Impact of Obesity on Microvascular Insulin Action and Cardiorespiratory Fitness in Type 1 Diabetes (ZQL010)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Overweight; Type 1 Diabetes
• Intervention / Treatment: Other: Exercise training

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lee Hartline, MEd; Phone Number: 434-924-5247; Email: lmh9d@virginia.edu
• Study Contact Backup: Name: Zhenqi Liu, MD; Email: zl3e@UVAhealth.org

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • University of Virginia
      • Principal Investigator: Zhenqi Liu, MD
      • Contact: Lee Hartline, MEd; Phone Number: 434-924-5247; Email: lmh9d@virginia.edu
      • Contact: Zhenqi Liu, MD; Phone Number: 434-924-5247; Email: zl3e@UVAhealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Type 1 diabetes - normal weight; Type 1 diabetes normal weight	Other: Exercise training; 15 weeks of HIIT exercise training
Active Comparator: Control - normal weight; healthy control - normal weight	Other: Exercise training; 15 weeks of HIIT exercise training
Active Comparator: Overweight control; Overweight, otherwise healthy	Other: Exercise training; 15 weeks of HIIT exercise training
Active Comparator: Type 1 diabetes - overweight	Other: Exercise training; 15 weeks of HIIT exercise training

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microvascular blood volume in skeletal and cardiac muscle - changes from baseline	insulin-mediated changes in skeletal and cardiac muscle as determined by insulin clamp	Before and after 15 weeks of exercise training
maximal aerobic exercise capacity	change in VO2max	before and after 15 weeks of exercise training

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
insulin-mediated whole body glucose disposal	insulin-mediated whole body glucose disposal during insulin clamp	before and after 15 weeks of exercise training
Muscle capillary density and satellite cells	Changes in muscle capillary density and satellite cells	before and after 15 weeks of exercise training

Collaborators and Investigators

• Sponsor: University of Virginia
• Investigators: Principal Investigator: Zhenqi Liu, MD, University of Virginia

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: April 14, 2026
• First Submitted That Met QC Criteria: May 1, 2026
• First Posted (Actual): May 7, 2026

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: overweight; Type 1 diabetes; Exercise training; healthy controls
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Diabetes Mellitus, Type 1; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: 302809; R01DK141617 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No