L-Cell Activity in Small Intestine as Biliopancreatic Loop in Obese Patients With DM2 Submitted to RYGBP

July 7, 2022 updated by: Marco Aurélio Santo, University of Sao Paulo General Hospital

Evaluation of L-Cell Activity in the Small Intestine as Biliopancreatic Loop Extension in Obese Patients With DM2 Submitted to Roux-en-Y Gastric Bypass

Prevalence of Obesity and its association with Diabetes Mellitus 2 (DM2) affect a significant percentage of the world's population with great socioeconomic impact, especially for developing countries. Several procedures and interventions are used in its treatment, and the most efficient and with a positive impact on the life of patients with severe obesity and DM2 is Bariatric Surgery.

The objective of is analyze the activity of L cells according to the extension of the bilio-pancreatic loop in T2DM patients undergoing GDYR.

This study 20 adults of both sexes, above 18 years,before and 6 moths after surgery baritric metabolic, randomized the bilio-pancreatic loop in a proportion of 1:1.

Keywords: Roux-en-Y gastroplasty, Immunohistochemistry, L cell, GLP-1, type 2 diabetes.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, randomized (paired) and morphological study involving 20 adult male and female patients (18-65 years) with severe obesity [body mass index (BMI) > 35 kg/m2] and DM2 undergoing Gastroplasty in Diversion Roux-en-Y in the Bariatric and Metabolic Surgery Unit, Department of Gastroenterology, HC-FMUSP, between February 2020 and December 2022. Patients were randomized (https://hcbredcap.com.br/) into two groups of 10 patients each, according to the extension of the bilio-pancreatic loop, in a proportion of 1:1 by computer model. Patients were evaluated preoperatively (T0) and 6 months (T1) after GDYR.

INTRODUTION: Patients with obesity have a suppressed incretin effect and a consequent imbalance of glycemic homeostasis. Bariatric surgery has the potential of T2DM control in up to 90% of patients with severe obesity due to caloric restriction, improvement of insulin resistance, pancreatic beta cell function, and the incretin effect of glycogen-like protein 1.

In this current scenario, metabolic surgery has taken a considerable role in weight loss, contributing to metabolic control, and showing improvement in the state of obesity and related comorbidities. We already know that conservative treatment has been failing 80% of obese patients, while 80% of obese patients who have undergone metabolic surgery are successful in long-term weight loss and resumption of metabolic functionality, showing better results than drug therapy or only lifestyle change 16 . This adaptive procedure, which is aimed at neuroendocrine improvements instead of gastrointestinal restriction and malabsorption 24 , leads to increased serum levels of the incretins (hormones that stimulate a decrease in blood glucose levels) glucagon- like peptide-1 (GLP-1) and peptide YY (PYY 3-36 ) in postprandial patients five years following surgery. They play key roles in stimulating the secretion of insulin by the endocrine pancreas . It is therefore of considerable importance to understand the secretion mechanisms of epithelial intestinal cells as well as the identity and location of cells responsible for the action of these peptides . In the intestinal epithelium we find cells that release incretins to the response of nutrients in contact with intestinal lumen called L cells . L cell found in the distal ileum and large intestine secretes GLP-1 and peptide YY (PYY) promotes they slow gastric emptying and act as a satiety signal to improve glycemic control.

JUSTIFICATION: number of L cells in activity implies better peptide signaling, response and functioning of the neuroendocrine system.

OBJECTIVE: To analize secretion of L cells in the small intestine for immunohistochemistry and mRNA expression levels before and after (6 months) induced by bariatric surgery .

METHODS: Ethic This study was elaborated and will be performed at the Clinical Hospital of the Medical School of the University of São Paulo (HCFMUSP). The patients involved will receive the Informed Consent Form (ICF) for their agreement to participate in the study.

The molecular markers(qRT-PCR) used will be the expression enterohormones themselves by the L cell, that is, GLP-1 and PYY.

The detection of incretin by Immunohistochemical assays, will enable cell labeling and localization, and evidence of cell occurrence/density in portions of the gastrointestinal tract.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Brazil
      • São Paulo, Brazil, 05403900

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Above 18 to 65 years
  • Both sexes
  • BMI ≥ 35 kg/m2
  • Presence of DM2:
  • Glycated Hb ≥ 7.0%
  • C-peptide ≥ 3 ng/dl
  • Fasting blood glucose ≥ 200 mg/dl (absence of treatment)
  • TCLE

Exclusion Criteria:

  • Corticosteroid use
  • Hepatitis B and C or HIV carriers
  • Previous abdominal or bariatric surgery
  • Cardiovascular impairment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: Prospective analisys

Immunohistochemical assays : biopsy sampled from each site was immediately fixated and then embedded in paraffin, cut in thin slide sections and dewaxed. Subsequently, antigen retrieval was performed, with incubations with (1) specific primary antibodies, (2) a second layer of antibodies and (3) a third layer of an avidin-biotin complex. Finally, counterstaining was performed, generating biopsy slides with cells positive for peptide YY (PYY), GLP-1, respectively.

Quantitative real-time polymerase chain reaction (qPCR) : the mRNA expression of the genes of interest glp-1,PYY 3-36 genes as well as the genes used for normalisation 18S were investigated. One biopsy sample from each biopsy site was immediately incubated in RNAlater solution (to preserve mRNA quality) (dna/rna Shield, USA). Subsequently, standard RNA purification, cDNA synthesis and quantitative PCR (qPCR) analysis were performed .
Other: Analyze basal expression incretin for immunolabeling and mRNA expression glucagon-like secretion peptide-1 (GLP-1) and peptide YY (PYY 3-36) incretins by L cells.
Preoperative and postoperative

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes number of active L cells
Time Frame: Before and 6 moths after bariatric surgery
The analysis of the samples of intestinal tract mucosa the patients with DM2 , immunolabeling for GLP-1 and for PYY 3-36 from number of active L cells, before and after bariatric surgery.
Before and 6 moths after bariatric surgery
Changes mRNA expression levels of active L cells
Time Frame: Before and 6 moths after bariatric surgery
The analysis of the samples of intestinal tract mucosa from the from patients with DM2 , mRNA expression levels of GLP-1 and PYY 3-36 for active L cells, before and after bariatric surgery.
Before and 6 moths after bariatric surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo General Hospital

Investigators

  • Principal Investigator: Marco Aurelio Santo, MD Phd, Clinical Hospital of University of Sao Paulo Medical School
  • Study Chair: Priscila Costa Estabile, MsC, Clinical Hospital of University of Sao Paulo Medical School

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 5, 2020

Primary Completion (ACTUAL)

July 7, 2022

Study Completion (ANTICIPATED)

December 5, 2022

Study Registration Dates

First Submitted

June 30, 2022

First Submitted That Met QC Criteria

June 30, 2022

First Posted (ACTUAL)

July 6, 2022

Study Record Updates

Last Update Posted (ACTUAL)

July 11, 2022

Last Update Submitted That Met QC Criteria

July 7, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 65854317800000068

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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