PDM: Metabolic Syndrome (2013)


Ng TW, Chan DC, Barrett PH, Watts GF. Effect of weight loss on HDL-apoA-II kinetics in the metabolic syndrome. Clin Sci (Lond). 2009; 118(1): 79-85.

PubMed ID: 19456294
Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To investigate the effect of short-term weight loss on HDL-apoA-II kinetics in subjects with metabolic syndrome. The researchers hypothesized that weight loss would decrease the fractional catabolic rate and production rate of HDL-apoA-II.

Inclusion Criteria:
  • Males with metabolic syndrome
  • Middle-aged
  • Centrally obese, normotensive, insulin-resistant and dyslipidemic
  • Provided informed consent.
Exclusion Criteria:

Not described.

Description of Study Protocol:


Randomized controlled trial.


Implied with measurements.


Randomized to hypocaloric low-fat diet for 14 weeks immediately followed by a two-week weight stabilization period or to weight maintenance on an isocaloric diet for 16 weeks.

Statistical Analysis

  • All analyses were carried out using SPSS
  • Skewed data were log-transformed where appropriate
  • Treatment effects of the weight loss group relative to the weight maintenance group were analyzed using general linear modeling with adjustments for baseline covariates
  • Associations between absolute changes in variable in the weight loss group were examined using simple regression model
  • Group differences at baseline were analyzed using independent Student T-tests
  • Statistical significance was defined as P<0.05.


Data Collection Summary:

Timing of Measurements

Measurements made at baseline and after 16 weeks.

Dependent Variables

  • Fractional catabolic rate
  • Production rate of HDL-apoA-II: HDL-apoA-II were isolated from plasma by sequential ultracentrifugation, separated by SDS/Page and blotted on to a PVDF membrane; apoA-II bands were excised from the PVDF membrane, hydrolyzed overnight and dried for derivatization
  • Isotopic enrichment of apoA-II was determined using negative chemical ionization by GC/MS
  • Fasting plasma lipid and lipoprotein concentrations were determined by standard methods
  • Plasma glucose and non-esterified fatty acids (NEFAs) were measured by enzymatic colorimetric models and insulin was determined by immunoenzymometry
  • HOMA-IR score was used as an estimate of IR
  • Plasma lathosterol concentration was measured by GC/MS.

Independent Variables

Randomized to hypocaloric low-fat diet for 14 weeks immediately followed by a two-week weight stabilization period or to weight maintenance on an isocaloric diet for 16 weeks.

Description of Actual Data Sample:
  • Initial N: Assumed 35 obese men (20 in the hypocaloric low-fat diet group and 15 in the weight maintenance diet group)
  • Attrition (final N): 35 obese men studied (20 in the hypocaloric low-fat diet group and 15 in the weight maintenance diet group)
  • Age: Described as middle-aged
  • Ethnicity: Caucasian
  • Anthropometrics:  No significant differences between groups at baseline
  • Location: Australia.
Summary of Results:

Key Findings

  • Average daily energy and nutrient intake of the subjects was 10,045±2,406kJ, 36%±6% energy from fat, 38%±8% energy from carbohydrates, 20%±3% energy from protein and 6%±6% energy from alcohol (values are means ±SD)
  • The low-fat diet achieved a significant reduction (P<0.01) in BMI, abdominal fat compartments and HOMA (homeostasis model assessment) score compared with weight maintenance
  • Weight loss also significantly decreased (P<0.05) both the production rate (-23%) and fractional catabolic rate (-12%) of HDL-apoA-II, accounting for a net decrease in apoA-II concentration (-9%)
  • Reductions in the HDL-apoA-II production rate were significantly associated with changes in body weight (R=0.683, P<0.01), plasma triacylglycerols (R=0.607, P<0.01) and to a lesser extent plasma insulin (R=0.440, P=0.059) and HOMA-IR (HOMA of insulin resistance) (R=0.425, P=0.069)
  • Changes in the apoA-II FCR were also significantly associated with reductions in visceral adipose tissue mass (R=0.561, P=0.010).



Author Conclusion:

The authors demonstrated that in men with metabolic syndrome, short-term weight loss with a low-fat diet lowers the plasma apoA-II concentration by decreasing both the production and catabolism of HDL apoA-II. Further investigations should explore the incremental effect of other pharmacotherapies added to a weight loss regimen on the functionality of HDL in these subjects.

Funding Source:
National Heart Foundation of Australia and the National Health Medical Research Foundation
Other non-profit:
Reviewer Comments:
  • Initial N unclear; groups not similarly sized. 
  • Only obese Caucasian men were studied. 
  • Limitation: The effects of weight loss on apoA-II kinetics cannot be fully dissociated from dietary effect, in particular changes in fat and carbohydrate intake.
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? No
  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? No
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? No
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
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? 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? ???
  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? ???
  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? Yes
  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.) Yes
  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? Yes
  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? 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? No
  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)? No
  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