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.
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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
40
Laparoscopic Sleeve Gastrectomy
Only during A1. 150mg every half hour for 6 hours. A total dose of 1800mg will be ingested.
centre de recherche du CHUS
Sherbrooke, Quebec, Canada
RECRUITINGChange in white adipose tissue dietary fatty acid (DFA) trapping and partitioning
\[18F\]-FTHA PET
Time frame: measured after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
Change in lean organ (liver, heart and muscle) DFA uptake and partitioning
\[18F\]-FTHA PET
Time frame: measured after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
Change in liver non-esterified fatty acid (NEFA) uptake, oxidation, esterification and secretion into very low-density lipoprotein (VLDL).
calculated from the same multicompartmental equation using liver \[11C\]-palmitate kinetics
Time frame: measured before and after liquid meal at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)
Change in Endogenous Glucose production and meal glucose systemic flux
i.v. and oral stable isotope tracer
Time frame: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
Change in cardiac non-esterified fatty acid (NEFA) uptake, oxidation and esterification
calculated from the same multicompartmental equation using cardiac \[11C\]-palmitate kinetics
Time frame: measured before and after liquid meal at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)
Change in plasma NEFA flux
calculated from i.v. stable isotope tracer (mass spectrometry).
Time frame: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
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Change in hepatic Triglyceride (TG) content
magnetic resonance imaging (MRI)
Time frame: measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)
Change in insulin secretion
Determined by measuring C-peptide kinetics following the liquid meal
Time frame: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
Change in total substrate utilisation
measured by using indirect calorimetry
Time frame: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
Change in gene and protein expression of white adipose tissue (WAT)
WAT biopsy
Time frame: measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)
Change in hormonal response
Multiplex assay
Time frame: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
Change in insulin resistance /sensitivity
Determined by measuring circulating glucose, NEFA and insulin following the liquid meal
Time frame: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
Change in histology of white adipose tissue (WAT)
WAT biopsy
Time frame: measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)
Change in metabolite response
Colorimetric assay
Time frame: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0
Change in plasma distribution of DFA metabolites (WAT DFA spillover)
calculated from i.v. and oral stable isotope tracers (mass spectrometry) incorporated into triglyceride-rich lipoproteins and NEFA.
Time frame: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
Change in glycerol turnover
calculated from \[1,1,2,3,3-2H\]-glycerol i.v.
Time frame: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)