Exercise Interventions for Prediabetes Fatigue

Overseen By Christopher Sundberg, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Marquette University

Must not be taking: Insulin, Hormone replacement

Disqualifiers: Neuropathy, Severe obesity, Smoking, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

80 Participants Needed

Trial Summary

What is the purpose of this trial?

Pre-diabetes (Pre-D) is a precursor to type 2 diabetes (T2D) and characterized by increased exercise fatigability of lower limb muscles, that can impede exercise performance. The cause for the increased fatigability in people with Pre-D is not known. Given the profound vascular disease present in people who have had uncontrolled diabetes for several years, we will determine whether dynamic, fatiguing contractions of the lower limb muscles in people with Pre-D are limited by vascular dysfunction at multiple levels along the vascular tree including the artery, arteriole, and/or capillary. This clinical trial involves a novel exercise training regime involving blood flow restriction to the exercising limb will be used as a probe to further understand the vascular mechanisms for increased fatigability in people with Pre-D and T2D. The long-term goal is to better understand what limits exercise and functional performance in people with diabetes to help develop targeted, more effective exercise programs.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on insulin, hormone replacement drugs, or vasoactive medications.

What data supports the effectiveness of the treatment Blood Flow Restriction Exercise for prediabetes fatigue?

Research shows that increasing physical activity can help prevent the progression from prediabetes to diabetes and improve heart health. Exercise, including resistance training, has been shown to be effective in managing prediabetes and reducing the risk of developing type 2 diabetes. ^{1 2 3 4 5}

Is blood flow restriction exercise safe for humans?

Blood flow restriction exercise is generally safe for healthy individuals, but it may cause increased blood pressure and other cardiovascular issues, especially in people with existing health conditions like heart disease, diabetes, or high blood pressure. It's important to have a medical screening before starting this type of exercise to ensure safety. ^{6 7 8 9 10}

How is Blood Flow Restriction Exercise different from other treatments for prediabetes fatigue?

Blood Flow Restriction Exercise is unique because it involves performing low-intensity exercises while restricting blood flow to the muscles, which can enhance muscle strength and endurance with less strain compared to traditional high-intensity workouts. This method may be particularly beneficial for individuals with prediabetes who might struggle with more intense exercise regimens. ^{1 2 11 12 13}

Eligibility Criteria

This trial is for adults aged 30-85 with pre-diabetes or type 2 diabetes, characterized by specific HbA1c and blood glucose levels. It's not open to smokers, those with poor glycemic control, severe obesity, untreated hypothyroidism, certain medication users, or individuals with cardiovascular or musculoskeletal conditions that limit exercise.

Inclusion Criteria

My HbA1c level is between 6.5% and 10%, indicating I have Type 2 Diabetes.

My blood sugar and HbA1c levels are within the normal range.

I have pre-diabetes with specific blood sugar levels.

Exclusion Criteria

You are a smoker.

Your blood sugar is not well controlled, with a HbA1c level above 10%.

I am taking medication for advanced type 2 diabetes, including insulin.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants perform 8 weeks of dynamic unilateral resistance exercise training with and without blood flow restriction

8 weeks

Weekly sessions

Follow-up

Participants are monitored for changes in strength, blood flow, muscle oxygenation, and other physiological measures

4 weeks

Treatment Details

Interventions

• Blood Flow Restriction Exercise
• Control Exercise

Trial Overview The study investigates why people with pre-diabetes experience increased muscle fatigue during exercise. Participants will undergo a novel exercise regimen that includes restricting blood flow to the limbs to understand vascular contributions to this fatigability.

Participant Groups

Group I: Control Exercise Experimental Treatment 1 Intervention

Low-load knee extension resistance training (20% of 1-RM) without blood flow restriction. A 10-cm wide inflatable cuff will be placed around the upper portion of the thigh but not inflated.

Group II: Blood Flow Restriction Exercise Experimental Treatment 1 Intervention

Low-load knee extension resistance training (20% of 1-RM) with blood flow restriction using a 10-cm wide inflatable cuff placed around the most proximal part of the exercising thigh. Blood flow will be restricted in the BFR leg at above the limb occlusion pressure of the and this will be determined prior to the exercise while the participant is seated in the knee extensor machine. The cuff pressure during the BFR protocol will be 10 mmHg above limb occlusion pressure.

Who Is Running the Clinical Trial?

Marquette University

Lead Sponsor

Trials

68

Recruited

202,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

University of Illinois at Chicago

Collaborator

Trials

653

Recruited

1,574,000+

Medical College of Wisconsin

Collaborator

Trials

645

Recruited

1,180,000+

Findings from Research

Lifestyle interventions, particularly increased physical activity, can prevent the progression from pre-diabetes to Type 2 diabetes and improve cardiovascular risk factors, as shown in various studies reviewed.

One recent trial indicated that such interventions may directly reduce cardiovascular events, including mortality, strokes, and heart attacks, highlighting the potential of physical activity in managing health risks for pre-diabetic individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance. Popp Switzer, M., Elhanafi, S., San Juan, ZT.[2018]

Prediabetes includes different phenotypes—impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and a combination of both—each associated with varying risks for developing type 2 diabetes and cardiovascular disease.

Understanding the distinct metabolic mechanisms behind these phenotypes can help tailor exercise interventions, as some individuals may not respond well to traditional exercise due to their specific prediabetes characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise resistance across the prediabetes phenotypes: Impact on insulin sensitivity and substrate metabolism. Malin, SK., Liu, Z., Barrett, EJ., et al.[2018]

High-intensity interval training (HIIT) significantly improves endothelial function and blood pressure in patients with type 2 diabetes by increasing levels of adropin and nitrite/nitrate (NOx), compared to moderate-intensity continuous training (MICT).

In a study of 66 participants over 12 weeks, both HIIT and MICT increased flow-mediated dilatation (FMD) and peak oxygen consumption, but HIIT resulted in greater increases in adropin and NOx, which are linked to better vascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved blood pressure and flow-mediated dilatation via increased plasma adropin and nitrate/nitrite induced by high-intensity interval training in patients with type 2 diabetes. Davoodi, M., Hesamabadi, BK., Ariabood, E., et al.[2022]

A systematic review of 47 studies involving over 8000 individuals with prediabetes or diabetes found that while there are some risks associated with increased physical activity, such as musculoskeletal injuries and hypoglycemia, the overall prevalence of severe adverse events is low.

The review supports that increased physical activity is generally safe for individuals with prediabetes and diabetes, and it led to the development of a new risk assessment algorithm to help guide safe exercise practices for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based risk assessment and recommendations for physical activity clearance: diabetes mellitus and related comorbidities. Riddell, MC., Burr, J.[2022]

A 24-month study involving 137 participants with prediabetes showed that aerobic training (AT), resistance training (RT), and combined training (AT + RT) significantly reduced the incidence of type 2 diabetes (T2D) by 74%, 65%, and 72% respectively, compared to a control group.

All exercise groups also demonstrated improved blood glucose and lipid profiles, indicating that both RT and combined training are effective alternatives to aerobic training alone in preventing T2D progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year-supervised resistance training prevented diabetes incidence in people with prediabetes: A randomised control trial. Dai, X., Zhai, L., Chen, Q., et al.[2020]

Blood flow restriction training (BFRT) can be beneficial for rehabilitation but poses risks such as increased blood pressure and adverse cardiovascular responses, especially in individuals with pre-existing conditions like hypertension and diabetes.

To ensure safety, a risk stratification tool is recommended for clinicians to assess patients' medical histories and identify those who may be at higher risk for complications when undergoing BFRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Useful Blood Flow Restriction Training Risk Stratification for Exercise and Rehabilitation. Nascimento, DDC., Rolnick, N., Neto, IVS., et al.[2022]

In a study involving 20 healthy participants, alternating (ALT) blood flow restriction (BFR) exercise resulted in significantly higher cardiovascular responses, including greater increases in aortic and mean arterial blood pressures compared to unilateral (UNI) and bilateral (BIL) patterns.

For individuals concerned about cardiovascular strain, unilateral or bilateral BFR exercises may be safer options than alternating patterns, as they produced lower cardiovascular responses during the exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute cardiovascular response to unilateral, bilateral, and alternating resistance exercise with blood flow restriction. Stanford, DM., Park, J., Jones, R., et al.[2021]

Blood flow restriction (BFR) training is gaining popularity for its ability to enhance muscle mass, strength, and cardiovascular function, making it a valuable tool in fitness and rehabilitation.

Despite its benefits, practitioners face challenges in implementing BFR training, such as determining appropriate pressure levels, ensuring access to technology, conducting thorough medical screenings, and managing the perceived discomfort of the training to encourage long-term adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perceived Barriers to Blood Flow Restriction Training. Rolnick, N., Kimbrell, K., Cerqueira, MS., et al.[2022]

Blood flow restriction training (BFRT) is generally safe for patients with musculoskeletal disorders, with a systematic review of 19 studies involving 322 participants showing that most did not report adverse events.

While some rare adverse events were noted, such as deep vein thrombosis and rhabdomyolysis, individuals undergoing BFRT did not experience more adverse events compared to those doing regular exercise, indicating its potential as a safe strengthening method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety of Blood Flow Restriction Training as a Therapeutic Intervention for Patients With Musculoskeletal Disorders: A Systematic Review. Minniti, MC., Statkevich, AP., Kelly, RL., et al.[2020]

Blood flow-restricted resistance training (BFR-RT) is safe and effective for improving systolic blood pressure in patients with coronary artery disease (CAD), showing a significant reduction of 10 mm Hg after 8 weeks of training.

BFR-RT combined with aerobic training did not negatively affect hemostatic markers, indicating it can be a beneficial addition to cardiac rehabilitation programs without adverse effects on blood clotting factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic and Hemostatic Response to Blood Flow Restriction Resistance Exercise in Coronary Artery Disease: A Pilot Randomized Controlled Trial. Kambič, T., Novaković, M., Tomažin, K., et al.[2021]

Regular physical activity significantly reduces the risk of developing impaired glucose tolerance and non-insulin-dependent diabetes mellitus (NIDDM), especially in individuals at high risk, as supported by various epidemiological and aging studies.

Exercise training, particularly vigorous and prolonged protocols, can improve insulin sensitivity and glucose tolerance by increasing muscle insulin action and promoting beneficial changes in muscle morphology, such as increased capillary density and the conversion of muscle fiber types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of exercise training in the prevention and treatment of insulin resistance and non-insulin-dependent diabetes mellitus. Ivy, JL.[2022]

In a study of 22 obese individuals with prediabetes, high-intensity interval training (INT) was found to significantly improve fat oxidation during exercise compared to continuous training (CONT), indicating a more effective approach for this population.

Participants who engaged in INT not only lost more body mass and increased their peak oxygen consumption (VO2peak) but also showed greater fat oxidation during exercise at the same relative intensity, suggesting that INT may be a superior training method for enhancing metabolic health in prediabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two Weeks of Interval Training Enhances Fat Oxidation during Exercise in Obese Adults with Prediabetes. Gaitán, JM., Eichner, NZM., Gilbertson, NM., et al.[2020]

Resistance training (RT) is as effective as aerobic training (AT) in improving metabolic control and preserving β-cell function in individuals with prediabetes, based on a study of 248 Chinese participants over 6 months.

Both RT and AT significantly reduced HbA1c levels compared to a control group, indicating that both forms of exercise can help manage blood sugar levels in people at risk for type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the effects of 6 months aerobic exercise and resistance training on metabolic control and β-cell function in Chinese patients with prediabetes: A multicenter randomized controlled trial. Yuan, X., Dai, X., Liu, L., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

Exercise resistance across the prediabetes phenotypes: Impact on insulin sensitivity and substrate metabolism. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Improved blood pressure and flow-mediated dilatation via increased plasma adropin and nitrate/nitrite induced by high-intensity interval training in patients with type 2 diabetes. [2022]

4. Canada pubmed.ncbi.nlm.nih.gov

Evidence-based risk assessment and recommendations for physical activity clearance: diabetes mellitus and related comorbidities. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Two-year-supervised resistance training prevented diabetes incidence in people with prediabetes: A randomised control trial. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

A Useful Blood Flow Restriction Training Risk Stratification for Exercise and Rehabilitation. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Acute cardiovascular response to unilateral, bilateral, and alternating resistance exercise with blood flow restriction. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Perceived Barriers to Blood Flow Restriction Training. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

The Safety of Blood Flow Restriction Training as a Therapeutic Intervention for Patients With Musculoskeletal Disorders: A Systematic Review. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Hemodynamic and Hemostatic Response to Blood Flow Restriction Resistance Exercise in Coronary Artery Disease: A Pilot Randomized Controlled Trial. [2021]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Role of exercise training in the prevention and treatment of insulin resistance and non-insulin-dependent diabetes mellitus. [2022]

12. Turkey pubmed.ncbi.nlm.nih.gov

Two Weeks of Interval Training Enhances Fat Oxidation during Exercise in Obese Adults with Prediabetes. [2020]

13. Australia pubmed.ncbi.nlm.nih.gov

Comparing the effects of 6 months aerobic exercise and resistance training on metabolic control and β-cell function in Chinese patients with prediabetes: A multicenter randomized controlled trial. [2022]