Improved acylated ghrelin suppression at 2 years in obese patients with type 2 diabetes: effects of bariatric surgery vs standard medical therapy

• Published in: International Journal of Obesity Vol. 38; no. 3; pp. 364 - 370
• Main Authors: Malin, S K, Samat, A, Wolski, K, Abood, B, Pothier, C E, Bhatt, D L, Nissen, S, Brethauer, S A, Schauer, P R, Kirwan, J P, Kashyap, S R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2014; Nature Publishing Group
• Subjects: 631/443/319; 692/699/2743/137/773; 692/699/2743/393; 692/700/565/545/2098; Absorptiometry, Photon; Acylation; Anti-Obesity Agents; Appetite; bariatric-and-metabolic-surgery-original-article; Beta cells; Biological and medical sciences; Blood Glucose - metabolism; Body composition; Body fat; Body Mass Index; Body size; Care and treatment; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - surgery; Diabetes. Impaired glucose tolerance; Dual energy X-ray absorptiometry; Endocrine pancreas. Apud cells (diseases); Endocrinology; Endocrinopathies; Epidemiology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fasting; Feeding Behavior; Female; Gastrectomy; Gastric Bypass; Gastrointestinal surgery; Ghrelin; Ghrelin - metabolism; Glucagon; Glucagon-like peptide 1; Glucose; Glucose metabolism; Glycated Hemoglobin A - metabolism; Health Promotion and Disease Prevention; Hemoglobin; Humans; Indexing; Insulin; Insulin - metabolism; Insulin resistance; Insulin Secretion; Internal Medicine; Laboratory testing; Male; Measurement; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolism; Middle Aged; Nutrition therapy; Obesity; Obesity, Morbid - complications; Obesity, Morbid - metabolism; Obesity, Morbid - surgery; Patient outcomes; Patients; Peptides; Physiological aspects; Postprandial Period; Prospective Studies; Public Health; Secretion; Stomach, duodenum, intestine, rectum, anus; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; Treatment Outcome; Type 2 diabetes; Weight control; Weight Loss; United States > US; bariatric surgery; insulin secretion; gastrointestinal hormones; glycemic control; diabetes; insulin resistance; Endocrinopathy; Type 2 diabetes; Pancreatic hormone; Suppression; Bariatric surgery; Gastrointestinal hormone; Ghrelin; Nutritional status; Human; Glycemic control; Obesity; Nutrition; Secretion; Nutrition disorder; Patient; Metabolic diseases; Insulin; Standards; Appetite stimulant; Medicine; Target tissue resistance; Treatment; Insulin resistance; Comparative study; Glycemia
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2013.196

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 (HbA 1c (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.