Top

Published in:

01-05-2014 | Pharmacologic Treatment of Type 2 Diabetes (A Vella, Section Editor)

The Sum of Many Parts: Potential Mechanisms for Improvement in Glucose Homeostasis After Bariatric Surgery

Authors: Kim T. Nguyen, Judith Korner

Published in: Current Diabetes Reports | Issue 5/2014

Abstract

Bariatric surgery has emerged as the most durably effective treatment of type 2 diabetes (DM). However, the mechanisms governing improvement in glucose homeostasis have yet to be fully elucidated. In this review we discuss the various types of surgical interventions and the multitude of factors that potentially mediate the effects on glycemia, such as altered delivery of nutrients to the distal ileum, duodenal exclusion, gut hormone changes, bile acid reabsorption, and amino acid metabolism. Accumulating evidence that some of these changes seem to be independent of weight loss questions the rationale of using body mass index as the major indication for surgery in diabetic patients. Understanding the complex mechanisms and interactions underlying improved glycemic control could lead to novel therapeutic targets and would also allow for greater individualization of therapy and optimization of surgical outcomes.

Vella A, Camilleri M, Rizza RA. The gastrointestinal tract and glucose tolerance. Curr Opin Clin Nutr Metab Care. 2004;7:479–84.PubMed

DeFronzo RA. Pathogenesis of type 2 (non-insulin dependent) diabetes mellitus: a balanced overview. Diabetologia. 1992;35:389–97.PubMed

Ali MK, Bullard KM, Saadine JB, Cowie CC, Imperatore G, Gregg EW. Achievement of goals in U.S. Diabetes Care, 1999–2010. N Engl J Med. 2013;369:287–8.PubMed

4.••

Stark Casagrande S, Fradkin JE, Saydah SH, Rust KF, Cowie CC. The prevalence of meeting A1C, blood pressure, and LDL goals among people with diabetes, 1988–2010. Diabetes Care. 2013;36:2271–9. The authors assess the improvements in achievement of ADA goals for diabetic care.PubMed

Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults—The Evidence Report. National Institutes of Health. Obes Res. 1998;6(Suppl 2):51S–209S.

Gregg EW, Cheng YJ, Narayan KM, Thompson TJ, Williamson DF. The relative contributions of different levels of overweight and obesity to the increased prevalence of diabetes in the United States: 1976–2004. Prev Med. 2007;45:348–52.PubMed

Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292:1724–37.PubMed

8.••

Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Leccesi L, et al. Bariatric surgery vs conventional medical therapy for type 2 diabetes. N Engl J Med. 2012;366:1577–85. A randomized control trial of RYGB or BPD vs medical management of diabetes.PubMed

9.••

Schauer PR, Kashyap SR, Wolsk K, Brethauer SA, Kirwan JP, Pothier CE, et al. Bariatric surgery vs intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012;366:1567–76. A randomized control trial of RYGB or sleeve gastrectomy vs medical management of diabetes.PubMedCentralPubMed

10.

Sjostrom L. Bariatric surgery and reduction in morbidity and mortality: experiences from the SOS study. Int J Obes. 2008;32 Suppl 7:S93–7.

11.

Sjöström L, Lindroos AK, Peltonen M, Torgerson J, Bouchard C, Carlsson B, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med. 2004;351:2683–93.PubMed

12.••

Ikramuddin S, Korner J, Lee WJ, Connett JE, Inabnet WB, Billington CJ, et al. Roux-en-Y gastric bypass vs intensive medical management for the control of type 2 diabetes, hypertension, and hyperlipidemia: the Diabetes Surgery Study randomized clinical trial. JAMA. 2013;309:2240–9. A randomized control trial of RYGB vs intensive lifestyle modification.PubMed

13.

Leslie DB, Dorman RB, Serro FJ, Swan TW, Kellogg TA, Torres-Villalobos G, et al. Efficacy of the Roux-en-Y gastric bypass compared with medically managed controls in meeting the American Diabetes Association composite endpoint goals for management of type 2 diabetes mellitus. Obes Surg. 2012;22:367–74.PubMed

14.

Buchwald H, Estok R, Fahrbach K, Banel D, Jensen MD, Pories WJ, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009;122:248–56, e5.PubMed

15.

Dixon JB, O’Brien PE, Playfair J, Chapman L, Schachter LM, Stewart Skinner S, et al. Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial. JAMA. 2008;299:316–23.PubMed

16.••

Sjostrom L. Review of the key results from the Swedish Obese Subjects (SOS) trial—a prospective controlled intervention study of bariatric surgery. J Intern Med. 2013;273:219–34. Long-term prospective controlled intervention study of bariatric surgery vs medical management.PubMed

17.••

Dixon JB, Zimmet P, Alberti KG, Rubino F. International Diabetes Federation Taskforce on Epidemiology and Prevention. Bariatric surgery: an IDF statement for obese Type 2 diabetes. Diabet Med. 2011;28:628–42. IDF statement regarding consideration of bariatric surgery for treatment of DMin patients with BMI <35 kg/m2.PubMedCentralPubMed

18.

Ahmad U, Danowski TS, Nolan S, Stephan T, Sunder JH, Bahl VK. Remissions of diabetes mellitus after weight reduction by jejunoileal bypass. Diabetes Care. 1978;1:158–65.PubMed

19.

Pories WJ, Swanson MS, MacDonald KG, Long SB, Morris PG, Brown BM, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995;222:339–50. discussion 350–2.PubMedCentralPubMed

20.

Guo X, Liu X, Wang M, Zhang Y, Zhan Y. The effects of bariatric procedures vs medical therapy for obese patients with type 2 diabetes: meta-analysis of randomized controlled trials. Biomed Res Int. 2013;2013:410609.PubMedCentralPubMed

21.••

Buse JB, Caprio S, Cefalu WT, Ceriello A, Del Prato S, Inzucchi SE, et al. How do we define cure of diabetes? Diabetes Care. 2009;32:2133–5. Definition of diabetes remission.PubMedCentralPubMed

22.

Pournaras DJ, Aasheim ET, Søvik TT, Andrews R, Mahon D, Welbourn R, et al. Effect of the definition of type II diabetes remission in the evaluation of bariatric surgery for metabolic disorders. Br J Surg. 2012;99:100–3.PubMed

23.

Still CWG, Benotti P, Petrick AT, Gabrielsen J, Strodel WE, Ibele A, et al. Preoperative prediction of type 2 diabetes remission after Roux-en-Y gastric bypass surgery: a retrospective cohort study. The Lancet Diabetes and Endocrinology. 2014;2:38–45.PubMed

24.

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;258:628–36. discussion 636–7.PubMed

25.

DiGiorgi M, Rosen DJ, Choi JJ, Milone L, Schrope B, Olivero-Rivera L, et al. Re-emergence of diabetes after gastric bypass in patients with mid- to long-term follow-up. Surg Obes Relat Dis. 2010;6:249–53.PubMed

26.

Arterburn DE, Bogart A, Sherwood NE, Sidney S, Coleman KJ, Haneuse S, et al. A multisite study of long-term remission and relapse of type 2 diabetes mellitus following gastric bypass. Obes Surg. 2013;23:93–102.PubMed

27.

Kelley DE, Wing R, Buonocore C, Sturis J, Polonsky K, Fitzsimmons M. Relative effects of calorie restriction and weight loss in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1993;77:1287–93.PubMed

28.

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;15:474–81.PubMed

29.

Schauer PR, Burguera B, Ikramuddin S, Cottam D, Gourash W, Hamad G, et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus. Ann Surg. 2003;238:467–84. discussion 84–5.PubMedCentralPubMed

30.

Isbell JM, Tamboli RA, Hansen EN, Saliba J, Dunn JP, Phillips SE, et al. The importance of caloric restriction in the early improvements in insulin sensitivity after Roux-en-Y gastric bypass surgery. Diabetes Care. 2010;33:1438–42.PubMedCentralPubMed

31.•

Jackness C, Karmally W, Febres G, Conwell IM, Ahmed L, Bessler M, et al. Very low-calorie diet mimics the early beneficial effect of Roux-en-Y gastric bypass on insulin sensitivity and betacell Function in type 2 diabetic patients. Diabetes. 2013;62:3027–32. Role of caloric restriction in acute improvement in beta cell function and insulin sensitivity.PubMed

32.

Nauck M, Stöckmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986;29:46–52.PubMed

33.

Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006;368:1696–705.PubMed

34.

Eckerle Mize DL, Salehi M. The place of GLP-1-based therapy in diabetes management: differences between DPP-4 inhibitors and GLP-1 receptor agonists. Curr Diabetes Rep. 2013;13:307–18.

35.

Laferrère B, Teixeira J, McGinty J, Tran H, Egger JR, Colarusso A, et al. Effect of weight loss by gastric bypass surgery vs hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin Endocrinol Metab. 2008;93:2479–85.PubMedCentralPubMed

36.

Korner J, Korner J, Inabnet W, Febres G, Conwell IM, McMahon DJ, et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes. 2009;33:786–95.

37.

Korner J, Bessler M, Inabnet W, Taveras C, Holst JJ. Exaggerated glucagon-like peptide-1 and blunted glucose-dependent insulinotropic peptide secretion are associated with Roux-en-Y gastric bypass but not adjustable gastric banding. Surg Obes Relat Dis. 2007;3:597–601.PubMedCentralPubMed

38.

Pournaras DJ, Osborne A, Hawkins SC, Vincent RP, Mahon D, Ewings P, et al. Remission of type 2 diabetes after gastric bypass and banding: mechanisms and 2 year outcomes. Ann Surg. 2010;252:966–71.PubMed

39.

Laferrère B, Heshka S, Wang K, Khan Y, McGinty J, Teixeira J, 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. 2007;30:1709–16.PubMedCentralPubMed

40.

le Roux CW, Aylwin SJ, Batterham RL, Borg CM, Coyle F, Prasad V, et al. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg. 2006;243:108–14.PubMedCentralPubMed

41.

McLaughlin T, Peck M, Holst J, Deacon C. Reversible hyperinsulinemic hypoglycemia after gastric bypass: a consequence of altered nutrient delivery. J Clin Endocrinol Metab. 2010;95:1851–5.PubMed

42.

Dirksen C, Hansen DL, Madsbad S, Hvolris LE, Naver LS, Holst JJ, 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;33:375–7.PubMedCentralPubMed

43.

Salehi M, Prigeon RL, D’Alessio DA. Gastric bypass surgery enhances glucagon-like peptide 1-stimulated postprandial insulin secretion in humans. Diabetes. 2011;60:2308–14.PubMedCentralPubMed

44.••

Jørgensen NB, Dirksen C, Bojsen-Møller KN, Jacobsen SH, Worm D, Hansen DL, et al. Exaggerated glucagon-like peptide 1 response is important for improved beta-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes. Diabetes. 2013;62:3044–52. Association between exaggerated GLP-1 response and improved beta cell function and glucose tolerance.PubMed

45.

Jiménez A, Casamitjana R, Viaplana-Masclans J, Lacy A, Vidal J. GLP-1 action and glucose tolerance in subjects with remission of type 2 diabetes after gastric bypass surgery. Diabetes Care. 2013;36:2062–9.PubMed

46.

Falkén Y, Hellström PM, Holst JJ, Näslund E. Changes in glucose homeostasis after Roux-en-Y gastric bypass surgery for obesity at day 3, 2 months, and 1 year after surgery: role of gut peptides. J Clin Endocrinol Metab. 2011;96:2227–35.PubMed

47.

Rubino F, Gagner M, Gentileschi P, Kini S, Fukuyama S, Feng J, 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;240:236–42.PubMedCentralPubMed

48.

Jørgensen NB, Jacobsen SH, Dirksen C, Bojsen-Møller KN, Naver L, Hvolris L, et al. Acute and long-term effects of Rouxen-Y gastric bypass on glucose metabolism in subjects with Type 2 diabetes and normal glucose tolerance. Am J Physiol Endocrinol Metab. 2012;303:E122–31.PubMed

49.

Drucker DJ. Glucagon-like peptide 2. J Clin Endocrinol Metab. 2001;86:1759–64.PubMed

50.

Meier JJ, Nauck MA, Pott A, Heinze K, Goetze O, Bulut K, et al. Glucagon-like peptide 2 stimulates glucagon secretion, enhances lipid absorption, and inhibits gastric acid secretion in humans. Gastroenterology. 2006;130:44–54.PubMed

51.

Nagell CF, Wettergren A, Pedersen JF, Mortensen D, Holst JJ. Glucagon-like peptide-2 inhibits antral emptying in man, but is not as potent as glucagon-like peptide-1. Scand J Gastroenterol. 2004;39:353–8.PubMed

52.

le Roux CW, Borg C, Wallis K, Vincent RP, Bueter M, Goodlad R, et al. Gut hypertrophy after gastric bypass is associated with increased glucagon-like peptide 2 and intestinal crypt cell proliferation. Ann Surg. 2010;252:50–6.PubMed

53.

Drucker DJ. The role of gut hormones in glucose homeostasis. J Clin Invest. 2007;117:24–32.PubMedCentralPubMed

54.

Habegger KM, Kirchner H, Yi CX, Heppner KM, Sweeney D, Ottaway N, et al. GLP-1R agonism enhances adjustable gastric banding in diet-induced obese rats. Diabetes. 2013;62:3261–7.PubMed

55.

Korner J, Bessler M, Cirilo LJ, Conwell IM, Daud A, Restuccia NL, 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. 2005;90:359–65.PubMed

56.

Morínigo R, Moizé V, Musri M, Lacy AM, Navarro S, Marín JL, et al. Glucagon-like peptide-1, peptide YY, hunger, and satiety after gastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab. 2006;91:1735–40.PubMed

57.

Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, et al. Plasma ghrelin levels after diet induced weight loss or gastric bypass surgery. N Engl J Med. 2002;346:1623–30.PubMed

58.

Peterli R, Steinert RE, Woelnerhanssen B, Peters T, Christoffel-Courtin C, Gass M, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg. 2012;22:740–8.PubMedCentralPubMed

59.

Bohdjalian A, Langer FB, Shakeri-Leidenmühler S, Gfrerer L, Ludvik B, et al. Sleeve gastrectomy as sole and definitive bariatric procedure: 5-year results for weight loss and ghrelin. Obes Surg. 2010;20:535–40.PubMed

60.

Harvey EJ, Arroyo K, Korner J, Inabnet WB. Hormone changes affecting energy homeostasis after metabolic surgery. Mt Sinai J Med. 2010;77:446–65.PubMed

61.

Peterli R, Wölnerhanssen B, Peters T, Devaux N, Kern B, Christoffel-Courtin C, et al. Improvement in glucose metabolism after bariatric surgery: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy: a prospective randomized trial. Ann Surg. 2009;250:234–41.PubMed

62.

le Roux CW, Welbourn R, Werling M, Osborne A, Kokkinos A, Laurenius A, et al. Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass. Ann Surg. 2007;246:780–5.PubMed

63.

Faraj M, Havel PJ, Phélis S, Blank D, Sniderman AD, Cianflone K. Plasma acylation-stimulating protein, adiponectin, leptin, and ghrelin before and after weight loss induced by gastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab. 2003;88:1594–602.PubMed

64.

Thaler JP, Cummings DE. Minireview: hormonal and metabolic mechanisms of diabetes remission after gastrointestinal surgery. Endocrinology. 2009;150:2518–25.PubMed

65.

Romero F, Nicolau J, Flores L, Casamitjana R, Ibarzabal A, Lacy A, 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;26:2231–9.PubMed

66.

Lee WJ, Chen CY, Chong K, Lee YC, Chen SC, Lee SD. Changes in postprandial gut hormones after metabolic surgery: a comparison of gastric bypass and sleeve gastrectomy. Surg Obes Relat Dis. 2011;7:683–90.PubMed

67.

Patriti A, Facchiano E, Annetti C, Aisa MC, Galli F, Fanelli C, et al. Early improvement of glucose tolerance after ileal transposition in a non-obese type 2 diabetes rat model. Obes Surg. 2005;15:1258–64.PubMed

68.

Cummings BP, Strader AD, Stanhope KL, Graham JL, Lee J, Raybould HE, et al. Ileal interposition surgery improves glucose and lipid metabolism and delays diabetes onset in the UCDT2DM rat. Gastroenterology. 2010;138:2437–46, 2446 e1.PubMedCentralPubMed

69.

Strader AD, Clausen TR, Goodin SZ, Wendt D. Ileal interposition improves glucose tolerance in low dose streptozotocin-treated diabetic and euglycemic rats. Obes Surg. 2009;19:96–104.PubMed

70.

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:E447–53.PubMed

71.

Gaitonde S, Kohli R, Seeley R. The role of the gut hormone GLP-1 in the metabolic improvements caused by ileal transposition. J Surg Res. 2012;178:33–9.PubMedCentralPubMed

72.

de Paula AL, Macedo AL, Prudente AS, Queiroz L, Schraibman V, Pinus J. Laparoscopic sleeve gastrectomy with ileal interposition (“neuroendocrine brake”)—pilot study of a new operation. Surg Obes Relat Dis. 2006;2:464–7.PubMed

73.••

De Paula AL, Stival AR, Macedo A, Ribamar J, Mancini M, Halpern A, et al. Prospective randomized controlled trial comparing 2 versions of laparoscopic ileal interposition associated with sleeve gastrectomy for patients with type 2 diabetes with BMI 21–34 kg/m(2). Surg Obes Relat Dis. 2010;6:296–304. Ileal interposition as a potential treatment for DM in humans.PubMed

74.

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.PubMedCentralPubMed

75.

Rubino F, Forgione A, Cummings DE, Vix M, Gnuli D, Mingrone G, 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;244:741–9.PubMedCentralPubMed

76.

Jiao J, Bae EJ, Bandyopadhyay G, Oliver J, Marathe C, Chen M, et al. Restoration of euglycemia after duodenal bypass surgery is reliant on central and peripheral inputs in Zucker fa/fa rats. Diabetes. 2013;62:1074–83.PubMedCentralPubMed

77.••

Klein S, Fabbrini E, Patterson BW, Polonsky KS, Schiavon CA, Correa JL, et al. Moderate effect of duodenal-jejunal bypass surgery on glucose homeostasis in patients with type 2 diabetes. Obesity. 2012;20:1266–72. Duodenal jejunal bypass and improvement in DM in humans.PubMedCentralPubMed

78.

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. 2008;16:2585–92.PubMedCentralPubMed

79.

Sandler BJ, Rumbaut R, Swain CP, Torres G, Morales L, Gonzales L, et al. Human experience with an endoluminal, endoscopic, gastrojejunal bypass sleeve. Surg Endosc. 2011;25:3028–33.PubMed

80.••

Verdam FJ, Schouten R, Greve JW, Koek GH, Bouvy ND. An update on less invasive and endoscopic techniques mimicking the effect of bariatric surgery. J Obes. 2012;2012:597871. Endoluminal sleeve as a novel surgical alternative.PubMedCentralPubMed

81.

Cummings DE, Overduin J, Shannon MH, Foster-Schubert KE, 2004 ABS Consensus Conference. Hormonal mechanisms of weight loss and diabetes resolution after bariatric surgery. Surg Obes Relat Dis. 2005;1:358–68.PubMed

82.

Olbers T, Björkman S, Lindroos A, Maleckas A, Lönn L, Sjöström L, et al. Body composition, dietary intake, and energy expenditure after laparoscopic Roux-en-Y gastric bypass and laparoscopic vertical banded gastroplasty: a randomized clinical trial. Ann Surg. 2006;244:715–22.PubMedCentralPubMed

83.

Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001;86:1930–5.PubMed

84.

Patti ME, Houten SM, Bianco AC, Bernier R, Larsen PR, Holst JJ, et al. Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism. Obesity. 2009;17:1671–7.PubMed

85.••

Mencarelli A, Renga B, D'Amore C, Santorelli C, Graziosi L, Bruno A, et al. Dissociation of intestinal and hepatic activities of FXR and LXRalpha supports metabolic effects of terminal ileum interposition in rodents. Diabetes. 2013;62:3384–93. Ileal interposition leads to increased expression of FXR and FXR regulated genes in the intestine, leading to decreased hepatic gluconeogenesis.PubMed

86.

Kohli R, Kirby M, Setchell KD, Jha P, Klustaitis K, Woollett LA, et al. Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities. Am J Physiol Gastrointest Liver Physiol. 2010;299:G652–60.PubMedCentralPubMed

87.

Pournaras DJ, Glicksman C, Vincent RP, Kuganolipava S, Alaghband-Zadeh J, Mahon D, et al. The role of bile after Roux-en-Y gastric bypass in promoting weight loss and improving glycaemic control. Endocrinology. 2012;153:3613–9.PubMedCentralPubMed

88.

Kohli R, Bradley D, Setchell KD, Eagon JC, Abumrad N, Klein S. Weight loss induced by Roux-en-Y gastric bypass but not laparoscopic adjustable gastric banding increases circulating bile acids. J Clin Endocrinol Metab. 2013;98:E708–12.PubMedCentralPubMed

89.

Jansen PL, van Werven J, Aarts E, Berends F, Janssen I, Stoker J, et al. Alterations of hormonally active fibroblast growth factors after Roux-en-Y gastric bypass surgery. Dig Dis. 2011;29:48–51.PubMed

90.

Sachdev S, Billington C, Ikramuddin S, Inabnet W, Ahmed L, Wang Q, et al. Effect of Rouxen- Y gastric bypass on fasting and postprandial concentrations of bile acids and fibroblast growth factor-19. Atlanta: The Obesity Society; 2013.

91.

Furet JP, Kong LC, Tap J, Poitou C, Basdevant A, Bouillot JL, et al. Differential adaptation of human gut subject to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes. 2010;59:3049–57.PubMedCentralPubMed

92.

Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, et al. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A. 2009;106:2365–70.PubMedCentralPubMed

93.

Aron-Wisnewsky J, Dore J, Clement K. The importance of the gut microbiota after bariatric surgery. Nat Rev Gastroenterol Hepatol. 2012;9:590–8.PubMed

94.

Liou AP, Paziuk M, Luevano Jr JM, Machineni S, Turnbaugh PJ, Kaplan LM. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med. 2013;5:178ra41.PubMedCentralPubMed

95.

Still CD, Wood GC, Chu X, Erdman R, Manney CH, Benotti PN, et al. High allelic burden of four obesity SNPs is associated with poorer weight loss outcomes following gastric bypass surgery. Obesity. 2011;19:1676–83.PubMed

96.

Sarzynski MA, Jacobson P, Rankinen T, Carlsson B, Sjöström L, Bouchard C, et al. Associations of markers in 11 obesity candidate genes with maximal weight loss and weight regain in the SOS bariatric surgery cases. Int J Obes. 2011;35:676–83.

97.

Mirshahi UL, Still CD, Masker KK, Gerhard GS, Carey DJ, Mirshahi T. The MC4R(I251L) allele is associated with better metabolic status and more weight loss after gastric bypass surgery. J Clin Endocrinol Metab. 2011;96:E2088–96.PubMedCentralPubMed

98.

Hatoum IJ, Stylopoulos N, Vanhoose AM, Boyd KL, Yin DP, Ellacott KL, et al. Melanocortin-4 receptor signaling is required for weight loss after gastric bypass surgery. J Clin Endocrinol Metab. 2012;97:E1023–31.PubMedCentralPubMed

99.

Florez JC, Jablonski KA, Bayley N, Pollin TI, de Bakker PI, Shuldiner AR, et al. Diabetes Prevention Program Research Group. TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med. 2006;355:241–50.PubMedCentralPubMed

100.

Smushkin G, Sathananthan M, Sathananthan A, Dalla Man C, Micheletto F, Zinsmeister AR, et al. Diabetes-associated common genetic variation and its association with GLP-1 concentrations and response to exogenous GLP-1. Diabetes. 2012;61:1082–9.PubMedCentralPubMed

101.

Pilgaard K, Jensen CB, Schou JH, Lyssenko V, Wegner L, Brøns C, et al. The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men. Diabetologia. 2009;52:1298–307.PubMed

102.

Schäfer SA, Tschritter O, Machicao F, Thamer C, Stefan N, Gallwitz B, et al. Impaired glucagon-like peptide-1-induced insulin secretion in carriers of transcription factor 7-like 2 (TCF7L2) gene polymorphisms. Diabetologia. 2007;50:2443–50.PubMedCentralPubMed

103.

Talchai C, Xuan S, Kitamura T, DePinho RA, Accili D. Generation of functional insulin-producing cells in the gut by Foxo1 ablation. Nat Genet. 2012;44:406–12, S1.PubMedCentralPubMed

104.

Depoortere I. Taste receptors of the gut: emerging roles in health and disease. Gut. 2014;63(1):179–90.PubMed

105.

Bojsen-Møller KN, Dirksen C, Jørgensen NB, Jacobsen SH, Hansen DL, Worm D, et al. Increased hepatic insulin clearance after Roux-en-Y gastric bypass. J Clin Endocrinol Metab. 2013;98:E1066–71.PubMed

106.

Dirksen C et al. Mechanisms of improved glycaemic control after Roux-en-Y gastric bypass. Diabetologia. 2012;55:1890–901.PubMed

107.

Bojsen-Møller KN, Dirksen C, Jørgensen NB, Jacobsen SH, Serup AK, Albers PH, et al. Early enhancements of hepatic and later of peripheral insulin sensitivity combined with increased postprandial insulin secretion contribute to improved glycemic control after Roux-en-Y gastric bypass. Diabetes. 2013. doi:10.2337/db13-1307.

108.

Troy S, Soty M, Ribeiro L, Laval L, Migrenne S, Fioramonti X, 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. 2008;8:201–11.PubMed

109.

Potier M, Darcel N, Tome D. Protein, amino acids and the control of food intake. Curr Opin Clin Nutr Metab Care. 2009;12:54–8.PubMed

110.

Tremblay F, Lavigne C, Jacques H, Marette A. Role of dietary proteins and amino acids in the pathogenesis of insulin resistance. Annu Rev Nutr. 2007;27:293–310.PubMed

111.

Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 2009;9:311–26.PubMedCentralPubMed

112.

Tomé D, Schwarz J, Darcel N, Fromentin G. Protein, amino acids, vagus nerve signaling, and the brain. Am J Clin Nutr. 2009;90:838S–43S.PubMed

113.

Laferrère B, Reilly D, Arias S, Swerdlow N, Gorroochurn P, Bawa B, et al. Differential metabolic impact of gastric bypass surgery vs dietary intervention in obese diabetic subjects despite identical weight loss. Sci Transl Med. 2011;3:80re2.PubMedCentralPubMed

114.••

Magkos F, Bradley D, Schweitzer GG, Finck BN, Eagon JC, Ilkayeva O, et al. Effect of Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding on branched-chain amino acid metabolism. Diabetes. 2013;62:2757–61. RYGB and LAGB affect amino acid metabolism in nondiabetic patients.PubMed

115.

Mutch DM, Fuhrmann JC, Rein D, Wiemer JC, Bouillot JL, Poitou C, et al. Metabolite profiling identifies candidate markers reflecting the clinical adaptations associated with Roux-en-Y gastric bypass surgery. PLoS One. 2009;4:e7905.PubMedCentralPubMed

Title: The Sum of Many Parts: Potential Mechanisms for Improvement in Glucose Homeostasis After Bariatric Surgery
Authors: Kim T. Nguyen
Judith Korner
Publication date: 01-05-2014
Publisher: Springer US
Published in: Current Diabetes Reports / Issue 5/2014
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI: https://doi.org/10.1007/s11892-014-0481-5

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2014

Bile Acid Sequestrants: Glucose-Lowering Mechanisms and Efficacy in Type 2 Diabetes

Diabetes Mellitus and Dementia

Review of Innovations in Digital Health Technology to Promote Weight Control

FTO and Obesity: Mechanisms of Association

Cardiovascular Actions of GLP-1 and Incretin-Based Pharmacotherapy

Long-Term Health Outcomes in Offspring Born to Women with Diabetes in Pregnancy

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials