Clinical trial NCT05446415: L-Cell Activity in Small Intestine as Biliopancreatic Loop in Obese Patients With DM2 Submitted to RYGBP
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Severe Obesity
Type 2 Diabetes Mellitus in Obese
Keywords: Roux-en-Y gastroplasty
Immunohistochemistry
L cell
GLP-1
PYY
type 2 diabetes
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
First posted: 2022-07-06
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes number of active L cells
timeFrame: Before and 6 moths after bariatric surgery
measure: Changes mRNA expression levels of active L cells
timeFrame: Before and 6 moths after bariatric surgery
Secondary outcomes:
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina da USP
Study officials:
affiliation: Clinical Hospital of University of Sao Paulo Medical School
name: Marco Aurelio Santo, MD Phd
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Hospital of University of Sao Paulo Medical School
name: Priscila Costa Estabile, MsC
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
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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.