Mechanisms of type 2 diabetes resolution after Roux-en-Y gastric bypass.

Abstract

BACKGROUND:

Bariatric surgery is the most effective treatment for the reduction of weight and resolution of type 2 diabetes mellitus (T2 DM). The objective of this study was to longitudinally assess hormonal and tissue responses after RYGB.

METHODS:

Eight patients (5 with T2 DM) were studied before and after RYGB. A standardized test meal (STM) was administered before and at 1, 3, 6, 9, 12, and 15 months. Separately, a 2-hour hyperinsulinemic-euglycemic clamp (E-clamp) and a 2-hour hyperglycemic clamp (H-clamp) were performed before and at 1, 3, 6, and 12 months. Glucagon-like peptide-1 (GLP-1) was infused during the last hour of the H-clamp. Body composition was assessed with DXA methodology.

RESULTS:

Enrollment body mass index was 49±3 kg/m(2) (X±SE). STM glucose and insulin responses were normalized by 3 and 6 months. GLP-1 level increased dramatically at 1, 3, and 6 months, normalizing by 12 and 15 months. Insulin sensitivity (M of E-clamp) increased progressively at 3-12 months as fat mass decreased. The insulin response to glucose alone fell progressively over 12 months but the glucose clearance/metabolism (M of H-clamp) did not change significantly until 12 months. In response to GLP-1 infusion, insulin levels fell progressively throughout the 12 months.

CONCLUSION:

The early hypersecretion of GLP-1 leads to hyperinsulinemia and early normalization of glucose levels. The GLP-1 response normalizes within 1 year after surgery. Enhanced peripheral tissue sensitivity to insulin starts at 3 months and is associated with fat mass loss. β-cell sensitivity improves at 12 months and after the loss of ≈33% of excess weight. There is a tightly controlled feedback loop between peripheral tissue sensitivity and β-cell and L-cell (GLP-1) responses.

• Authors: Dariush Elahi, Panagis Galiatsatos, Atoosa Rabiee, Rocio Salas-Carrillo, Amin Vakilipour, Olga D Carlson, Franca S Angeli, Richard P Shannon, Josephine M Egan, Dana K Andersen
• Journal: Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery (Surg Obes Relat Dis) 2014 Nov-Dec Vol. 10 Issue 6 Pg. 1028-39 ISSN: 1878-7533 [Electronic] United States
• PMID: 25443077 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 American Society for Bariatric Surgery. All rights reserved.

Chemical References

• Biomarkers
• Blood Glucose
• C-Peptide
• Insulin
• Glucagon-Like Peptide 1
• Glucagon

Topics

• Absorptiometry, Photon
• Biomarkers (blood)
• Blood Glucose (analysis)
• Body Composition
• Body Mass Index
• C-Peptide (blood)
• Diabetes Mellitus, Type 2 (prevention & control)
• Enzyme-Linked Immunosorbent Assay
• Female
• Gastric Bypass (methods)
• Glucagon (blood)
• Glucagon-Like Peptide 1 (administration & dosage, blood)
• Glucose Clamp Technique
• Humans
• Insulin (blood)
• Male
• Middle Aged
• Obesity, Morbid (surgery)
• Weight Loss