Impact of Obesity on Microvascular Insulin Action and Cardiorespiratory Fitness in Type 1 Diabetes

Official title

Impact of Obesity on Microvascular Insulin Action and Cardiorespiratory Fitness in Type 1 Diabetes (

Overview

The purpose of this study is: * To see if insulin resistance (how sensitive your muscle tissue is to insulin) is associated with lower cardio fitness in people with Type 1 diabetes compared to healthy controls, before and after a High Intensity Interval Training (HIIT) exercise program. * To see if being overweight and having Type 1 diabetes is associated with lower cardio fitness compared to overweight healthy controls, before and after a HIIT exercise program.

Detailed description

This study will test the hypothesis that in humans with T1D skeletal muscle microvascular insulin resistance predicts a reduction in Cardiorespiratory Fitness (CRF) and obesity exacerbates microvascular insulin resistance, leading to further CRF decline, which is mechanistically linked to increased muscle microvascular endothelial oxidative stress, impaired muscle mitochondrial function, reduced muscle capillary density and decreased satellite cells.

Interventions

• Other Exercise training
  15 weeks of HIIT exercise training

Primary outcome measures

• Microvascular blood volume in skeletal and cardiac muscle - changes from baseline [Time frame: Before and after 15 weeks of exercise training]
• maximal aerobic exercise capacity [Time frame: before and after 15 weeks of exercise training]

Secondary outcome measures (2)

• insulin-mediated whole body glucose disposal [Time frame: before and after 15 weeks of exercise training]
• Muscle capillary density and satellite cells [Time frame: before and after 15 weeks of exercise training]

Eligibility criteria

Inclusion criteria

• • Male or female ≥21 and ≤50 years old

• For persons with T1D: Disease duration ≥ 5 years and HbA1c ≤ 8.5% on multiple daily insulin injection or insulin pump
• Body mass index: ≥19 and ≤27 kg/m2 for control and T1D, ≥30 and ≤40 kg/m2 (27.5 to 37.5 for Asian Americans) for obesity and T1D + obesity. BMI is limited to ≤40 kg/m2 (37.5 for Asian Americans) for easier vascular access and cardiac imaging.
• Stable use of non-insulin medications for over 6 months other than estrogen/progesterone containing medications which must be discontinued at least 3 months prior to the study (intrauterine devices may be continued due to limited systemic absorption)

Exclusion criteria

• • Acute or chronic disease other than T1D or obesity

• History of microvascular or macrovascular diabetes complications
• History of diabetic ketoacidosis in the past 24 months
• History of hypoglycemia unawareness
• Recently active (>20 min of moderate/high intensity exercise, 2 times/week)
• Subjects who are smokers or who have quit smoking <5 years
• Subjects with hypertriglyceridemia (>400 mg/dl)
• Current use of vasoactive medications (i.e. calcium channel blockers, angiotensin-converting enzyme or renin inhibitors, angiotensin-receptor blockers, nitrates, alpha- or beta-blockers, or diuretics).
• Females taking oral contraceptives in the past 3 months
• Subjects with a history of significant metabolic, cardiac, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or malignancy
• Pregnant (as evidenced by positive pregnancy test) or nursing women
• Musculoskeletal condition preventing participation in exercise testing or exercise training
• History of gastroparesis
• Pulse oximetry <90%

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 1 center

• University of Virginia — Charlottesville

Identifiers

NCT: NCT07573228 · 302809 · R01DK141617

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗