Prospective evaluation of insulin and incretin dynamics in obese adults with and without diabetes for 2 years after Roux-en-Y gastric bypass

Jonathan Q. Purnell, Geoffrey S. Johnson, Abdus S. Wahed, Chiara Dalla Man, Francesca Piccinini, Claudio Cobelli, Ronald L. Prigeon, Bret H. Goodpaster, David E. Kelley, Myrlene A. Staten, Karen E. Foster-Schubert, David E. Cummings, David R. Flum, Anita P. Courcoulas, Peter J Havel, Bruce M. Wolfe

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.govNCT00433810

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalDiabetologia
DOIs
StateAccepted/In press - Feb 10 2018

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Incretins
Gastric Bypass
Type 2 Diabetes Mellitus
Insulin
Meals
Islets of Langerhans
Weight Loss
Gastrointestinal Hormones
Glucose
Glucagon-Like Peptide 1
Bariatric Surgery
Glucagon
Population
Insulin Resistance
Life Style
Hormones
Prospective Studies

Keywords

  • Disposition index
  • Frequently-sampled intravenous glucose tolerance test
  • Gastric bypass
  • GIP
  • GLP-1
  • Glucagon
  • Insulin secretion
  • Insulin sensitivity
  • Lipids
  • Meal test
  • Obesity
  • Proinsulin
  • Remission

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Purnell, J. Q., Johnson, G. S., Wahed, A. S., Dalla Man, C., Piccinini, F., Cobelli, C., ... Wolfe, B. M. (Accepted/In press). Prospective evaluation of insulin and incretin dynamics in obese adults with and without diabetes for 2 years after Roux-en-Y gastric bypass. Diabetologia, 1-13. https://doi.org/10.1007/s00125-018-4553-y

Prospective evaluation of insulin and incretin dynamics in obese adults with and without diabetes for 2 years after Roux-en-Y gastric bypass. / Purnell, Jonathan Q.; Johnson, Geoffrey S.; Wahed, Abdus S.; Dalla Man, Chiara; Piccinini, Francesca; Cobelli, Claudio; Prigeon, Ronald L.; Goodpaster, Bret H.; Kelley, David E.; Staten, Myrlene A.; Foster-Schubert, Karen E.; Cummings, David E.; Flum, David R.; Courcoulas, Anita P.; Havel, Peter J; Wolfe, Bruce M.

In: Diabetologia, 10.02.2018, p. 1-13.

Research output: Contribution to journalArticle

Purnell, JQ, Johnson, GS, Wahed, AS, Dalla Man, C, Piccinini, F, Cobelli, C, Prigeon, RL, Goodpaster, BH, Kelley, DE, Staten, MA, Foster-Schubert, KE, Cummings, DE, Flum, DR, Courcoulas, AP, Havel, PJ & Wolfe, BM 2018, 'Prospective evaluation of insulin and incretin dynamics in obese adults with and without diabetes for 2 years after Roux-en-Y gastric bypass', Diabetologia, pp. 1-13. https://doi.org/10.1007/s00125-018-4553-y
Purnell, Jonathan Q. ; Johnson, Geoffrey S. ; Wahed, Abdus S. ; Dalla Man, Chiara ; Piccinini, Francesca ; Cobelli, Claudio ; Prigeon, Ronald L. ; Goodpaster, Bret H. ; Kelley, David E. ; Staten, Myrlene A. ; Foster-Schubert, Karen E. ; Cummings, David E. ; Flum, David R. ; Courcoulas, Anita P. ; Havel, Peter J ; Wolfe, Bruce M. / Prospective evaluation of insulin and incretin dynamics in obese adults with and without diabetes for 2 years after Roux-en-Y gastric bypass. In: Diabetologia. 2018 ; pp. 1-13.
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AU - Purnell, Jonathan Q.

AU - Johnson, Geoffrey S.

AU - Wahed, Abdus S.

AU - Dalla Man, Chiara

AU - Piccinini, Francesca

AU - Cobelli, Claudio

AU - Prigeon, Ronald L.

AU - Goodpaster, Bret H.

AU - Kelley, David E.

AU - Staten, Myrlene A.

AU - Foster-Schubert, Karen E.

AU - Cummings, David E.

AU - Flum, David R.

AU - Courcoulas, Anita P.

AU - Havel, Peter J

AU - Wolfe, Bruce M.

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N2 - 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.govNCT00433810

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KW - Glucagon

KW - Insulin secretion

KW - Insulin sensitivity

KW - Lipids

KW - Meal test

KW - Obesity

KW - Proinsulin

KW - Remission

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