AIDS, Cardiovascular Disease, HIV, HIV Infections, Lipodystrophy, Obesity, Type 2 Diabetes
Conditions
Keywords
PPAR-gamma agonist, glucose metabolism, inflammation, adipose tissue distribution, cardiac function, vascular function, mass spectrometry, Treatment Experienced
Brief summary
The purpose is to examine the safety and efficacy of 16wks of pioglitazone (Actos; 30mg/d) with and without aerobic and strength exercise training for reducing glucose intolerance and central adiposity in HIV-infected people. We anticipate that pioglitazone + exercise training will improve glucose metabolism and insulin sensitivity, and reduce central adiposity more than pioglitazone alone. These improvements should translate into reduced cardiovascular disease risk in HIV-infected people.
Detailed description
Our prior research has examined the pathogenesis and potential treatments for metabolic complications in people living with HIV. We have adopted the lipotoxicity hypothesis for Metabolic Syndrome X to explain the pathogenesis of impaired glucose tolerance (IGT) and fat redistribution in HIV: increased lipolysis and mobilization of lipids and free fatty acids from subcutaneous adipose depots leads to their excessive deposition in muscle and liver which contributes to dyslipidemia, insulin resistance, increased hepatic glucose output, and possibly visceral fat accumulation. Effective treatments have not been identified. Consensus groups recommend regular exercise and dietary modifications as primary and pharmacologic interventions as secondary treatments for the syndromes. We propose to test the efficacy of aerobic and weight lifting exercise training and an oral insulin-sensitizing agent (pioglitazone) as treatments for HIV-associated IGT and fat redistribution. We propose a 4-month, 2-group randomized study to evaluate the efficacy of pioglitazone and exercise + pioglitazone in 40 men and 40 women living with HIV and IGT and fat redistribution. We will measure: insulin sensitivity, glucose disposal rate, hepatic glucose production rate (5hr-hyperinsulinemic euglycemic clamp with 6,6-\[2H2\]-glucose); whole-body and regional fat and muscle content (1H-MRI of the abdomen and thigh & DEXA), soleus muscle and liver lipid content (1H-MRS), muscle and fat PPARgamma/alpha mRNA and protein expression, serum lipid profiles, and serum adiponectin levels before and at the end of 4 months of treatment. We hypothesize that exercise training + pioglitazone will be more effective than pioglitazone alone at improving insulin sensitivity, reducing visceral fat, liver and muscle lipid content, and increasing peripheral subcutaneous fat content in HIV-infected people. We hypothesize that combined treatment will be more effective because exercise training will activate PPARalpha expression in muscle and pioglitazone will activate PPARy expression in fat and muscle. We anticipate that this project will provide direct evidence that supports the combined use of exercise training and pioglitazone in people living with HIV and experiencing metabolic and anthropomorphic disorders that increase cardiovascular disease risk.
Interventions
DRUGPioglitazone
Oral 30mg/day for 16 weeks
BEHAVIORALExercise training
Supervised aerobic and resistance exercise training (1.5hrs/day x 3 days/wk) for 16 weeks
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. 18-65 yr old HIV-infected men (n=40) and women (n=40). 2. Source documentation of HIV status. 3. Stable on highly active antiretroviral therapy (HAART) that may or may not include HIV-protease inhibitors for at least 3 months prior to enrollment. As of Jan 2005, HIV-infected long-term non-progressors will be included, even though they are not receiving HAART because it is likely that their disease status will not advance during the study period. 4. Impaired glucose tolerance (IGT) or type 2 diabetes and fat redistribution. IGT is defined as: fasting (8hr) plasma glucose 100-126mg/dL or plasma glucose \>140 mg/dL 2-hours after a 75g-oral glucose load. This definition (proposed/revised May 2006) includes volunteers with adult onset type 2 diabetes (non-insulin dependent diabetes), because we believe that these volunteers may benefit from the potential glucose-lowering actions of pioglitazone with or without exercise training. Fat redistribution is defined as any 2 of the following: waist-to-hip ratio \>0.85 women or \>0.95 men, or trunk/appendicular adipose ratio using whole-body DEXA \>0.85 women or \>1.3 men, or \<15% leg fat (DEXA; (leg fat/total body fat) x100), or visceral adiposity VAT \>120 cm2 women or \>140 cm2 men, or a VAT/TAT ratio \>0.30 women or \>0.40 men. Overall, the eligibility criteria are designed to include subjects with metabolic syndromes that increase CVD risk, and the potential to gain the greatest benefit from pioglitazone and exercise training. These inclusion criteria will help select/maintain homogeneous groups of study participants. 5. Plasma HIV RNA (Roche Amplicor® assay) \<5000 copies/ml OR a CD4 T-cell count \>100 cells/µL and stable for previous 3 months. 6. BMI 20-40kg/m2. 7. Normal blood chemistries for at least 1 month prior to enrollment; platelet count \>30,000/mm3, absolute neutrophil count \<750/mm3, transaminases \<2.5x the upper limit of normal (ULN), creatinine \<3x ULN, fasting triglycerides \<500 mg/dL.
Exclusion criteria
1. Medications or agents that might alter/impair glucose metabolism (insulin, glucocorticoids, corticosteroids, megace) during the 3 months prior to enrollment or at any time during enrollment. Volunteers who developed type 2 diabetes after HIV-infection or after starting anti-HIV medications, who are receiving insulin sensitizers (metformin, meglitinides, alpha-glucosidase inhibitors) or insulin secretagogues (sulfonylureas), but still do not have their blood sugars in control (defined as IGT above) are eligible. 2. Abnormal or unstable (for 3 months prior to enrollment) endocrine blood chemistries that might otherwise explain insulin resistance. TSH \<0.2 or \>12µIU/mL, morning cortisol \>22µg/dL, IGF-1 \<115ng/mL, total testosterone \<200ng/dL (men) \<15ng/dL (women). Use of testosterone, ACTH, thyroid hormone, or rhGH replacement to normalize low levels is permitted, but must be stable on hormone replacement for 3 months prior to enrollment and will not discontinue this replacement during enrollment. Hormone replacement cannot be started during treatment. 3. Allergy or hypersensitivity to thiazolidinediones. Currently taking a thiazolidinedione. 4. Anti-obesity or anorectic medications during the 3 months prior to enrollment or at any time during enrollment. Lipid-lowering medications are permitted (fibrate or statin), but the subject must be stable on that agent for at least 3 months prior to enrollment. Lipid-lowering agents cannot be started during the treatment period. 5. Chronic hepatitis B infection (HB surface antigen positive). Active hepatitis C infection (detectable Hep C RNA). Those who have cleared hepatitis B or C infection are eligible. This was revised in May 2006 to better clarify some uncertainties about hepatitis and eligibility. 6. History of serious cardiovascular conditions or NY Heart Association (NYHA) cardiac status Class III or IV, (e.g., recent MI, unstable angina, edema, CHF, CAD, CABG, valve disease (murmur), stroke, uncontrolled high blood pressure (resting \>140/90 mmHg on 3 occasions), irregular heart rhythm, bundle-branch block, aortic stenosis, resting ST-segment depression \>1mm) that would preclude exercise testing/training, or substantially increase risk of a CV-event during exercise, or would limit the subjects ability to participate in exercise training. Treatment with medications for a cardiovascular condition (cardiac glycosides, alpha- or beta-blockers). Some antihypertensive medications (Ca++-channel blocker, diuretic, or ACE inhibitor) will be permitted. 7. Insulin-dependent diabetes mellitus (IDDM) or a history of ketoacidosis, symptomatic diabetic neuropathy or retinopathy, or renal disease (creatinine \>3x ULN). 8. Hematocrit \<34% in men or \<25% in women with symptoms (fatigue, tired-legs, shortness of breath). Hemoglobin \<10 gm/100ml with symptoms. 9. History of eating disorder, significant GI-disease 10. Nausea, vomiting, diarrhea (\>4 loose stools/day) that are unresponsive to treatment during 2wks prior to enrollment or that persists for \>2wks during enrollment. 11. Active secondary infection. Any significant change in chronic suppressive therapy for an opportunistic infection during the 1-month prior to enrollment. 12. During the 3 months prior to enrollment, regular aerobic or weight lifting exercise training that exceeds the minimum (45min/d, 3d/wk, \>75% exercise capacity) required for the metabolic, biochemical, and anthropomorphic benefits of exercise to be attained as described in the American College of Sports Medicine Guidelines. In Apr 2006, this exclusion criterion was modified in order to facilitate enrollment of volunteers who are moderately-highly active during the 3months prior to screening for this study. We will randomize volunteers who exercise regularly into the two treatment groups. This will reduce the potential confounding effects of regular exercise on the metabolic, biochemical, and anthropomorphic benefits of exercise training that is prescribed during the treatment phase. We have excluded several volunteers who are regular exercisers, and we believe we may be unnecessarily excluding them. They can be included, enrollment will be facilitated, and the study design will not be adversely affected, as long as we randomize them into pioglitazone or exercise+pioglitazone (1:1). 13. Unwilling or unable to do supervised exercise 3 sessions/wk at the Medical School exercise facility. Any condition that might be contraindicated for exercise training (disabling joint, cartilage or muscle injury/disorder that prohibits or severely limits participation in regular exercise, disabling arthritis, severe physical disabilities, claudication, pulmonary disease, sinus tachycardia, arrhythmias, premature atrial or ventricular contractions). 14. Pregnancy or nursing mothers. Women cannot be pregnant and must agree to use an acceptable form of birth control during the treatment period. If birth control pills are used, the woman must be stable on these medications for at least 6 months prior to enrollment. All metabolic testing will be done in the early follicular phase. Urine pregnancy tests (hCG) will be done at baseline and every month the woman is enrolled in the study. 15. Pancreatitis within prior 1 year. Serum triglycerides \>500mg/dL esp. with history of pancreatitis, or otherwise at high risk for pancreatitis. 16. Medications that inhibit or slow blood coagulation (ie., blood thinners). Prothrombin (clotting) time exceeds 2 sec \> control (only in subjects who agree to muscle/fat biopsies). 17. Active malignancy or treatment with chemotherapeutic agents or radiation therapy during the 3 months prior to enrollment. 18. Excessive weight loss (\>10% body weight) during the 3 months prior to enrollment. History of hyperlactatemia or lactic acidosis, esp. with rapid weight loss. 19. Blinded investigational drugs/medications during the 3 months prior to enrollment that will not be unblinded before enrollment. Open-label investigational drugs are permitted. Must be stable on these for 3 months prior to enrollment, must remain stable on them during the treatment period, and they must be known not to affect glucose, lipid, adipose tissue or liver metabolism. 20. Non-prescription over the counter drugs/supplements that might alter glucose, lipid, or adipose tissue metabolism (eg., creatine monohydrate, chromium picolinate, amino acid/protein supplements, beta-hydroxy-beta-methyl-butyrate, anabolic-androgenic steroids, medium- or long-chain fatty acids, branched chain amino acid supplements, amino acids that potentially increase insulin or GH secretion (eg., arginine)) within 1 month of enrollment. These supplements will not be permitted during the treatment period. 21. Dementia or reduced cognitive function or unable to provide voluntary informed consent. Prisoners will not be enrolled. 22. Active substance abuse (e.g., alcoholism, cocaine, heroin, crack, methamphetamine, phencyclidine). Upon evaluation, if the physician-investigator considers that this substance abuse does not put the volunteer at risk for an adverse (ie. cardiovascular) event, or if the physician-investigator feels that the volunteer will be reliable and compliant with the treatment regimens, and that this substance abuse will not interfere with the study medications, exercise regimens, or data interpretation, then at the physician-investigators discretion the volunteer may be eligible. 23. Any cytokine or anti-cytokine therapy during the 3 months prior to enrollment. 24. Patients felt by the Physician Investigator to have uncontrolled hypertension or other diseases (i.e. vasculitis, pulmonary HTN) that otherwise may be a cause of significant underlying or variable endothelial dysfunction 25. Receiving vasoactive substances (i.e. nitrates, viagra) other than antihypertensives that cannot be discontinued at least 12 hours before endothelial function testing (BART).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin-stimulated Glucose Disposal Rate | Baseline and week16 | Insulin-mediated glucose disposal rate per kg of fat free mass per min |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Abdominal Subcutaneous Fat Volume | Baseline and week 16 | — |
| Hepatic Lipid Content | Baseline and week 16 | — |
| Hepatic Glucose Production Rate | Baseline and week 16 | ability of insulin to suppress hepatic glucose production = hepatic insulin sensitivity |
| Serum Lipid and Lipoprotein Levels | Baseline and week 16 | — |
| Liver Enzyme Levels | Baseline and week 16 | — |
| Hemoglobin | Baseline and Week 16 | — |
| Visceral Fat Volume | Baseline and week 16 | — |
| Serum Adiponectin Levels | Baseline and week 16 | — |
| Myocardial Contractility | Baseline and week 16 | E/A ratio; ratio of the early (E) to late (A) ventricular filling velocities |
| Myocardial Contractility-LV Ejection Time | Baseline and week 16 | Time required to empty the left ventricle into the aorta |
| Myocardial Contractility-DT | Baseline and week 16 | Deceleration time; time from the peak of early diastolic filling to baseline |
| Myocardial Contractility-SBP | Baseline and week 16 | Systolic blood pressure; peak vascular pressure during ventricular contraction |
| Myocardial Contractility-DBP | Baseline and week 16 | Diastolic blood pressure; vascular pressure during ventricular relaxation (diastole) |
| Hematocrit | Baseline and Week 16 | Percentage of blood volume that is red cells |
Countries
United States
Participant flow
Recruitment details
HIV-infected men and women (18 - 60 yr old) were recruited from the AIDS Clinical Trials Unit, the Infectious Diseases Clinic, and the Volunteers for Health Program at Washington University School of Medicine, St. Louis MO between Jan 2005-Dec 2010. Participants were randomly assigned (1:1) to 4 mo of pioglitazone with or without exercise training.
Pre-assignment details
Exclusion: AIDS diagnosis, non-compliant with anti-HIV medications, unstable CD4+ T-cell count or plasma HIV viremia, illegal drug abuse.
Participants by arm
| Arm | Count |
|---|---|
| Pioglitazone Pioglitazone (Actos; 30mg/day) for 16 weeks. | 22 |
| Pioglitazone + Exercise Training Pioglitazone (Actos; 30mg/day) plus progressive aerobic and weight lifting exercise training (1.5hr/day x 3 days/wk)supervised and monitored by a personal exercise trainer. | 22 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Pioglitazone + Exercise Training | Pioglitazone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 22 Participants | 44 Participants |
| Age Continuous | 46 years STANDARD_DEVIATION 2 | 44 years STANDARD_DEVIATION 2 | 45 years STANDARD_DEVIATION 2 |
| Region of Enrollment United States | 22 participants | 22 participants | 44 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 20 Participants | 19 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 19 |
| serious Total, serious adverse events | 0 / 20 | 0 / 19 |
Outcome results
Primary
Insulin-stimulated Glucose Disposal Rate
Insulin-mediated glucose disposal rate per kg of fat free mass per min
Time frame: Baseline and week16
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Insulin-stimulated Glucose Disposal Rate | Baseline | 30 µmol glucose/kg FFM/min | Standard Error 4 |
| Pioglitazone | Insulin-stimulated Glucose Disposal Rate | Week 16 | 37 µmol glucose/kg FFM/min | Standard Error 6 |
| Pioglitazone + Exercise Training | Insulin-stimulated Glucose Disposal Rate | Baseline | 34 µmol glucose/kg FFM/min | Standard Error 4 |
| Pioglitazone + Exercise Training | Insulin-stimulated Glucose Disposal Rate | Week 16 | 48 µmol glucose/kg FFM/min | Standard Error 6 |
Secondary
Abdominal Subcutaneous Fat Volume
Time frame: Baseline and week 16
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Abdominal Subcutaneous Fat Volume | Baseline | 2101 cm3 | Standard Error 293 |
| Pioglitazone | Abdominal Subcutaneous Fat Volume | Week 16 | 2164 cm3 | Standard Error 286 |
| Pioglitazone + Exercise Training | Abdominal Subcutaneous Fat Volume | Baseline | 1877 cm3 | Standard Error 197 |
| Pioglitazone + Exercise Training | Abdominal Subcutaneous Fat Volume | Week 16 | 1905 cm3 | Standard Error 230 |
Secondary
Hematocrit
Percentage of blood volume that is red cells
Time frame: Baseline and Week 16
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Hematocrit | Baseline Hematocrit | 39.9 % red cells | Standard Error 0.7 |
| Pioglitazone | Hematocrit | Week 16 Hematocrit | 39.6 % red cells | Standard Error 0.7 |
| Pioglitazone + Exercise Training | Hematocrit | Baseline Hematocrit | 40.7 % red cells | Standard Error 1.4 |
| Pioglitazone + Exercise Training | Hematocrit | Week 16 Hematocrit | 39.7 % red cells | Standard Error 1.3 |
Secondary
Hemoglobin
Time frame: Baseline and Week 16
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Hemoglobin | Baseline Hemoglobin | 13.8 g/L | Standard Error 0.3 |
| Pioglitazone | Hemoglobin | Week 16 Hemoglobin | 13.7 g/L | Standard Error 0.3 |
| Pioglitazone + Exercise Training | Hemoglobin | Baseline Hemoglobin | 13.8 g/L | Standard Error 0.5 |
| Pioglitazone + Exercise Training | Hemoglobin | Week 16 Hemoglobin | 13.6 g/L | Standard Error 0.4 |
Secondary
Hepatic Glucose Production Rate
ability of insulin to suppress hepatic glucose production = hepatic insulin sensitivity
Time frame: Baseline and week 16
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Hepatic Glucose Production Rate | Baseline | 32 percent suppression | Standard Error 3 |
| Pioglitazone | Hepatic Glucose Production Rate | Week 16 | 40 percent suppression | Standard Error 6 |
| Pioglitazone + Exercise Training | Hepatic Glucose Production Rate | Week 16 | 42 percent suppression | Standard Error 7 |
| Pioglitazone + Exercise Training | Hepatic Glucose Production Rate | Baseline | 37 percent suppression | Standard Error 5 |
Secondary
Hepatic Lipid Content
Time frame: Baseline and week 16
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Hepatic Lipid Content | Baseline | 12.1 percent of water | Standard Error 2 |
| Pioglitazone | Hepatic Lipid Content | Week 16 | 10.7 percent of water | Standard Error 2.4 |
| Pioglitazone + Exercise Training | Hepatic Lipid Content | Baseline | 8.0 percent of water | Standard Error 1.7 |
| Pioglitazone + Exercise Training | Hepatic Lipid Content | Week 16 | 5.5 percent of water | Standard Error 0.8 |
Secondary
Liver Enzyme Levels
Time frame: Baseline and week 16
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Liver Enzyme Levels | Week 16 AST | 30 U/L | Standard Error 4 |
| Pioglitazone | Liver Enzyme Levels | Week 16 ALT | 39 U/L | Standard Error 8 |
| Pioglitazone | Liver Enzyme Levels | Baseline ALT | 38 U/L | Standard Error 7 |
| Pioglitazone | Liver Enzyme Levels | Baseline AST | 34 U/L | Standard Error 7 |
| Pioglitazone + Exercise Training | Liver Enzyme Levels | Baseline ALT | 34 U/L | Standard Error 6 |
| Pioglitazone + Exercise Training | Liver Enzyme Levels | Week 16 AST | 27 U/L | Standard Error 3 |
| Pioglitazone + Exercise Training | Liver Enzyme Levels | Baseline AST | 27 U/L | Standard Error 4 |
| Pioglitazone + Exercise Training | Liver Enzyme Levels | Week 16 ALT | 32 U/L | Standard Error 6 |
Secondary
Myocardial Contractility
E/A ratio; ratio of the early (E) to late (A) ventricular filling velocities
Time frame: Baseline and week 16
Population: Number of participants for measures of myocardial contractility is less than that for all other measures. These measures were added to the protocol (after \~50% enrollment) after some reports suggested that this drug class (thiazolidinediones) may adversely affect heart function.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Myocardial Contractility | Baseline E/A ratio | 1.3 ratio | Standard Error 0.2 |
| Pioglitazone | Myocardial Contractility | Week 16 E/A ratio | 1.4 ratio | Standard Error 0.2 |
| Pioglitazone + Exercise Training | Myocardial Contractility | Baseline E/A ratio | 1.2 ratio | Standard Error 0.1 |
| Pioglitazone + Exercise Training | Myocardial Contractility | Week 16 E/A ratio | 1.4 ratio | Standard Error 0.1 |
Secondary
Myocardial Contractility-DBP
Diastolic blood pressure; vascular pressure during ventricular relaxation (diastole)
Time frame: Baseline and week 16
Population: Number of participants for measures of myocardial contractility is less than that for all other measures. These measures were added to the protocol (after \~50% enrollment) after some reports suggested that this drug class (thiazolidinediones) may adversely affect heart function.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Myocardial Contractility-DBP | Baseline DBP | 65 mmHg | Standard Error 3 |
| Pioglitazone | Myocardial Contractility-DBP | Week 16 DBP | 67 mmHg | Standard Error 4 |
| Pioglitazone + Exercise Training | Myocardial Contractility-DBP | Baseline DBP | 68 mmHg | Standard Error 5 |
| Pioglitazone + Exercise Training | Myocardial Contractility-DBP | Week 16 DBP | 61 mmHg | Standard Error 4 |
Secondary
Myocardial Contractility-DT
Deceleration time; time from the peak of early diastolic filling to baseline
Time frame: Baseline and week 16
Population: Number of participants for measures of myocardial contractility is less than that for all other measures. These measures were added to the protocol (after \~50% enrollment) after some reports suggested that this drug class (thiazolidinediones) may adversely affect heart function.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Myocardial Contractility-DT | Baseline DT | 204 msec | Standard Error 7 |
| Pioglitazone | Myocardial Contractility-DT | Week 16 DT | 193 msec | Standard Error 6 |
| Pioglitazone + Exercise Training | Myocardial Contractility-DT | Baseline DT | 214 msec | Standard Error 12 |
| Pioglitazone + Exercise Training | Myocardial Contractility-DT | Week 16 DT | 190 msec | Standard Error 4 |
Secondary
Myocardial Contractility-LV Ejection Time
Time required to empty the left ventricle into the aorta
Time frame: Baseline and week 16
Population: Number of participants for measures of myocardial contractility is less than that for all other measures. These measures were added to the protocol (after \~50% enrollment) after some reports suggested that this drug class (thiazolidinediones) may adversely affect heart function.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Myocardial Contractility-LV Ejection Time | Baseline LV ejection time | 296 msec | Standard Error 8 |
| Pioglitazone | Myocardial Contractility-LV Ejection Time | Week 16 LV ejection time | 294 msec | Standard Error 9 |
| Pioglitazone + Exercise Training | Myocardial Contractility-LV Ejection Time | Baseline LV ejection time | 281 msec | Standard Error 12 |
| Pioglitazone + Exercise Training | Myocardial Contractility-LV Ejection Time | Week 16 LV ejection time | 305 msec | Standard Error 9 |
Secondary
Myocardial Contractility-SBP
Systolic blood pressure; peak vascular pressure during ventricular contraction
Time frame: Baseline and week 16
Population: Number of participants for measures of myocardial contractility is less than that for all other measures. These measures were added to the protocol (after \~50% enrollment) after some reports suggested that this drug class (thiazolidinediones) may adversely affect heart function.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Myocardial Contractility-SBP | Baseline SBP | 114 mmHg | Standard Error 2 |
| Pioglitazone | Myocardial Contractility-SBP | Week 16 SBP | 114 mmHg | Standard Error 2 |
| Pioglitazone + Exercise Training | Myocardial Contractility-SBP | Baseline SBP | 121 mmHg | Standard Error 4 |
| Pioglitazone + Exercise Training | Myocardial Contractility-SBP | Week 16 SBP | 114 mmHg | Standard Error 3 |
Secondary
Serum Adiponectin Levels
Time frame: Baseline and week 16
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Serum Adiponectin Levels | Baseline serum adiponectin | 4.7 µg/mL | Standard Error 0.8 |
| Pioglitazone | Serum Adiponectin Levels | Week 16 serum adiponectin | 7.0 µg/mL | Standard Error 0.7 |
| Pioglitazone + Exercise Training | Serum Adiponectin Levels | Baseline serum adiponectin | 4.8 µg/mL | Standard Error 0.8 |
| Pioglitazone + Exercise Training | Serum Adiponectin Levels | Week 16 serum adiponectin | 6.5 µg/mL | Standard Error 0.9 |
Secondary
Serum Lipid and Lipoprotein Levels
Time frame: Baseline and week 16
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Serum Lipid and Lipoprotein Levels | Baseline Triglycerides | 2.3 mM/L | Standard Error 0.3 |
| Pioglitazone | Serum Lipid and Lipoprotein Levels | Week 16 Triglycerides | 2.5 mM/L | Standard Error 0.3 |
| Pioglitazone | Serum Lipid and Lipoprotein Levels | Baseline Total Cholesterol | 4.9 mM/L | Standard Error 0.2 |
| Pioglitazone | Serum Lipid and Lipoprotein Levels | Week 16 Total cholesterol | 4.6 mM/L | Standard Error 0.2 |
| Pioglitazone | Serum Lipid and Lipoprotein Levels | Baseline LDL cholesterol | 2.8 mM/L | Standard Error 0.2 |
| Pioglitazone | Serum Lipid and Lipoprotein Levels | Week 16 LDL cholesterol | 2.5 mM/L | Standard Error 0.1 |
| Pioglitazone | Serum Lipid and Lipoprotein Levels | Baseline HDL cholesterol | 0.99 mM/L | Standard Error 0.05 |
| Pioglitazone | Serum Lipid and Lipoprotein Levels | Week 16 HDL cholesterol | 0.98 mM/L | Standard Error 0.05 |
| Pioglitazone + Exercise Training | Serum Lipid and Lipoprotein Levels | Week 16 HDL cholesterol | 1.09 mM/L | Standard Error 0.05 |
| Pioglitazone + Exercise Training | Serum Lipid and Lipoprotein Levels | Baseline Triglycerides | 2.1 mM/L | Standard Error 0.4 |
| Pioglitazone + Exercise Training | Serum Lipid and Lipoprotein Levels | Baseline LDL cholesterol | 2.7 mM/L | Standard Error 0.2 |
| Pioglitazone + Exercise Training | Serum Lipid and Lipoprotein Levels | Week 16 Triglycerides | 1.8 mM/L | Standard Error 0.2 |
| Pioglitazone + Exercise Training | Serum Lipid and Lipoprotein Levels | Baseline HDL cholesterol | 1.06 mM/L | Standard Error 0.05 |
| Pioglitazone + Exercise Training | Serum Lipid and Lipoprotein Levels | Baseline Total Cholesterol | 4.7 mM/L | Standard Error 0.2 |
| Pioglitazone + Exercise Training | Serum Lipid and Lipoprotein Levels | Week 16 LDL cholesterol | 2.6 mM/L | Standard Error 0.2 |
| Pioglitazone + Exercise Training | Serum Lipid and Lipoprotein Levels | Week 16 Total cholesterol | 4.5 mM/L | Standard Error 0.2 |
Secondary
Visceral Fat Volume
Time frame: Baseline and week 16
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone | Visceral Fat Volume | Baseline | 1933 cm3 | Standard Error 150 |
| Pioglitazone | Visceral Fat Volume | Week 16 | 1970 cm3 | Standard Error 164 |
| Pioglitazone + Exercise Training | Visceral Fat Volume | Baseline | 1890 cm3 | Standard Error 217 |
| Pioglitazone + Exercise Training | Visceral Fat Volume | Week 16 | 1746 cm3 | Standard Error 177 |