Surgical Innovation for Diabetes Treatment

Study Overview
=================
Brief Summary
-----------------
This study will determine how two variants of gastric bypass induce changes in dynamic endocrine response in the fasting and post-prandial state, both before and at different time points after the surgical interventions. This study will monitor the endocrine dynamics after different anatomical modifications produced by Roux-en-Y gastric bypass procedures in diabetic participants and normoglycemic participants, to gain insights into the mechanisms beyond the metabolic improvement after the two surgical variants through participants re-evaluation at different time points.

Detailed Description
-----------------
Abstract Obesity prevalence is a major risk factor for the onset of type 2 diabetes. Diabetic patients are frequently overweight or obese and diabetes complications are the main cause of obesity-related morbimortality, demanding proper and effective clinical management. Bariatric surgery, originally conceived for obesity treatment, has proven not only to be the most effective weight loss intervention but also for comorbidity management, with a strong impact on type 2 diabetes. As the antidiabetic effects of bariatric surgery largely exceed the metabolic improvement predicted by the caloric restriction and weight loss, which are mostly driven by the enteroendocrine response, this challenges the academic and medical communities with the need to learn how to leverage the enteroendocrine system to achieve glucose homeostasis. Supported on the investigators' previous work focusing on gastro-intestinal hormones and glucose metabolism after bariatric surgery, the investigators now aim to monitor the intestinal hormone after different anatomical modifications produced by Roux-en-Y gastric bypass procedures in diabetic participants and normoglycemic individuals. The utmost goal will be to unravel the endocrine mechanisms beyond the metabolic improvement observed after the surgical manipulations, towards the identification of novel targets for hormone based treatments in an individualised clinical approach. Study Overview: Participants in this study will be submitted to either short or long BPL RYGB surgery. Participants visits will be scheduled before surgery and after surgery at 3, 6 and 12 months for detailed participants assessment that will include anthropometric and biochemical evaluation and the performance of a MMTT with plasma sampling for hormonal profiles. Participant Enrolment: Participants will be selected from the cohort of patients referred for multidisciplinary evaluation by the clinical team for surgical treatment of obesity of the Centro Hospitalar Entre Douro e Vouga (CHEDV). Participants found to be suitable according to the entry criteria and accept to participate will be enrolled in the study and assigned to one of the three study groups according to participants clinical features. Study Chair: Mário Nora, MD Principal Investigator: Marta Guimarães, MD, PhD

Official Title
-----------------
Characterization of Intestinal Hormone and Glucose Dynamics to Unravel the Antidiabetic Effect of Bariatric Surgery

Conditions
-----------------
Obesity, Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Procedure: Short BPL RYGB
* Procedure: Long BPL RYGB


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: BMI between 35 and 45 kg/m2 with indication for bariatric surgery Aged between 18 and 65 years at surgery Exclusion Criteria: Unwillingness, inability or intolerance to complete the MMTT (ingest 200 mL in 15 minutes or less)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Short BPL RYGB in glucose-tolerant participants<br>Procedure: short biliopancreatic limb (BPL) Roux en Y Gastric Bypass (RYGB) Obese patients without type 2 diabetes mellitus (T2DM) to be submitted to short BPL (n=10) | Procedure: Short BPL RYGB<br>* Alimentary limb (AL) with 120 cm and BPL with 100 cm.<br>|
| Active Comparator: Long BPL RYGB in glucose-tolerant participants<br>Procedure: long BPL RYGB Obese patients with metabolic syndrome without T2DM to be submitted to long BPL (n=10) | Procedure: Long BPL RYGB<br>* AL with 120 cm and BPL with 200 cm.<br>|
| Active Comparator: Long BPL RYGB in diabetic participants<br>Procedure: long BPL RYGB Obese patients with metabolic syndrome and T2DM to be submitted to long BPL (n=10) | Procedure: Long BPL RYGB<br>* AL with 120 cm and BPL with 200 cm.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body mass index | Body mass index (BMI) combines height (in meters) and weight (in kilograms) and is calculated as weight over (height)^2. Therefore, it will be reported in kg/m^2. This parameter will be determined at each study timepoint (pre-operatory, 3, 6 and 12 months post-surgery) at presential visits to the clinic. | From enrolment to 12 months post-intervention in 4 visits: preoperative, 3, 6 and 12 months post-surgery | 
| Change in glycated haemoglobin | Glycated haemoglobin (HbA1c) will be measured in percentage (%). This parameter will be assessed at each study timepoint (pre-operatory, 3, 6 and 12 months post- surgery) through routine complete biochemical evaluation. | From enrolment to 12 months post-intervention in 4 visits: preoperative, 3, 6 and 12 months post-surgery | 
| Change in glucose dynamic profile | Glucose will be measured in mmol/L. This parameter will be assessed at each study timepoint (pre-operatory, 3, 6 and 12 months post-surgery) under fasting conditions and during a mixed-meal tolerance teste (MMTT) with blood collection at eight timed intervals (-10, 0, 15, 30, 45, 60, 90 and 120 minutes). | Time Frame: From enrolment to 12 months post-intervention in 4 visits: preoperative, 3, 6 and 12 months post-surgery | 
| Change in insulin dynamic profile | Insulin will be measured in mIU/L. This parameter will be assessed at each study timepoint (pre-operatory, 3, 6 and 12 months post-surgery) under fasting conditions and during a mixed-meal tolerance teste (MMTT) with blood collection at eight timed intervals (-10, 0, 15, 30, 45, 60, 90 and 120 minutes). | Time Frame: From enrolment to 12 months post-intervention in 4 visits: preoperative, 3, 6 and 12 months post-surgery | 
| Change in glucagon dynamic profile | Glucagon will be measured in pmol/L. This parameter will be assessed at each study timepoint (pre-operatory, 3, 6 and 12 months post-surgery) under fasting conditions and during a mixed-meal tolerance teste (MMTT) with blood collection at eight timed intervals (-10, 0, 15, 30, 45, 60, 90 and 120 minutes). | Time Frame: From enrolment to 12 months post-intervention in 4 visits: preoperative, 3, 6 and 12 months post-surgery | 
| Change in GLP-1 dynamic profile | Glucagon-like peptide-1 (GLP-1) will be measured in pmol/L. This parameter will be assessed at each study timepoint (pre-operatory, 3, 6 and 12 months post-surgery) under fasting conditions and during a mixed-meal tolerance teste (MMTT) with blood collection at eight timed intervals (-10, 0, 15, 30, 45, 60, 90 and 120 minutes). | Time Frame: From enrolment to 12 months post-intervention in 4 visits: preoperative, 3, 6 and 12 months post-surgery | 
| Change in GIP dynamic profile | Glucose-dependent insulinotropic polypeptide (GIP) will be measured in pmol/L. This parameter will be assessed at each study timepoint (pre-operatory, 3, 6 and 12 months post-surgery) under fasting conditions and during a mixed-meal tolerance teste (MMTT) with blood collection at eight timed intervals (-10, 0, 15, 30, 45, 60, 90 and 120 minutes). | Time Frame: From enrolment to 12 months post-intervention in 4 visits: preoperative, 3, 6 and 12 months post-surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bariatric Surgery, Gastric Bypass, Obesity, Type 2 Diabetes Mellitus, Metabolic Syndrome