H/A: Body Composition Measurement (2009)

Citation:
 
Study Design:
Class:
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Quality Rating:
Research Purpose:

To determine how well measurements of fat distribution derived from anthropometry, dual-energy X-ray absorptiometry (DXA) and computed tomography (CT) predict hyperinsulinemia in HIV-positive males.

Inclusion Criteria:
  • 41 previously studied HIV-positive males (21 with fat redistribution and 20 without fat redistribution) were matched for age and body mass index (BMI) to 20 HIV-negative male control subjects
  • Fat redistribution was determined on the basis of a waist-to-hip ratio (WHR) of 0.95 or more
  • All subjects had to sign informed consent. 
Exclusion Criteria:
  • Subjects were excluded if they received testosterone, growth hormone, anabolic hormones, glucocorticoids, anti-diabetic agents or megestrol acetate
  • Diabetes
  • Age older than 60 years or younger than 18 years
  • BMI less than 20
  • Subjects whose antiretroviral medications were changed within the six weeks prior to the study were excluded.
Description of Study Protocol:

Recruitment

Subjects were recruited via community-based advertisements from October 1999 to June 2000. 

Design

A retrospective analysis of body composition data from a previously studied population of HIV-positive men with and without fat redistribution were compared with a control group of HIV-negative men without fat redistribution, matched for age and BMI.

Intervention

21 HIV-positive males with fat redistribution were compared with 20 HIV-positive men without fat redistribution, and matched to a control group of HIV-negative men matched for age and BMI.

Fat redistribution was confirmed physical exam on the basis of a WHR more than 0.95.

Metabolic data including weight, growth hormone, insulin concentrations, body composition and bone density were previously reported on these subjects. Body composition was previously measured with three different techniques. 

Subjects underwent a standard 75g oral glucose tolerance test after a 12-hour fast (at 8:00 a.m.). Insulin and glucose concentrations were measured at zero, 30, 60, 90 and 120 minutes. Fasting glycated hemoglobin (HbA1c), CD4 count and viral load were determined.

Total body fat, fat-free mass, and trunk and extremity fat were determined by DXA

Cross-sectional abdominal CT scanning was used as previously described to assess subcutaneous and visceral abdominal fat areas. 

Insulin was measured with radioimmunoassay. 

Statistical Analysis

Variables were compared between groups with the use of Wilcoxon rank-sum test.

Multivariate regression analysis was used to determine the effect of WHR, DXA-derived trunk and extremity fat and CT-derived abdominal visceral and subcutaneous fat on insulin and glucose while controlling for age, BMI and current protease inhibitor use.

Repeat multivariate regression was done in those patients with fat redistribution and among the healthy control subjects.  Non-normally distributed data were log transformed and these ratios were also tested in multivariate models. 

Data Collection Summary:

Timing of Measurements

After a 12-hour overnight fast, a 75-g oral glucose tolerance test (OGTT) was given. Glucose and insulin were measured at zero, 30, 60, 90 and 120 minutes. Fasting HbA1c, weight and WHR were also measured. 

Dependent Variables

  • Insulin was assessed by radioimmunoassay
  • CD4 count and viral load were measured by previously published techniques
  • Glucose and HbA1c levels were measured by previously published techniques.

Independent Variables

  • Total body fat, fat-free mass, and trunk and extremity fat were measured by DXA with a Hologic-4000 densitometer
  • Cross-sectional abdominal CT scanning (described in a previous study) assesses subcutaneous and visceral abdominal fat areas
  • WHR was calculated from the waist circumference measured at the horizontal level of maximum extension of the buttocks.  

Control Variables

  • Age
  • BMI
  • Protease inhibitor use.
Description of Actual Data Sample:

Initial N

HIV-positive, n=41; HIV-negative, n=20.

Attrition (final N)

A total of 61 subjects were analyzed.  None were reported as leaving the study.

Age

Mean age was 43 years in both the HIV-positive and the control group.

Ethnicity

Not described in this study, possibly described in previously reported data.

Other relevant demographics

Of the HIV-positive males, 21 had fat redistribution (as evidenced by a WHR more than 0.95) and 20 subjects did not.

Anthropometrics 

No significant differences in any baseline data between the HIV-positive group and the control group except for:

  • WHR (P<0.001)
  • Extremity fat (P<0.05)
  • Subcutaneous fat (P<0.05)
  • OGTT glucose response, area under the curve (AUC) (P<0.05)
  • Fasting insulin (P<0.001).

Location

Massachusetts Institute of Technology and Massachusetts General Hospital.

Summary of Results:

Multivariate Models to Predict Fasting Insulin Concentration and Insulin AUC in HIV-positive Men (Both With and Without Fat Redistribution)

Variable Fasting Insulin Model Insulin AUC Model
Estimate 95% CI P Estimate 95% CI P
Model 1a            
Age (years) -4.9 -10.4, 0.7 0.097 1020.2 -1698.7, 3739.2 0.451
BMI (kg/m2) 18.8 7.6, 29.9  0.002  8974.3  3694.7, 14253.2  0.002
WHRb 773.7 186.1, 1361.23  0.011  409145.9  130622.3, 687671.0  0.005
PI usec -73.6  -143.1, -4.9  0.037  -4739.3  -37546.1, 28068.2  0.771
Model 2d            
Age (years) -1.4 -6.9, 4.2 0.593 2153.6 -261.1, 4568.2 0.079
BMI (kg/m2) 22.2 5.6, 39.6 0.012 14920.0 7633.2, 22206.6 0.0002

Trunk fat (DXA) (g)

0.007 -0.007, 0.02 0.468 2.1 -3.5, 8.3 0.436
Extremity fat (DXA) (g) -0.007 -0.03, 0.01 0.325 -13.9 -22.9, -4.9 0.003
PI usec -61.1 -144.5, 22.2 0.146 -16388.1 -52127.1, 19350.9 0.357
Model 3e            
Age -2.8 -8.3, 3.5 0.385 1297.3 -1284.1, 3878.8 0.314
BMI (kg/m2) 16.0 -0.1, 32.6 0.052 12437.8 5340.0, 19535.6 0.001
Intra-abdominal fat (CT) (mm2) 0.007 -0.001, 0.01 0.139 3.5 0.7, 6.9 0.015
Subcutaneous fat (CT) (mm2) 0.001 -0.007, 0.007 0.902 -4.2 -7.6, -0.7 0.019
PI usec -49.3 -125.0, 25.7 0.109 -7479.8 -40106.7, 25147.2 0.644

ar2=0.415 for the fasting insulin model and 0.524 for the insulin AUC model

bEstimate refers to a change of 773.7pmol/L in insulin concentration for a 1.0-unit change in WHR. The equivalent change in insulin concentration for a 0.1-unit change in WHR would be 77.4 pmol/L

cTreated as a dichotomous variable (0=no PI use, 1=PI use)

dr2=0.314 for the fasting insulin model and 0.542 for the insulin AUC model

er2=0.338 for the fasting insulin model and 0.552 for the insulin AUC model.

Other Findings

For all HIV-positive males, WHR was significantly associated with intra-abdominal fat measured by CT (r=0.7289, P<0.0001), trunk fat measured by DXA (r=0.387, P<0.012) and ratio of trunk fat to extremity fat measured by DXA (r=0.6844, P<0.0001).

WHR was a better measure than other body-composition measures in predicting fasting hyperinsulinemia. WHR was a strong predictor of insulin AUC in HIV-positive men.

Fasting insulin increased by 77.4pmol/L for each 0.1 unit change in WHR (P=0.01) in a model also including age, BMI and PI use. 

Intra-abdominal and subcutaneous fat did not predict fasting hyperinsulinemia, but were independent predictors of insulin AUC.

The ratio of visceral to subcutaneous abdominal fat predicted the largest degree of variance in insulin AUC.

Author Conclusion:

Fat redistribution contributes to hyperinsulinemia in HIV-positive men, independent of BMI and protease inhibitor use.

WHR is an integrated index of body-composition changes and strongly predicts both fasting hyperinsulinemia and insulin AUC in HIV-positive men.

The degree of body fat redistribution, in addition to weight alone, is a critical determinant of the metabolic abnormalities seen in HIV-positive males. 

Data in this study was limited to men, and important sex differences may exist in the metabolic profile of individuals with HIV.

Funding Source:
Government: NIH grants: R01-DK59535, MO1-RR01066, K23-DK02844
Industry:
Reviewer Comments:
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? Yes
  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? Yes
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) Yes
  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? Yes
  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? ???
  4.1. Were follow-up methods described and the same for all groups? ???
  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%.) ???
  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? N/A
  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? No
  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? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? Yes
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? N/A
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  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? N/A
  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? Yes
  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)? N/A
  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? No
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
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