Adipose Tissue Storage in the Rapid Remission of Hepatic and Cardiac Metabolic Dysfunction After Bariatric Surgery

Not Applicable

Recruiting

• Conditions: Diabetes Mellitus Type 2
• Interventions: Procedure: Bariatric surgery; Drug: Nicotinic Acid

• Registration Number: NCT05934409
• Lead Sponsor: Université de Sherbrooke

Brief Summary

The present protocol aims to understand and establish whether there is a causal link between adipose tissue metabolic remodeling and Type 2 Diabetes (T2D) remission after bariatric surgery.

All participants will have a bariatric surgery, divided in 2 groups: with or without T2D.

Detailed Description

This clinical assay will include 5 visits: the screening visit and four 9-hour postprandial metabolic sessions (A0, A1, B0 and C0) before and after surgery:

* initial visit: screening

* before surgery: 2 metabolic sessions A0 and A1 (without/with niacin) will be performed, in random order, at least one week interval.

* 12 days post surgery: 1 metabolic session B0 (without niacin)

* 1 year post surgery: 1 metabolic session C0 (without niacin)

Each metabolic visit will last 9 hours with:

* perfusion of stable tracers,

* ingestion of a liquid meal

* Positron-Emitting-Tomography (PET) acquisitions using radiopharmaceuticals such as \[18F\]-fluoro-6-thia-heptadecanoic acid (\[18F\]-FTHA) and \[11C\]-palmitate,

* MRI acquisitions.\[18F\]fluoro-6-thia-heptadecanoic acid (FTHA).

The niacin will be given during metabolic visits A1 as a regulator of lipids metabolism. During these visits, the subjects will ingest 150mg every half hour for 6 hours. Niacin will be used as a pharmacological suppressor of dietary fatty acid (DFA) spillover in order to determine the role played by this mechanism in the reduction of postprandial endogen glucose production (EGP) in T2D after bariatric surgery.

Study Timeline

• Study First Submitted: 2023-06-08
• Study First Submitted QC: 2023-06-27
• Study First Posted: 2023-07-07
• Study Start: 2023-11-01
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-04
• Last Update Posted: 2024-12-09
• Primary Completion: 2028-01-31
• Study Completion: 2028-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Aged 18 to 65
• BMI 35 kg/m2
• Diagnosed T2D - according to Diabetes Canada diagnostics criteria.
• Diagnosed non-T2D - according to Diabetes Canada diagnostics criteria.
• Women with a negative serum pregnancy test.

Exclusion Criteria

• Treatment with an oral contraceptive;
• Treatment with fibrate, thiazolidinedione, insulin, or beta-blocker, drugs that affect metabolism and cannot be stopped temporarily or which have long-lasting effects;
• Presence of overt cardiovascular disease, liver or renal failure or other uncontrolled medical conditions;
• Any other contraindication to surgery or to temporarily suspending current medications for diabetes, lipids or hypertension;
• Smoking or consumption of more than 2 alcoholic beverages per day;
• Any contraindication to MRI;
• A Diabetes Remission (DiaRem) score >8 (low probability of T2D remission);
• Having participated to a research study with exposure to radiation in the last two years before the start of the study;
• Pregnant or breastfeeding women;
• Patients weighing more than 200 kg to respect the weight and gantry limit of our MRI and PET/CT scanners.
• Being allergic to eggs

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group	Bariatric surgery	without T2D according to Diabetes Canada diagnostics criteria:
group with Type 2 diabetes	Bariatric surgery	with T2D according to Diabetes Canada diagnostics criteria:
Control group	Nicotinic Acid	without T2D according to Diabetes Canada diagnostics criteria:
group with Type 2 diabetes	Nicotinic Acid	with T2D according to Diabetes Canada diagnostics criteria:

Primary Outcome Measures

Name	Time	Method
Change in lean organ (liver, heart and muscle) DFA uptake and partitioning	measured after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)	\[18F\]-FTHA PET
Change in cardiac non-esterified fatty acid (NEFA) uptake, oxidation and esterification	measured before and after liquid meal at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)	calculated from the same multicompartmental equation using cardiac \[11C\]-palmitate kinetics
Change in white adipose tissue dietary fatty acid (DFA) trapping and partitioning	measured after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)	\[18F\]-FTHA PET
Change in liver non-esterified fatty acid (NEFA) uptake, oxidation, esterification and secretion into very low-density lipoprotein (VLDL).	measured before and after liquid meal at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)	calculated from the same multicompartmental equation using liver \[11C\]-palmitate kinetics
Change in Endogenous Glucose production and meal glucose systemic flux	measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)	i.v. and oral stable isotope tracer

Secondary Outcome Measures

Name	Time	Method
Change in hepatic Triglyceride (TG) content	measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)	magnetic resonance imaging (MRI)
Change in insulin secretion	measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)	Determined by measuring C-peptide kinetics following the liquid meal
Change in histology of white adipose tissue (WAT)	measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)	WAT biopsy
Change in gene and protein expression of white adipose tissue (WAT)	measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)	WAT biopsy
Change in hormonal response	measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)	Multiplex assay
Change in insulin resistance /sensitivity	measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)	Determined by measuring circulating glucose, NEFA and insulin following the liquid meal
Change in glycerol turnover	measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)	calculated from \[1,1,2,3,3-2H\]-glycerol i.v.
Change in plasma NEFA flux	measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)	calculated from i.v. stable isotope tracer (mass spectrometry).
Change in total substrate utilisation	measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)	measured by using indirect calorimetry
Change in metabolite response	measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0	Colorimetric assay
Change in plasma distribution of DFA metabolites (WAT DFA spillover)	measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)	calculated from i.v. and oral stable isotope tracers (mass spectrometry) incorporated into triglyceride-rich lipoproteins and NEFA.

Trial Locations

Locations (1)

centre de recherche du CHUS; 🇨🇦 Sherbrooke, Quebec, Canada