Diabetologia

, Volume 56, Issue 12, pp 2564–2572 | Cite as

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

  • Katherine Samaras
  • Alexander Viardot
  • Natalia K. Botelho
  • Alicia Jenkins
  • Reginald V. Lord
Article

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.

Keywords

Adipokine Bariatric surgery Diabetes Glucose Immune cells Inflammation Insulin resistance Lymphocyte Obesity Tumour necrosis factor-α Weight loss 

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. 1.
    Adams TD, Davidson LE, Litwin SE et al (2012) Health benefits of gastric bypass surgery after 6 years. J Am Med Assoc 308:1122–1131CrossRefGoogle Scholar
  2. 2.
    Adams TD, Gress RE, Smith SC et al (2007) Long-term mortality after gastric bypass surgery. N Engl J Med 357:753–761PubMedCrossRefGoogle Scholar
  3. 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) 18:121–130CrossRefGoogle Scholar
  4. 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 34:561–567PubMedCrossRefGoogle Scholar
  5. 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 51–52Google Scholar
  6. 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 22:367–374PubMedCrossRefGoogle Scholar
  7. 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 28:2703–2709PubMedCrossRefGoogle Scholar
  8. 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 21:880–888PubMedCrossRefGoogle Scholar
  9. 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 27:155–161PubMedCrossRefGoogle Scholar
  10. 10.
    Sjostrom L, Narbro K, Sjostrom CD et al (2007) Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 357:741–752PubMedCrossRefGoogle Scholar
  11. 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 366:1567–1576PubMedCrossRefGoogle Scholar
  12. 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 299:316–323CrossRefGoogle Scholar
  13. 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 366:1577–1585PubMedCrossRefGoogle Scholar
  14. 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 146:143–148PubMedCrossRefGoogle Scholar
  15. 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 4:521–525PubMedCrossRefGoogle Scholar
  16. 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 25:439–447CrossRefGoogle Scholar
  17. 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 54:718–726PubMedCrossRefGoogle Scholar
  18. 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 10:40–48PubMedCrossRefGoogle Scholar
  19. 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) 30:1632–1638CrossRefGoogle Scholar
  20. 20.
    Samaras K (2013) Bariatric surgery for type 2 diabetes: to whom and when? Minerva Endocrinol 38:47–58PubMedGoogle Scholar
  21. 21.
    Donath MY, Shoelson SE (2011) Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 11:98–107PubMedCrossRefGoogle Scholar
  22. 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 51:1901–1911PubMedCrossRefGoogle Scholar
  23. 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 122:435–442PubMedCrossRefGoogle Scholar
  24. 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 22:950–955PubMedCrossRefGoogle Scholar
  25. 25.
    Mather KJ, Funahashi T, Matsuzawa Y et al (2008) Adiponectin, change in adiponectin, and progression to diabetes in the Diabetes Prevention Program. Diabetes 57:980–986PubMedCrossRefGoogle Scholar
  26. 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 52:812–817PubMedCrossRefGoogle Scholar
  27. 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 28:447–454PubMedCrossRefGoogle Scholar
  28. 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 95:2845–2850PubMedCrossRefGoogle Scholar
  29. 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 24:539–548PubMedCrossRefGoogle Scholar
  30. 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 46:323–335PubMedCrossRefGoogle Scholar
  31. 31.
    Taylor R (2013) Banting Memorial Lecture 2012. Reversing the twin cycles of type 2 diabetes. Diabet Med 30:267–275PubMedCrossRefGoogle Scholar
  32. 32.
    Matarese G, Procaccini C, de Rosa V (2012) At the crossroad of T cells, adipose tissue, and diabetes. Immunol Rev 249:116–134PubMedCrossRefGoogle Scholar
  33. 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 238:467–484Google Scholar
  34. 34.
    Guidone C, Manco M, Valera-Mora E et al (2006) Mechanisms of recovery from type 2 diabetes after malabsorptive bariatric surgery. Diabetes 55:2025–2031PubMedCrossRefGoogle Scholar
  35. 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 54:2506–2514PubMedCrossRefGoogle Scholar
  36. 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 28:1304–1310PubMedCrossRefGoogle Scholar
  37. 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 15:914–920PubMedCrossRefGoogle Scholar
  38. 38.
    Procaccini C, de Rosa V, Galgani M et al (2010) An oscillatory switch in mTOR kinase activity sets regulatory T cell responsiveness. Immunity 33:929–941PubMedCrossRefGoogle Scholar
  39. 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 13:49–57PubMedCrossRefGoogle Scholar
  40. 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 18:394–401PubMedCrossRefGoogle Scholar
  41. 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 22:910–917PubMedCrossRefGoogle Scholar
  42. 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 25:2650–2659CrossRefGoogle Scholar
  43. 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 35:2022–2030PubMedCrossRefGoogle Scholar
  44. 44.
    Miller GD, Nicklas BJ, Fernandez A (2011) Serial changes in inflammatory biomarkers after Roux-en-Y gastric bypass surgery. Surg Obesity Rel Dis 7:618–624CrossRefGoogle Scholar
  45. 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 23:1042–1047PubMedCrossRefGoogle Scholar
  46. 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 59:1259–1264PubMedCrossRefGoogle Scholar
  47. 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 33:1438–1442PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Katherine Samaras
    • 1
    • 2
  • Alexander Viardot
    • 1
  • Natalia K. Botelho
    • 3
  • Alicia Jenkins
    • 4
  • Reginald V. Lord
    • 3
    • 5
  1. 1.Diabetes and Obesity Research ProgramGarvan Institute of Medical ResearchDarlinghurstAustralia
  2. 2.Department of EndocrinologySt Vincent’s HospitalDarlinghurstAustralia
  3. 3.St Vincent’s Centre for Applied Medical ResearchUniversity of NSWDarlinghurstAustralia
  4. 4.Department of EndocrinologySt Vincent’s HospitalMelbourneAustralia
  5. 5.Department of SurgeryNotre Dame School of MedicineSydneyAustralia

Personalised recommendations