Brown Fat Activation Treatments for Type 2 Diabetes
(GB8 Trial)
Recruiting in Palo Alto (17 mi)
Overseen byAndré Carpentier
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Université de Sherbrooke
Must not be taking: Fibrates, Thiazolidinediones, Insulin, others
Disqualifiers: Cardiovascular, Liver, Renal, Smoking, others
No Placebo Group
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial requires that you stop taking certain medications that affect lipid or carbohydrate metabolism, except for statins, metformin, sulfonylurea, DPP-IV inhibitors, and some antihypertensive agents, which can be temporarily stopped safely before the study.
What data supports the effectiveness of the treatment for activating brown fat in type 2 diabetes?
Research shows that short-term cold exposure can improve insulin sensitivity in people with type 2 diabetes by activating brown fat, which helps the body use sugar more effectively. This suggests that cold treatments might be beneficial for managing diabetes.
12345Is cold exposure treatment safe for humans?
Cold exposure, used to activate brown fat, has been studied in humans and generally appears safe, with some studies showing improved insulin sensitivity and glucose metabolism. However, more research is needed to fully understand its long-term safety and effects.
12467How does cold exposure treatment for type 2 diabetes differ from other treatments?
Cold exposure treatment is unique because it activates brown fat, which can improve insulin sensitivity and glucose metabolism by increasing the activity of brown adipose tissue and enhancing glucose uptake in skeletal muscle, unlike traditional treatments that primarily focus on medication or lifestyle changes.
12368Eligibility Criteria
This trial is for 20 individuals with Type 2 Diabetes (T2D) and 20 non-diabetic individuals, both groups balanced in terms of sex, body mass index (BMI), and age. Participants should not have serious heart, liver or kidney conditions, be on certain diabetes or lipid-altering medications except for some like statins or metformin, smoke heavily, drink more than two alcoholic beverages daily, have had radiation exposure from research within the last two years, have MRI contraindications or significant weight/lifestyle changes recently.Inclusion Criteria
I am a non-diabetic person matched in sex, BMI, and age with a Type 2 diabetes participant.
I am a man/woman with type 2 diabetes.
I am a non-diabetic person matched in sex, BMI, and age with a Type 2 diabetes participant.
+1 more
Exclusion Criteria
You have been in another research study involving radiation in the past two years.
You have a medical reason that makes it unsafe for you to have an MRI scan.
I have a serious heart, liver, kidney, or other medical condition.
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1 visit
1 visit (in-person)
Imaging Studies
Participants undergo PET/MRI imaging studies with and without nicotinic acid, including acute cold exposure to stimulate brown adipose tissue.
2 visits over 2-4 weeks
2 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after imaging studies
4 weeks
Participant Groups
The study tests how brown adipose tissue (BAT) metabolism can be activated in people with T2D using cold exposure and oral Nicotinic acid. It will use advanced imaging techniques like PET/CT scans with a new tracer C11-palmitate to measure BAT activity more accurately compared to traditional methods.
4Treatment groups
Experimental Treatment
Active Control
Group I: Subject without type 2 Diabetes- cold exposure and nicotinic acidExperimental Treatment2 Interventions
3-hour cold exposure with oral nicotinic acid: Protocol A
Group II: Subject with type 2 Diabetes- cold exposure and nicotinic acidExperimental Treatment2 Interventions
3-hour cold exposure with oral nicotinic acid: Protocol A
Group III: Subject without Type 2 Diabetes- cold exposureActive Control1 Intervention
3-hour cold exposure: Protocol B
Group IV: Subject with Type 2 Diabetes- cold exposureActive Control1 Intervention
3-hour cold exposure: Protocol B
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Centre de recherche du CHUSSherbrooke, Canada
Loading ...
Who Is Running the Clinical Trial?
Université de SherbrookeLead Sponsor
References
Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus. [2022]Cold exposure may be a potential therapy for diabetes by increasing brown adipose tissue (BAT) mass and activity. Here we report that 10 d of cold acclimation (14-15 °C) increased peripheral insulin sensitivity by ∼43% in eight type 2 diabetes subjects. Basal skeletal muscle GLUT4 translocation markedly increased, without effects on insulin signaling or AMP-activated protein kinase (AMPK) activation and only a minor increase in BAT glucose uptake.
Comparative transcriptome analysis of human skeletal muscle in response to cold acclimation and exercise training in human volunteers. [2021]Cold acclimation and exercise training were previously shown to increase peripheral insulin sensitivity in human volunteers with type 2 diabetes. Although cold is a potent activator of brown adipose tissue, the increase in peripheral insulin sensitivity by cold is largely mediated by events occurring in skeletal muscle and at least partly involves GLUT4 translocation, as is also observed for exercise training.
The future of brown adipose tissues in the treatment of type 2 diabetes. [2018]The recent recognition that humans possess active depots of brown adipose tissue has boosted the interest in this tissue as a potential target for the prevention and treatment of obesity and related metabolic disorders. Furthermore, it was also revealed that brown adipose tissue (BAT) in humans may consist of so-called beige or brite adipocytes. So far, cold exposure is recognised as the strongest activator of BAT in humans, but there is much ongoing research focused on finding alternative activators of BAT. The consequences of long-term BAT activation and/or cold exposure on metabolic health are still unknown, and this represents an area of intensive research. This is one of a series of commentaries under the banner '50 years forward', giving personal opinions on future perspectives in diabetes, to celebrate the 50th anniversary of Diabetologia (1965-2015).
Kinetics of human brown adipose tissue activation and deactivation. [2020]Brown adipose tissue (BAT) has been identified as a potential target in the treatment and prevention of obesity and metabolic disease. The precise kinetics of BAT activation and the duration of stimulus required to recruit metabolically active BAT, and its subsequent deactivation, are not well-understood. In this clinical trial, 19 healthy adults (BMI: 23.7 ± 0.7 kg/m2, Age: 31.2 ± 2.8 year, 12 female) underwent three different cooling procedures to stimulate BAT glucose uptake, and active BAT volume was determined using 18F-Fluorodeoxyglucose (FDG) PET/CT imaging. We found that 20 min of pre-injection cooling produces activation similar to the standard 60 min (39.9 mL vs. 44.2 mL, p = 0.52), indicating that BAT activity approaches its peak function soon after the initiation of cooling. Furthermore, upon removal of cold exposure, active BAT volume declines (13.6 mL vs. 44.2 mL, p = 0.002), but the deactivation process persists even hours following cessation of cooling. Thus, the kinetics of human BAT thermogenesis are characterized by a rapid increase soon after cold stimulation but a more gradual decline after rewarming. These characteristics reinforce the feasibility of developing mild, short-duration cold exposure to activate BAT and treat obesity and metabolic disease.
Thyroid hormone induced brown adipose tissue and amelioration of diabetes in a patient with extreme insulin resistance. [2022]Brown adipose tissue (BAT) found by positron emission/computed tomography (PET-CT) using flouro-deoxyglucose (FDG) is inducible by cold exposure in men. Factors leading to increased BAT are of great interest for its potential role in the treatment of diabetes and obesity.
Short-term Cold Acclimation Recruits Brown Adipose Tissue in Obese Humans. [2018]Recruitment of brown adipose tissue (BAT) has emerged as a potential tool to combat obesity and associated metabolic complications. Short-term cold acclimation has been shown not only to enhance the presence and activity of BAT in lean humans but also to improve the metabolic profile of skeletal muscle to benefit glucose uptake in patients with type 2 diabetes. Here we examined whether short-term cold acclimation also induced such adaptations in 10 metabolically healthy obese male subjects. A 10-day cold acclimation period resulted in increased cold-induced glucose uptake in BAT, as assessed by [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography. BAT activity was negatively related to age, with a similar trend for body fat percentage. In addition, cold-induced glucose uptake in BAT was positively related to glucose uptake in visceral white adipose tissue, although glucose uptake in visceral and subcutaneous white adipose tissue depots was unchanged upon cold acclimation. Cold-induced skeletal muscle glucose uptake tended to increase upon cold acclimation, which was paralleled by increased basal GLUT4 localization in the sarcolemma, as assessed through muscle biopsies. Proximal skin temperature was increased and subjective responses to cold were slightly improved at the end of the acclimation period. These metabolic adaptations to prolonged exposure to mild cold may lead to improved glucose metabolism or prevent the development of obesity-associated insulin resistance and hyperglycemia.
Brown adipose tissue and thermogenesis. [2018]The growing understanding of adipose tissue as an important endocrine organ with multiple metabolic functions has directed the attention to the (patho)physiology of distinct fat depots. Brown adipose tissue (BAT), in contrast to bona fide white fat, can dissipate significant amounts of chemical energy through uncoupled respiration and heat production (thermogenesis). This process is mediated by the major thermogenic factor uncoupling protein-1 and can be activated by certain stimuli, such as cold exposure, adrenergic compounds or genetic alterations. White adipose tissue (WAT) depots, however, also possess the capacity to acquire brown fat characteristics in response to thermogenic stimuli. The induction of a BAT-like cellular and molecular program in WAT has recently been termed "browning" or "beiging". Promotion of BAT activity or the browning of WAT is associated with in vivo cold tolerance, increased energy expenditure, and protection against obesity and type 2 diabetes. These preclinical observations have gained additional significance with the recent discovery that active BAT is present in adult humans and can be detected by 18fluor-deoxy-glucose positron emission tomography coupled with computed tomography. As in rodents, human BAT can be activated by cold exposure and is associated with increased energy turnover and lower body fat mass. Despite the tremendous progress in brown fat research in recent years, pharmacological concepts to harness BAT function therapeutically are currently still lacking.
Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. [2021]In recent years, it has been shown that humans have active brown adipose tissue (BAT) depots, raising the question of whether activation and recruitment of BAT can be a target to counterbalance the current obesity pandemic. Here, we show that a 10-day cold acclimation protocol in humans increases BAT activity in parallel with an increase in nonshivering thermogenesis (NST). No sex differences in BAT presence and activity were found either before or after cold acclimation. Respiration measurements in permeabilized fibers and isolated mitochondria revealed no significant contribution of skeletal muscle mitochondrial uncoupling to the increased NST. Based on cell-specific markers and on uncoupling protein-1 (characteristic of both BAT and beige/brite cells), this study did not show "browning" of abdominal subcutaneous white adipose tissue upon cold acclimation. The observed physiological acclimation is in line with the subjective changes in temperature sensation; upon cold acclimation, the subjects judged the environment warmer, felt more comfortable in the cold, and reported less shivering. The combined results suggest that a variable indoor environment with frequent cold exposures might be an acceptable and economic manner to increase energy expenditure and may contribute to counteracting the current obesity epidemic.