Brown Fat Activation Treatments for Type 2 Diabetes

(GB8 Trial)

Overseen By Frédérique Frisch

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Université de Sherbrooke

Must not be taking: Fibrates, Thiazolidinediones, Insulin, others

Disqualifiers: Cardiovascular, Liver, Renal, Smoking, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how activating brown fat, a special type of body fat that burns calories, can aid individuals with Type 2 Diabetes. Researchers use cold exposure (also known as cold stimulation or cold acclimation) and a new fat-tracking method to understand brown fat's function and its potential in diabetes control. Participants will undergo cold exposure alone or with a small dose of nicotinic acid (a form of vitamin B3) to determine which is more effective. Individuals with Type 2 Diabetes or those without, who have stable weight and no major recent lifestyle changes, might be suitable for this trial. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on diabetes management.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that exposure to cold can activate brown fat, which helps burn energy and manage weight. This activation might also improve insulin use, benefiting people with type 2 diabetes. Studies have not identified major safety concerns with cold exposure itself, so it is generally considered safe.

However, nicotinic acid (a form of niacin) presents some safety issues. Some studies indicate it can raise blood sugar levels, posing risks for people with diabetes. High doses over long periods can also cause liver problems. Consulting a healthcare provider about these risks before starting nicotinic acid is important.

Overall, cold exposure appears well-tolerated, but nicotinic acid requires careful monitoring, especially for those with diabetes. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for Type 2 Diabetes because they focus on activating brown fat through cold exposure, which is a novel approach compared to traditional methods like insulin therapy or oral medications that target blood sugar levels. This method leverages the body's natural ability to burn energy and increase metabolism through brown fat, potentially offering a new way to manage diabetes. Additionally, the combination of cold exposure with nicotinic acid could enhance this effect, providing an innovative angle to boost metabolic health. This approach is particularly interesting as it explores non-pharmaceutical interventions that could complement or even reduce the need for standard diabetes medications.

What evidence suggests that this trial's treatments could be effective for Type 2 Diabetes?

Research has shown that exposure to cold, one of the treatments in this trial, can improve insulin response in people with type 2 diabetes. Insulin sensitivity, which measures how well the body uses insulin, improved by about 43% after 10 days of cold acclimation in one study. Cold exposure also enhances the body's ability to manage sugar.

Nicotinic acid, or niacin, is another treatment option in this trial. It effectively lowers certain blood fats and improves overall fat levels without affecting blood sugar. Studies suggest that niacin can help manage fat-related issues in people with type 2 diabetes. Both cold exposure and niacin offer promising methods for managing diabetes. ^{2 3 6 7 8}

Who Is on the Research Team?

André Carpentier

Principal Investigator

Université de Sherbrooke

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Cold exposure
• Oral Nicotinic acid

Trial Overview 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.

How Is the Trial Designed?

Group I: Subject without type 2 Diabetes- cold exposure and nicotinic acid Experimental Treatment 2 Interventions

3-hour cold exposure with oral nicotinic acid: Protocol A

Group II: Subject with type 2 Diabetes- cold exposure and nicotinic acid Experimental Treatment 2 Interventions

3-hour cold exposure with oral nicotinic acid: Protocol A

Group III: Subject without Type 2 Diabetes- cold exposure Active Control 1 Intervention

3-hour cold exposure: Protocol B

Group IV: Subject with Type 2 Diabetes- cold exposure Active Control 1 Intervention

3-hour cold exposure: Protocol B

Who Is Running the Clinical Trial?

Université de Sherbrooke

Lead Sponsor

Trials

317

Recruited

79,300+

Published Research Related to This Trial

Humans have active brown adipose tissue (BAT), which is gaining attention as a potential target for preventing and treating obesity and metabolic disorders.

Cold exposure is currently the most effective way to activate BAT, but researchers are exploring other methods to stimulate this tissue, with ongoing studies investigating the long-term effects of BAT activation on metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The future of brown adipose tissues in the treatment of type 2 diabetes. Schrauwen, P., van Marken Lichtenbelt, WD., Spiegelman, BM.[2018]

A 10-day cold acclimation protocol in humans significantly increased the activity of brown adipose tissue (BAT) and nonshivering thermogenesis (NST), suggesting a potential method to enhance energy expenditure and combat obesity.

The study found no significant changes in skeletal muscle mitochondrial uncoupling or 'browning' of white adipose tissue, indicating that the increased energy expenditure was primarily due to BAT activation rather than changes in muscle metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. van der Lans, AA., Hoeks, J., Brans, B., et al.[2021]

Cold acclimation for 10 days at temperatures of 14-15 °C significantly improved insulin sensitivity by approximately 43% in eight subjects with type 2 diabetes.

The increase in insulin sensitivity was associated with enhanced GLUT4 translocation in skeletal muscle, suggesting a mechanism of action that does not rely on changes in insulin signaling or AMPK activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus. Hanssen, MJ., Hoeks, J., Brans, B., et al.[2022]

Cold acclimation and exercise training both lead to significant changes in gene expression in human skeletal muscle, with cold acclimation affecting 756 genes and exercise training affecting 665 genes, indicating a potential overlap in their adaptive responses.

However, the overlapping genes primarily relate to tissue remodeling rather than insulin signaling or glucose metabolism, suggesting that while both interventions improve insulin sensitivity, they may do so through different molecular mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative transcriptome analysis of human skeletal muscle in response to cold acclimation and exercise training in human volunteers. Nascimento, EBM., Hangelbroek, RWJ., Hooiveld, GJEJ., et al.[2021]

A 10-day cold acclimation in 10 metabolically healthy obese men increased glucose uptake in brown adipose tissue (BAT), suggesting potential benefits for glucose metabolism and obesity management.

The study found that cold acclimation also improved glucose uptake in skeletal muscle, likely due to increased GLUT4 localization, which may help prevent insulin resistance and hyperglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term Cold Acclimation Recruits Brown Adipose Tissue in Obese Humans. Hanssen, MJ., van der Lans, AA., Brans, B., et al.[2018]

In a clinical trial with 19 healthy adults, just 20 minutes of cooling was found to activate brown adipose tissue (BAT) similarly to the standard 60 minutes, suggesting that BAT can be quickly stimulated for potential metabolic benefits.

After cold exposure ends, the active volume of BAT decreases significantly, indicating that while BAT activation is rapid, its deactivation is slower, which could inform strategies for using cold exposure in obesity treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kinetics of human brown adipose tissue activation and deactivation. Leitner, BP., Weiner, LS., Desir, M., et al.[2020]

Brown adipose tissue (BAT) is a unique type of fat that can burn energy and produce heat, which is important for regulating body temperature and metabolism, and can be activated by cold exposure and certain compounds.

The ability of white adipose tissue (WAT) to transform into a BAT-like state, known as 'browning', is linked to increased energy expenditure and protection against obesity and type 2 diabetes, highlighting the potential for therapeutic strategies targeting BAT in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brown adipose tissue and thermogenesis. Fenzl, A., Kiefer, FW.[2018]

In a case study of a patient with an insulin receptor mutation, discontinuing levothyroxine therapy led to a decrease in brown adipose tissue (BAT) volume and activity, as evidenced by reduced FDG uptake on PET-CT scans.

The findings suggest a relationship between thyroid hormone levels and BAT activity, indicating that thyroid hormones may play a role in glucose metabolism and diabetic control, although further research is needed to confirm this association.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thyroid hormone induced brown adipose tissue and amelioration of diabetes in a patient with extreme insulin resistance. Skarulis, MC., Celi, FS., Mueller, E., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7943816/

Metabolic responses to mild cold acclimation in type 2 ... Mild cold acclimation for 10 days has been previously shown to markedly improve insulin sensitivity in patients with type 2 diabetes.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26147760/

Short-term cold acclimation improves insulin sensitivity in ... Here we report that 10 d of cold acclimation (14-15 °C) increased peripheral insulin sensitivity by ∼43% in eight type 2 diabetes subjects.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0306456525000452

Daily brief whole-body immersion in 14 °C water ... This is the first study to show that cold acclimation induced by brief CWIs temporarily decreases insulin sensitivity and glucose tolerance, whereas REE and ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0011224023000639

Short-duration cold exposure decreases fasting-induced ... In conclusion, cold exposure had no effect on REE but decreased fasting-induced glucose intolerance which was accompanied by a maintained insulin sensitivity.

5. tandfonline.com tandfonline.com/doi/full/10.2147/IJN.S441847

Cold Exposure Alleviates T2DM Through Plasma-Derived ... Our data indicate that cold exposure may have a potentially beneficial effect on the development of T2DM, mainly through the anti-diabetic ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12263699/

Integrated effects of cold acclimation: physiological ... Research has found that cold exposure activates BAT, leading to increased energy expenditure, which supports weight management and improves ...

7. digitalcommons.georgefox.edu digitalcommons.georgefox.edu/cgi/viewcontent.cgi?article=1039&context=dmsc

Deliberate Cold Exposure as Augmentation for Diabetic ... Deliberate cold exposure (CE) could be a complementary treatment for patients with T2DM through the activation of BAT and mitochondrial ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4861190/

Body temperature regulation in diabetes - PubMed Central - NIH Most of the research regarding the effects of cold exposure in type 2 diabetes is associated with its therapeutic potential. ... cold acclimation improves insulin ...