Bariatric Surgeries and Glucose Homeostasis During a Mixed Meal Test (BASMEAL)

Effects of Bariatric Surgeries on Glucose Homeostasis and Its Determinants During a Mixed Meal Tolerance Test

Bariatric surgery can lead to improvement or even resolution of type 2 diabetes Mellitus (T2DM) with the spectrum of responses depending also on operation procedures. However, many mechanisms of metabolic action of different surgical techniques still are unclear.

The aim of this study is to provide a better understanding of the effects of three types of bariatric surgery (lap banding, gastric bypass and sleeve gastrectomy) on beta-cell function and incretin secretion. A mixed meal tolerance (MMT) test will be performed before and 1 and 12 months after surgery to assess beta cell adequacy and glucagon-like-peptide-1 (GLP1)/glucose-dependent insulinotropic polypeptide (GIP) bioavailability.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Procedure: Roux-en-Y-gastric bypass; Procedure: laparoscopic adjustable gastric banding; Procedure: laparoscopic sleeve gastrectomy; Other: diet treatment

Detailed Description

The effects of different kind of bariatric surgery on glucose homeostasis and its primary determinants (insulin sensitivity and secretion) may differ from one procedure to another. In spite being able to promote improvement/resolution of T2DM, many mechanisms of metabolic action of weight-loss surgery are still unclear. It has been hypothesized that changing the nutrient route through the gut may be a key factor in changing beta cell function and/or insulin sensitivity.

In this study a mixed meal test will be used to assess changes in glucose regulation, beta cell function and incretin bioavailability brought about by different bariatric surgeries in obese patients.

All participants will ingest a standardized mixed meal (163 Kcal; 57% carbohydrate, 33% fat, 22% prot) and will be monitored for 300 minutes thereafter.

Baseline (-20', -10', 0') blood samples will be collected to measure plasma glucose, insulin, C-peptide, incretins and the 13-Carbon-glucose/12-Carbon-glucose (13C-/12C-glucose) ratio (the last one by isotope ratio mass spectrometry).

At time 0', subjects will ingest a standardized mixed meal containing 30 g corn flour and 20 g cheese (parmesan) over 20 minutes. Plasma glucose, insulin, C-peptide, GLP1/GIP and the 13C-/12C-glucose ratio will be assessed at +10', +20', +30', +45', +60', +75', +90', +105', +120', +140', +160', +180', +200', +220', +240', +270', +300'.

Blood samples will be quickly spun at 1500 g at +4°C, plasma/serum will be collected and stored at -80°C.

The 13-Carbon content of maize starch is higher than most of non maize derived sugars. Thus, in individuals on maize and cane sugar free diets, the 13-Carbon/12-Carbon (13C/12C) maize starch ratio is higher (about 10:1000) than the 13C/12C ratio of endogenous glucose derived from glycogenolysis/gluconeogenesis. When these individuals ingest maize starch, the glucose molecules appearing in the systemic circulation which are derived from maize starch will display a 13C-/12C ratio which is identical to maize starch and higher than endogenous glucose. Thus, by measuring the time course of plasma 13C-/12C-glucose ratio, it will be possible to distinguish meal derived glucose from endogenous glucose output (glycogenolysis and gluconeogenesis).

This mixed meal test will be performed before and 1 and 12 months after bariatric surgery. The same tests with the same timing will be performed in a control group of obese patients not undergoing bariatric surgery, being treated with diet only.

• Study Type: Observational
• Enrollment (Actual): 16

Contacts and Locations

Study Locations

• Italy
  • Verona, Italy, 37126
    • AOUI Verona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

A total of 64 morbidly obese patients will be studied, composed of:

• 16 subjects scheduled for Roux-en-Y-gastric bypass;
• 16 subjects scheduled for laparoscopic adjustable gastric banding;
• 16 subjects scheduled for laparoscopic sleeve gastrectomy;
• 16 subjects not undergoing bariatric surgery, on diet treatment (control group)

Description

Inclusion Criteria:

• BMI > 40 kg/m2.
• BMI ≥ 35 kg/m2 and comorbidities.
• No major organ disease unrelated to excess body weight.
• Mentally able to understand the study and willingness to participate in the study

Exclusion Criteria:

• BMI< 35 kg/m2.
• pregnancy/lactation.
• prior bariatric or gastrointestinal surgery. Malignancies; mental incapacity; unwillingness or language barriers precluding adequate understanding or cooperation

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Roux-en-Y-gastric bypass; morbidly obese subjects undergoing gastric bypass surgery	Procedure: Roux-en-Y-gastric bypass; Gastric bypass consisted of creation of a 15-20 ml gastric pouch, a 150 cm Roux limb, and a 50 cm biliopancreatic limb; Other Names: RYGB
gastric banding; morbidly obese subjects undergoing laparoscopic adjustable gastric banding	Procedure: laparoscopic adjustable gastric banding; Gastric banding functions by limiting food intake after the placement of an inflatable tube around the stomach just below the gastroesophageal junction, which allows for adjustment of the size of the outlet via the addition or removal of saline through a subcutaneous port.; Other Names: LAGB
sleeve gastrectomy; morbidly obese subjects undergoing laparoscopic sleeve gastrectomy	Procedure: laparoscopic sleeve gastrectomy; Sleeve gastrectomy involved a gastric reduction of 75 to 80% by resecting the stomach alongside a 30-French endoscope beginning 3 cm from pylorus and ending at the angle of His; Other Names: SG
control group; morbidly obese subjects not undergoing bariatric surgery, on diet treatment	Other: diet treatment; Hypocaloric diet providing a 1000 Kcal/d deficit from total energy expenditure assessed by indirect calorimetry and physical activity determination; Other Names: diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in glucose response (pAUC) to mixed meal test between baseline and 1 month after undergoing bariatric surgery or being put on low calorie diet	Blood samples will be taken at basal (-20',-10' and 0'), and after the ingestion of a standardized mixed meal (+10', +20', +30',+45', +60', +75', +90', +105', +120', +140', +160', +180', +200', +220', +240', +270', +300').	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in glucose response (pAUC) to mixed meal test between baseline and 12 months after undergoing bariatric surgery or being put on low calorie diet	Blood samples will be taken at basal(-20',-10' and 0'), and after the ingestion of a standardized mixed meal (+10', +20', +30',+45', +60', +75', +90', +105', +120', +140', +160', +180', +200', +220', +240', +270', +300').	12 months
changes in β-cell response mixed meal test between baseline and 1 and 12 months after undergoing bariatric surgery or being put on low calorie diet	Beta-cell function will be assessed by a state of art mathematical model applied to glucose and C-peptide curves during a standardized mixed meal. Two main metrics of beta cell function will be derived from modeling: 1) derivative or dynamic control of beta cell function, and 2) proportional or static control of beta cell function.	1 month and 12 months
changes in active GLP1 systemic bioavailability during a mixed meal test between baseline and 1 or 12 months after undergoing bariatric surgery or being put on low calorie diet.	Blood samples will be taken at basal(-20',-10' and 0'), and after the ingestion of a standardized mixed meal (+10', +20', +30',+45', +60', +75', +90', +105', +120', +140', +160', +180', +200', +220', +240', +270', +300').	1 month and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in HbA1c between baseline and 1 or 12 months after undergoing bariatric surgery or being put on low calorie diet.	high pressure liquid chromatography (HPLC) method	1 month and 12 months

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera Universitaria Integrata Verona
• Collaborators: Universita di Verona
• Investigators: Principal Investigator: Maria Grazia Zenti, MD, Division of Endocrinology and Metabolic Diseases, AOUI Verona, Italy; Study Director: Enzo Bonora, Professor, Division of Endocrinology and Metabolic Diseases, University Hospital of Verona

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: January 11, 2013
• First Submitted That Met QC Criteria: January 11, 2013
• First Posted (ESTIMATE): January 14, 2013

Study Record Updates

• Last Update Posted (ACTUAL): February 24, 2020
• Last Update Submitted That Met QC Criteria: February 21, 2020
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: obesity; bariatric surgery; weight loss; Type 2 Diabetes mellitus; sleeve gastrectomy; gastric bypass; gastric banding; GLP1; mixed meal test
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: MGZenti MMT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO