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

NCT05446415 | Unknown

• 1 other identifier: 65854317800000068
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Severe Obesity; Type 2 Diabetes Mellitus in Obese

Keywords

Roux-en-Y gastroplasty; Immunohistochemistry; L cell; GLP-1; PYY; type 2 diabetes

Outcome Measures

Primary Outcomes (2)

• Changes number of active L cells

  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

  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

Study Arms (1)

Prospective analisys

OTHER

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.

Interventions

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. OTHER

Preoperative and postoperative

Prospective analisys

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• University of Sao Paulo General Hospital: lead

Study Sites (1)

Hospital das Clinicas da Faculdade de Medicina da USP

São Paulo, 05403900, Brazil

RECRUITING

Related Publications (4)

• Miras AD, Kamocka A, Perez-Pevida B, Purkayastha S, Moorthy K, Patel A, Chahal H, Frost G, Bassett P, Castagnetto-Gissey L, Coppin L, Jackson N, Umpleby AM, Bloom SR, Tan T, Ahmed AR, Rubino F. The Effect of Standard Versus Longer Intestinal Bypass on GLP-1 Regulation and Glucose Metabolism in Patients With Type 2 Diabetes Undergoing Roux-en-Y Gastric Bypass: The Long-Limb Study. Diabetes Care. 2021 May;44(5):1082-1090. doi: 10.2337/dc20-0762. Epub 2020 Nov 6.

  PMID: 33158945 BACKGROUND

• Estabile PC, Almeida MC, Campagnoli EB, Santo MA, Rodrigues MRDS, Milleo FQ, Artoni RF. IMMUNOHISTOCHEMICAL DETECTION OF L CELLS IN GASTROINTESTINAL TRACT MUCOSA OF PATIENTS AFTER SURGICAL TREATMENT FOR CONTROL OF TYPE 2 DIABETES MELLITUS. Arq Bras Cir Dig. 2022 Jun 17;35:e1651. doi: 10.1590/0102-672020210002e1651. eCollection 2022.

  PMID: 35730880 BACKGROUND

• Jorsal T, Rhee NA, Pedersen J, Wahlgren CD, Mortensen B, Jepsen SL, Jelsing J, Dalboge LS, Vilmann P, Hassan H, Hendel JW, Poulsen SS, Holst JJ, Vilsboll T, Knop FK. Enteroendocrine K and L cells in healthy and type 2 diabetic individuals. Diabetologia. 2018 Feb;61(2):284-294. doi: 10.1007/s00125-017-4450-9. Epub 2017 Sep 28.

  PMID: 28956082 BACKGROUND

• Guedes TP, Martins S, Costa M, Pereira SS, Morais T, Santos A, Nora M, Monteiro MP. Detailed characterization of incretin cell distribution along the human small intestine. Surg Obes Relat Dis. 2015 Nov-Dec;11(6):1323-31. doi: 10.1016/j.soard.2015.02.011. Epub 2015 Feb 17.

  PMID: 26048514 BACKGROUND

MeSH Terms

Conditions

Obesity, Morbid; Diabetes Mellitus, Type 2

Interventions

Glucagon-Like Peptide 1; Peptide YY; peptide YY (3-36)

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Marco Aurelio Santo, MD Phd

  Clinical Hospital of University of Sao Paulo Medical School

  PRINCIPAL INVESTIGATOR

• Priscila Costa Estabile, MsC

  Clinical Hospital of University of Sao Paulo Medical School

  STUDY CHAIR

Central Study Contacts

Marco Aurelio Santo, MD PhD

CONTACT

+55 1126617560; marco.santo@hc.fm.usp.br

Priscila Costa Estabile, MsC

CONTACT

+55 21 979994911; priscila.estabile@hc.fm.usp.br

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: Study is randomized by the RedCap program, until the time of surgical intervention Researcher and Participant do not know the model. On the day of the Bariatric Surgery, the Participant's data are placed in the program to generate randomization, after the result, only the Researcher and team will know the model chosen by the program.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Roux-en-Y bypass gastroplasty (GDYR) by laparoscopy, with production of a gastric pouch with a volume between 30 and 50 ml, with a biliopancreatic loop measuring 100 (G1) and 200 cm (G2), anastomosis of the alimentary loop of 100 cm in the groups G1 and G2. Immunohistochemistry analysis assays were made from intestinal biopsies in 3 segments: gastrointestinal anastomosis (GEA = Point A), enteroenteral anastomosis (EEA = Point B ) and (Ileocecal valve =Point C). Expression and secretion of GLP-1 and PYY3-36, incretins hormones by Lcells.

Study Record Dates

• First Submitted: June 30, 2022
• First Posted: July 6, 2022
• Study Start: February 5, 2020
• Primary Completion: July 7, 2022
• Study Completion: December 5, 2022
• Last Updated: July 11, 2022

Record last verified: 2022-07

Locations

BR (1)