Prospective Evaluation of Insulin and Incretin Dynamics in Obese Adults With and Without Diabetes for 2 Years After Roux-en-Y Gastric Bypass

Diabetologia. 2018 May;61(5):1142-1154. doi: 10.1007/s00125-018-4553-y. Epub 2018 Feb 10.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes Mellitus / metabolism*
  • Female
  • Gastric Bypass*
  • Humans
  • Incretins / metabolism*
  • Insulin / metabolism*
  • Islets of Langerhans / metabolism
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Obesity / metabolism*
  • Obesity / surgery*
  • Postoperative Period
  • Prospective Studies
  • Remission Induction
  • Time Factors
  • Weight Loss

Substances

  • Incretins
  • Insulin

Associated data

  • ClinicalTrials.gov/NCT00433810