Scholar 

  15. Pinheiro JS, Schiavon CA, Pereira PB, Correa JL, Noujaim P, Cohen R (2008) Long-long limb Roux-en-Y gastric bypass is more efficacious in treatment of type 2 diabetes and lipid disorders in super-obese patients. Surg Obes Relat Dis 4:521–525

    Article  PubMed  Google Scholar 

  16. Ikonomidis I, Mazarakis A, Papadopoulos C et al (2007) Weight loss after bariatric surgery improves aortic elastic properties and left ventricular function in individuals with morbid obesity: a 3-year follow-up study. J Hypertension 25:439–447

    Article  CAS  Google Scholar 

  17. Rider OJ, Francis JM, Ali MK et al (2009) Beneficial cardiovascular effects of bariatric surgical and dietary weight loss in obesity. J Am Coll Cardiol 54:718–726

    Article  PubMed  Google Scholar 

  18. Samaras K, Viardot A, Lee PN et al (2013) Reduced arterial stiffness after weight loss in obese type 2 diabetes and impaired glucose tolerance: the role of immune cell activation and insulin resistance. Diab Vasc Dis Res 10:40–48

    Article  PubMed  Google Scholar 

  19. Shargorodsky M, Fleed A, Boaz M, Gavish D, Zimlichman R (2006) The effect of a rapid weight loss induced by laparoscopic adjustable gastric banding on arterial stiffness, metabolic and inflammatory parameters in patients with morbid obesity. Int J Obes (Lond) 30:1632–1638

    Article  CAS  Google Scholar 

  20. Samaras K (2013) Bariatric surgery for type 2 diabetes: to whom and when? Minerva Endocrinol 38:47–58

    PubMed  CAS  Google Scholar 

  21. Donath MY, Shoelson SE (2011) Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 11:98–107

    Article  PubMed  CAS  Google Scholar 

  22. Swarbrick MM, Stanhope KL, Austrheim-Smith IT et al (2008) Longitudinal changes in pancreatic and adipocyte hormones following Roux-en-Y gastric bypass surgery. Diabetologia 51:1901–1911

    Article  PubMed  CAS  Google Scholar 

  23. Trakhtenbroit MA, Leichman JG, Algahim MF et al (2009) Body weight, insulin resistance, and serum adipokine levels 2 years after 2 types of bariatric surgery. Am J Med 122:435–442

    Article  PubMed  CAS  Google Scholar 

  24. Illan-Gomez F, Gonzalvez-Ortega M, Orea-Soler I et al (2012) Obesity and inflammation: change in adiponectin, C-reactive protein, tumour necrosis factor-alpha and interleukin-6 after bariatric surgery. Obes Surg 22:950–955

    Article  PubMed  Google Scholar 

  25. Mather KJ, Funahashi T, Matsuzawa Y et al (2008) Adiponectin, change in adiponectin, and progression to diabetes in the Diabetes Prevention Program. Diabetes 57:980–986

    Article  PubMed  CAS  Google Scholar 

  26. Spranger J, Kroke A, Mohlig M et al (2003) Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 52:812–817

    Article  PubMed  CAS  Google Scholar 

  27. Viardot A, Heilbronn LK, Samocha-Bonet D, Mackay F, Campbell LV, Samaras K (2012) Obesity is associated with activated and insulin resistant immune cells. Diabetes Metab Res Rev 28:447–454

    Article  PubMed  CAS  Google Scholar 

  28. Viardot A, Lord RV, Samaras K (2010) The effects of weight loss and gastric banding on the innate and adaptive immune system in type 2 diabetes and prediabetes. J Clin Endocrinol Metab 95:2845–2850

    Article  PubMed  CAS  Google Scholar 

  29. Mari A, Pacini G, Murphy E, Ludvik B, Nolan JJ (2001) A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care 24:539–548

    Article  PubMed  CAS  Google Scholar 

  30. Seltzer HS, Allen EW, Herron AL Jr, Brennan MT (1967) Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus. J Clin Invest 46:323–335

    Article  PubMed  CAS  Google Scholar 

  31. Taylor R (2013) Banting Memorial Lecture 2012. Reversing the twin cycles of type 2 diabetes. Diabet Med 30:267–275

    Article  PubMed  CAS  Google Scholar 

  32. Matarese G, Procaccini C, de Rosa V (2012) At the crossroad of T cells, adipose tissue, and diabetes. Immunol Rev 249:116–134

    Article  PubMed  CAS  Google Scholar 

  33. Schauer PR, Burguera B, Ikramuddin S et al (2003) Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus. Annals Surg 238:467–484

    Google Scholar 

  34. Guidone C, Manco M, Valera-Mora E et al (2006) Mechanisms of recovery from type 2 diabetes after malabsorptive bariatric surgery. Diabetes 55:2025–2031

    Article  PubMed  CAS  Google Scholar 

  35. Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R (2011) Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 54:2506–2514

    Article  PubMed  CAS  Google Scholar 

  36. Kintscher U, Hartge M, Hess K et al (2008) T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol 28:1304–1310

    Article  PubMed  CAS  Google Scholar 

  37. Nishimura S, Manabe I, Nagasaki M et al (2009) CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nature Med 15:914–920

    Article  PubMed  CAS  Google Scholar 

  38. Procaccini C, de Rosa V, Galgani M et al (2010) An oscillatory switch in mTOR kinase activity sets regulatory T cell responsiveness. Immunity 33:929–941

    Article  PubMed  CAS  Google Scholar 

  39. Cottam DR, Schaefer PA, Shaftan GW, Angus LD (2003) Dysfunctional immune-privilege in morbid obesity: implications and effect of gastric bypass surgery. Obes Surg 13:49–57

    Article  PubMed  CAS  Google Scholar 

  40. Fraser DA, Thoen J, Reseland JE, Forre O, Kjeldsen-Kragh J (1999) Decreased CD4+ lymphocyte activation and increased interleukin-4 production in peripheral blood of rheumatoid arthritis patients after acute starvation. Clin Rheumatol 18:394–401

    Article  PubMed  CAS  Google Scholar 

  41. Hirsch FF, Pareja JC, Geloneze SR, Chaim E, Cazzo E, Geloneze B (2012) Comparison of metabolic effects of surgical-induced massive weight loss in patients with long-term remission versus non-remission of type 2 diabetes. Obes Surg 22:910–917

    Article  PubMed  Google Scholar 

  42. Brethauer SA, Heneghan HM, Eldar S et al (2011) Early effects of gastric bypass on endothelial function, inflammation, and cardiovascular risk in obese patients. Surg Endoscopy 25:2650–2659

    Article  Google Scholar 

  43. Marantos G, Daskalakis M, Karkavitsas N, Matalliotakis I, Papadakis JA, Melissas J (2011) Changes in metabolic profile and adipoinsular axis in morbidly obese premenopausal females treated with restrictive bariatric surgery. World J Surg 35:2022–2030

    Article  PubMed  Google Scholar 

  44. Miller GD, Nicklas BJ, Fernandez A (2011) Serial changes in inflammatory biomarkers after Roux-en-Y gastric bypass surgery. Surg Obesity Rel Dis 7:618–624

    Article  Google Scholar 

  45. Kopp HP, Kopp CW, Festa A et al (2003) Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vasc Biol 23:1042–1047

    Article  PubMed  CAS  Google Scholar 

  46. Moschen AR, Molnar C, Geiger S et al (2010) Anti-inflammatory effects of excessive weight loss: potent suppression of adipose interleukin 6 and tumour necrosis factor alpha expression. Gut 59:1259–1264

    Article  PubMed  CAS  Google Scholar 

  47. Isbell JM, Tamboli RA, Hansen EN et al (2010) The importance of caloric restriction in the early improvements in insulin sensitivity after Roux-en-Y gastric bypass surgery. Diabetes Care 33:1438–1442

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Our thanks go to the staff of the Garvan Clinical Research Facility (particularly Angela Peris and Jennifer Hansen) and to all the volunteers who participated in the study.

Funding

This study was part-funded by a competitive, peer reviewed research grant from The Ladies Committee–Sister Bernice Award of the St Vincent’s Clinic Foundation and by philanthropic grants from the GP Harris Foundation and an anonymous donor. All researchers were independent of the funding bodies, which did not play any role in study design, data collection and analysis, and submission for publication.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

All authors contributed to study conception and design, data acquisition or analysis and interpretation, as well as to the drafting or critical revising of the manuscript for important intellectual content. All authors gave final approval of the version to be published.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Katherine Samaras.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Samaras, K., Viardot, A., Botelho, N.K. et al. Immune cell-mediated inflammation and the early improvements in glucose metabolism after gastric banding surgery. Diabetologia 56, 2564–2572 (2013). https://doi.org/10.1007/s00125-013-3033-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00125-013-3033-7

Keywords

Navigation