EAL

PDM: Metabolic Syndrome (2013)

Citation:

Hartwich J, Leszczynska-Golabek I, Kiec-Wilk B, Siedlecka D, Perez-Martinez P, Marin C, Lopez-Miranda J, Tierney A, Monagle JM, Roche HM, Defoort C, Wolkow P, Dembinska-Kiec A. Lipoprotein profile, plasma ischemia modified albumin and LDL density change in the course of postprandial lipemia. Insights from the LIPGENE study. Scand J Clin Lab Invest. 2010; 70(3): 201-208.

PubMed ID: 20233037

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 define the effect of four isocaloric fatty meals optionally supplemented with saturated, monounsaturated or polyunsaturated n-3 fatty acids (EPA, DHA) and complex-carbohydrate on plasma lipoprotein profile, Ischemia Modified Albumin and LDL density in free-living subjects with metabolic syndrome
To investigate the possible associations between measures of central adiposity (waist, WHR), adipose tissue insulin resistance (Adipo-IR) and postprandial responses of TG, TC, LDL-C, HDL-C, LDL density and IMA/Alb ratio in fatty meal sub-groups.

Inclusion Criteria:

Provided written informed consent
Underwent a comprehensive medical history, physical examination and the standard laboratory medicine analysis before enrollment
Encouraged to maintain their regular habits and were asked to record in a diary any event that could affect the outcome of the study.

Exclusion Criteria:

Not described.

Description of Study Protocol:

Recruitment

Subgroups of patients with the symptoms of metabolic syndrome (MetS) of the LIPGENE cohort were included in the present work.

Design

Randomized controlled trial.

Blinding Used

Implied with measurements.

Intervention

Each participant was randomized to receive one of the four oral fat tolerance tests (OFTT)

OFTT A, HSFA (N=40): High fat (38% energy, SFA-rich meal, 16% SFA, 12% MUFA, 6% PUFA)
OFTT B, HMUFA (N=42): High-fat (38% energy, MUFA rich meal, 8% SFA, 20% MUFA, 6% PUFA)
OFTT C, LFHCC (N=41): Isocaloric low-fat (28% energy, high-complex carbohydrate meal with 8% SFA, 11% MUFA, 6% PUFA, with 1.24g high oleic sunflower oil supplement containing C18:1 n-9 oleic acid and C18:2 n-6 linoleic acid)
OFTT D, LFHCC n-3 (N=41): Isocaloric low-fat (28% energy, high-complex carbohydrate meal with 8% SFA, 11% MUFA, 6% PUFA, with 1.24g LC n-3 PUFA fish oil supplement containing C20:5 n-3 EPA and C22:6 n-3 DHA).

Statistical Analysis

To test differences between time points repeated measures analysis of variance under generalized linear model algorithms was used
The effect of meals on studied parameters at various time points during the OFTT was estimated after assignment of each patient to one of the four meal groups
To compare various time points of OFTT, Mauchly's sphericity test followed when appropriate with either MANOVA with F approximations or univariate tests with Huynh Feldt's adjusted P values were used
P values of less than 0.05 were interpreted as statistically significant
To assess the magnitude of change of parameters total (area under the curve) and incremental area under the curve was calculated
Pearson's correlation coefficients between the results of LDL cholesterol homogenous assay obtained from pilot postprandial samples of whole plasma and plasma cleared of TRL by ultracentrifugation ranged from 0.91 to 0.98.

Data Collection Summary:

Timing of Measurements

Blood samples were drawn for biochemical testing at zero, two, four, six and eight hours after ingestion of breakfast at 8 AM.

Dependent Variables

Venous blood was sampled from the antecubital vein and collected into Vacutainer tubes with no anticoagulant and to tubes containing EDTA, and immediately transferred to 4°
Cholesterol and triacylglycerols in plasma were assayed by standard enzymatic tests. HDL and LDL cholesterol were determined using an automated homogenous direct assay
Fasting plasma insulin (FPI) was measured using a radioimmunoassay and the analysis of plasma non-esterified fatty acids (NEFA) was done using a Shimadzu GC-14A gas-liquid chromatograph fitted with a Simadzu C-r6A integrator and a 25N BP 21 polar aluminum silica column
The marker of oxidative stress:thiobarbituric acid reactive substances (TBARs) plasma level was determined by colorimetric assay to assess the plasma antioxidant capacity
Plasma lipoprotein profile, Ischemia Modified Albumin and LDL density: Ischemia modified albumin (IMA) was determined in serum using albumin cobalt binding test (ACB) described by Bar-Or at al. and commercially available calibrators. The LDL subfraction profile was determined after KBr density gradient ultracentrifugation of plasma stained with Coomassie Brilliant Blue.

Independent Variables

Each participant was randomized to receive one of the four oral fat tolerance tests (OFTT):

OFTT A, HSFA (N=40): High fat (38% energy, SFA-rich meal, 16% SFA, 12% MUFA, 6% PUFA)
OFTT B, HMUFA (N=42): High-fat (38% energy, MUFA rich meal, 8% SFA, 20% MUFA, 6% PUFA)
OFTT C, LFHCC (N=41): Isocaloric low-fat (28% energy, high-complex carbohydrate meal with 8% SFA, 11% MUFA, 6% PUFA with 1.24g high oleic sunflower oil supplement containing C18:1 n-9 oleic acid and C18:2 n-6 linoleic acid)
OFTT D, LFHCC n-3 (N=41): Isocaloric low-fat (28% energy, high-complex carbohydrate meal with 8% SFA, 11% MUFA, 6% PUFA, with 1.24g LC n-3 PUFA fish oil supplement containing C20:5 n-3 EPA and C22:6 n-3 DHA).

Description of Actual Data Sample:

Initial N: 164 (104 females and 60 men)
Attrition (final N): 164 (104 females and 60 men)
Age: Mean age:
- OFTT A HSFA group: 55 years
- OFTT B HMUFA group: 54 years
- OFTT C LFHCC: 54 years
- OFTT D LFTCC n-3: 53 years.

Anthropometrics

Groups did not differ in basic anthropometric and biochemical blood parameters, i.e., NEFA, TG, total cholesterol, LDL-C, HDL-C, LDL density and IMA/Alb ratio

Mean BMI (kg/m²)
- OFTT A HSFA: 35.2
- OFTT B HMUFA: 34.1
- OFTT C LFHCC: 35.4
- OFTT D LFHCC: 35.0.
Mean WHR (cm):
- OFTT A HSFA: 0.91
- OFTT B HMUFA: 0.92
- OFTT C LFHCC: 0.91
- OFTT D LFHCC group: 0.93.

Location

Department of Clinical Biochemistry, Jagiellonian University School of Medicine and in Lipid and Atherosclerosis Unit at the Reina Sofia University Hospital.

Summary of Results:

Key Findings

All types of OFTT transiently increased plasma triglyceride and LDL density; it was paralleled by temporal decrease in TC, LDL-C, and HDL-C
A statistically significant transient increase of IMA/Alb ratio was documented only in HSFA and HMUFA meal consumers
Postprandial FRAP and TBARs kinetic curves presented transient negative and positive increments respectively and statistically significant time interaction (P<0.01) but no significant differences in the postprandial responses to tested fatty meals were found
A gradual increase of LDL cholesterol iAUC and a gradual decrease of IMA/Alb ratio iAUC. It could suggest that n-3 PUFA in combined with high carbohydrate meals minimalized postprandial IMA increase
Subgroup analysis indicated lack of statistically significant associations between measures of central adiposity (waist, WHR), adipose tissue insulin resistance and postprandial responses of TG, TC, LDL-C, HDL-C, LDL density and IMA/Alb ratio.

Author Conclusion:

Overall, all types of meals in this study transiently increased plasma triglycerides followed by increased LDL density. It was paralleled by a temporal, reversible decrease in LDL and HDL cholesterol. The implementation of new parameters that could be easily applied in day-long profiles seems to be a promising diagnostic modality.

Funding Source:

Other:

No funding was accepted for this project

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?	No
	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.)	N/A
	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?	Yes
	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?		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?	Yes
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