Influence of Endothelial Function on Central and Peripheral Causes Of Exercise Impairment in Type 2 Diabetes (InsITE)

Influence Of Endothelial Function On Central and Peripheral Causes Of Exercise Impairment In Type 2 Diabetes

This study will evaluate the effects of impaired blood flow regulation on exercise. It will also determine whether the effects are more important in the heart or in the skeletal muscle tissue during exercise. In addition, this study will decide whether temporarily reversing these problems will improve blood flow control, improve heart and muscle tissue function and help improve exercise capacity in person with type 2 diabetes. This study will do so using two methods: (1) by giving vitamin C intravenously (IV) and (2) a three month exercise training program. Up to 100 subjects will be enrolled in this study.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Behavioral: Exercise program; Drug: Ascorbic Acid (Vitamin C)

Detailed Description

The investigators have found that persons with type 2 diabetes have an impaired ability to perform exercise even without clinically apparent complications. The reasons for this marked abnormality are unknown but are important as the decreased ability to exercise could contribute to the decreased expenditure of physical activity frequently observed in this population and may potentially constitute an early marker of cardiovascular disease.

The investigators wish to evaluate the effects of impaired blood flow regulation on exercise capacity and whether the effects are more important in the heart or in the skeletal muscle tissue during exercise. In addition, the investigators are determining whether correcting these abnormalities by two methods of improving blood flow regulation (acutely infusing Vitamin C or three months of chronic exercise training) leads to improved blood flow regulation, improved heart and skeletal muscle tissue function and hence to better exercise capacity in person with type 2 diabetes. This information will provide a more mechanistic understanding of causes of abnormal exercise responses observed in person with type 2 diabetes as well as whether and to what degree responses are modifiable. Interventions that reverse the exercise defect may facilitate patient adherence to prescribed physical activity programs and potentially decrease cardiovascular mortality in this large segment of the population.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Men and women with uncomplicated Type 2 Diabetes
• Healthy men and women without Type 2 Diabetes
• Patients with Type 2 Diabetes may be taking metformin or sulfonylurea drugs to treat diabetes
• Persons with history of hypercholesteremia if controlled with statins and/or diet
• Patients who are moderately overweight (BMI 25-37.5)
• Must be sedentary (defined as regular exercise < 2 times a week at a low to moderate level).
• Patients with Hemoglobin A1c (HBA1C) <8%
• Patients between the ages of 30 to 55 years
• Premenopausal women.
• Former smokers who have quit smoking for at least one year
• Absence of comorbid conditions
• Mild neuropathy is O.K. as long as it will not hamper exercise performance.
• Resting systolic blood pressure (SBP) < 140, Resting diastolic blood pressure (DBP) < 90
• Total Cholesterol < 205 Triglycerides < 250 low density lipoprotein (LDL) < 130
• Control subjects with a normal A1C and fasting glucose

Exclusion Criteria:

• People with T2DM taking oral medications, other than metformin or sulfonylurea drugs to control their diabetes.
• Persons treated with insulin will be excluded
• People who are currently smoking or have not quit for at least one year
• Controls who have immediate family history of T2DM
• Peri-menopausal or post-menopausal women.
• Peripheral neuropathy
• Total cholesterol > 205
• Regional wall motion abnormalities
• LV wall thickness ≥1.1 cm
• Decreased contractility (fractional shortening <30%)
• Ischemic heart disease (abnormal resting or exercise ECG)
• Presence of angina that would limit exercise performance
• Pulmonary problems that would limit exercise performance
• Systolic blood pressure >140 mmHg at rest or >250 mmHg with exercise or diastolic pressure >90 mmHg at rest or >105 mmHg with exercise
• Persons with autonomic insufficiency, assessed by measuring variation in RR intervals with cycled breathing and by presence of a >20 mm fall in upright blood pressure without a change in heart rate
• Proteinuria (urine protein >200 mg/dl) or a creatinine > 2 mg/dl
• Renal disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ascorbic acid; All study subjects have ascorbic acid infusion during one exercise visit as well as a three month exercise training intervention.

Behavioral: Exercise program; Three month exercise program located at the Anschutz Medical Campus at I-225 and Colfax. The program runs three times per week for about an hour each session. Gym is open Monday - Saturday during specific hours (morning, noon, evening).; Other Names: Exercise Training; Drug: Ascorbic Acid (Vitamin C); During one exercise study visit, 0.06 grams of Vitamin C per kilogram fat-free mass per 100 milliliters (mL) of normal saline administered; Subjects will receive a bolus of 100mL Vitamin C solution given at 5ml/minute over 20 minutes followed by a "drip-infusion" given at 1.7ml/minute.; Other Names: Vitamin C; Ascorbic Acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Circumferential Strain Before and After Exercise at Baseline, After Vitamin C Infusion, and After Exercise Training	Characterize the purported cardiac dysfunction during exercise in people with type 2 diabetes (T2D). In a normal patient when measuring circumferential strain, results are negative with downward tracing (as strain is a relative change in length). Circumferential strain is a measurement of ventricular circumference within the heart vessels, measured via echocardiography.	7 months; Measures are made at rest and after exercise for baseline, at rest and after infusion for Vitamin C administration, and at rest and after exercise following the exercise training
Ejection Fraction: Percentage of Blood Leaving the Heart Before and After Exercise at Baseline, After a Vitamin C Infusion, and After Exercise Training	Evaluate potential changes in cardiac function by echocardiography following 2 interventions: Three months of exercise training and acute vitamin C administration. Ejection fraction (EF) is a measurement of the percentage of blood leaving your heart each time it contracts, typically measure by echocardiography. Numbers listed are absolute EF values.	7 months; Measures are made at rest for baseline, at rest for Vitamin C administration, and at rest following the exercise training

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Institutes of Health (NIH); American Diabetes Association
• Investigators: Principal Investigator: Judith G Regensteiner, PhD, University of Colorado, Denver

Publications and helpful links

General Publications

• Scalzo RL, Bauer TA, Harrall K, Moreau K, Ozemek C, Herlache L, McMillin S, Huebschmann AG, Dorosz J, Reusch JEB, Regensteiner JG. Acute vitamin C improves cardiac function, not exercise capacity, in adults with type 2 diabetes. Diabetol Metab Syndr. 2018 Feb 14;10:7. doi: 10.1186/s13098-018-0306-9. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: November 4, 2008
• First Submitted That Met QC Criteria: November 4, 2008
• First Posted (Estimated): November 5, 2008

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 10, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Diabetes; Exercise; Women; Intervention; Function; Blood; C; Men; Type; 2; Vitamin; Program; Vessel; Blood vessel function
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Antioxidants; Vitamins; Ascorbic Acid
• Other Study ID Numbers: 07-1152; UL1TR000154 (U.S. NIH Grant/Contract)