TY - JOUR
T1 - Mechanisms of type 2 diabetes resolution after Roux-en-Y gastric bypass
AU - Elahi, Dariush
AU - Galiatsatos, Panagis
AU - Rabiee, Atoosa
AU - Salas-Carrillo, Rocio
AU - Vakilipour, Amin
AU - Carlson, Olga D.
AU - Angeli, Franca S.
AU - Shannon, Richard P.
AU - Egan, Josephine M.
AU - Andersen, Dana K.
N1 - Publisher Copyright:
© 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - 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/m2 (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.
AB - 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/m2 (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.
KW - Hyperglycemic clamp
KW - Hyperinsulinemic-euglycemic clamp
KW - RYGB
KW - Standardized test meal
KW - Type 2 diabetes mellitus
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U2 - 10.1016/j.soard.2014.07.011
DO - 10.1016/j.soard.2014.07.011
M3 - Article
C2 - 25443077
AN - SCOPUS:84916937997
SN - 1550-7289
VL - 10
SP - 1028
EP - 1039
JO - Surgery for Obesity and Related Diseases
JF - Surgery for Obesity and Related Diseases
IS - 6
ER -