Improved Adipose Tissue Storage of Dietary Fatty Acids as a New Mechanism for the Rapid Remission of Hepatic and Cardiac Metabolic Dysfunction After Bariatric Surgery
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Change in lean organ (liver, heart and muscle) DFA uptake and partitioning
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Control group
without T2D according to Diabetes Canada diagnostics criteria:
干预措施: Bariatric surgery (Procedure)
Control group
without T2D according to Diabetes Canada diagnostics criteria:
干预措施: Nicotinic Acid (Drug)
group with Type 2 diabetes
with T2D according to Diabetes Canada diagnostics criteria:
干预措施: Bariatric surgery (Procedure)
group with Type 2 diabetes
with T2D according to Diabetes Canada diagnostics criteria:
干预措施: Nicotinic Acid (Drug)
结局指标
主要结局
Change in lean organ (liver, heart and muscle) DFA uptake and partitioning
时间窗: 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
时间窗: 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
时间窗: 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).
时间窗: 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
时间窗: 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
次要结局
- Change in insulin secretion(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)(measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0))
- Change in hepatic Triglyceride (TG) content(measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0))
- Change in gene and protein expression of white adipose tissue (WAT)(measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0))
- Change in hormonal response(measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0))
- Change in insulin resistance /sensitivity(measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0))
- Change in glycerol turnover(measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0))
- Change in plasma NEFA flux(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 before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0))
- Change in metabolite response(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)(measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0))
研究者
André Carpentier
Tenure professor
Université de Sherbrooke