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PDM: Metabolic Syndrome (2013)

Citation:

Straznicky NE, Grima MT, Lambert EA, Eikelis N, Dawood T, Lambert GW, Nestel PJ, Masuo K, Sari CI, Chopra R, Mariani JA, Schlaich MP. Exercise augments weight loss induced improvement in renal function in obese metabolic syndrome individuals. J Hypertens. 2011; 29(3): 553-564.

PubMed ID: 21119532
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
  • To determine whether dietary weight loss alone (WL) or in combination with aerobic exercise (WL + EX) is accompanied by improvement in renal parameters [serum creatinine, eGFR, albuminuria and plasma renin activity (PRA)] in metabolic syndrome (MetS) patients without chronic kidney disease (CKD)
  • To examine the correlates of change in renal function following lifestyle intervention, with a focus on resting sympathetic nervous system (SNS) activity, hemodynamic, anthropometric, metabolic and fitness measures.
Inclusion Criteria:

Participants in a larger clinical trial examining the effects of lifestyle intervention on autonomic function who were:

  • Overweight or obese (BMI 25 to 40)
  • Nonsmoking
  • Men and post-menopausal women
  • Fulfilled Adult Treatment Panel III MetS criteria 
  • Stable body weight (within 1kg)
  • Serum creatinine less than 0.12mmol per L.

 

 

Exclusion Criteria:

 

  • History of:
    • Type 2 diabetes
    • Renal, cardiovascular (secondary hypertension, congestive heart failure, previous myocardial infarction), cerebrovascular, liver or thyroid diseases
  • Use of drugs known to affect measured parameters.

 

 

 

Description of Study Protocol:

Recruitment

Participants were recruited from a larger clinical trial examining the effects of lifestyle intervention on autonomic function.

Design

Parallel group, randomized, controlled design with participant allocation to one of three groups:

  • Weight loss by caloric restriction alone (WL)
  • Weight loss by combined caloric restriction and aerobic exercise (WL+ EX)
  • No treatment.

Blinding Used

All laboratory analyses, dual-energy X-ray absorptiometry (DEXA) scans, microneurographic recordings and analyses, and fitness testing were performed with blinding of laboratory and research staff to treatment allocation.

Intervention

  • Weight loss: A modified DASH diet was used as the background diet, with relative protein content increased to 22% of energy intake, to maximize fat loss. A calorie reduction of 600 calories per day from estimated requirements was initiated at the end of baseline testing. Participants were provided with 14-day menu plans, recipes and prepared meals in their homes. They attended fortnightly for dietary counseling. Compliance was assessed by four-day diet records, analyzed using Australian Food Composition Tables (FoodWorks Professional V3.02; Xyris Software,Highgate Hill, Australia).
  • Exercise: Exercise training comprised 40 minutes of bicycle riding on alternate days at a moderate intensity of 65% of pre-determined maximum heart rate.Workload was increased as necessary to maintain target heart rate. Once a week participants exercised under supervision in the Alfred Hospital; remaining sessions were performed in their homes, using provided exercise bicycles and heart rate monitors. Compliance was assessed by maximal oxygen consumption expressed as ml per kg fat-free mass per minute) measurement during an incremental cycle ergometry protocol.

Statistical Analysis

Treatment group, time effects and interactions were tested for by two-way repeat measures ANOVA. The Holm-Sidak test was used for post-hoc comparisons, with adjustment for multiple comparisons. Non-parametric variables such as albuminuria were log-transformed prior to analysis. Differences in proportions between groups were tested by changes in renal and selected variables were assessed using Pearson’s and Spearman’s rank correlations, as appropriate. Forward stepwise regressions were carried out with those correlations where study end-point was eGFR (Lin MDRD).

Data Collection Summary:

Timing of Measurements

Baseline and after 12-week intervention period.

Dependent Variables

  • Blood pressure: Average of five measures
  • Sodium, potassium, urea, creatinine, albumin: 24-hour urine collection
  • eGFR: Creatinine clearance using the MDRD equations among participants with normal kidney function
  • Sympathetic nervous system: Efferent multi-unit post-ganglionic muscle sympathetic nervous activity (MSNA) were made from a tungsten microelectrode (FHC, Bowdoinham, Maine,USA) inserted into the right peroneal nerve at the fibular head. The nerve signal was amplified (50 000), filtered (bandpass, 700 to 2,000 Hz), and integrated. Intra-arterial blood pressure, ECG, respiration and MSNA were digitized with a sampling frequency of 1,000 Hz (PowerLab recording, model ML 785/8SP, ADI Instruments). Resting measurements were recorded over a 15-minute period and averaged.
  • Anthropometric measures: Body weight was measured in light indoor clothes without shoes, using a digital scale; waist circumference at the midpoint between the lowest rib and iliac crest, and hip circumference at the level of the greater trochanters.Total body, trunk, abdominal (measured post-hoc at the L1–L4 cut), android and gynoid fat and lean masses were quantified by DEXA scan (GE-LUNAR Prodigy Advance PAþ130510; GE Medical Systems, Lunar, Madison, Wisconsin, USA).
  • Metabolic measures: Each participant underwent a standard 75g oral glucose tolerance test (OGTT; Glucaid, Fronine, Australia) with 30-minute determination of glucose and insulin concentration. Whole-body insulin sensitivity was calculated from OGTT parameters. Fasting blood samples were also collected for plasma leptin, uric acid, non-esterified fatty acid (NEFA), high sensitivity C-reactive protein (hs-CRP) and lipid profile measurements.

Independent Variables

  • Participant allocation to one of three groups:
    • Weight loss by caloric restriction alone (WL)
    • Weight loss by combined caloric restriction and aerobic exercise (WL+ EX)
    • No treatment
  • Weight loss: A modified DASH diet was used as the background diet, with relative protein content increased to 22% of energy intake, to maximize fat loss. A calorie reduction of 600 calories per day from estimated requirements was initiated at the end of baseline testing. Participants were provided with 14-day menu plans, recipes and prepared meals in their homes. They attended fortnightly for dietary counseling. Compliance was assessed by four-day diet records, analyzed using Australian Food Composition Tables (FoodWorks Professional V3.02; Xyris Software,Highgate Hill, Australia).
  • Exercise: Exercise training comprised of 40 minutes of bicycle riding on alternate days at a moderate intensity of 65% of pre-determined maximum heart rate.Workload was increased as necessary to maintain target heart rate. Once a week participants exercised under supervision in the Alfred Hospital; remaining sessions were performed in their homes, using provided exercise bicycles and heart rate monitors. Compliance was assessed by maximal oxygen consumption expressed as ml per kg fat-free mass per minute) measurement during an incremental cycle ergometry protocol.
Description of Actual Data Sample:
  • Initial N: 38 men and women
  • Attrition (final N): None mentioned
  • Age: Mean age 55±1 year
  • Ethnicity: Australian
  • Other relevant demographics: BMI 32.7±0.6kg/m2
  • Anthropometrics: Similar across groups
  • Location: Melbourne, Australia.
Summary of Results:

Key Findings

Change from Baseline in Selected Outcome Measures by Treatment Group

Variables Control (N=12) Weight Loss (N=13 Weight Loss + Exercise (N=13) Statistical Significance of Group Difference
BMI, kg/m2 0.5±0.1 -2.7±0.3 -3.4±0.3 <0.001
Lean mass 1.1±0.3 -1.6±0.7 -1.2±0.5 0.002
Abdominal fat mass 0.1±0.1 -0.6±0.1 -1.0±0.2 <0.001
VO2 max -1.4±0.5 -0.8±1.1 4.2±1.5 0.012
Systolic blood pressure, mm Hg -3±3 -10±2 -14±3 0.026
Diastolic blood pressure, mm Hg -2±1 -2±2 -4±2 0.432
Whole-body insulin sensitivity -0.02±0.20 0.72±0.20 1.53±0.53 0.004 
HDL cholesterol -0.02±0.04 -0.05±0.03 -0.06±0.05 0.733
LDL cholesterol -0.2±0.1 -0.4±0.1 -0.6±0.1 0.037
Serum creatinine -2.1±1.6 -7.2±3.9 -11.2±2.5 0.132

 

Other Findings

  • Body weight decreased by -8.2±0.8% in the caloric restriction and -10.7±0.9% in the caloric restriction and aerobic exercise groups (both P<0.001)
  • There were significant decreases in weight and fasting glucose in both weight loss groups (all P<0.001), compared to the control group
  • There was a significant decrease in triglyceride levels in the caloric restriction and aerobic exercise group (P<0.001), compared to the control group
  • There was a significant decrease in waist circumference in both weight loss groups (all P<0.001) compared to the control group
  • Waist-to-hip ratio was significantly decreased in both weight loss groups compared to baseline (both P<0.05)
  • Systolic blood pressure was significantly decreased in both weight loss groups compared to baseline (both P<0.001)
  • Significance of changes in eGFR was sensitive to estimation method (Table 4 of paper presents four measures with two of the MDRD methods significant, but the Cockcroft-Gault was not) 
  • SNS: MSNA expressed as burst frequency decreased by -12±3 (-30±9%) and -16±2 EX groups, P<0.001), but did not change in MSNA expressed as burst frequency decreased by (–40±5%) bursts per minute in the WL and WL+EX respectively (both P<0.001), but did not change in Controls
  • Albuminuria decreased in both groups compared to baseline (-30±24mg per 24 hours in the caloric restriction group, P<0.01 and -15±6mg per 24 hours in the caloric restriction and aerobic exercise group, P<0.05). However, changes in albumin:creatinine ratio were not significant between groups.
Author Conclusion:

This study demonstrates that in obese MetS patients without overt renal disease, moderate weight loss is accompanied by improvement in eGFR and reduction in albuminuria and that exercise co-intervention confers additional benefits on anthropometric, inflammatory, hemodynamic and renal parameters. These findings support the inclusion of an exercise component in weight loss programs for renal protection in MetS obesity.

 

 

Funding Source:
Not-for-profit
2008 Diabetes Australia Research Trust Grant and National Health and Medical Research Council of Australia Project Grant
Other non-profit:
Reviewer Comments:

Small number of subjects in groups.

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) No
  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%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  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? 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? 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)? 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