Metabolic Syndrome, Obese, Sedentary
Conditions
Keywords
mitochondria, fitness, statins, cholesterol, metabolic syndrome
Brief summary
Here we tested if statins or exercise plus statins had a greater capacity to lower metabolic syndrome risk factors in sedentary individuals with at least 2 metabolic syndrome risk factors. We also examined if statins impacted exercise response for mitochondrial content in muscle or aerobic fitness.
Detailed description
OBJECTIVES: Determine if simvastatin impairs exercise training adaptations. BACKGROUND: Statins are commonly prescribed in combination with therapeutic lifestyle changes, including exercise, to reduce cardiovascular disease risk in patients with the metabolic syndrome. Statin use has been linked to skeletal muscle myopathy and impaired mitochondrial function, but it is unclear whether statin use alters adaptations to exercise training. METHODS: We examined the effects of simvastatin on changes in cardiorespiratory fitness and skeletal muscle mitochondrial content in response to aerobic exercise training. Sedentary overweight or obese adults with at least 2 metabolic syndrome risk factors (defined according to National Cholesterol Education Panel Adult Treatment Panel III criteria) were randomized to 12 weeks of aerobic exercise training or to exercise in combination with simvastatin (40 mg per day). The primary outcomes were cardiorespiratory fitness and skeletal muscle (vastus lateralis) mitochondrial content (citrate synthase enzyme activity).
Interventions
DRUGStatin
Statins (40mg/day)for 12 weeks
OTHERExercise only
12 weeks of exercise training (5 days a week for 45-50 min a session)
OTHERStatins + Exercise
Statins (40mg/day of simvastatin) plus exercise training (5 days/wk for 45-50 min a session) for 12 weeks
Sponsors
University of Missouri-Columbia
American Heart Association
University of Kansas Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Years to 59 Years
Healthy volunteers
Yes
Inclusion criteria
* Sedentary metabolic syndrome subjects will be 25-59 y of age * overweight to Class I or II obese (BMI 25-39 kg/m2) men and women * 2 of 4 other characteristics of the metabolic syndrome including fasting glucose of 100 to 125 mg/dl; waist circumference greater than 102 cm in men and 88 cm in women, serum triglyceride concentration greater than 150 mg/dl, HDL-C concentrations less than 40 mg/dl in men and 50 mg/dl in women, and blood pressure greater than 130/85 mmHG * Women must be taking birth control or be postmenopausal.
Exclusion criteria
* Diagnosed cardiovascular disease or diabetes or disease * Symptoms that could alter their ability to perform exercise * Fasting blood glucose of greater than 126 mg/dl * Smoking * Taking any medications or supplements (e.g., statins, fibrates, metformin, thiazolidenediones, anti-hypertensives (ACE-inhibitors and angiotensin blockers) which could affect blood lipids or insulin sensitivity. * Women who are pregnant or plan to become pregnant during the duration of the study * Individuals exercising regularly (more than one 30 min session per week) * Individuals with an orthopedic limitations for walking. * Report any allergies to the medications (statins, lidocaine)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| % Change in VO2max (Fitness) | Change from Baseline to 12 weeks | % change in fitness between baseline and after 12 weeks of treatment will be assessed by VO2max |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Skeletal Muscle Mitochondrial Content (Citrate Synthase Enzyme Activity) | 12 weeks | % change in skeletal muscle mitochondrial content (measured by citrate synthase enzyme activity) from pre to post intervention |
Countries
United States
Participant flow
Recruitment details
If meeting qualifications after initial phone screening, subject consented followed by another round of screening to determine if they had 2/5 risk factors or not which eliminated many subjects. Thus the difference between the 121 subjects reported for who signed consents and the 50 who entered the participant flow module.
Participants by arm
| Arm | Count |
|---|---|
| Statin Statins (40mg/day)for an average of 12 weeks
Statin: Statins (40mg/day)for 12 weeks | 9 |
| Exercise Only 12 weeks of exercise training (5 days a week for 45-50 min a session)
Exercise only: 12 weeks of exercise training (5 days a week for 45-50 min a session) | 21 |
| Statins + Exercise Statins (40mg/day of simvastatin) plus exercise training (5 days/wk) for 12 weeks
Statins + Exercise: Statins (40mg/day of simvastatin) plus exercise training (5 days/wk for 45-50 min a session) for 12 weeks | 20 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 3 | 1 |
Baseline characteristics
| Characteristic | Statin | Exercise Only | Statins + Exercise | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 21 Participants | 20 Participants | 50 Participants |
| Age, Continuous | 44 years STANDARD_DEVIATION 10 | 44 years STANDARD_DEVIATION 12 | 43 years STANDARD_DEVIATION 9 | 44 years STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 9 participants | 21 participants | 20 participants | 50 participants |
| Sex: Female, Male Female | 4 Participants | 13 Participants | 11 Participants | 28 Participants |
| Sex: Female, Male Male | 5 Participants | 8 Participants | 9 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 9 | 0 / 21 | 0 / 20 |
| serious Total, serious adverse events | 0 / 9 | 0 / 21 | 0 / 20 |
Outcome results
Primary
% Change in VO2max (Fitness)
% change in fitness between baseline and after 12 weeks of treatment will be assessed by VO2max
Time frame: Change from Baseline to 12 weeks
Population: Statins blocked exercise induced change in fitness
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Statin | % Change in VO2max (Fitness) | 0 percentage change of VO2max | Standard Deviation 6 |
| Exercise Only | % Change in VO2max (Fitness) | 10 percentage change of VO2max | Standard Deviation 5 |
| Statins + Exercise | % Change in VO2max (Fitness) | 1.5 percentage change of VO2max | Standard Deviation 6 |
p-value: <0.05ANOVA
Secondary
Skeletal Muscle Mitochondrial Content (Citrate Synthase Enzyme Activity)
% change in skeletal muscle mitochondrial content (measured by citrate synthase enzyme activity) from pre to post intervention
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Statin | Skeletal Muscle Mitochondrial Content (Citrate Synthase Enzyme Activity) | 0 percent change | Standard Error 10 |
| Exercise Only | Skeletal Muscle Mitochondrial Content (Citrate Synthase Enzyme Activity) | 13 percent change | Standard Error 7 |
| Statins + Exercise | Skeletal Muscle Mitochondrial Content (Citrate Synthase Enzyme Activity) | -4.5 percent change | Standard Error 8 |