EAL

H/A: Hyperlipidemia (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine whether an individualized and supervised progressive resistance exercise-training program improves the metabolic complications associated with HIV
Hypothesized that weight lifting exercises training (four days per week for 16 weeks) would increase skeletal muscle cross-sectional area, increase maximum voluntary muscle strength, reduce central adipose tissue mass and reduce serum cholesterol and total triglyceride concentrations in HIV-infected men.

Inclusion Criteria:

Asymptomatic HIV-infected males with stable antiviral therapy for at least one month before enrollment, no history of cardiovascular disease (CVD) and normal resting electrocardiograms.

Exclusion Criteria:

Excluded if testosterone derivatives or recombinant human growth hormone within 60 days before enrollment
Physical activity patterns exceeded the minimum guidelines for exercise training established by the American College of Sports Medicine.

Description of Study Protocol:

Recruitment

Methods not reported.

Design

Non-randomized clinical trial.

Intervention

Weight-lifting program which consisted of three upper and four lower body exercises
Required one to 1.5 hours per day, four days per week for 64 sessions
Initial sessions were low intensity (50% to 65% of maximum strength) and high repetition (10 or more lifts); each exercise was done two to three times per session.

Statistical Analysis

Means ±SE; two-tailed, paired T-tests used to compare baseline to week 16 measurement
Linear regression analysis was used to examine the relationship between exercise-induced changes in the body composition and fasting serum triglyceride concentrations
P-value less than 0.05 for statistical significance.

Data Collection Summary:

Timing of Measurements

Before (baseline) and after 16 weeks of intervention.

Dependent Variables

Triglyceride levels, total and HDL-C; measured by using enzymatic kits from Bayer and diagnostics on a Hitachi 917 analyzer. LDL-C was estimated by using Friedewald equation.
Insulin, C-peptide, glucagon and pro-insulin concentrations were measured in a commercial radioimmunoassay laboratory. All baseline and post-exercise blood samples were obtained after a 10-hour to 12-hour overnight fast.
Whole body and regional lean and adipose tissue masses were measured using a Hologic QDR-2000 dual-energy X-ray absorptiometer
Thigh muscle and adipose tissue cross-sectional areas were measured by using proton-magnetic resonance imaging.

Independent Variables

Exercise: Weight-lifting consisting of three upper and four lower body exercises for one to 1.5 hours per day, four days per week for 64 sessions
Macronutrient and energy intakes using three-day diet records.

Description of Actual Data Sample:

Initial N: N=18 (18 males, zero females)
Age: Mean age 42±2 years.

Other Relevant Demographics

Plasma viral load copies per ml less than or equal to 400 in 11 subjects
CD4 counts per uL (range) equals 152 to 840.

Anthropometrics

Height (cm): 177±2
Weight (kg): 23±1
Whole body adiposity (percentage): 19±1
Trunk/appendicular adiposity: 1.53±0.16.

Location

Washington University Medical School, St. Louis, MO.

Summary of Results:

Variables	Baseline Measures and Confidence Intervals	After 16-week Intervention Measures and Confidence Intervals	Statistical Significance of Group Difference
Body weight (kg)	70.8±2.5	72.2±2.6	P=0.001
Whole body lean mass (kg)	56.6±1.5	58.0±1.6	P=0.005
Trunk lean mass (kg)	27.7±0.7	28.3±0.8	P=0.020
Arms lean mass (kg)	6.6±0.2	6.9±0.2	P=0.001
Legs lean mass (kg)	16.7±0.6	17.0±0.6	P=0.097
Whole body adipose mass	14.2±1.3	14.2±1.3	P=0.95
Trunk adipose mass (kg)	7.8±0.9	8.0±0.9	P=0.53
Arms adipose mass (kg)	1.7±0.2	1.5±0.1	P=0.098
Legs adipose mass (kg)	3.7±0.3	3.7±0.4	P=0.74
Trunk appendicular adipose ratio	1.53±0.16	1.61±0.16	P=0.23
Muscle area (right thigh)cm²	71.3±3.9	76.5±4.4	P=0.005
Adipose area (right thigh) cm²	28.8±2.9	28.9±3.1	NS
Intramuscular adipose area right thigh (cm²⁾	5.6±0.4	5.7±4.5	NS
Muscle area (left thigh) cm²	70.5±4.2	75.4±4.5	P=0.001
Adipose area (left thigh) cm²	28.8±2.9	28.9±3.1	NS
Intramuscular adipose area (left thigh) cm²	5.8±0.5	6.0±0.5	NS

Other Findings

Exercise training increased whole body lean mass 1.4kg (P=0.005) but did not reduce adipose tissue mass (P=NS)
Thigh muscle cross-sectional area increased 5 to 7cm² (P<0.005)
Muscle strength increased 23% to 38% (P<0.0001) on all exercises
Fasting serum TG concentrations were reduced after the exercise program (281 to 204mg per dL, P=0.022)
Total, HDL-C, and LDL-C, insulin, C-peptide, pro-insulin and glucagon concentrations were not affected by exercise
There was no relationship between the reduction in TG and baseline trunk adiposity (R²=0.05) or the initial-to-final change in insulin concentration (R²=0.02)
Trends toward greater reductions in fasting serum TG concentrations with greater increases in whole body lean mass (P<0.07, R²=0.19) and greater reductions in trunk fat (P<0.07, R²=0.20) were noted
Macronutrient and energy intakes were similar at baseline and at the end of exercise (no significant differences found); 2,311±182kcal per day (baseline), 2,646±219kcal per day after exercise; percentage kcal from CHO, 53±2 (baseline), 51±3 end; for fat=32±2 (baseline) vs. 33±2 end and for protein, 16±1 (baseline) vs. 17±1; alcohol = zero (baseline) vs. 4±4g at end of exercise.

Author Conclusion:

We have confirmed that progressive resistance exercise training increases lean tissue mass in men infected with HIV
A novel observation is the reduction in fasting serum triglyceride concentrations at the end of the 16-week exercise training program. This was especially evident in the subjects with baseline hypertriglyceridemia, and it tended to correlate with the exercise-induced increase in lean mass and the small change in trunk adipose mass.
The authors contended that they cannot clearly attribute the reduction in TG to either of these alterations in body composition. Neither can the authors exclude all possible confounders for the reduction in TG levels.
The reduction in TG may reflect a change in disease status or treatment rather than a response to exercise training. However, this is unlikely because none of the subjects changed medications during the course of the study.
At best, the resistance exercise training reduced TG level in hypertriglyceridemic men. At worst, resistance exercise training prevented an upward drift in TG that might normally occur in non-exercising HIV-infected men.
Conclusion is that progressive resistance exercise training program increases lean mass, muscle cross-sectional area and maximum voluntary muscle strength, and reduces serum TG in HIV-infected men, especially those with baseline hypertriglyceridemia and trunk adiposity
Because the metabolic complications associated with HIV infection include muscle wasting and hypertriglyceridemia, these findings suggest that progressive resistance exercise training, along with nutrition counseling, weight management and compliance to medication regimens, be recommended to maintain effective viral suppression and manage the metabolic complications associated with HIV infection.

Funding Source:

Government:

NIH DK-49393 and DK-54163

Industry:

University/Hospital:

General Clinical Research Center

Reviewer Comments:

Overall, the study was positive for outcomes, which include increases in lean mass and muscle area, but it lacks evidence in terms of the other metabolic factors (lipid profile). Only TG was significantly reduced and despite the explanations, one cannot truly exclude all the other potential factors for the reduction. A study with a larger sample size is needed.
Another problem I encountered was that the authors did not describe how the sample size was obtained in the methods, but in the discussion section it seemed that from a database, a random sample of 28 was selected. No mention was made of this in the methods, neither did the authors discuss what happened to 10 of the subjects since the final count was N=18.
No discussion was made on limitations in the study. It would have been a good idea to address the sample size and its potential impact on the findings.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		???
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	No
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	No
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		No
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	No
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	No
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	No
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	No
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	No
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		No
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	No
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes