GB8: Brown Adipose Tissue Metabolism in Type 2 Diabetes
Study Details
Study Description
Brief Summary
Activation of brown adipose tissue (BAT) by cold exposure.
BAT thermogenesis and BAT volume of metabolic activity will be assessed by Positron-Emitting-Tomography (PET/CT) and MRI/MRS imaging and new pharmacological methods to modulate BAT thermogenesis.
All previous data on the functioning of Brown Adipose Tissue (BAT) were obtained by Positron-Emitting-Tomography (PET) imaging studies using fluorodeoxyglucose F18 ( [18F]- FDG). This approach underestimates the actual activity of the BAT. In this study, the investigator is going to use a new PET tracer (C11-palmitate) which is a fat molecule. This will allow to quantify more accurately the activity of brown fat.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
The study protocol includes three visits: the screening visit (V1) and two PET/MRI imaging studies (V2 and V3) performed in random order at an interval of 7 to 14 days.
PET/ MRI studies will be performed with and without nicotinic acid. A total of 500 mg of nicotinic acid will be given orally, at a rate of 2 doses of 150 mg and 2 doses of 100 mg, through V2 (protocol A): one dose at time 0, 60 minutes, 120 minutes and 180 minutes.
During V2 and V3, participants will undergo Acute Cold Exposure to stimulate brown adipose tissue.
The morning of each PET imaging study, the participants will follow an MRI acquisition to determine hepatic, pancreatic, visceral and BAT lipid content, followed by an MRS acquisition in the hepatic and cervico-thoracic region. MRI and MRS acquisition of the hepatic and cervico-thoracic region will be repeated again at the end of the day.
The radioactive PET tracers used in this study are the [11C]-acetate, [11C]-palmitate and [18F]-FDG followed by dynamic and whole-body scans.
Stable isotopes such as [U-13C]-palmitate (0.08 umol/kg/min), 5D-glycérol (0.1 µmol/kg/min,) and tritiated glucose (of 1.5 uCi/min) will be perfused from the start of the day until time 180 min.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Subject with Type 2 Diabetes- cold exposure 3-hour cold exposure: Protocol B |
Other: Cold exposure
The liquid-conditioned tube suit will be perfused with 18°C water using a temperature- and flow-controlled circulation bath from time 0 to 180 min.
|
| Experimental: Subject with type 2 Diabetes- cold exposure and nicotinic acid 3-hour cold exposure with oral nicotinic acid: Protocol A |
Other: Cold exposure
The liquid-conditioned tube suit will be perfused with 18°C water using a temperature- and flow-controlled circulation bath from time 0 to 180 min.
Drug: Oral Nicotinic acid
A total of 500 mg of nicotinic acid will be given orally, at a rate of 2 doses of 150 mg and 2 doses of 100 mg: one dose of 150 mg at time 0 and 60 minutes, one dose of 100 mg at time 120 minutes and 180 minutes.
Other Names:
|
| Active Comparator: Subject without Type 2 Diabetes- cold exposure 3-hour cold exposure: Protocol B |
Other: Cold exposure
The liquid-conditioned tube suit will be perfused with 18°C water using a temperature- and flow-controlled circulation bath from time 0 to 180 min.
|
| Experimental: Subject without type 2 Diabetes- cold exposure and nicotinic acid 3-hour cold exposure with oral nicotinic acid: Protocol A |
Other: Cold exposure
The liquid-conditioned tube suit will be perfused with 18°C water using a temperature- and flow-controlled circulation bath from time 0 to 180 min.
Drug: Oral Nicotinic acid
A total of 500 mg of nicotinic acid will be given orally, at a rate of 2 doses of 150 mg and 2 doses of 100 mg: one dose of 150 mg at time 0 and 60 minutes, one dose of 100 mg at time 120 minutes and 180 minutes.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- BAT volume [180 minutes after the start of the cold exposure]
Assessed using i.v. injection of 18FDG with whole-body PET/CT acquisition.
- Brown Adipose Tissue (BAT) Glucose uptake [150 minutes after the start of the cold exposure]
Assessed using i.v. injection of 18FDG with sequential dynamic PET/CT scanning
Secondary Outcome Measures
- Activation of BAT (oxidative metabolism) [90 minutes after beginning cold exposure]
Measured with 11C-acetate using dynamic PET/CT acquisition.
- Fatty Acid uptake and metabolism [at baseline and at time 120 minutes after beginning cold exposure]
Measured with 11C-palmitate using dynamic PET/CT acquisition.
- BAT triglyceride content [at baseline and at time 180 (for CT) and 240 (for MR) after cold exposure.]
Estimated by CT and MR using 1H-MRS and Dixon sequences on a 3T clinical MRI system.
- Whole-body lipolysis [-150 and 0 minutes before and 60, 120 and 180 minutes after cold exposure.]
Systemic appearance rate of glycerol and fatty acid determined by perfusion of [1,1,2,3,3-2H]-glycerol, [U-13C]-palmitate tracers and concentration of total NEFA, triglycerides, palmitate, oleate, linoleate, glycerol.
- Hepatic Glucose production [-150 and 0 minutes before and 60, 120 and 180 minutes after cold exposure.]
Systemic appearance rate of glucose determined by perfusion of [3-3H]-glucose.
- Substrate utilisation [-150 and 0 minutes before and 60, 120 and 180 minutes after cold exposure.]
VO2 and VCO2 will be measured by indirect calorimetry to calculate carbohydrate and fatty acid oxidation rates.
- Changes in insulin level and secretion [-150 and 0 minutes before and 60, 120 and 180 minutes after cold exposure.]
measured with ELISA and Milliplex.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
10 men and 10 women with T2D.
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10 non-diabetic men and 10 non-diabetic women (matched for sex, BMI and age to the T2D participants).
Exclusion Criteria:
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Change in weight of more than 2 kg over the past 3 months or recent changes in lifestyle;
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Treatment with a fibrate, thiazolidinedione, insulin, beta-blocker, GLP-1 agonist, or other drug known to affect lipid or carbohydrate metabolism, except statins, metformin, sulfonylurea, DPP-IV inhibitor and other antihypertensive agents that can be temporarily stopped safely prior to the studies, as per our approved protocols;
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Presence of overt cardiovascular, liver, renal or other medical conditions;
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Smoking or consumption of more than 2 alcoholic beverages per day;
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Any other contraindication to temporarily suspending current medications for lipids or hypertension;
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Any contraindication to MRI scanning.
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Having participated to a research study with exposure to radiation in the last two years before the start of the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Centre de recherche du CHUS | Sherbrooke | Quebec | Canada | J1H 5N4 |
Sponsors and Collaborators
- Université de Sherbrooke
Investigators
- Principal Investigator: André Carpentier, Université de Sherbrooke
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2019-2990