Diabetes Mellitus Type 2
Conditions
Keywords
Bariatric surgery, remission from Type 2 diabetes, PET imaging, adipose tissue
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.
Interventions
PROCEDUREBariatric surgery
Laparoscopic Sleeve Gastrectomy
DRUGNicotinic Acid
Only during A1. 150mg every half hour for 6 hours. A total dose of 1800mg will be ingested.
Sponsors
Université de Sherbrooke
Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
Centre de recherche du Centre hospitalier universitaire de Sherbrooke
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
It will be a randomized crossover study prior to bariatric surgery (visits A0 and A1) followed by a longitudinal follow-up study after surgery (visits B0 and C0) in two groups (type 2 diabetes vs. controls). Inside each group, the protocol will be carried out as a within-subject, in which each subject will serve as his/her own control.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 histology of white adipose tissue (WAT) | measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0) | WAT biopsy |
| 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 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 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. |
| 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 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 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 |
Countries
Canada
Contacts
CONTACTFrédérique Frisch
PRINCIPAL_INVESTIGATORAndré Carpentier, MD
Université de Sherbrooke
Outcome results
None listed