@article{8811e0abf4e44894bafc9587b0bd2180,
title = "Prospective evaluation of insulin and incretin dynamics in obese adults with and without diabetes for 2 years after Roux-en-Y gastric bypass",
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.",
keywords = "Disposition index, Frequently-sampled intravenous glucose tolerance test, GIP, GLP-1, Gastric bypass, Glucagon, Insulin secretion, Insulin sensitivity, Lipids, Meal test, Obesity, Proinsulin, Remission",
author = "Purnell, {Jonathan Q.} and Johnson, {Geoffrey S.} and Wahed, {Abdus S.} and {Dalla Man}, Chiara and Francesca Piccinini and Claudio Cobelli and Prigeon, {Ronald L.} and Goodpaster, {Bret H.} and Kelley, {David E.} and Staten, {Myrlene A.} and Foster-Schubert, {Karen E.} and Cummings, {David E.} and Flum, {David R.} and Courcoulas, {Anita P.} and Havel, {Peter J.} and Wolfe, {Bruce M.}",
note = "Funding Information: Funding This clinical study was a cooperative agreement funded by the NIDDK (grant nos R01-DK103842, DCC-U01 DK066557). The following grants were received by the study centres: Columbia–U01-DK66667 (in collaboration with Cornell University Medical Center CTRC, Grant UL1-RR024996); University of Washington–U01-DK66568 (in collaboration with CTRC, Grant M01RR-00037); Neuropsychiatric Research Institute–U01-DK66471; East Carolina University–U01-DK66526; University of Pittsburgh Medical Center–U01-DK66585 (in collaboration with CTRC, Grant UL1-RR024153) and Oregon Health & Science University–U01-DK66555. PJH{\textquoteright}s laboratory receives funding from NIH grants DK-09596, DK-092993, HL-107256 and HL-121324 and a Multi-campus Award from the University of California, Office of the President. Funding Information: Duality of interest JQP receives consultant income for services on an advisory board for Novo Nordisk and receives grant funding from the NIH. CC holds ten patents and patent applications related to glucose sensors and artificial pancreas, received non-financial support from Roche and Dexcom, Inc., research support from Dexcom, Inc., Sanofi Aventis and Adocia and consultant income for services on an advisory board for Novo Nordisk. From 2007–2017, DEK was a full-time employee of Merck & Co. Inc., receiving salary and stock, but is now retired. DEC receives research support from Johnson & Johnson, the NIH and Medtronic. DRF receives consulting fees from Pacira Pharm and Patient Centered outcomes with Surgical Consulting LLC. APC receives grant support from the NIH and Covidien/Ethicon J&J. All other authors declare that there is no duality of interest associated with their contribution to this manuscript. Funding Information: We would like to thank J. Ng and J. Lowry, at the University of Pittsburgh for their contributions to the conduct of the study. We also thank the LABS personnel at Oregon Health & Science University, Portland, OR, USA (C. Cassady, E. Coburn, E. Moher, C. Deveney, K. Elder, S. Greene, J. Purnell, R. O?Rourke, C. Sorenson, B. M. Wolfe), Legacy Good Samaritan Hospital, Portland, OR, USA (E. Patterson, W. Raum, L. VanDerWerff, J. Kwiatkowski), University of Pittsburgh Medical Center, Pittsburgh, PA, USA (A. P. Courcoulas, W. Gourash, C. A. McCloskey, R. Ramanathan, M. Kalarchian, M. Marcus, E. Shirley, A. Turo), University of Washington, Seattle, WA, USA (D. R. Flum, E. Patchen Dellinger, S. Khandelwal, S. D. Stewart, M. M. Cooley, R. Blissell, M. J. Miller, D. E. Cummings, K.E. Foster-Schubert), Virginia Mason Medical Center, Seattle, WA, USA (R. Thirlby, L. Chang, J. Hunter, R. Moonka, D. Ng), MA Data Coordinating Center, Graduate School of Public Health at the University of Pittsburgh, Pittsburgh, PA, USA (S. H. Belle, W. C. King, D. Martin, R. Mercurio, A. Wahed, F. Averbach) and RDN National Institute of Diabetes and Digestive and Kidney Diseases (M. Horlick, C. W. Miles, M. A. Staten, S. Z. Yanovski). JQP contributed to study design, data acquisition and data analysis. GSJ, ASW, CDM, FP, CC, and RLP analysed data. KEF-S contributed to data acquisition. BHG, PJH, DEK, MAS, DEC, DRF and APC contributed to study conception and design. BMW contributed to study design and data acquisition. All authors contributed to the drafting and revision of this manuscript and provided approval of this final version. JQP is the guarantor of this work. JQP receives consultant income for services on an advisory board for Novo Nordisk and receives grant funding from the NIH. CC holds ten patents and patent applications related to glucose sensors and artificial pancreas, received non-financial support from Roche and Dexcom, Inc., research support from Dexcom, Inc., Sanofi Aventis and Adocia and consultant income for services on an advisory board for Novo Nordisk. From 2007?2017, DEK was a full-time employee of Merck & Co. Inc., receiving salary and stock, but is now retired. DEC receives research support from Johnson & Johnson, the NIH and Medtronic. DRF receives consulting fees from Pacira Pharm and Patient Centered outcomes with Surgical Consulting LLC. APC receives grant support from the NIH and Covidien/Ethicon J&J. All other authors declare that there is no duality of interest associated with their contribution to this manuscript. Publisher Copyright: {\textcopyright} 2018, Springer-Verlag GmbH Germany, part of Springer Nature.",
year = "2018",
month = may,
day = "1",
doi = "10.1007/s00125-018-4553-y",
language = "English (US)",
volume = "61",
pages = "1142--1154",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "5",
}