Type 2 Diabetes
Conditions
Keywords
Type, 2, Diabetes, Blood, Vessel, Function, Exercise, Program, Intervention, Vitamin, C, Men, Women, Blood vessel function
Brief summary
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.
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.
Interventions
BEHAVIORALExercise 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).
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.
Sponsors
American Diabetes Association
National Institutes of Health (NIH)
University of Colorado, Denver
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Circumferential Strain Before and After Exercise at Baseline, After Vitamin C Infusion, and After Exercise Training | 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 | 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. |
| Ejection Fraction: Percentage of Blood Leaving the Heart Before and After Exercise at Baseline, After a Vitamin C Infusion, and After Exercise Training | 7 months; Measures are made at rest for baseline, at rest for Vitamin C administration, and at rest following the 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ascorbic Acid - Control All study subjects have ascorbic acid infusion during one exercise visit as well as a three month exercise training intervention.
Exercise program: Three month exercise program located at the Anschutz Medical Campus. The program runs three times per week for about an hour each session.
Ascorbic Acid (Vitamin C): During one exercise study visit, 0.06 grams of Vitamin C per kilogram (kg) 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. | 20 |
| Ascorbic Acid - Type 2 Diabetes All study subjects have ascorbic acid infusion during one exercise visit as well as a three month exercise training intervention.
Exercise program: Three month exercise program located at the Anschutz Medical Campus. The program runs three times per week for about an hour each session.
Ascorbic Acid (Vitamin C): During one exercise study visit, 0.06 grams of Vitamin C per kilogram (kg) 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. | 27 |
| Total | 47 |
Baseline characteristics
| Characteristic | Ascorbic Acid - Type 2 Diabetes | Total | Ascorbic Acid - Control |
|---|---|---|---|
| Age, Continuous | 46.5 years STANDARD_DEVIATION 5.7 | 46.0 years STANDARD_DEVIATION 6 | 45.4 years STANDARD_DEVIATION 6 |
| Body Fat Percentage (%) | 32.61 percentage STANDARD_DEVIATION 6.1 | 33.63 percentage STANDARD_DEVIATION 6.5 | 35.00 percentage STANDARD_DEVIATION 7 |
| Body Mass Index (BMI) | 31.75 kg/m^2 STANDARD_DEVIATION 4.7 | 31.26 kg/m^2 STANDARD_DEVIATION 4 | 30.60 kg/m^2 STANDARD_DEVIATION 3 |
| Glucose (mg/dL) | 118.33 mg/dL STANDARD_DEVIATION 22.2 | 105.06 mg/dL STANDARD_DEVIATION 23.1 | 87.15 mg/dL STANDARD_DEVIATION 5.7 |
| HDL Cholesterol (mg/dL) | 38.26 mg/dL STANDARD_DEVIATION 8.1 | 44.19 mg/dL STANDARD_DEVIATION 12.5 | 52.2 mg/dL STANDARD_DEVIATION 13 |
| Height (cm) | 175.17 centimeters STANDARD_DEVIATION 8.7 | 173.52 centimeters STANDARD_DEVIATION 9.7 | 171.30 centimeters STANDARD_DEVIATION 10.8 |
| Hemoglobin A1c | 6.85 percentage STANDARD_DEVIATION 0.7 | 6.22 percentage STANDARD_DEVIATION 1 | 5.37 percentage STANDARD_DEVIATION 0.4 |
| Insulin (uIU/mL) | 29.93 uIU/mL STANDARD_DEVIATION 19.6 | 23.77 uIU/mL STANDARD_DEVIATION 17.1 | 15.45 uIU/mL STANDARD_DEVIATION 7.7 |
| LDL Cholesterol (mg/dL) | 87.33 mg/dL STANDARD_DEVIATION 19.2 | 94.85 mg/dL STANDARD_DEVIATION 22.2 | 105.00 mg/dL STANDARD_DEVIATION 22.4 |
| Peak VO2 (absolute) | 2076.67 mL/min STANDARD_DEVIATION 531.6 | 2055.81 mL/min STANDARD_DEVIATION 525.3 | 2027.65 mL/min STANDARD_DEVIATION 529.2 |
| Peak VO2 (relative) | 20.93 mL/kg/min STANDARD_DEVIATION 3.8 | 21.52 mL/kg/min STANDARD_DEVIATION 4.3 | 22.32 mL/kg/min STANDARD_DEVIATION 4.9 |
| Race/Ethnicity, Customized American Indian | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Black/African American | 7 Participants | 13 Participants | 6 Participants |
| Race/Ethnicity, Customized Hispanic | 5 Participants | 9 Participants | 4 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 11 Participants | 21 Participants | 10 Participants |
| Region of Enrollment United States | 27 Participants | 47 Participants | 20 Participants |
| Sex: Female, Male Female | 6 Participants | 17 Participants | 11 Participants |
| Sex: Female, Male Male | 21 Participants | 30 Participants | 9 Participants |
| Total Cholesterol (mg/dL) | 147.30 mg/dL STANDARD_DEVIATION 20.6 | 158.43 mg/dL STANDARD_DEVIATION 27.5 | 173.45 mg/dL STANDARD_DEVIATION 28.8 |
| Triglycerides (mg/dL) | 151.52 mg/dL STANDARD_DEVIATION 65.5 | 133.23 mg/dL STANDARD_DEVIATION 58.8 | 108.55 mg/dL STANDARD_DEVIATION 37.1 |
| Weight (kg) | 97.89 kilograms STANDARD_DEVIATION 18 | 94.39 kilograms STANDARD_DEVIATION 15.8 | 89.67 kilograms STANDARD_DEVIATION 10.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 2 / 27 |
| serious Total, serious adverse events | 1 / 20 | 1 / 27 |
Outcome results
Primary
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.
Time frame: 7 months; Measures are made at rest for baseline, at rest for Vitamin C administration, and at rest following the exercise training
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Circumferential Strain - Control | Ejection Fraction: Percentage of Blood Leaving the Heart Before and After Exercise at Baseline, After a Vitamin C Infusion, and After Exercise Training | Post Exercise Training | 61 percentage of blood leaving the heart | Standard Deviation 3 |
| Circumferential Strain - Control | Ejection Fraction: Percentage of Blood Leaving the Heart Before and After Exercise at Baseline, After a Vitamin C Infusion, and After Exercise Training | Baseline | 65 percentage of blood leaving the heart | Standard Deviation 2 |
| Circumferential Strain - Control | Ejection Fraction: Percentage of Blood Leaving the Heart Before and After Exercise at Baseline, After a Vitamin C Infusion, and After Exercise Training | Vitamin C | 67 percentage of blood leaving the heart | Standard Deviation 2 |
| Circumferential Strain - Type 2 Diabetes | Ejection Fraction: Percentage of Blood Leaving the Heart Before and After Exercise at Baseline, After a Vitamin C Infusion, and After Exercise Training | Baseline | 65 percentage of blood leaving the heart | Standard Deviation 1 |
| Circumferential Strain - Type 2 Diabetes | Ejection Fraction: Percentage of Blood Leaving the Heart Before and After Exercise at Baseline, After a Vitamin C Infusion, and After Exercise Training | Post Exercise Training | 65 percentage of blood leaving the heart | Standard Deviation 3 |
| Circumferential Strain - Type 2 Diabetes | Ejection Fraction: Percentage of Blood Leaving the Heart Before and After Exercise at Baseline, After a Vitamin C Infusion, and After Exercise Training | Vitamin C | 63 percentage of blood leaving the heart | Standard Deviation 1 |
Primary
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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Circumferential Strain - Control | Percent Change in Circumferential Strain Before and After Exercise at Baseline, After Vitamin C Infusion, and After Exercise Training | Baseline | -24 percentage of change in length | Standard Deviation 1 |
| Circumferential Strain - Control | Percent Change in Circumferential Strain Before and After Exercise at Baseline, After Vitamin C Infusion, and After Exercise Training | Vitamin C | -23 percentage of change in length | Standard Deviation 1 |
| Circumferential Strain - Control | Percent Change in Circumferential Strain Before and After Exercise at Baseline, After Vitamin C Infusion, and After Exercise Training | Post Exercise Training | -22 percentage of change in length | Standard Deviation 1 |
| Circumferential Strain - Type 2 Diabetes | Percent Change in Circumferential Strain Before and After Exercise at Baseline, After Vitamin C Infusion, and After Exercise Training | Baseline | -20 percentage of change in length | Standard Deviation 1 |
| Circumferential Strain - Type 2 Diabetes | Percent Change in Circumferential Strain Before and After Exercise at Baseline, After Vitamin C Infusion, and After Exercise Training | Vitamin C | -21 percentage of change in length | Standard Deviation 1 |
| Circumferential Strain - Type 2 Diabetes | Percent Change in Circumferential Strain Before and After Exercise at Baseline, After Vitamin C Infusion, and After Exercise Training | Post Exercise Training | -22 percentage of change in length | Standard Deviation 1 |