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

Severe Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05446415
• Other study ID #: 65854317800000068
• Status: Recruiting
• Phase: N/A
• Start date: February 5, 2020
• Est. completion date: December 5, 2022

Study information

• Verified date: July 2022
• Source: University of Sao Paulo General Hospital
• Contact: Marco Aurelio Santo, MD PhD
• Phone: +55 1126617560
• Email: marco.santo[@]hc.fm.usp.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 5, 2022
• Est. primary completion date: July 7, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Obesity, Morbid
• Severe Obesity
• Type 2 Diabetes Mellitus in Obese

Intervention

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

Locations

Country	Name	City	State
Brazil	Hospital das Clinicas da Faculdade de Medicina da USP	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital

Country where clinical trial is conducted

Brazil, 

References & Publications (4)

Estabile PC, Almeida MC, Campagnoli EB, Santo MA, Rodrigues MRDS, Milléo 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. — View Citation

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. — View Citation

Jorsal T, Rhee NA, Pedersen J, Wahlgren CD, Mortensen B, Jepsen SL, Jelsing J, Dalbøge LS, Vilmann P, Hassan H, Hendel JW, Poulsen SS, Holst JJ, Vilsbøll 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. — View Citation

Miras AD, Kamocka A, Pérez-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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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