Clinical trial NCT01767441: Bariatric Surgeries and Glucose Homeostasis During a Mixed Meal Test
Official title: Effects of Bariatric Surgeries on Glucose Homeostasis and Its Determinants During a Mixed Meal Tolerance Test
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obesity
Keywords: bariatric surgery
gastric bypass
gastric banding
sleeve gastrectomy
weight loss
Type 2 Diabetes mellitus
GLP1
obesity
mixed meal test
Lead sponsor: Azienda Ospedaliera Universitaria Integrata Verona
Sponsor class: OTHER
Collaborators: name: Universita di Verona
First posted: 2013-01-14
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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)

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 1 month
Secondary outcomes:
measure: 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
timeFrame: 12 months
measure: 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
timeFrame: 1 month and 12 months
measure: 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.
timeFrame: 1 month and 12 months
Other outcomes:
measure: change in HbA1c between baseline and 1 or 12 months after undergoing bariatric surgery or being put on low calorie diet.
timeFrame: 1 month and 12 months
Locations:
city: Verona
country: Italy
facility: AOUI Verona
Study officials:
affiliation: Division of Endocrinology and Metabolic Diseases, AOUI Verona, Italy
name: Maria Grazia Zenti, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Endocrinology and Metabolic Diseases, University Hospital of Verona
name: Enzo Bonora, Professor
role: STUDY_DIRECTOR
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