Obesity, Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of the present study is to determine the effects of increased walking and lower body heating on leg vascular function in patients with type 2 diabetes (T2D).
Detailed description
The notion that habitual aerobic exercise increases insulin-induced vasodilation is largely founded on rodent studies, hence the urgent need for human studies, especially in patients with type 2 diabetes (T2D). For example, it remains unknown if increased walking, the most common form of physical activity, enhances skeletal muscle vasodilator actions of insulin in T2D. In addition, the molecular mechanisms by which exercise improves vasoreactivity to insulin have not been examined in humans. The investigators propose that in T2D patients who are sedentary (i.e., the vast majority), increased leg blood flow with walking or local heating signifies a vital strategy to correct vascular insulin resistance. This study will establish whether increased physical activity and associated hemodynamic forces (e.g., shear stress) are a direct form of vascular medicine in humans.
Interventions
BEHAVIORALWalking: Intervention arm in diabetics
The walking program will consist of 45 minutes of walking (at a moderate pace) 5 days per week for 8 weeks.
OTHERWalking: No intervention in diabetics
Subjects will be instructed to continue their usual lifestyle for 8 weeks.
BEHAVIORALLower body heating: Intervention arm in diabetics
This intervention consists of 60 minutes of lower body heating (40-42 degree C) 7 days per week for 7 days.
OTHERWalking: Healthy cohort as reference controls
Subjects will be studied at one time only.
BEHAVIORALLower body heating: Intervention arm in healthy subjects
This intervention consists of 60 minutes of lower body heating (40-42 degree C).
OTHERLower body heating: Healthy cohort as reference controls
Subjects will be studied at one time only.
Sponsors
University of Missouri-Columbia
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will be assigned to either a walking, a lower body heating, or no intervention.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Patients with type 2 diabetes who are overweight and obese (BMI 25-50 kg/m2), 35 to 65 years of age, and sedentary (\<60 minutes structured exercise/week). Healthy volunteers without type 2 diabetes: 18 to 65 years of age.
Exclusion criteria
1. Cardiovascular disease including myocardial infraction, heart failure, coronary artery disease, stroke; 2. renal or hepatic diseases; 3. active cancer; 4. autoimmune diseases; 5. immunosuppressant therapy; 6. excessive alcohol consumption (\>14 drinks/week for men; \>7 drinks/week for women); 7. current tobacco use; 8. pregnancy; 9. mobility limitations; 10. foot ulcers; 11. diabetic neuropathy 12. uncontrolled hypertension (\>=180 systolic / 100 diastolic mmHg)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin-stimulated Leg Blood Flow Calculated as Percent Change (t0, t60) | Percent change from baseline leg blood flow during 60 minutes of insulin stimulation. | Measure of blood flow in response to insulin. Blood flow is measured via Doppler ultrasound at the femoral artery. Measurements are performed at baseline (t0) and after 60 minutes of insulin stimulation (t60). |
| Net Change in Insulin-stimulated Leg Blood Flow Calculated as Percent Change From Pre-intervention (t0,t60) to Post-intervention (t0,t60). | Change from baseline insulin-stimulated leg blood flow following 1 heating session, 7 days of heating intervention, or 8 weeks of walking intervention/no intervention. | Measure of blood flow in response to insulin. Blood flow is measured via Doppler ultrasound at the femoral artery. Measurements are performed pre-intervention and post-intervention at baseline (t0) and after 60 minutes of insulin stimulation (t60). Outcome measure indicates whether percent change in insulin-stimulated blood flow increased or decreased following intervention. Interventions that show an increase demonstrate an improvement in insulin-stimulated blood flow. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Walking: Intervention Arm in Diabetics The walking program will consist of 45 minutes of walking (at a moderate pace) 5 days per week for 8 weeks.
Walking: Intervention arm in diabetics: The walking program will consist of 45 minutes of walking (at a moderate pace) 5 days per week for 8 weeks. | 13 |
| Walking: No Intervention in Diabetics Subjects will be instructed to continue their usual lifestyle for 8 weeks.
Walking: No intervention in diabetics: Subjects will be instructed to continue their usual lifestyle for 8 weeks. | 13 |
| Walking: Healthy Cohort as Reference Controls Subjects will be studied at one time only.
Walking: Healthy cohort as reference controls: Subjects will be studied at one time only. | 15 |
| Lower Body Heating: Intervention Arm in Healthy Subjects This intervention consists of 60 minutes of lower body heating (40-42 degree C).
Lower body heating: Intervention arm in healthy subjects: This intervention consists of 60 minutes of lower body heating (40-42 degree C). | 18 |
| Lower Body Heating: Intervention Arm in Diabetics This intervention consists of 60 minutes of lower body heating (40-42 degree C) 7 days per week for 7 days.
Lower body heating: Intervention arm in diabetics: This intervention consists of 60 minutes of lower body heating (40-42 degree C) 7 days per week for 7 days. | 20 |
| Lower Body Heating: Healthy Cohort as Reference Controls Subjects will be studied at one time only.
Lower body heating: Healthy cohort as reference controls: Subjects will be studied at one time only. | 20 |
| Total | 99 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Walking: No Intervention in Diabetics | Walking: Healthy Cohort as Reference Controls | Lower Body Heating: Intervention Arm in Healthy Subjects | Walking: Intervention Arm in Diabetics | Lower Body Heating: Intervention Arm in Diabetics | Lower Body Heating: Healthy Cohort as Reference Controls | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 15 Participants | 18 Participants | 13 Participants | 20 Participants | 20 Participants | 99 Participants |
| Body Mass Index (BMI) | 36.2 kg/m^2 STANDARD_DEVIATION 1.7 | 23.5 kg/m^2 STANDARD_DEVIATION 2.3 | 25.1 kg/m^2 STANDARD_DEVIATION 4.2 | 36.9 kg/m^2 STANDARD_DEVIATION 1.6 | 35.9 kg/m^2 STANDARD_DEVIATION 1.2 | 23.7 kg/m^2 STANDARD_DEVIATION 2.2 | 29.6 kg/m^2 STANDARD_DEVIATION 2.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 4 Participants | 1 Participants | 0 Participants | 4 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 12 Participants | 14 Participants | 12 Participants | 20 Participants | 16 Participants | 87 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 15 Participants | 17 Participants | 13 Participants | 15 Participants | 20 Participants | 92 Participants |
| Region of Enrollment United States | 13 Participants | 15 Participants | 18 Participants | 13 Participants | 20 Participants | 20 Participants | 99 Participants |
| Sex: Female, Male Female | 6 Participants | 10 Participants | 8 Participants | 6 Participants | 12 Participants | 12 Participants | 54 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 10 Participants | 7 Participants | 8 Participants | 8 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 | 0 / 15 | 0 / 18 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 1 / 13 | 0 / 13 | 0 / 15 | 1 / 18 | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 | 0 / 15 | 0 / 18 | 0 / 20 | 0 / 20 |
Outcome results
Primary
Insulin-stimulated Leg Blood Flow Calculated as Percent Change (t0, t60)
Measure of blood flow in response to insulin. Blood flow is measured via Doppler ultrasound at the femoral artery. Measurements are performed at baseline (t0) and after 60 minutes of insulin stimulation (t60).
Time frame: Percent change from baseline leg blood flow during 60 minutes of insulin stimulation.
Population: Outcomes data from participants who were assigned to an intervention arm are reported under Outcome 2 (change from baseline to post-intervention).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Walking: Healthy Cohort as Reference Controls | Insulin-stimulated Leg Blood Flow Calculated as Percent Change (t0, t60) | 133.6 percentage change | Standard Error 48.7 |
| Lower Body Heating: Healthy Cohort as Reference Controls | Insulin-stimulated Leg Blood Flow Calculated as Percent Change (t0, t60) | 8.92 percentage change | Standard Error 2.26 |
Primary
Net Change in Insulin-stimulated Leg Blood Flow Calculated as Percent Change From Pre-intervention (t0,t60) to Post-intervention (t0,t60).
Measure of blood flow in response to insulin. Blood flow is measured via Doppler ultrasound at the femoral artery. Measurements are performed pre-intervention and post-intervention at baseline (t0) and after 60 minutes of insulin stimulation (t60). Outcome measure indicates whether percent change in insulin-stimulated blood flow increased or decreased following intervention. Interventions that show an increase demonstrate an improvement in insulin-stimulated blood flow.
Time frame: Change from baseline insulin-stimulated leg blood flow following 1 heating session, 7 days of heating intervention, or 8 weeks of walking intervention/no intervention.
Population: Outcomes data from participants who were not assigned a treatment arm are reported under Outcome 1 (Percent change in insulin-stimulated blood flow).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Walking: Intervention Arm in Diabetics | Net Change in Insulin-stimulated Leg Blood Flow Calculated as Percent Change From Pre-intervention (t0,t60) to Post-intervention (t0,t60). | 15.9 percent change | Standard Error 47.3 |
| Walking: No Intervention in Diabetics | Net Change in Insulin-stimulated Leg Blood Flow Calculated as Percent Change From Pre-intervention (t0,t60) to Post-intervention (t0,t60). | -17.6 percent change | Standard Error 21.4 |
| Lower Body Heating: Intervention Arm in Healthy Subjects | Net Change in Insulin-stimulated Leg Blood Flow Calculated as Percent Change From Pre-intervention (t0,t60) to Post-intervention (t0,t60). | 60.2 percent change | Standard Error 18.5 |
| Experimental: Lower Body Heating: Intervention Arm in Diabetics | Net Change in Insulin-stimulated Leg Blood Flow Calculated as Percent Change From Pre-intervention (t0,t60) to Post-intervention (t0,t60). | 11.1 percent change | Standard Error 3.5 |