EAL

PDM: Metabolic Syndrome (2013)

Citation:

Muzio F, Mondazzi L, Harris WS, Sommariva D, Branchi A. Effects of moderate variations in the macronutrient content of the diet on cardiovascular disease risk factors in obese patients with the metabolic syndrome. Am J Clin Nutr. 2007; 86 (4): 946-951.

PubMed ID: 17921369

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 compare the effects of either a low-carbohydrate or high-carbohydrate diet on cardiovascular disease risk factors in obese patients with the metabolic syndrome.

Inclusion Criteria:

Obese patients (BMI over 30kg/m²)
Over 18 years old
With metabolic syndrome, as diagnosed according to the criteria of the National Cholesterol Education Program Adult Treatment Panel III
Willing to adhere to the prescribed diet.

Exclusion Criteria:

History of thyroid disease or diabetes mellitus
Current pregnancy
Unstable medical condition
Current use of medication known to affect weight, appetite or blood lipids.

Description of Study Protocol:

Recruitment

Subjects were recruited from the G Salvini Hospital in Milan, Italy, between July 2005 and September 2006.

Design

Randomized controlled trial:

100 subjects were randomly-assigned into either a high-carbohydrate diet or a low-carbohydrate diet
The high-carb diet consisted of 65% of energy as carbohydrate, 13% as protein and 22% as fat
The low-carb diet consisted of 48% of energy as carbohydrate, 19% as protein and 33% as fat.

Blinding Used

Researchers performing data analysis were blinded to the treatment diet group that subjects were in.

Intervention

Subjects were randomly-assigned into either the high- or low-carbohydrate diet group
Both diets provided approximately a 500-kcal-per-day energy deficit, as determined on the basis of each patient's estimated daily energy expenditure
After the initial visit, subjects met monthly with the Nutrition Unit staff in group sessions lasting two hours for five months and each session included only those patients receiving the same diet.

Statistical Analysis

Within-group treatment effects on body weight, blood pressure and metabolic markers were analyzed by using a Student's T-test for paired data
Comparisons between groups were analyzed by using Student's T-test for unpaired data
Group-by-time interactions were evaluated by a split-plot analysis of variance
A chi-squared test was used to compare discrete variables
The relationship between basal body weight and its change was evaluated by calculating Pearson's correlation coefficients
Multiple backward step-wise regression analysis was used to study the independent variables able to predict blood pressure and lipid changes during the study
P<0.05 was considered significant.

Data Collection Summary:

Timing of Measurements

Body weight, height, BMI, waist girth and blood pressure were measured at each visit (upon enrollment into the study and at monthly follow-up sessions).

Dependent Variables

Body weight: Measured with light clothing and no shoes on
Height: Measured with a stadiometer
BMI: Calculated as kg/m²
Waist girth: Measured as the narrowest circumference between the bottom of the rib cage and the iliac crest, by using an unstretched tape measure
Blood pressure: Average of two measurements using a standard mercury sphygmomanometer after the patient had been sitting for 15 minutes
Total cholesterol: Measured using the CHOD-PAP method
Serum triacylglycerol: Measured using the GPO-PAP method
HDL-cholesterol: Measured with HDL-C Olympus System
LDL-cholesterol: Calculated according to Friedewald et al
Insulin: Determined with radioimmunoassay kit. HOMA-IR used to measure insulin-sensitivity.

Independent Variables

Dietary intervention: Either a high-carbohydrate diet (65% carbohydrates, 13% protein, 22% fat); or a low-carbohydrate diet (48% carbohydrates, 19% protein, 33% fat)
Adherence to the study diet was assessed at the last visit by administering a 20-item questionnaire
Patients were encouraged to increase their physical activity throughout the study and patients were asked about their physical activity at the last visit
Physical activity was monitored via questionnaire.

Control Variables

Anti-hypertensive medications were held consistent
Both diets were deficient in calories by approximately 500kcal per day, based on estimated caloric needs.

Description of Actual Data Sample:

Initial N: 112 subjects were recruited; 100 subjects entered the study
Attrition (final N): 100 subjects finished the study
Age: Average of 52.1 years for the High-Carbohydrate Group, and 52.7 years for the Low-Carbohydrate Group (no significant difference)
Ethnicity: Not specified.

Other Relevant Demographics

27 males, 73 females.
15 subjects missed at least one session
Both groups were well-matched for physical characteristics and metabolic profile.

Anthropometrics

There was no significant difference between the two dietary intervention groups on gender, age, initial body weight, BMI, waist girth, BP, heart rate, total cholesterol, HDL, LDL, TG, glucose, insulin or HOMA-IR
There were no significant differences between the two dietary intervention groups in terms of initial metabolic syndrome risk components, including prevalence of low HDL-cholesterol, hypertriglyceridemia, hyperglycemia, HTN or central obesity.

Location

Single-center study conducted at the G Salvini Hospital in Milan, Italy.

Summary of Results:

Components of metabolic syndrome (body weight, BMI, waist girth, systolic and diastolic blood pressures, total cholesterol, serum triacylglycerol, blood glucose, insulin, and the homeostasis model assessment of insulin resistance) decreased significantly in both dietary groups with no difference between groups, with the exception of HDL-cholesterol, which remained unchanged in both groups and a significant decrease in LDL-cholesterol for those consuming the high-carbohydrate diet.
The Low-Carb Diet Group was associated with a greater decrease in the prevalence of HTN (P<0.05) and hypertriglyceridemia (P<0.001)
92% of the High-Carb Group and 84% of the Low-Carb Group reached a weight loss of more than 5%
Body weight, BMI, waist girth, systolic and diastolic blood pressure, insulin and HOMA-IR decreased significantly in both dietary groups at the end of the study
No relationship was found between baseline body weight and the change in body weight at the end of the study (Low-Carb R=0.12; High-Carb R=0.11)
Analysis of variance did not show a group-by-time interaction
Via multiple regression, protein content of the diet was the only variable significantly associated with the percentage change in systolic blood pressure
Multiple regression analyses showed that the protein content of the diet was the only variable significantly associated with the percentage changes in systolic blood pressure (beta=-0.0018, P<0.05) and that the carbohydrate content of the diet (beta=-0.049, P<0.05) and weight loss (beta=1.860, P<0.01) were independent predictors of the percentage changes in serum triacylglycerol concentrations.
Prevalence of central obesity decreased significantly in both groups. HTN and hypertriglyceridemia decreased in the Low-Carb Group.

Percentage Reduction of Positive Diagnostic Criteria of the Metabolic Syndrome in Comparison with Baseline: All Patients¹

	High Carb Diet (N=50)	LowCarb Diet (N=50)	P²
Central Obesity (percentage)³	26⁴	28⁴	NS
Hyperglycemia (percentage)⁵	44	36	NS
Hypertension (HTN) (percentage)⁶	12	27⁷	<0.05
Hypertriacylglycerolemia (percentage)⁹	36	81⁴	<0.001
Low HDL-Cholesterol (percentage)⁹	15	29	NS
Metabolic Syndrome	40⁴	54⁴	NS

1: Patients were randomly-allocated to consume a high-carbohydrate diet or a low-carbohydrate diet. The prevalence of central obesity decreased in both dietary groups and that of HTN and hypertriglyceridemia decreased in patients with the low-carbohydrate diet. The extent of recovery from the metabolic syndrome was not significantly different between the two dietary groups.
2: Chi-square test
3: Defined as waist girth over 82cm in women and over 102cm in men
4, 7: Significantly different from baseline (chi-square test). 4: P<0.001. 7: P<0.05.
5: Defined as fasting blood sugar concentration of at least 100mg per dL
6: Defined as systolic BP over 130mmHg and diastolic BP over 85mmHg or the use of hypotensive therapy
8: Defined as serum triacylglycerol concentration of at least 150mg per dL
9: Defined as HDL-cholesterol of over 40mg per dL in men and more than 50mg per dL in women.

Other Findings

Subjects showed a satisfactory knowledge of the prescribed diet at the end of the study
Only five patients (three in the Low-Carb Group and two in the High-Carb Group) increased physical activity during the study (mostly consisting of walking over 30 minutes per day). Other patients did not change their habitual physical activity.
At the end of the study, 40% of the patients receiving the high-carbohydrate diet and 54% of those receiving the low-carbohydrate diet no longer fulfilled the diagnostic criteria of the metabolic syndrome, but this difference between groups was not statistically significant.
Renal outcomes were not reported.

Author Conclusion:

A moderate low-calorie diet, relatively rich in protein and in monounsaturated fat and poor in carbohydrates, can improve blood pressure and fasting triacylglycerol concentrations
This gives an additional benefit to the expected reduction of cardiovascular disease risk factors determined by weight loss
Tailoring diet interventions to the specific presentation of the metabolic syndrome may be the best way of reducing the risk factors for cardiovascular disease.

Funding Source:

University/Hospital:

University of Milan, Fondo Interno Ricerca Scientifica e Tecnologica grant

Reviewer Comments:

Large sample size
Five-month intervention.

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)	???
	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?	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?	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?		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?	Yes
	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)?	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?	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