PDM: Metabolic Syndrome (2013)


Seligman BG, Polanczyk CA, Santos AS, Foppa M, Junges M, Bonzanini L, Nicolaidis G, Carney S, Lopes AL, Sehl P, Duncan BB, Clausell N. Intensive practical lifestyle intervention improves endothelial function in metabolic syndrome independent of weight loss: A randomized controlled trial. Metabolism. 2011; 60(12): 1,736-1,740.

PubMed ID: 21700302
Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To evaluate the effects of two practical lifestyle interventions with different levels of exercise intensity in non-diabetic subjects with metabolic syndrome and without overt cardiovascular disease.

Inclusion Criteria:
  • 30 to 55 years old
  • Waist circumference of 95cm or more
  • Three Adult Treatment Panel III metabolic syndrome criteria 
  • Body mass index (BMI) 30 to 40kg/m2 
  • Normal treadmill test result.
Exclusion Criteria:
  • Pregnancy
  • Lactation
  • Creatinine 1.5mg per dL or more
  • Cardiovascular, musculoskeletal, inflammatory or chronic diseases
  • Liver or thyroid dysfunction
  • Corticosteroid or appetite suppressant use.
Description of Study Protocol:


The recruitment strategy was not explicitly stated, but the authors acknowledged the hospital de Clinicas de Porto Alegre (FIPE), Brazil as a funding source.


Randomized controlled trial; participants were randomized to a 12-week intervention of:

  • Healthy diet and step counter
  • Healthy diet and fitness
  • Standard-of-care strategy.

Blinding Used

Physicians measuring flow mediated dilation were blind to intervention assignment.


  • Healthy diet and step counter: Dietary booklet (described below) and pedometer (Omron HJ 005E, Omron Electronic Components Europe, Hoofddorp, The Netherlands) with a goal of 10,000 or more steps daily
  • Healthy diet and fitness: Dietary booklet and stationary cycling sessions (described below) three times weekly with a goal of one hour of brisk walking on the remaining days
  • Standard-of-care: Dietary advice was to consume 20% of total calories from fat (7% to 8% saturated), 50% to 65% from carbohydrates and 15% to 20% from protein. The individual daily calories were calculated by allocating 30kcal per kg of ideal body weight, assuming a BMI of 25kg⁄m2. Daily one-hour walking was advised.
  • Description of Intervention components:
    • Dietary booklet: Comprised of evidence-based advice on healthy eating and scheduled servings based on hand size with low carbohydrates, high protein and vegetable content, outlining goals for appetite regulation and food replacements. Refined sugar use was restricted.
    • Stationary cycling sessions: Exercise progressed from 15 minutes at 60% of the individual maximum attainable heart rate (HRpeak) to 45 minutes per session at 75% to 85% of HRpeak, and intensity was set using workloads adjusted to the target HR.

Statistical Analysis

  • Kruskal-Wallis test; analyses to compare baseline characteristics
  • Generalized linear models for repeated measures
  • Adjusted for sex, intervention group and time. Mean percentage of weight loss was included as a between-subjects covariate when specified.
  • χ2 test to compare the metabolic syndrome criteria between groups.
Data Collection Summary:

Timing of Measurements

Baseline and 12 week measures are reported in the manuscript. The authors indicate clinical parameters were also reassessed at six and 12 months, but results beyond the 12-week intervention are only reported for flow mediated dilation in the text.

Dependent Variables

  • Flow-mediated vasodilation was defined as the maximum percentage change in brachial arterial diameter relative to the baseline after cuff deflation
  • Fasting blood samples to assess:
    • Insulin: Electrochemiluminescence (Roche, Basel, Switzerland)
    • Insulin growth factor: Immunometric radioimmunoassay (Quest Diagnostics, London, UK).
    • C-reactive protein (CRP) levels
    • Urinary albumin excretion (UAE) rate: Immunonephelometry (Roche, Basel, Switzerland)
    • Low-density lipoprotein cholesterol: Friedewald formula 
    • Homeostasis model assessment of insulin resistance.

Independent Variables

  • Healthy diet and step counter: Dietary booklet and pedometer (Omron HJ 005E, Omron Electronic Components Europe, Hoofddorp, The Netherlands) with a goal of 10 000 steps or more daily.
  • Healthy diet and fitness: Dietary booklet and stationary cycling sessions (described below) three times weekly with a goal of one hour of brisk walking on the remaining days
  • Standard-of-care: Dietary advice was to consume 20% of total calories from fat (7% to 8% saturated), 50% to 65% from carbohydrates and 15% to 20% from protein. The individual daily calories were calculated by allocating 30kcal per kg of ideal body weight, assuming a BMI of 25kg⁄m2. Daily one-hour walking was advised.
  • All participants completed diaries to record daily food intake (by servings) and physical activity
  • Individual two-week counseling and evaluation were performed until 12 weeks

Control Variables

  • Gender
  • Weight loss for flow mediated dilation.
Description of Actual Data Sample:
  • Initial N: 75
  • Attrition (final N): 8% after 12-week intervention 
  • Age: Mean (SEM) was 44 (7), 43 (8), and 42 (8) for groups one, two and three
  • Ethnicity: Brazilian 
  • Other relevant demographics: Fewer women (N=26) participated in the study compared to men
  • Anthropometrics: Groups were similar in their distribution by gender. Mean age, weight, BMI and other characteristics were similar across groups.
  • Location: Porto Alegre, Brazil.
Summary of Results:

Key Findings

  • After 12 weeks, all parameters improved (P<0.001) equally between groups
  • Mean flow mediated dilation increased from 5.03%±0.52% to 6.58%±0.73% in all groups (P=0.0007)
  • Metabolic syndrome was resolved in 64% (P<0.001).

Healthy Diet Step Counter


Healthy Diet Fitness


Standard Care Strategy


Contrast P-Value
Baseline 12 Weeks Baseline 12 Weeks Baseline 12 Weeks For Time Effect

HD Fitness vs. Standard Care

HD Step Counter vs. Standard Care
Weight (kg 99 (2.8)  90 (2.5)  100 (1.8)  89 (1.6)  100 (2.4)  92 (2.2)  0.0001  NS  NS 
BMI (kg/m2 34.4 (0.6)  31.5 (0.6)  35.2 (0.5)  31.7 (0.6)  34.7 (0.6)  31.8 (0.6)  0.0001  NS  NS 
Fat mass (%)  36 (1.1)  33 (1.3)  36 (1.1)  33 (1.4)  35 (1.1)  33 (1.2)  0.0001  NS  NS 
Waist (cm)  106 (1.5)  92 (1.4)  106 (1.3)  92 (1.2)  108 (1.8)  94 (1.8)  0.0001  NS  NS 
HOMA-IR units  3.3 (2)  2.5 (1.3) 3.5 (1.3)  1.7 (1.4)  3.6 (1.5)  2.2 (1.1)  0.0001  NS  NS 
IFG-1 (μg per dL)  198 (12)  262 (27)  172 (13)  230 (17)  215 (17)  256 (20)  0.0001  NS  NS 
UAE (mg per dL)  5.7 (1–76)  5.9 (1-53)  8.8 (1-52)  4.8 (1–46)  4.5 (190.1)  3.7 (1–90.1)  0.043 0.05  NS 

Other Findings

Arterial pressure decreased even after adjustment for weight loss and remained reduced after one year (P=0.0001).

Author Conclusion:

The present study demonstrated distinct vascular improvement after vigorous exercise combined with practical low-carbohydrate counseling in non-diabetic subjects with MetS. Compared with the active control, the healthy low-sugar diet and fitness program group had significantly higher FMD and lower pulse pressure. Risk parameters reversal (including flow mediated dilation) was significant, with further vascular improvement associated with vigorous exercise and accessible healthy eating with sugar restriction. This strategy may be an acceptable practical intervention for the general population.

Funding Source:
Government: Brazilian Reserach National Council (CNPq)
University/Hospital: Hospital de Clinicas de Porto Alegre (FIPE), Brazil
Reviewer Comments:
  • Recruitment of study population was not clearly defined
  • Unclear if counseling provided only at two weeks or every two weeks
  • Adherence was assessed using diaries, but the authors didn't report on process measures (i.e., whether likelihood of following diet and exercise goals differed by intervention group)
  • Groups were similar in their distribution of men and women, but they adjusted for sex
  • Dietary goals for "healthy diet" arm were not descriptive enough to be reproducible (i.e., no definition of "low carbohydrate, high and vegetable content."
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? 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? 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? 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? ???
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? No
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