Clinical trial NCT04442451: Mechanisms of Fatigability With Diabetes
Official title: Mechanisms of Fatigability and the Protective Effects of Exercise in People With Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Pre-diabetes
Type 2 Diabetes
Keywords: Diabetes
Pre-diabetes
Fatigability
Blood Flow Restriction Training
Vascular Function
Muscle Fatigue
Lead sponsor: Marquette University
Sponsor class: OTHER
Collaborators: name: University of Illinois at Chicago
name: Medical College of Wisconsin
name: University of Michigan
First posted: 2020-06-22
Enrollment: 80
Sex: ALL
Minimum age (years): 30
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Each participant will attend 3 sessions per week for 8 weeks. A training session will start with a 10-minute warm up on a bike ergometer. Each leg will then perform low-load resistance training (\~20% of 1-RM) for 4 sets of contractions with 15 contractions per set of contractions with a 30 second rest between each set of contractions while seated in a knee extension weight machine. One leg will be randomized to always perform the training with blood flow restriction (BFR leg) while the contralateral leg performs the exercise training without blood flow occlusion (Control leg).
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Fatigability - Reduction in Power
timeFrame: One session before and then after 8 weeks of training
measure: Strength - 1 Repetition Maximum
timeFrame: One session before and then after 8 weeks of training
measure: Strength - Maximal Voluntary Contraction (MVC)
timeFrame: One session before and then after 8 weeks of training
measure: Leg Blood Flow
timeFrame: One session before and then after 8 weeks of training
measure: Skeletal Muscle Oxygenation
timeFrame: One session before and then after 8 weeks of training
measure: Vasodilation in Skeletal Muscle Arterioles
timeFrame: One session before and then after 8 weeks of training
measure: Muscle Metabolism - Phosphorus Nuclear Magnetic Resonance Spectroscopy (31P-MRS))
timeFrame: One session before and then after 8 weeks of training
measure: Capillary density
timeFrame: One session before and after 8 weeks of training
Secondary outcomes:
Other outcomes:
Locations:
city: Milwaukee
country: United States
facility: Marquette University
state: Wisconsin
Study officials:
References: