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  • Bariatric and Metabolic Surgery Original Article
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Improved acylated ghrelin suppression at 2 years in obese patients with type 2 diabetes: effects of bariatric surgery vs standard medical therapy

International Journal of Obesity volume 38, pages 364–370 (2014)Cite this article

Subjects

Abstract

Objective:

Roux-en-Y gastric bypass (RYGB) produces more durable glycemic control than sleeve gastrectomy (SG) or intensive medical therapy (IMT). However, the contribution of acylated ghrelin (AG), a gluco-regulatory/appetite hormone, to improve glucose metabolism and body composition in patients with type 2 diabetes (T2D) following RYGB is unknown.

Design:

STAMPEDE (Surgical Treatment and Medication Potentially Eradicate Diabetes Efficiently) was a prospective, randomized controlled trial.

Subjects:

Fifty-three (body mass index: 36±3 kg m−2, age: 49±9 years) poorly controlled patients with T2D (HbA1c (glycated hemoglobin): 9.7±2%) were randomized to IMT, IMT+RYGB or IMT+SG and underwent a mixed-meal tolerance test at baseline, 12, and 24 months for evaluation of AG suppression (postprandial minus fasting) and beta-cell function (oral disposition index; glucose-stimulated insulin secretion × Matsuda index). Total/android body fat (dual-energy X-ray absorptiometry) was also assessed.

Results:

RYGB and SG reduced body fat comparably (15–23 kg) at 12 and 24 months, whereas IMT had no effect. Beta-cell function increased 5.8-fold in RYGB and was greater than IMT at 24 months (P<0.001). However, there was no difference in insulin secretion between SG vs IMT at 24 months (P=0.32). Fasting AG was reduced fourfold following SG (P<0.01) and did not change with RYGB or IMT at 24 months. AG suppression improved more following RYGB than SG or IMT at 24 months (P=0.01 vs SG, P=0.07 vs IMT). At 24 months, AG suppression was associated with increased postprandial glucagon-like peptide-1 (r=−0.32, P<0.02) and decreased android fat (r=0.38; P<0.006).

Conclusions:

Enhanced AG suppression persists for up to 2 years after RYGB, and this effect is associated with decreased android obesity and improved insulin secretion. Together, these findings suggest that AG suppression is partly responsible for the improved glucose control after RYGB surgery.

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Acknowledgements

SKM, KW and SRK share responsibility for the integrity of analysis. All authors contributed to data collection and organization. Sarah Neale from the Cleveland Clinic Preventive Research Lab performed blood analysis. The Cleveland Clinic Coordinating Center for Clinical Research provided the database and statistical analysis. SKM wrote the manuscript and all authors provided edits. We thank the CRU and bariatric surgery nursing staff for their outstanding assistance and all the participants for their efforts. This research was supported by Ethicon endo-surgery EESIIS 19900 (PRS), American Diabetes Association clinical translational award 1-11-26 CT (SRK), NIH RO1-DK089547 (PRS, SRK, JPK), and the National Institutes of Health National Center for Research Resources, 1UL1RR024989, Cleveland, OH, USA. SKM was supported by a T32 DK007319 Grant.

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Authors and Affiliations

  1. Department of Pathobiology, Cleveland Clinic, Cleveland, OH, USA

    S K Malin & J P Kirwan

  2. Department of Nutrition, Case Western Reserve University, Cleveland Clinic, Cleveland, OH, USA

    S K Malin & J P Kirwan

  3. Department of Endocrinology, Cleveland Clinic, Cleveland, OH, USA

    A Samat, B Abood & S R Kashyap

  4. Department of Heart and Vascular, Cleveland Clinic, Cleveland, OH, USA

    K Wolski, C E Pothier & S Nissen

  5. Veterans Affairs Boston Healthcare System, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA

    D L Bhatt

  6. Department of Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, OH, USA

    S A Brethauer & P R Schauer

  7. Metabolic Translational Research Center, Endocrine and Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA

    S A Brethauer, P R Schauer, J P Kirwan & S R Kashyap

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Correspondence to S R Kashyap.

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Competing interests

SRK obtained research grants from Ethicon Endo-surgery, National Institutes of Health and American Diabetes Association. DLB—Advisory Board: Medscape Cardiology; Board of Directors: Boston VA Research Institute, Society of Chest Pain Centers; Chair: American Heart Association Get With The Guidelines Science Subcommittee; Honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention) and WebMD (CME steering committees); research grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis and The Medicines Company; unfunded research: PLx Pharma and Takeda. PRS obtained research grants from Ethicon Endo-surgery, National Institutes of Health and Bard-Davol; educational grants from Stryker Endoscopy, Gore, Baxter, Covidien and Allergan: honoraria from Ethicon Endo-surgery as scientific advisory board member, consultant and speaker. He has been a consultant/advisory board member for RemedyMD, StrykerEndoscopy, Bard-Davol, Gore, Barosense, Surgiquest and Carefusion. SAB receives honoraria from Ethicon Endo-Surgery as scientific advisory board member, consultant and speaker and honoraria from Covidien for speaking. SN has consulted with Orexigen and Vivus. JPK receives grant funding from the National Institutes of Health, Nestle Inc. and ScottCare. All the other authors declare no conflict of interest.

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Malin, S., Samat, A., Wolski, K. et al. Improved acylated ghrelin suppression at 2 years in obese patients with type 2 diabetes: effects of bariatric surgery vs standard medical therapy. Int J Obes 38, 364–370 (2014). https://doi.org/10.1038/ijo.2013.196

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