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Obesity Surgery

, Volume 29, Issue 1, pp 149–158 | Cite as

Comprehensive Assessment of the Effects of Sleeve Gastrectomy on Glucose, Lipid, and Amino Acid Metabolism in Asian Individuals with Morbid Obesity

  • Jie Yao
  • Jean-Paul Kovalik
  • Oi Fah Lai
  • Phong Ching Lee
  • Alvin Eng
  • Weng Hoong Chan
  • Kwang Wei Tham
  • Eugene Lim
  • Yong Mong Bee
  • Hong Chang TanEmail author
Original Contributions
  • 100 Downloads

Abstract

Background

Obesity-induced insulin resistance leads to abnormalities in glucose, lipid, and amino acid metabolism. Our study examined the differences in insulin-mediated glucose, amino acid, and lipid metabolism between morbidly obese subjects with non-obese controls and the associated changes following sleeve gastrectomy (SG).

Methods

Non-obese controls and individuals with morbid obesity and scheduled for SG were recruited. Metabolic assessments were performed for all subjects at baseline and at 6 months after SG for eight subjects. The hyperinsulinemic-euglycemic clamp technique together with comprehensive metabolomic profiling was used to quantify insulin-mediated glucose, amino acid, and lipid metabolism.

Results

Eleven morbidly obese non-diabetic subjects scheduled for SG and nine non-obese controls were recruited. Compared to controls, obese subjects had significantly lower glucose uptake (4.4 ± 0.6 vs. 17.3 ± 2.4 mg/kg FFM/min per μU/mL·100) and higher concentration of branched-chain amino acids (BCAAs, 332.5 ± 26.8 vs. 235.3 ± 11.0 μM), non-esterified fatty acid (52.9 ± 9.9 vs. 25.6 ± 6.7 μM), and lipid-related acylcarnitines (intermediate chain 389.8 ± 32.5 vs. 285.9 ± 20.5; long chain 301.7 ± 22.1 vs. 236.0 ± 13.3 nM) during insulin clamp. Body weight significantly reduced at 6 months after bariatric surgery (92.5 ± 6.3 vs. 115.2 ± 6.9 kg), together with improvements in insulin-mediated glucose uptake, and suppression of BCAAs, non-esterified fatty acids, and lipid-related metabolites.

Conclusions

Morbid obesity in Asian individuals was associated with impairment in the regulatory actions of insulin on glucose, amino acid, and lipid metabolism, and these obesity-induced regulatory dysfunctions improved significantly 6 months after SG.

Keywords

Metabolomics Sleeve gastrectomy Hyperinsulinemic-euglycemic clamp Branched-chain amino acids Asians Morbid obesity 

Notes

Acknowledgments

All authors were involved in writing the paper and had final approval of the submitted and published version. The authors would like to thank Vieon Wu and Valerie Lai for their research coordinating efforts and Mhd Asyraf Razali for his assistance in conducting the study. We gratefully acknowledge SingHealth IMU for their site and support and Garrett Ong, Chng Jian Hong, Tan Tsze Yin, and Ee Kim Huey for their laboratory expertise. We would like to thank all the study volunteers.

Funding

This study was supported by the SingHealth Foundation Grant.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Consent Statement

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

Supplementary material

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Supplementary Figure 1

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Supplementary Figure 2

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High resolution image (TIFF 446 kb)

References

  1. 1.
    Heymsfield SB, Wadden TA. Mechanisms, pathophysiology, and management of obesity. N Engl J Med. 2017;376(3):254–66.CrossRefGoogle Scholar
  2. 2.
    Torgerson JS, Hauptman J, Boldrin MN, et al. 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. 2004;27(1):155–61.Google Scholar
  3. 3.
    Cercato C, Roizenblatt VA, Leanca CC, et al. A randomized double-blind placebo-controlled study of the long-term efficacy and safety of diethylpropion in the treatment of obese subjects. Int J Obes (2005). 2009;33(8):857–65.Google Scholar
  4. 4.
    Sjostrom L, Narbro K, Sjostrom CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741–52.Google Scholar
  5. 5.
    Grenier-Larouche T, Carreau AM, Carpentier AC. Early metabolic improvement after bariatric surgery: the first steps toward remission of type 2 diabetes. Can J Diabetes 2017;41(4):418–425. Epub 2017/03/21. eng.Google Scholar
  6. 6.
    Dimitriadis G, Mitrou P, Lambadiari V, et al. Insulin effects in muscle and adipose tissue. Diabetes Res Clin Pract. 2011;93(Suppl 1):S52–9.Google Scholar
  7. 7.
    Caballero B, Wurtman RJ. Differential effects of insulin resistance on leucine and glucose kinetics in obesity. Metabolism: Clin Exp. 1991;40(1):51–8.CrossRefGoogle Scholar
  8. 8.
    Newgard CB, An J, Bain JR, 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(4):311–26.Google Scholar
  9. 9.
    Mihalik SJ, Goodpaster BH, Kelley DE, et al. Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity. Obesity (Silver Spring, Md). 2010 Sep;18(9):1695–700.Google Scholar
  10. 10.
    Laferrere B, Reilly D, Arias S, et al. Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss. Sci Transl Med. 2011;3(80):80re2.Google Scholar
  11. 11.
    Khoo CM, Muehlbauer MJ, Stevens RD, et al. Postprandial metabolite profiles reveal differential nutrient handling after bariatric surgery compared with matched caloric restriction. Ann Surg. 2014 Apr;259(4):687–93.Google Scholar
  12. 12.
    Sinclair P, Docherty N, le Roux CW. Metabolic effects of bariatric surgery. Clin Chem. 2018;64(1):72–81.CrossRefGoogle Scholar
  13. 13.
    Lomanto D, Lee WJ, Goel R, et al. Bariatric surgery in Asia in the last 5 years (2005-2009). Obes Surg. 2012;22(3):502–6.Google Scholar
  14. 14.
    Toh BC, Chan WH, Eng AKH, et al. Five-year long-term clinical outcome after bariatric metabolic surgery: a multi-ethnic Asian population in Singapore. Diabetes Obes Metab. 2018;20Google Scholar
  15. 15.
    Chan JC, Malik V, Jia W, et al. Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA. 2009;301(20):2129–40.Google Scholar
  16. 16.
    Nanditha A, Ma RC, Ramachandran A, et al. Diabetes in Asia and the Pacific: implications for the global epidemic. Diabetes Care. 2016;39(3):472–85.Google Scholar
  17. 17.
    Tan HC, Khoo CM, Tan MZ, et al. The effects of sleeve gastrectomy and gastric bypass on branched-chain amino acid metabolism 1 year after bariatric surgery. Obes Surg. 2016;26(8):1830–5.Google Scholar
  18. 18.
    Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985 Jul;28(7):412–9. Epub 1985/07/01. engGoogle Scholar
  19. 19.
    Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999;22(9):1462–70.CrossRefGoogle Scholar
  20. 20.
    DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Phys. 1979;237(3):E214–23.Google Scholar
  21. 21.
    Kim SH. Measurement of insulin action: a tribute to Sir Harold Himsworth. Diabetic Medicine. 2011;28(12):1487–93.CrossRefGoogle Scholar
  22. 22.
    Vencio S, Stival A, Halpern A, et al. Early mechanisms of glucose improvement following laparoscopic ileal interposition associated with a sleeve gastrectomy evaluated by the euglycemic hyperinsulinemic clamp in type 2 diabetic patients with BMI below 35. Dig Surg. 2011;28(4):293–8.Google Scholar
  23. 23.
    Immonen H, Hannukainen JC, Iozzo P, et al. Effect of bariatric surgery on liver glucose metabolism in morbidly obese diabetic and non-diabetic patients. J Hepatol. 2014 Feb;60(2):377–83.Google Scholar
  24. 24.
    Bradley D, Magkos F, Eagon JC, et al. Matched weight loss induced by sleeve gastrectomy or gastric bypass similarly improves metabolic function in obese subjects. Obesity (Silver Spring, Md). 2014;22(9):2026–31.Google Scholar
  25. 25.
    Casella G, Soricelli E, Castagneto-Gissey L, et al. Changes in insulin sensitivity and secretion after sleeve gastrectomy. Br J Surg. 2016;103(3):242–8.Google Scholar
  26. 26.
    Wang TJ, Larson MG, Vasan RS, et al. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011;17(4):448–53.Google Scholar
  27. 27.
    Lynch CJ, Adams SH. Branched-chain amino acids in metabolic signalling and insulin resistance. Nat Rev Endocrinol. 2014;10(12):723–36.CrossRefGoogle Scholar
  28. 28.
    Lips MA, Van Klinken JB, van Harmelen V, et al. Roux-en-Y gastric bypass surgery, but not calorie restriction, reduces plasma branched-chain amino acids in obese women independent of weight loss or the presence of type 2 diabetes. Diabetes Care. 2014;37(12):3150–6.Google Scholar
  29. 29.
    Jensen MD, Haymond MW. Protein metabolism in obesity: effects of body fat distribution and hyperinsulinemia on leucine turnover. Am J Clin Nutr. 1991;53(1):172–6.CrossRefGoogle Scholar
  30. 30.
    Luzi L, Castellino P, DeFronzo RA. Insulin and hyperaminoacidemia regulate by a different mechanism leucine turnover and oxidation in obesity. Am J Phys. 1996;270(2 Pt 1):E273–81.Google Scholar
  31. 31.
    Magkos F, Bradley D, Schweitzer GG, et al. Effect of Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding on branched-chain amino acid metabolism. Diabetes. 2013;62(8):2757–61.Google Scholar
  32. 32.
    Glynn EL, Piner LW, Huffman KM, et al. Impact of combined resistance and aerobic exercise training on branched-chain amino acid turnover, glycine metabolism and insulin sensitivity in overweight humans. Diabetologia. 2015;58(10):2324–35.Google Scholar
  33. 33.
    Wang W, Wu Z, Dai Z, et al. Glycine metabolism in animals and humans: implications for nutrition and health. Amino Acids. 2013 Sep;45(3):463–77.Google Scholar
  34. 34.
    Chng CL, Lim AY, Tan HC, et al. Physiological and metabolic changes during the transition from hyperthyroidism to euthyroidism in Graves’ disease. Thyroid : Off J Am Thyroid Assoc. 2016;26(10):1422–30.Google Scholar
  35. 35.
    Camastra S, Gastaldelli A, Mari A, et al. Early and longer term effects of gastric bypass surgery on tissue-specific insulin sensitivity and beta cell function in morbidly obese patients with and without type 2 diabetes. Diabetologia. 2011;54(8):2093–102.Google Scholar
  36. 36.
    Kelley DE, Goodpaster B, Wing RR, et al. Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. Am J Phys. 1999;277(6 Pt 1):E1130–41.Google Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Duke-NUS Medical SchoolSingaporeSingapore
  2. 2.Cardiovascular Metabolic ProgramDuke-NUS Medical SchoolSingaporeSingapore
  3. 3.Department of Clinical ResearchSingapore General HospitalSingaporeSingapore
  4. 4.Department of Endocrinology, The Academia Level 3Singapore General HospitalSingaporeSingapore
  5. 5.Department of Upper Gastrointestinal and Bariatric SurgerySingapore General HospitalSingaporeSingapore

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