EAL

PDM: Metabolic Syndrome (2013)

Citation:

Paniagua JA, Perez-Martinez P, Gjelstad IM, Tierney AC, Delgado-Lista J, Defoort C, Blaak EE, Riserus U, Drevon CA, Kiec-Wilk B, Lovegrove JA, Roche HM, Lopez-Miranda J, LIPGENE Study Investigators. A low-fat high-carbohydrate diet supplemented with long-chain n-3 PUFA reduces the risk of the metabolic syndrome. Atherosclerosis. 2011; 218(2): 443-450.

PubMed ID: 21839455

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

To assess the effects of isoenergetic diets with different fat quantity and quality on the incidence and regression of the metabolic syndrome (METS) from the LIPGENE project.

Inclusion Criteria:

Age: 30 to 70 years
BMI: 20 to 49kg/m²
Based on ATPIII criteria for metabolic syndrome (METS), three or more updated MetS criteria.

Exclusion Criteria:

Diabetes and other endocrine disorders
Inflammatory diseases
Use of anti-inflammatory drugs, fatty acid supplements, red rice yeast, statins and other lipid-lowering drugs
Alcohol abuse
Recent weight change of 2kg or more.

Description of Study Protocol:

Recruitment

Study participants recruited into the LIPGENE human dietary interventional trial between Feb 1, 2004 and Jan 30, 2007.

Design

Randomized controlled trial

Blinding Used

Implied with measurements.

Intervention

Randomized to one of four isoenergetic intervention diets:

High-fat (38% energy), high saturated fatty acids-rich (SFA) diet (16% SFA, 12% MUFA, 6% PUFA) (HSFA)
High-fat (38% energy), high monounsaturated fatty acids-rich (MUFA) diet (8% SFA, 20% MUFA, 6% PUFA) (HMUFA)
Low-fat (28% energy), high complex carbohydrate diet (8% SFA, 11% MUFA, 6% PUFA) with 1g per day high oleic acid sunflower oil supplement (LFHCC)
Low-fat (28% energy), high complex carbohydrate diet (8% SFA, 11% MUFA, 6% PUFA) with 124g per day very long chain n-3 polyunsaturated fatty acids supplement (LFHCC n-3).

Statistical Analysis

Cohen’s statistical power analysis was used to sample size estimation
ANOVA and Chi-square tests were used to compared qualitative traits and means of quantitative variables between intervention groups between baseline and after 12 weeks intervention
P-values for multiple comparisons were adjusted by Hommel’s test
The chi-square tests was used to compare the percentage of final prevalence of the METS between the four diets
The odds ratio (OR) was used to compare the probability. The two sided level of significance was set at P<0.05.

Data Collection Summary:

Timing of Measurements

Baseline, week six and week 12.

Dependent Variables

Body weight
Blood samples analyzed for fasting plasma glucose, total cholesterol, LDL-C, HDL-C, triglycerides, fasting insulin and HOMA-IR was calculated.

Independent Variables

Randomized to one of four isoenergetic intervention diets:

High-fat (38% energy), high saturated fatty acids-rich (SFA) diet (16% SFA, 12% MUFA, 6% PUFA) (HSFA)
High-fat (38% energy), high monounsaturated fatty acids-rich (MUFA) diet (8% SFA, 20% MUFA, 6% PUFA) (HMUFA)
Low-fat (28% energy), high complex carbohydrate diet (8% SFA, 11% MUFA, 6% PUFA) with 1g per day high oleic acid sunflower oil supplement (LFHCC)
Low-fat (28% energy), high complex carbohydrate diet (8% SFA, 11% MUFA, 6% PUFA) with 124g per day very long chain n-3 polyunsaturated fatty acids supplement (LFHCC n-3).

Control Variables

24-hour dietary recall and Baecke questionnaire was used for physical activity
Alcohol consumption and smoking habits were recorded.

Description of Actual Data Sample:

Initial N

N=535 were originally randomized:

21 dropped before study commencement
87 subjects excluded because they did not fulfill three or more updated METS criteria.

Attrition (final N)

337 subjects included in post-hoc analysis;149 males and 188 females.

Age

30 to 70 years.

Anthropometrics

No significant differences between groups at baseline.

Location

Europe.

Summary of Results:

Key Findings

An enlarged waist circumference (88cm or more for women and 102cm or more for men) was present among 95% of the participants, 88% had elevated blood pressure (more than 130/85mm Hg or antihypertensive drugs), 77% had elevated fasting plasma glucose (5.55mmol per L or more), 51% were hypertriacylglycerolemic (1.7mmol per L or more) and 72% had low HDL cholesterol (less than 1.0mmol per L for men and less than 1.3mmol per L for women)
The prevalence of enlarged waist circumference, hypertension and hypertriacylglycerolemia were reduced after the LFHCC n-3 diet (P<0.05)
The prevalence of METS fell by 20.5% after LFHCC n-3 diet compared with the HSFA (10.6%), HMUFA (12%) diet or LFHCC (10.4%) diets (P<0.028).

Author Conclusion:

The consumption of a low-fat, high-carbohydrate diet supplemented with n-3 reduced the risk of metabolic syndrome as compared with isoenergetic high-fat (HSFA and HMUFA) and LFHCC diets.

Funding Source:

Government:

Lipgene- an EU 6th Frame work programme integrated project and a research grant for the Ministerio de Ciencia e Innovacion; EU6 Framework Food Safety and Quality Programme, Contract no:505944

Not-for-profit

Thorne Holst Foundation for Nutrition Research, Freia Medical Research Foundation and Health South-East

Other non-profit:

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?	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%.)	Yes
	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?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	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)?	Yes
	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?		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