Jonathan Q Purnell1, Geoffrey S Johnson2, Abdus S Wahed2, Chiara Dalla Man3, Francesca Piccinini3, Claudio Cobelli3, Ronald L Prigeon4, Bret H Goodpaster5, David E Kelley6, Myrlene A Staten7, Karen E Foster-Schubert8, David E Cummings8, David R Flum9, Anita P Courcoulas10, Peter J Havel11, Bruce M Wolfe12. 1. Department of Medicine, The Knight Cardiovascular Institute, Mailcode MDYMI, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA. purnellj@ohsu.edu. 2. Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. 3. Department of Information Engineering, University of Padova, Padova, Italy. 4. VA Maryland Health Care System, Baltimore, MD, USA. 5. Translational Research Institute for Metabolism and Diabetes, Sanford-Burnham Institute, Orlando, FL, USA. 6. Merck & Co., Whitehouse, NJ, USA. 7. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD, USA. 8. Department of Medicine, University of Washington, Seattle, WA, USA. 9. Department of Surgery, University of Washington, Seattle, WA, USA. 10. Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA. 11. Departments of Molecular Biosciences and Nutrition, University of California, Davis, Davis, CA, USA. 12. Department of Surgery, Oregon Health & Science University, Portland, OR, USA.
Abstract
AIMS/HYPOTHESIS: In this prospective case-control study we tested the hypothesis that, while long-term improvements in insulin sensitivity (SI) accompanying weight loss after Roux-en-Y gastric bypass (RYGB) would be similar in obese individuals with and without type 2 diabetes mellitus, stimulated-islet-cell insulin responses would differ, increasing (recovering) in those with diabetes but decreasing in those without. We investigated whether these changes would occur in conjunction with favourable alterations in meal-related gut hormone secretion and insulin processing. METHODS: Forty participants with type 2 diabetes and 22 participants without diabetes from the Longitudinal Assessment of Bariatric Surgery (LABS-2) study were enrolled in a separate, longitudinal cohort (LABS-3 Diabetes) to examine the mechanisms of postsurgical diabetes improvement. Study procedures included measures of SI, islet secretory response and gastrointestinal hormone secretion after both intravenous glucose (frequently-sampled IVGTT [FSIVGTT]) and a mixed meal (MM) prior to and up to 24 months after RYGB. RESULTS: Postoperatively, weight loss and SI-FSIVGTT improvement was similar in both groups, whereas the acute insulin response to glucose (AIRglu) decreased in the non-diabetic participants and increased in the participants with type 2 diabetes. The resulting disposition indices (DIFSIVGTT) increased by three- to ninefold in both groups. In contrast, during the MM, total insulin responsiveness did not significantly change in either group despite durable increases of up to eightfold in postprandial glucagon-like peptide 1 levels, and SI-MM and DIMM increased only in the diabetes group. Peak postprandial glucagon levels increased in both groups. CONCLUSIONS/ INTERPRETATION: For up to 2 years following RYGB, obese participants without diabetes showed improvements in DI that approach population norms. Those with type 2 diabetes recovered islet-cell insulin secretion response yet continued to manifest abnormal insulin processing, with DI values that remained well below population norms. These data suggest that, rather than waiting for lifestyle or medical failure, RYGB is ideally considered before, or as soon as possible after, onset of type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00433810.
AIMS/HYPOTHESIS: In this prospective case-control study we tested the hypothesis that, while long-term improvements in insulin sensitivity (SI) accompanying weight loss after Roux-en-Y gastric bypass (RYGB) would be similar in obese individuals with and without type 2 diabetes mellitus, stimulated-islet-cell insulin responses would differ, increasing (recovering) in those with diabetes but decreasing in those without. We investigated whether these changes would occur in conjunction with favourable alterations in meal-related gut hormone secretion and insulin processing. METHODS: Forty participants with type 2 diabetes and 22 participants without diabetes from the Longitudinal Assessment of Bariatric Surgery (LABS-2) study were enrolled in a separate, longitudinal cohort (LABS-3 Diabetes) to examine the mechanisms of postsurgical diabetes improvement. Study procedures included measures of SI, islet secretory response and gastrointestinal hormone secretion after both intravenous glucose (frequently-sampled IVGTT [FSIVGTT]) and a mixed meal (MM) prior to and up to 24 months after RYGB. RESULTS: Postoperatively, weight loss and SI-FSIVGTT improvement was similar in both groups, whereas the acute insulin response to glucose (AIRglu) decreased in the non-diabeticparticipants and increased in the participants with type 2 diabetes. The resulting disposition indices (DIFSIVGTT) increased by three- to ninefold in both groups. In contrast, during the MM, total insulin responsiveness did not significantly change in either group despite durable increases of up to eightfold in postprandial glucagon-like peptide 1 levels, and SI-MM and DIMM increased only in the diabetes group. Peak postprandial glucagon levels increased in both groups. CONCLUSIONS/ INTERPRETATION: For up to 2 years following RYGB, obeseparticipants without diabetes showed improvements in DI that approach population norms. Those with type 2 diabetes recovered islet-cell insulin secretion response yet continued to manifest abnormal insulin processing, with DI values that remained well below population norms. These data suggest that, rather than waiting for lifestyle or medical failure, RYGB is ideally considered before, or as soon as possible after, onset of type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00433810.
Authors: Chiara Dalla Man; Marco Campioni; Kenneth S Polonsky; Rita Basu; Robert A Rizza; Gianna Toffolo; Claudio Cobelli Journal: Diabetes Date: 2005-11 Impact factor: 9.461
Authors: N B Jørgensen; S H Jacobsen; C Dirksen; K N Bojsen-Møller; L Naver; L Hvolris; T R Clausen; B S Wulff; D Worm; D Lindqvist Hansen; S Madsbad; J J Holst Journal: Am J Physiol Endocrinol Metab Date: 2012-04-24 Impact factor: 4.310
Authors: Steven H Belle; Paul D Berk; Anita P Courcoulas; David R Flum; Carolyn W Miles; James E Mitchell; Walter J Pories; Bruce M Wolfe; Susan Z Yanovski Journal: Surg Obes Relat Dis Date: 2007 Mar-Apr Impact factor: 4.734
Authors: John B Buse; Sonia Caprio; William T Cefalu; Antonio Ceriello; Stefano Del Prato; Silvio E Inzucchi; Sue McLaughlin; Gordon L Phillips; R Paul Robertson; Francesco Rubino; Richard Kahn; M Sue Kirkman Journal: Diabetes Care Date: 2009-11 Impact factor: 19.112
Authors: Bart J Van der Schueren; Peter Homel; Mariam Alam; Keesandra Agenor; Gary Wang; David Reilly; Blandine Laferrère Journal: Diabetes Care Date: 2011-11-28 Impact factor: 19.112
Authors: Philippe A Halban; Kenneth S Polonsky; Donald W Bowden; Meredith A Hawkins; Charlotte Ling; Kieren J Mather; Alvin C Powers; Christopher J Rhodes; Lori Sussel; Gordon C Weir Journal: Diabetes Care Date: 2014-05-08 Impact factor: 19.112
Authors: Cui Yang; Julia Brecht; Christel Weiß; Christoph Reissfelder; Mirko Otto; Jane N Buchwald; Georgi Vassilev Journal: Obes Surg Date: 2021-08-30 Impact factor: 3.479
Authors: Jonathan Q Purnell; Elizabeth N Dewey; Blandine Laferrère; Faith Selzer; David R Flum; James E Mitchell; Alfons Pomp; Walter J Pories; Thomas Inge; Anita Courcoulas; Bruce M Wolfe Journal: J Clin Endocrinol Metab Date: 2021-03-08 Impact factor: 5.958
Authors: Steven E Kahn; Yi-Chun Chen; Nathalie Esser; Austin J Taylor; Daniël H van Raalte; Sakeneh Zraika; C Bruce Verchere Journal: Endocr Rev Date: 2021-09-28 Impact factor: 25.261