Mechanisms of Fatigability With Diabetes

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.

Eligibility

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

Conditions3

Locations1 site

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