PDM: Metabolic Syndrome (2013)

Citation:

Chan DC, Watts GF, Ng TWK, Yamashita S, Barrett, PHR. Effect of weight loss on markers of triglyceride-rich lipoprotein metabolism in the metabolic syndrome. Eur J Clin Invest. 2008; 38 (10): 743-751.

PubMed ID: 18837799
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To determine the effect of weight loss by dietary restriction on markers of triglyceride-rich lipoprotein (TRL) metabolism and plasma adipocytokines.

Inclusion Criteria:

Subjects were males, non-smoking, with central obesity and metabolic syndrome. 

Exclusion Criteria:

Subjects were excluded if they had diabetes mellitus, CVD, apoE2/E2 or E4/E4 genotype, macro proteinuria, creatinaemia (greater than 120mcmol/L), hypothyroidism, abnormal liver enzymes, or consumed greater than 40g alcohol per day, or were taking agents affecting lipid metabolism. 

Description of Study Protocol:

Recruitment

Recruitment methods not described. 

Design

  • Randomized controlled trial
  • Subjects were randomly assigned into one of two dietary intervention groups: A hypocaloric diet group or an isocaloric weight maintenance group.

Blinding Used

Implied with laboratory measures.

Intervention

All subjects underwent an initial weight stabilization period of four weeks. They were then randomly assigned into one of two treatment groups:

  • A 14-week hypocaloric weight loss group followed by a two-week weight stabilization
  • A 16-week isocaloric weight maintenance group designed to maintain weight.  

Statistical Analysis

  • Independent T-tests were used to compare baseline characteristics of subjects by groups 
  • Changes in the weight loss group were compared to the weight maintenance group using linear models with adjustments made for baseline covariates 
  • Student's paired T-test was used to evaluate significant changes within groups
  • Associations were examined using simple correlations and both simple and multivariate linear regression. Significance was defined as P<0.05.
Data Collection Summary:

Timing of Measurements

Initially all subjects entered into four weeks of a weight stabilization period. During this time, baseline measurements for anthropometric data and biochemical data were obtained and data was obtained again at 16 weeks after the intervention. All subjects were studied after a 14-hour fast

Dependent Variables

  • Fasting plasma cholesterol, triglycerides and HDL-cholesterol were determined by standard enzymatic methods. LDL-cholesterol was calculated using Friedewald's equation. 
  • Plasma non-esterified fatty acids (NEFAs) and insulin were measured by enzymatic methods
  • Glucose was measured by hexokinase method
  • Insulin resistance was estimated by HOMA score 
  • Plasma lathosterol concentration was measured by GCMS
  • VLDL fraction was isolated with ultracentrifugation. VLDL-apoB fraction was precipitated.
  • Plasma apoB-48 levels were measured by a sandwich ELISA
  • Plasma apoC-III was measured by immunoturbidimetric assay
  • Plasma RLP-cholesterol was determined from plasma via immunoseparation technique assay
  • Total and HMW adiponectin concentrations were determined using immunoassay
  • Plasma RBP-4 concentrations were determined using enzyme immunoasssay kit.

Independent Variables

  • The dietary intervention: Either a 14-week hypocaloric diet (followed by two weeks of weight stabilization diet) or a 16-week isocaloric weight maintenance diet
  • Dietary intake was assessed by seven-day recall questionnaires and three-day food diaries, which were completed every three weeks by both groups. 

Control Variables

Subjects were required to maintain their usual level of physical activity and alcohol intake during the study.

Description of Actual Data Sample:
  • Initial N: 35 male subjects started the study and finished the study
  • Attrition (final N): N=35 male subjects. No attrition reported. 
  • Age: 46±8 years
  • Ethnicity: Caucasian.

Other Relevant Demographics

At baseline

  • Weight: 107±11kg
  • BMI: 34±3kg/m2
  • Waist circumference: 113±7cm
  • Glucose: 5.6±0.6mmol per L
  • Insulin: 16±9mU per L
  • HOMA score: 4.0±2.4
  • Cholesterol: 5.9±1.1mmol per L
  • TG: 3.1±2.3mmol per L
  • HDL cholesterol:1.0±2.0mmol per L
  • LDL cholesterol: 3.5±0.8mmol per L
  • Non-HDL cholesterol: 4.9±1.1mmol per L.

Anthropometrics

  • No significant differences existed between groups on the above listed data at baseline 
  • Average daily energy intakes 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. Nutrient intakes did not differ between patients randomized to either intervention group. 

Location

Was not specified. The authors are affiliated with the School of Medicine and Pharmacology, University of Western Australia, Perth, Australia and Osaka University Graduate School of Medicine, Osaka Japan.

Summary of Results:

Key Findings

  • In the weight reduction group, total calories and total fat was significantly reduced and carbohydrate intake was increased 
  • Nutrient intake did not change in the weight maintenance group during the 16 weeks and their weight did not vary by more than 1% 
  • The weight loss diet significantly reduced body weight, BMI, waist circumference, body fat, cholesterol, TG, non-HDL cholesterol, LDL, total apoB, lathosterol, insulin, and HOMA score compared to the weight maintenance group
  • No effects were seen on plasma concentrations of HDL-cholesterol, apoA-I, NEFAs and glucose, or on mean blood pressure
  • Weight loss had a significant effect of lowering plasma apoC-III, apoB-48, VLDL-apoB, and RLP cholesterol. 

Anthropometric Characteristics, Plasma Lipids and Lipoproteins and Measures of Insulin Resistance Before and After Weight Loss and Weight Maintenance

  Weight
(N=20)
Loss Weight
(N=15) 
Maintenance 
  Zero weeks  16 weeks  Zero weeks  16 weeks 
Weight (kg)  109±2 96±3* 105±3 109±2
BMI (kg/m2)  35±1.0  31±0.7*  33±0.7  35±0.9
Waist Circumference (cm)  112±2 103±2* 113±2 113±2
Visceral ATM (kg)  7.1±0.5  5.4±0.4*  6.9±0.4  6.7±0.4
Subcutaneous ATM (kg)  8.4±0.7 6.5±0.4* 9.6±0.7 9.9±0.7
Mean BP (mmHg)  95.4±2.8  86.4±2.8  96.6±3.0 94.7±3.1
Cholesterol (mmol/L)  6.0±0.3 5.2±0.2+ 6.0±0.2 6.0±0.2
TG (mmol/L)  3.5±0.6 2.0±0.2* 2.9±0.6 2.7±0.4
HDL-Cholesterol (mmol/L)  1.0±0.04 1.1±0.05 1.0±0.04 1.0±0.04
LDL-Cholesterol (mmol/L)  3.3±0.2 3.0±0.2+ 3.9±0.2 3.9±0.29
Non-HDL-Cholesterol (mmol/L)  4.9±0.3 4.2±0.2+ 4.8±0.2 4.9±0.2
Total apoB-100 (g/L)  1.2±0.06 1.0±0.06+ 1.2±0.06 1.2±0.05
Total apoA-1 (g/L)  1.3±0.05 1.3±0.04 1.2±0.04 1.2±0.02
Lathosterol (μmol/L)  17.4±3.4 11.9±2.4++  14.5±2.1 14.4±2.0
Glucose (mmol/L)  5.7±0.2 5.3±0.1 5.4±0.2 5.5±0.3
Insulin (mU/L)  14±2 8±1* 18±3 16±2
HOMA Score  3.7±0.5 2.0±0.2+ 4.6±0.8 4.0±0.6
NEFAs (mmol/L) 0.96±0.07  0.86±0.08 0.81±0.05 0.82±0.05

All values are mean ±SEM
Effect of weight loss was tested using general linear modeling after adjusting for the weight maintenance groups
*P, 0.001
+P<0.01
++P<0.05
BMI: Body  mass index
ATM: Adipose tissue mass
HDL: High-density lipoprotein
LDL: Low density lipoprotein
Apo: Apolipoprotein
HOMA: Homeostasis model assessment. 

Plasma ApoC-III, ApoB-48, VLDL-apoB, RLP-cholesterol and Adipocytokines Before and After Weight Loss and Weight Maintenance

  Weight Loss Weight Maintenance
  Zero weeks 16 weeks Zero weeks 16 weeks
ApoC-III (mg/L)  171±16 114±9 131±16 139±15
ApoB-48 (mg/L)  9.9±1.4 6.3±1.0++ 8.1±1.5 7.0±1.4
VLDL-apoB (mg/dL)  103±18 59±6++ 86±18 96±14
RLP cholesterol (mg/L)  36±8 9±3* 37±9 35±7
Total adiponectin (mg/L)  2.9±0.3 3.4±0.3++ 2.3±0.2 2.3±0.3
HMW adiponectin (mg/L)  1.0±0.2 1.2±0.2++ 0.5±0.1 0.5±0.1
RBP-4 (mg/L)  38±2 30±2c  36±3 35±3

All values are mean ±SEM
Statistical significance for changes in the weight loss group (week zero vs. week 16) were compared with the weight maintenance group using general linear models with adjustment for baseline covariates
*P<0.001
+P<0.01
++P<0.05
Apo: Apolipoprotein
VLDL: Very low-density lipoprotein
RLP: Remnant-like particle
HMW: High-molecular weight
RBP-4: Retinol-binding protein-4.

Associations (Pearson correlation coefficients) Between Changes in Markers of TRL Metabolism and Plasma Adipocytokines in the Weight Loss Group

  ApoC-III ApoB-48 VLDL-apoB RLP-Cholesterol TG Total Adiponectin HMW Adiponectin
ApoB-48 0.599*            
VLDL-apoB 0.533+ 0.733*          
RLP-Cholesterol 0.633* 0.745* 0.950*        
TG 0.551+ 0.558+ 0.751* 0.508+      
Total Adiponectin -0.127 -0.228 -0.493+ -0.369 -0.522+    
HMW Adiponectin 0.146 0.203 -0.002 0.047 -0.209 0.812*  
RBP-4 0.380 0.022 0.046 0.207 0.004 0.362 0.250

P-value: *<0.01, +<0.05
TRL: Triglyceride-rich lipoprotein; apo, apolipoprotein
VLDL: Very-low density lipoprotein
TG: Triglyceride
RLP: Remnant-like particle, HMW, high-molecular weight
RBP-4: Retinol-binding protein-4.

Other Findings

  • Reduction in plasma apoC-III with weight loss was significantly and directly associated with a reduction in apoB-48, VLDL apoB, RLP-cholesterol and TG (P<0.05) 
  • Lower apoC-III was also associated with a reduction in insulin (R=0.456, P<0.05) and with a borderline significant association with reduced HOMA score (R=0.423, P=0.07) 
  • Lower plasma apoB-48 was associated with the reduction in plasma VLDL apoB, RLP cholesterol, and TG (P<0.05) 
  • Increase in total adiponectin was associated with the reduction in plasma VLDLapoB and TG (P<0.05)
  • The changes in HMW-adiponectin and RBP-4 were not associated with changes in plasma apoB-48, apoC-III, VLDL apo B, RLP cholesterol or TG 
  • In multiple regression analysis, the fall in plasma apoC-III concentration was an independent predictor of the reductions in plasma apoB-48, VLDL apoB, RLP-cholesterol and TG
  • The reduction in apoC-II concentration was a significant predictor of the fall in plasma triglycerides, apoB-48, VLDL-apoB and RLP cholesterol independent of changes in insulin, adiponectin, or visceral adipose tissues.
Author Conclusion:

In men with metabolic syndrome, weight loss decreases the plasma concentrations of apoB-48, VLDL-apoB, RLP-cholesterol, and triglycerides. 

This effect may be partly due to concomitant changes in plasma apoC-III and adiponectin concentrations that accelerate the catabolism of TRLs.

Funding Source:
Government: National Heart Foundation of Australia, National Health and Medical Research Foundation (NHMRC), National Institutes of Health
Reviewer Comments:

Recruitment methods not described. The authors stated that one limitation is that only obese Caucasian males were studied, and it is possible that the lipoprotein effects of weight loss might have been different in women.

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? No
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? ???
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? No
  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%.) No
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? ???
  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? ???
  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? No
  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? 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)? 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? 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