Changes in Glucose Metabolism After Roux-en-Y Gastric Bypass

Besides causing weight loss Roux-en-Y gastric bypass (RYGB) has profound effect on glucose metabolism leading to remission of type 2 diabetes early after surgery. However the mechanisms for this improvement remain uncertain. The aim of this study is to investigate the changes in insulin sensitivity and beta-cell function 1 week and 3 months following RYGB using oral and intravenous test.

Study Overview

• Status: Unknown
• Conditions: Obesity; Type 2 Diabetes

Detailed Description

Investigators plan to study 24 obese patients already enrolled for Roux-en-y gastric bypass surgery (RYGB). 8 with type 2 diabetes (DM2), 8 with impaired glucose tolerance (IGT) and 8 with normal glucose tolerance (NGT) before, within the first week and 3 month after RYGB using a liquid mixed meal test (MMT) and an insulin modified frequently sampled intravenous glucose tolerance test (IM-FSIGT). Furthermore, an oral glucose tolerance test (OGTT) will be performed before and after 3 months. Blood will be sampled in fasting and during the tests measuring plasma glucose, insulin and C-peptid (OGTT, MMT and IM-FSIGT) and GLP-1, glucagon, GIP and GLP-2 (MMT). Beta-cell function will be assessed from the MMT (insulinogenic index - IGI), OGTT (IGI) and the IM-FSIGT (Acute insulin response, AIR) in order to examine whether changes in beta-cell function after RYGB depend on an oral stimulus. Insulin sensitivity will be assessed in fasting (HOMA-IR), during the IM-FSIGT (minimal model: Si) and from MMT/OGTT (Matsuda index). Insulin clearance/hepatic extraction of insulin will be assessed in fasting and during the intravenous and oral test.

• Study Type: Observational
• Enrollment (Anticipated): 24

Contacts and Locations

• Study Contact: Name: Anna Kirstine Bojsen-Møller, MD; Phone Number: +45 30 25 22 06; Email: kirstine.bojsen-moeller@regionh.dk
• Study Contact Backup: Name: Christoffer Martinussen, student; Phone Number: +45 22 44 55 30; Email: hjz387@alumni.ku.dk

Study Locations

• Denmark
  • Hvidovre
    • Copenhagen, Hvidovre, Denmark, 2650
      • Recruiting
      • Hvidovre University Hospital
      • Contact: Anna Kirstine Bojsen-Møller, MD; Phone Number: +45 30 25 22 06; Email: kirstine.bojsen-moeller@regionh.dk
      • Principal Investigator: Anna Kirstine Bojsen-Møller, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Morbid obese patients who are already enrolled for Roux-en-y gastric bypass surgery will be invited to participate (investigators do not assign patients to the surgery). 8 with type 2 diabetes, 8 with impaired glucose tolerance and 8 with normal glucose tolerance. Glucose tolerance will be assessed with an oral glucose tolerance test (OGTT) prior to surgery and prior to the other tests. Plasma glucose 120 minutes after OGTT will define glucose tolerance. Normal: < 7,8 mM. Impaired: 7,8 - 11,1 mM. Diabetic: >11,1 mM.

Subjects are recruited from the outpatient clinic of endocrinology and gastrosurgical clinic at Hvidovre University Hospital.

Description

Inclusion Criteria:

• patients eligible for RYGB, Age 18-60 years, BMI 35-60 kg/m2 at time of referral to operation, blood pressure <145/85, C-peptid>700 pmol/l.

Exclusion Criteria:

• Obesity caused by medical treatment for psychiatric disease. Mental retardation. Alcohol or drug abuse. Severe cardiopulmonary disease. History of peritonitis, ventricular disease, upper gastrointestinal surgery, recurrent oesophagitis or severe complications to general anesthesia. Bad compliance. Treatment with thyroid hormones or antithyroid treatment. Treatment with anorectic medicine later than 3 months prior to surgery. Furthermore prior to surgery each patient has to loose 8 % of bodyweight to reduce the risk of operative complications.

Before each test day all glucose lowering medication will be paused for an appropriate amount of time depending on the type of medicine.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
RYGB patients with type 2 diabetes; Preoperative oral glucose tolerance test with 2 h P-glucose >11.1 mmol/L
RYGB patients with IGT; Preoperative oral glucose tolerance test with 2 h p-glucose >7.8 and <11.1 mmol/L
RYGB patients with NGT; Preoperative oral glucose tolerance test with 2 h p-Glucose <7.8 mmol/L

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in beta-cell function after RYGB.	Beta-cell function will be assessed with both intravenous tests (acute insulin response to glucose - AIRg) and oral tests (insulinogenic index - IGI).	1 week and 3 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in insulin sensitivity after RYGB.	Insulin sensitivity will be assessed in fasting and by intravenous tests (sensitivity index - Si) and oral tests (Matsuda index).	1 week and 3 months.

Other Outcome Measures

Outcome Measure	Time Frame
Change in glucagon and gastrointestinal hormone secretion after RYGB.	1 week and 3 months
Change in insulin clearance after RYGB.	1 week and 3 months

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital
• Investigators: Principal Investigator: Anna Kirstine Bojsen-Moeller, MD, Hvidovre University Hospital

Publications and helpful links

General Publications

• Palleja A, Kashani A, Allin KH, Nielsen T, Zhang C, Li Y, Brach T, Liang S, Feng Q, Jorgensen NB, Bojsen-Moller KN, Dirksen C, Burgdorf KS, Holst JJ, Madsbad S, Wang J, Pedersen O, Hansen T, Arumugam M. Roux-en-Y gastric bypass surgery of morbidly obese patients induces swift and persistent changes of the individual gut microbiota. Genome Med. 2016 Jun 15;8(1):67. doi: 10.1186/s13073-016-0312-1.
• Martinussen C, Bojsen-Moller KN, Dirksen C, Jacobsen SH, Jorgensen NB, Kristiansen VB, Holst JJ, Madsbad S. 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (ANTICIPATED): June 1, 2014
• Study Completion (ANTICIPATED): June 1, 2014

Study Registration Dates

• First Submitted: November 12, 2013
• First Submitted That Met QC Criteria: November 20, 2013
• First Posted (ESTIMATE): November 25, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): November 25, 2013
• Last Update Submitted That Met QC Criteria: November 20, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Other Study ID Numbers: SHJNBJ-FX10