Mechanisms of Fatigability With Diabetes

Официальное название

Mechanisms of Fatigability and the Protective Effects of Exercise in People With Diabetes

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое 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.
• Другое 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.

Первичные конечные точки

• Fatigability - Reduction in Power [Срок оценки: One session before and then after 8 weeks of training]
• Strength - 1 Repetition Maximum [Срок оценки: One session before and then after 8 weeks of training]
• Strength - Maximal Voluntary Contraction (MVC) [Срок оценки: One session before and then after 8 weeks of training]
• Leg Blood Flow [Срок оценки: One session before and then after 8 weeks of training]
• Skeletal Muscle Oxygenation [Срок оценки: One session before and then after 8 weeks of training]
• Vasodilation in Skeletal Muscle Arterioles [Срок оценки: One session before and then after 8 weeks of training]
• Muscle Metabolism - Phosphorus Nuclear Magnetic Resonance Spectroscopy (31P-MRS)) [Срок оценки: One session before and then after 8 weeks of training]
• Capillary density [Срок оценки: One session before and after 8 weeks of training]

Критерии участия

Критерии включения

• 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 \[elevated glycosylated hemoglobin (HbA1c) >6.5% and <10%\]

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

США · 1 центр

• University of Michigan — Ann Arbor

Идентификаторы

NCT: NCT04442451 · HUM00255375 · 5R01AG077688-03

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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