Mechanisms of Fatigability With Diabetes

NCT ID: NCT04442451

Last Updated: 2025-10-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-01
• Study Completion Date: 2027-08-31

Brief Summary

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.

Detailed Description

The aim of the clinical trial is to determine the effectiveness of dynamic resistance exercise training coupled with blood flow restriction to improve fatigability and vascular function in people with Pre-D and T2D. People with Pre-D and T2D from Aim 1 will perform 8 weeks of dynamic unilateral resistance exercise training in which one leg is exercised with freely perfused conditions and the other leg with blood flow restriction.

We will assess fatigability, skeletal muscle metabolism, capillary density, and vascular function in people with Pre-D and T2D before and after a novel training intervention that couples dynamic resistance training with blood flow restriction to the exercising limb. This novel intervention has been shown to improve vascular function in young and older adults but has not been investigated in people with Pre-D and T2D. Endothelial function in intact large conduit arteries and arterioles isolated from skeletal muscle biopsies will be measured before and after the training intervention to assess whether the novel training improves vascular function along multiple levels of the vascular tree in people with Pre-D and T2D. Skeletal muscle blood flow through the femoral artery will be quantified with Doppler ultrasonography and skeletal muscle oxygenation will be measured with near infrared spectroscopy (NIRS) during a dynamic fatiguing knee extension exercise. We will closely match participant groups for physical activity levels, age, sex, and body mass index (BMI), because these confounders are not typically controlled for in other human studies.

Conditions

Pre-diabetes; Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Control Exercise

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 Type: EXPERIMENTAL

Control Exercise

Intervention Type: OTHER

Each participant will attend 3 sessions per week for 8 weeks. Participants will perform low-load knee extension resistance training (20% of 1-RM) without blood flow restriction on the designated leg for 4 sets of contractions with 15 contractions per set of contractions with a 30 second rest between each set of contractions.

Blood Flow Restriction Exercise

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.

Group Type: EXPERIMENTAL

Blood Flow Restriction Exercise

Intervention Type: OTHER

Each participant will attend 3 sessions per week for 8 weeks. Participants will perform low-load knee extension resistance training (20% of 1-RM) with blood flow restriction on the designated leg for 4 sets of contractions with 15 contractions per set of contractions with a 30 second rest between each set of contractions.

Interventions

Control Exercise

Each participant will attend 3 sessions per week for 8 weeks. Participants will perform low-load knee extension resistance training (20% of 1-RM) without blood flow restriction on the designated leg for 4 sets of contractions with 15 contractions per set of contractions with a 30 second rest between each set of contractions.

Intervention Type: OTHER

Blood Flow Restriction Exercise

Each participant will attend 3 sessions per week for 8 weeks. Participants will perform low-load knee extension resistance training (20% of 1-RM) with blood flow restriction on the designated leg for 4 sets of contractions with 15 contractions per set of contractions with a 30 second rest between each set of contractions.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Men and women adults 30 years to 85 years or less
• Pre-diabetes [glycosylated hemoglobin (HbA1c) of 5.7-6.4% and fasting plasma glucose 100-125 mg/dL at the time of initial screening]
• Controls [normoglycemic with a HbA1c level ≤5.6% and fasting blood glucose ≤ 99 mg/dL (5.5 mmol/L)]
• Type 2 Diabetes Mellitus [elevated glycosylated hemoglobin (HbA1c) >6.5% and <10%]

Exclusion Criteria

• Signs or symptoms of neuropathy
• Medications associated with advanced stages of T2D including insulin
• Poor glycemic control (HbA1c>10%)
• Peripheral edema
• Severe obesity (BMI, >45kg·m-2)
• Untreated hypothyroidism
• Smoking
• Hypertension
• Cardiovascular or musculoskeletal disease that preclude exercise testing
• Hormone replacement drugs or vasoactive medications

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Illinois at Chicago

OTHER

Sponsor Role: collaborator

Medical College of Wisconsin

OTHER

Sponsor Role: collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role: collaborator

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Marquette University

OTHER

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: lead

Responsible Party

Sandra Hunter

Francie Kraker Goodridge Collegiate Professor of Kinesiology and Professor of Kinesiology, School of Kinesiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Michigan

Ann Arbor, Michigan, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sandra Hunter, PhD

Role: CONTACT

sandrahu@umich.edu

(734) 647-9819

Sarah Lessila, MSc

Role: CONTACT

slessila@umich.edu

Facility Contacts

Sandra Hunter, PhD

Role: primary

sandrahu@umich.edu

(734) 647-9819

Sarah Lessila, MS

Role: backup

slessila@umich.edu

(734) 647-6019

Other Identifiers

5R01AG077688-03

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HUM00255375

Identifier Type: -

Identifier Source: org_study_id