EAL

PDM: Metabolic Syndrome (2013)

Citation:

Khoury DE, Hwalla N, Frochot V, Lacorte JM, Chabert M, Kalopissis AD. Postprandial metabolic and hormonal responses of obese dyslipidemic subjects with metabolic syndrome to test meals, rich in carbohydrate, fat or protein. Atherosclerosis. 2010; 210(1): 307-313.

PubMed ID: 20031131

Study Design:

Randomized Crossover Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To study metabolic syndrome subjects with the same abnormalities (abdominal obesity, hypertriglyceridemia and low plasma HDL) and assess postprandial variations of metabolic parameters with three test meals (high carbohydrate, fat or protein).

Inclusion Criteria:

Adult males with abdominal obesity and dyslipidemia (elevated triglycerides and low levels of HDL-cholesterol)
Control subjects were free of selection criteria
Metabolic syndrome (MS) was defined according to International Diabetes Federation (IDF) criteria, stating central obesity (waist circumference 94cm or more) as an obligatory component plus any two of the following:
- Raised fasting plasma glucose (100mg per dL or more)
- Blood pressure (systolic 130mm Hg or more, diastolic 85mm Hg or more)
- Triglyceride (150mg per dL or more)
- Reduced HDL-cholesterol (less than 40mg per dL).

Exclusion Criteria:

Hypertension
Diabetes.

Description of Study Protocol:

Recruitment

Recruitment methods were not described. All participants were recruited from the American Hospital of Beirut, Lebanon.

Design

Randomized, double-blind cross-over design.

Blinding Used

Three test meals were liquid shakes and were not distinguishable from one another by their appearance or taste. Double blind method was stated; however, no method was described and the reader assumes blinded to both subject and researcher.

Intervention

All subjects (MS and control) consumed a liquid shake breakfast on three occasions, one week apart. Before each test meal, subjects received a three-day weight-maintaining meal (20% protein, 50% carbohydrate, 30% fat) based on their calculated daily energy needs.
On the morning of the meal, subjects arrived at 8:00 a.m. in a fasted state (12 hours) to the American Hospital of Beirut, had an intravenous catheter placed into an antecubital vein and consumed a test breakfast shake within 15 minutes. The meals contained 30% of each subject's resting energy expenditure and were either high carbohydrate (60% carbohydrate, 20% protein, 20% fat), high protein (50% protein, 30% carbohydrate, 20% fat) or high fat (50% fat, 30% carbohydrate, 20% protein). The shake did not contain fiber and ranged from 445 to 708kcal for metabolic syndrome subjects and 485 543kcal for control subjects. Blood samples (12ml) were taken at zero (immediately before) and at six time points postprandial.
Table 2 in the article highlights composition of the meals:
- Ensure®
- Soy/whey protein
- Sugar
- Sunflower oil
- Water.

Statistical Analysis

Data were reported as means ± SEM. One-way ANOVA (MS vs. control) was used to compare metabolic and hormonal profiles. Repeated measures ANOVA was used to compare meal and time.
Post-hoc analysis was performed: One-way ANOVA to compare meal and time between groups and Tukey's test for contrast analysis to compare means at different times within groups and test meals.
Pearson's correlation to compare plasma leptin with BMI.
Area under the curve and repeated measures ANOVA (followed by Tukey's test) to compare postprandial responses among three meals for within groups. Statistical significance set at P<0.05.
No mention of sample size calculation.

Data Collection Summary:

Timing of Measurements

Blood sample taken at zero (immediately before meal) and 15, 30, 60, 120, 180 and 240 minutes postprandial.

Dependent Variables

BMI
Fasting glucose
Fasting lipid profile
Fasting insulin
Insulin resistance (predicted using the homeostasis model assessment)
Appetite hormones (leptin, ghrelin and polypeptide PYY)
Inflammatory marker (interleukin-6).

Note that none of the methods were described beyond the statement, "All plasma parameters were measured with commercially available kits. See details in Supplemental data." There is a reference to Appendix A Supplementary data at the end of the article, which is online at doi:10.1016/j.atherosclerosis.2009.11.017.

Independent Variables

All subjects (MS and control) consumed a liquid shake breakfast on three occasions, one week apart. Before each test meal, subjects received a three-day weight-maintaining meal (20% protein, 50% carbohydrate, 30% fat) based on their calculated daily energy needs
On the morning of the meal, subjects arrived at 8:00 a.m. in a fasted state (12 hours) to the American Hospital of Beirut, had an intravenous catheter placed into an antecubital vein, and consumed a test breakfast shake within 15 minutes. The meals contained 30% of each subject's resting energy expenditure and were either high carbohydrate (60% carbohydrate, 20% protein, 20% fat), high protein (50% protein, 30% carbohydrate, 20% fat) or high fat (50% fat, 30% carbohydrate, 20% protein). The shake did not contain fiber and ranged from 445 to 708kcal for metabolic syndrome subjects and 485 to 543kcal for control subjects. Blood samples (12ml) were taken at zero (immediately before) and at six time points postprandial.

Description of Actual Data Sample:

Initial N: N=20; 10 MS and 10 control males
Attrition (final N): Assume N=20, but not stated
Age: MS group mean 32.1 ± 2.9 years, Control group mean age 23.8 ± 1.3 years (P<0.05)
Ethnicity: Lebanese.

Anthropometrics

Groups were significantly different (P<0.01) for:

Mean BMI (kg/m²): 35.5±1.3 MS group vs. 22.5±0.5 control group
Mean waist circumference (cm): 112.7±2.0 MS group vs. 81.4±1.8 control group
Mean fasting TG (mg per dL): 200.3±20.3 MS group vs. 74.1±7.3 control group
Mean fasting HDL-C (mg per dL): 31.7±1.7 MS group vs. 47.5±3.2 control group
No significant difference between systolic and diastolic blood pressure, fasting glucose, fasting insulin and HOMA.

Location

The American Hospital of Beirut, Lebanon.

Summary of Results:

Key Findings

Results were presented as figures (no tables used). Authors referred to supplement data.

Baseline leptin levels were fourfold greater in MS compared to control subjects and correlated with BMI (no data provided, referenced online appendix)
Polypeptide PYY increased postprandial with no significant difference between groups
Ghrelin decreased postprandial in all subjects (except for HP meal; time effect P<0.001, meal-times-time effect P=0.004) and were not significant different between group
Glucose varied significantly postprandial among meals (P<0.001) and over time (P<0.001), with MS exhibiting higher postprandial glucose increases compared to the control, despite their normal fasting glycemia
Insulin varied significantly postprandial among meals (P<0.001) and over time (P<0.001) and were consistently greater for MS group compared to controls with all meals, despite their normal fasting insulinemia
Triglyceride concentrations were significantly higher for MS group and was highest following high fat meal (P<0.001). Sustained hypertriglyceridemia of MS subjects regardless of test-meal suggests defective triglyceride-rich lipoprotein (TRL) catabolism
Interleukin-6 was twofold higher in MS subjects at baseline (P=0.002) and increased significantly over time in all subjects.

Author Conclusion:

Meal challenge yielded a higher postprandial hyperinsulinemia and hyperglycemia in MS compared to control, despite normal fasting state
No apparent dysregulation of appetite hormones were exhibited with ghrelin and PYY
Obesity was associated with higher plasma leptin and interleukin-6 levels
Higher levels of tryiglyceridemia are suspected to be related to defective TRL catabolism in the MS group.

Funding Source:

University/Hospital:	American University of Beirut
Other:	INSERM (Paris France) and Lebanese CNRS (acronyms not defined)

Reviewer Comments:

Small sample size (N=10 each group) and no statement of estimated power analysis despite some variables with negative findings
No description of recruitment, randomization assignment and the methods used to assess outcome variables (referred to online Appendix). There were no clear primary and secondary variables mentioned. The variables were mentioned sporadically within the methods and results. For instance, fat mass, nonfat mass, percent fat and blood pressure were used for descriptive baseline data in a table, but not mentioned otherwise.
No mention of compliance with the three-day pre-experiment weight maintaining meal; unsure if given the meal or just provided with a meal plan
One test meal may be effective to assess appetite hormones and biochemical indices at one point in time (up to 240 minutes postprandial) but most likely not adequate to understand if consistent on a daily basis
The authors did not adjust their analysis for the significant age difference
The authors often referred to the online supplementary data, making it difficult for the reader to gain a complete picture
Authors note the following limitations:
- Age difference between MS (approximately 32 years) vs. control (approximately 23 years) may bias since metabolic abnormalities occur with age
- Fatty acid composition of high fat meal (78% unsaturated and 21% saturated) is atypical of Lebanese meal.

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?		???
	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?		???
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	No
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	No
	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?		N/A
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	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%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	N/A
	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?	Yes
	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?		???
	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?	No
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	No
	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?		???
	7.1.	Were primary and secondary endpoints described and relevant to the question?	???
	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?	No
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	???
	7.5.	Was the measurement of effect at an appropriate level of precision?	???
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	No
	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)?	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