Glucose Metabolism in Brown Adipose Tissue (BAT) in Young Healthy Men Evaluated by Deuterium Metabolic Imaging (DMI)

Summary

In this study the investigators wish to evaluate the glucose metabolism in brown adipose tissue (BAT) in young healthy men (aged 18-35). The investigators wish to validate a novel MR modality - Deuterium Metabolic Imaging (DMI), which is a non-radioactive, non-invasive method that allows for spatial as well as metabolic imaging after oral administration of deuterium-labelled glucose. Deuterium is a stable isotope of hydrogen that can be bound to different metabolites, in this case glucose. This method allows for metabolic imaging and production of 2H MR spectra of metabolites downstream from glucose uptake that can be quantified. DMI has not yet been used to evaluate BAT in humans. Currently, FDG PET/CT is the most widely used method for BAT evaluation in humans, but due to the radiation-exposure associated with FDG PET/CT repetitive studies of BAT in healthy subjects are limited. Therefore, new in vivo methods (preferably non-invasive) are warranted.

However, since FDG PET/CT is the most widely used method, the investigators wish to use this modality as reference.

The investigators plan to screen 10-12 subjects with an individualized cooling protocol and FDG PET/CT. Only the BAT positive subjects will be included in the DMI study. In the DMI study, the BAT positive subjects will enter in a randomized two-phased cross-over study. The subjects will have 2 DMI scans performed after ingestion of deuterium-labelled glucose; one after 2h of cooling, another in thermoneutrality. Primary outcome is the differences in glucose metabolites between cooling and thermoneutrality. The investigators hypothesize that during cooling uptake of glucose and its metabolites such as glutamine/glutamate and water may be enhanced. Moreover, glucose metabolism may shift towards anaerobic metabolism with increased lactate production as observed in a previous rodent study by the investigators group.

Conditions

• Type2 Diabetes
• Obesity
• Metabolic Syndrome

Interventions

OTHER

cooling using a water-perfused vest

BAT is activated by cold exposure. Each participant will have a shivering threshold test performed before entering the cooling arm. Participants will be gradually cooled (decreasing the temperature in the cooling vest by 0.6C every 15 min. until 3.8C) using a perfused cooling vest until they start to shiver. The temperature in which they start to shiver will be noted. If shivering has not occurred at 3.8C after 15 min. they will stay at the temperature for 45 min. in total or until shivering occurs. Shivering is defined by subjective perception of shivering by the participant in a numeric scale (NRS) where "0" refers to "I'm not shivering" and 10 refers to "I'm shivering a lot" and visual inspection by the investigator. The temperature used in the cooling arm will be set a few degrees above the shivering threshold test or at 3.8C if shivering did not occur. During cooling indirect calorimetry and OGTT will be performed and finally the DMI scan will be performed

OTHER

thermoneutrality

In the thermoneutrality arm participants will rest in thermoneutrality (22C) for one hour. Before the DMI scan indirect calorimetry will be performed

Sponsors & Collaborators

• Aarhus University Hospital

  collaborator OTHER

• Steno Diabetes Center Copenhagen

  collaborator OTHER

• University of Aarhus

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

35 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2019-08-01

Primary Completion

2022-12-01

Completion

2022-12-01

Countries

• Denmark

Study Locations