Immediate enhancement of first-phase insulin secretion and unchanged glucose effectiveness in patients with type 2 diabetes after Roux-en-Y gastric bypass

Am J Physiol Endocrinol Metab. 2015 Mar 15;308(6):E535-44. doi: 10.1152/ajpendo.00506.2014. Epub 2015 Jan 27.

Abstract

Roux-en-Y gastric bypass surgery (RYGB) in patients with type 2 diabetes often leads to early disease remission, and it is unknown to what extent this involves improved pancreatic β-cell function per se and/or enhanced insulin- and non-insulin-mediated glucose disposal (glucose effectiveness). We studied 30 obese patients, including 10 with type 2 diabetes, 8 with impaired glucose tolerance, and 12 with normal glucose tolerance before, 1 wk, and 3 mo after RYGB, using an intravenous glucose tolerance test (IVGTT) to estimate first-phase insulin response, insulin sensitivity (Si), and glucose effectiveness with Bergman's minimal model. In the fasting state, insulin sensitivity was estimated by HOMA-S and β-cell function by HOMA-β. Moreover, mixed-meal tests and oral GTTs were performed. In patients with type 2 diabetes, glucose levels normalized after RYGB, first-phase insulin secretion in response to iv glucose increased twofold, and HOMA-β already improved 1 wk postoperatively, with further enhancements at 3 mo. Insulin sensitivity increased in the liver (HOMA-S) at 1 wk and at 3 mo in peripheral tissues (Si), whereas glucose effectiveness did not improve significantly. During oral testing, GLP-1 responses and insulin secretion increased regardless of glucose tolerance. Therefore, in addition to increased insulin sensitivity and exaggerated postprandial GLP-1 levels, diabetes remission after RYGB involves early improvement of pancreatic β-cell function per se, reflected in enhanced first-phase insulin secretion to iv glucose and increased HOMA-β. A major role for improved glucose effectiveness after RYGB was not supported by this study.

Trial registration: ClinicalTrials.gov NCT01993511.

Keywords: first-phase insulin secretion; glucose effectiveness; insulin sensitivity; type 2 diabetes; β-cell function.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism*
  • Body Weight / physiology
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / surgery*
  • Fasting / metabolism
  • Gastric Bypass* / rehabilitation
  • Glucose Intolerance / metabolism
  • Glucose Intolerance / surgery
  • Glucose Tolerance Test
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Middle Aged
  • Obesity / metabolism
  • Obesity / surgery
  • Postoperative Period

Substances

  • Blood Glucose
  • Insulin

Associated data

  • ClinicalTrials.gov/NCT01993511