title: Improved acylated ghrelin suppression at 2 years in obese patients with type 2 diabetes: effects of bariatric surgery vs standard medical therapy.
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.
  
  
  METHODS
  STAMPEDE (Surgical Treatment and Medication Potentially Eradicate Diabetes Efficiently) was a prospective, randomized controlled trial.
  
  
  METHODS
  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.
authors.affiliation: 1] Department of Pathobiology, Cleveland Clinic, Cleveland, OH, USA [2] Department of Nutrition, Case Western Reserve University, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Malin
authors.affiliation: Department of Endocrinology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: A
authors.initials: A
authors.lastname: Samat
authors.affiliation: Department of Heart and Vascular, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: K
authors.initials: K
authors.lastname: Wolski
authors.affiliation: Department of Endocrinology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: B
authors.initials: B
authors.lastname: Abood
authors.affiliation: Department of Heart and Vascular, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Pothier
authors.affiliation: Veterans Affairs Boston Healthcare System, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Bhatt
authors.affiliation: Department of Heart and Vascular, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: S
authors.initials: S
authors.lastname: Nissen
authors.affiliation: 1] Department of Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, OH, USA [2] Metabolic Translational Research Center, Endocrine and Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Brethauer
authors.affiliation: 1] Department of Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, OH, USA [2] Metabolic Translational Research Center, Endocrine and Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: P R
authors.initials: PR
authors.lastname: Schauer
authors.affiliation: 1] Department of Pathobiology, Cleveland Clinic, Cleveland, OH, USA [2] Department of Nutrition, Case Western Reserve University, Cleveland Clinic, Cleveland, OH, USA [3] Metabolic Translational Research Center, Endocrine and Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Kirwan
authors.affiliation: 1] Department of Endocrinology, Cleveland Clinic, Cleveland, OH, USA [2] Metabolic Translational Research Center, Endocrine and Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Kashyap
mesh_terms: D015502:Absorptiometry, Photon; D000215:Acylation; D019440:Anti-Obesity Agents; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000601:surgery; D005247:Feeding Behavior; D005260:Female; D015390:Gastric Bypass; D054439:Ghrelin / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000150:complications / Q000378:metabolism* / Q000601:surgery; D019518:Postprandial Period; D011446:Prospective Studies; D016896:Treatment Outcome; D015431:Weight Loss
chemical_list: D019440:Anti-Obesity Agents; D001786:Blood Glucose; D054439:Ghrelin; D006442:Glycated Hemoglobin; D007328:Insulin; C517652:hemoglobin A1c protein, human