Advertisement

Obesity Surgery

, Volume 28, Issue 9, pp 2672–2686 | Cite as

Increased Bile Acids and FGF19 After Sleeve Gastrectomy and Roux-en-Y Gastric Bypass Correlate with Improvement in Type 2 Diabetes in a Randomized Trial

  • Reza Nemati
  • Jun LuEmail author
  • Dech Dokpuang
  • Michael Booth
  • Lindsay D. Plank
  • Rinki MurphyEmail author
Original Contributions
  • 296 Downloads

Abstract

Background

Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are both effective bariatric procedures to treat type 2 diabetes (T2DM) and obesity. The contribution of changes in bile acids (BAs) and fibroblast growth factor19 (FGF19) to such metabolic improvements is unclear.

Methods

We examined associations between changes in BAs, FGF19 (fasting and prandial), with changes in body weight, glycemia, and other metabolic variables in 61 obese patients with T2DM before and 1 year after randomization to SG or RYGB.

Results

Weight loss and diabetes remission (defined by HbA1c < 39 mmol/mol [< 5.7%] in the absence of glucose-lowering therapy) after RYGB and SG was similar (mean weight loss − 29 vs − 31 kg, p = 0.50; diabetes remission proportion 37.5 vs 34%, p = 1.0). Greater increments in fasting and prandial levels of total, secondary, and unconjugated BAs were seen after RYGB than SG. Fasting and prandial increases in total (r = − 0.3, p = 0.01; r = − 0.2, p = 0.04), secondary (r = − 0.3, p = 0.01; r = − 0.4, p = 0.01) and unconjugated BA (r = − 0.3, p = 0.01; r = 0.4, p < 0.01) correlated with decreases in HbA1c, but not weight. Changes in 12α-OH/non 12α-OH were positively associated with prandial glucose increments (r = 0.2, p = 0.03), HbA1c (r = 0.3, p = 0.01), and negatively associated with changes in insulinogenc index (r = − 0.3, p = 0.01). Only changes in prandial FGF19 were negatively associated with HbA1c (r = − 0.4, p < 0.01) and visceral fat (r = − 0.3, p = 0.04).

Conclusions/interpretation

The association between increases in secondary, unconjugated BAs and improvements in HBA1c (but not weight) achieved after both RYGB and SG suggest manipulation of BA as a potential strategy for controlling T2DM through weight-independent means.

Keywords

Bile acids Bariatric surgery Sleeve gastrectomy Roux-en-Y gastric bypass HbA1c Energy expenditure 

Notes

Acknowledgments

We thank all the participants who took part in this study and the larger clinical research team who made this study possible. We would like to thank Dr. Ashveen Nand from Auckland University of Technology for the assistance in LC-MS/MS analysis and Dr. Ian Ong from North Shore Hospital, Waitemata District Health Board, for the assistance with ascertainment of cholecystectomy status from clinical records.

Author Contributions

R.M., J.L., and L.P. conceived the project and designed study. R.N., M.B., D.D., J.L., and L.P. performed sample and/or data collection. R.N., J.L., L.P., and R.M. analyzed the data. R.N., R.M., L.P., and J.L. wrote the manuscript. All authors have read and agreed with the final version of this manuscript.

Funding

The main clinical trial was funded by Waitemata District Health Board. Additional grant for biochemical analyses was obtained from the Maurice Wilkins Centre for Biodiscovery. The funders had no role in the analyses, interpretation of findings, manuscript review or decision to submit the manuscript for publication.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Ethical Approval Statement

All procedures performed in this study involving human participants were in accordance with the ethical standards of the New Zealand national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent Statement

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11695_2018_3216_MOESM1_ESM.jpg (525 kb)
ESM 1 (JPEG 525 kb)
11695_2018_3216_MOESM2_ESM.docx (185 kb)
ESM 2 (DOCX 184 kb)

References

  1. 1.
    Association AD. Standards of medical care in diabetes—2017: summary of revisions. Diabetes Care. 2017;40:S4–5.CrossRefGoogle Scholar
  2. 2.
    Buchwald H, Oien DM. Metabolic/bariatric surgery worldwide 2011. Obes Surg. 2013;23:427–36.CrossRefGoogle Scholar
  3. 3.
    Schauer PR, Bhatt DL, Kirwan JP, et al. Bariatric surgery versus intensive medical therapy for diabetes—5-year outcomes. N Engl J Med. 2017;376:641–51.CrossRefGoogle Scholar
  4. 4.
    Keidar A, Hershkop KJ, Marko L, et al. Roux-en-Y gastric bypass vs sleeve gastrectomy for obese patients with type 2 diabetes: a randomised trial. Diabetologia. 2013;56:1914–8.CrossRefGoogle Scholar
  5. 5.
    Cho J-M, Kim HJ, Menzo EL, et al. Effect of sleeve gastrectomy on type 2 diabetes as an alternative treatment modality to Roux-en-Y gastric bypass: systemic review and meta-analysis. Surg Obes Relat Dis. 2015;11:1273–80.CrossRefGoogle Scholar
  6. 6.
    Murphy R, Clarke MG, Evennett NJ, et al. Laparoscopic sleeve gastrectomy versus banded Roux-en-Y gastric bypass for diabetes and obesity: a prospective randomised double-blind trial. Obes Surg. 2017; 1–10Google Scholar
  7. 7.
    Kaska L, Sledzinski T, Chomiczewska A, et al. Improved glucose metabolism following bariatric surgery is associated with increased circulating bile acid concentrations and remodeling of the gut microbiome. World J Gastroenterol. 2016;22:8698–719.CrossRefGoogle Scholar
  8. 8.
    Vítek L, Haluzík M. The role of bile acids in metabolic regulation. J Endocrinol. 2016;228:R85–96.CrossRefGoogle Scholar
  9. 9.
    Penney N, Kinross J, Newton R, et al. The role of bile acids in reducing the metabolic complications of obesity after bariatric surgery: a systematic review. Int J Obes. 2015;39:1565–74.CrossRefGoogle Scholar
  10. 10.
    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;154:2341–51.CrossRefGoogle Scholar
  11. 11.
    Ryan KK, Tremaroli V, Clemmensen C, et al. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature. 2014;509:183–8.CrossRefGoogle Scholar
  12. 12.
    Taoka H, Yokoyama Y, Morimoto K, et al. Role of bile acids in the regulation of the metabolic pathways. World J Diabetes. 2016;7:260–70.CrossRefGoogle Scholar
  13. 13.
    Schaap FG. Role of fibroblast growth factor 19 in the control of glucose homeostasis. Curr Opin Clin Nutr Metab Care. 2012;15:386–91.CrossRefGoogle Scholar
  14. 14.
    Fu L, John LM, Adams SH, et al. Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin-deficient diabetes. Endocrinology. 2004;145:2594–603.CrossRefGoogle Scholar
  15. 15.
    Gerhard GS, Styer AM, Wood GC, et al. A role for fibroblast growth factor 19 and bile acids in diabetes remission after Roux-en-Y gastric bypass. Diabetes Care. 2013;36:1859–64.CrossRefGoogle Scholar
  16. 16.
    Sachdev S, Wang Q, Billington C, et al. FGF 19 and bile acids increase following Roux-en-Y gastric bypass but not after medical management in patients with type 2 diabetes. Obes Surg. 2016;26:957–65.CrossRefGoogle Scholar
  17. 17.
    Haluzíková D, Lacinová Z, Kaválková P, et al. Laparoscopic sleeve gastrectomy differentially affects serum concentrations of FGF-19 and FGF-21 in morbidly obese subjects. Obesity. 2013;21:1335–42.CrossRefGoogle Scholar
  18. 18.
    Escalona A, Muñoz R, Irribarra V, et al. Bile acids synthesis decreases after laparoscopic sleeve gastrectomy. Surg Obes Relat Dis. 2016;12:763–9.CrossRefGoogle Scholar
  19. 19.
    Steinert RE, Peterli R, Keller S, et al. Bile acids and gut peptide secretion after bariatric surgery: a 1-year prospective randomized pilot trial. Obesity. 2013;21:E660–8.CrossRefGoogle Scholar
  20. 20.
    Nakatani H, Kasama K, Oshiro T, et al. Serum bile acid along with plasma incretins and serum high–molecular weight adiponectin levels are increased after bariatric surgery. Metabolism. 2009;58:1400–7.CrossRefGoogle Scholar
  21. 21.
    Stubbs RJ, Hughes DA, Johnstone AM, et al. The use of visual analogue scales to assess motivation to eat in human subjects: a review of their reliability and validity with an evaluation of new hand-held computerized systems for temporal tracking of appetite ratings. Br J Nutr. 2000;84:405–15.CrossRefGoogle Scholar
  22. 22.
    Tagliacozzi D, Mozzi AF, Casetta B, et al. Quantitative analysis of bile acids in human plasma by liquid chromatography-electrospray tandem mass spectrometry: a simple and rapid one-step method. Clin Chem Lab Med. 2003;41:1633–41.CrossRefGoogle Scholar
  23. 23.
    Muniyappa R, Lee S, Chen H, et al. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab. 2008;294:E15–26.CrossRefGoogle Scholar
  24. 24.
    Khan FH, Shaw L, Zhang W, et al. Fibroblast growth factor 21 correlates with weight loss after vertical sleeve gastrectomy in adolescents. Obesity. 2016;24:2377–83.CrossRefGoogle Scholar
  25. 25.
    Schmidt JB, Pedersen SD, Gregersen NT, et al. Effects of RYGB on energy expenditure, appetite and glycaemic control: a randomized controlled clinical trial. Int J Obes. 2013;40:281–90.CrossRefGoogle Scholar
  26. 26.
    De Giorgi S, Campos V, Egli L, et al. Long-term effects of Roux-en-Y gastric bypass on postprandial plasma lipid and bile acids kinetics in female non diabetic subjects: a cross-sectional pilot study. Clin Nutr. 2014;34:911–7.CrossRefGoogle Scholar
  27. 27.
    Ahmad N, Pfalzer A, Kaplan L. Roux-en-Y gastric bypass normalizes the blunted postprandial bile acid excursion associated with obesity. Int J Obes. 2013;37:1553–9.CrossRefGoogle Scholar
  28. 28.
    Kohli R, Bradley D, Setchell KD, et al. 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.CrossRefGoogle Scholar
  29. 29.
    Werling M, Vincent RP, Cross GF, et al. Enhanced fasting and post-prandial plasma bile acid responses after Roux-en-Y gastric bypass surgery. Scand J Gastroenterol. 2013;48:1257–64.CrossRefGoogle Scholar
  30. 30.
    Steinert R, Feinle-Bisset C, Geary N, et al. Digestive physiology of the pig symposium: secretion of gastrointestinal hormones and eating control. J Anim Sci. 2013;91:1963–73.CrossRefGoogle Scholar
  31. 31.
    Dutia R, Embrey M, O’Brien S, et al. Temporal changes in bile acid levels and 12α-hydroxylation after Roux-en-Y gastric bypass surgery in type 2 diabetes. Int J Obes. 2015;39:806–13.CrossRefGoogle Scholar
  32. 32.
    Ferrannini E, Camastra S, Astiarraga B, et al. Increased bile acid synthesis and deconjugation after biliopancreatic diversion. Diabetes. 2015;64:3377–85.CrossRefGoogle Scholar
  33. 33.
    Risstad H, Kristinsson JA, Fagerland MW, et al. Bile acid profiles over 5 years following gastric bypass and duodenal switch—results from a randomized clinical trial. Surg Obes Relat Dis. 2017;13:1544–53.CrossRefGoogle Scholar
  34. 34.
    Thöni V, Pfister A, Melmer A, et al. Dynamics of bile acid profiles, GLP-1 and FGF19 after laparoscopic gastric banding. J Clin Endocrinol Metab. 2017;102:2974–84.CrossRefGoogle Scholar
  35. 35.
    Pournaras DJ, Glicksman C, Vincent RP, 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.CrossRefGoogle Scholar
  36. 36.
    Belgaumkar AP, Vincent RP, Carswell KA, et al. Changes in bile acid profile after laparoscopic sleeve gastrectomy are associated with improvements in metabolic profile and fatty liver disease. Obes Surg. 2016;26:1195–202.CrossRefGoogle Scholar
  37. 37.
    Yip S, Signal M, Smith G, et al. Lower glycemic fluctuations early after bariatric surgery partially explained by caloric restriction. Obes Surg. 2014;24:62–70.CrossRefGoogle Scholar
  38. 38.
    Fiorucci S, Distrutti E. Bile acid-activated receptors, intestinal microbiota, and the treatment of metabolic disorders. Trends Mol Med. 2015;21:702–14.CrossRefGoogle Scholar
  39. 39.
    Chiang JY. Bile acids: regulation of synthesis. J Lipid Res. 2009;50:1955–66.CrossRefGoogle Scholar
  40. 40.
    Haeusler RA, Astiarraga B, Camastra S, et al. Human insulin resistance is associated with increased plasma levels of 12α-hydroxylated bile acids. Diabetes. 2013;62:4184–91.CrossRefGoogle Scholar
  41. 41.
    Simonen M, Dali-Youcef N, Kaminska D, et al. Conjugated bile acids associate with altered rates of glucose and lipid oxidation after Roux-en-Y gastric bypass. Obes Surg. 2012;22:1473–80.CrossRefGoogle Scholar
  42. 42.
    Patti ME, Houten SM, Bianco AC, 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.CrossRefGoogle Scholar
  43. 43.
    Albaugh VL, Flynn CR, Cai S, et al. Early increases in bile acids post Roux-en-Y gastric bypass are driven by insulin-sensitizing, secondary bile acids. J Clin Endocrinol Metab. 2015;100:E1225–33.CrossRefGoogle Scholar
  44. 44.
    Jørgensen NB, Dirksen C, Bojsen-Møller KN, et al. Improvements in glucose metabolism early after gastric bypass surgery are not explained by increases in total bile acids and fibroblast growth factor 19 concentrations. J Clin Endocrinol Metab. 2014;100:E396–406.CrossRefGoogle Scholar
  45. 45.
    Albaugh VL, Banan B, Ajouz H, et al. Bile acids and bariatric surgery. Mol Asp Med. 2017;56:75–89.CrossRefGoogle Scholar
  46. 46.
    Dietschy JM. Mechanisms for the intestinal absorption of bile acids. J Lipid Res. 1968;9:297–309.Google Scholar
  47. 47.
    Ferrebee CB, Dawson PA. Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids. Acta Pharm Sin B. 2015;5:129–34.CrossRefGoogle Scholar
  48. 48.
    Vincent RP, Omar S, Ghozlan S, et al. Higher circulating bile acid concentrations in obese patients with type 2 diabetes. Ann Clin Biochem. 2013;50:360–4.CrossRefGoogle Scholar
  49. 49.
    Wewalka M, Patti M-E, Barbato C, et al. Fasting serum taurine-conjugated bile acids are elevated in type 2 diabetes and do not change with intensification of insulin. J Clin Endocrinol Metab. 2014;99:1442–51.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Science, Faculty of Health and Environmental SciencesAuckland University of TechnologyAucklandNew Zealand
  2. 2.College of Life and Marine SciencesShenzhen UniversityShenzhenChina
  3. 3.School of Interprofessional Health Studies, Faculty of Health and Environmental SciencesAuckland University of TechnologyAucklandNew Zealand
  4. 4.Institute of Biomedical TechnologyAuckland University of TechnologyAucklandNew Zealand
  5. 5.Division of Medical Technology, School of Allied Health SciencesUniversity of PhayaoPhayaoThailand
  6. 6.Department of Surgery, North Shore HospitalWaitemata District Health BoardAucklandNew Zealand
  7. 7.Department of Surgery, Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand
  8. 8.Auckland Diabetes Centre, Auckland District Health BoardAucklandNew Zealand
  9. 9.Whitiora Diabetes DepartmentCounties Manukau District Health BoardAucklandNew Zealand
  10. 10.Department of Medicine, Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand
  11. 11.Maurice Wilkins Centre for BiodiscoveryAucklandNew Zealand

Personalised recommendations