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PDM: Prediabetes (2013)

Citation:

Desch S, Sonnabend M, Niebauer J, Sixt S, Sareban M, Eitel I, de Waha S, Thiele H, Bluher M, Schuler G. Effects of physical exercise versus rosiglitazone on endothelial function in coronary artery disease patients with prediabetes. Diabetes Obes Metab. 2010; 12(9): 825-828.

PubMed ID: 20649635
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

To evaluate the effects of rosiglitazone and physical exercise on endothelial function in patients with coronary artery disease (CAD) and prediabetes over a six-month period. 

Inclusion Criteria:
  • CAD
  • Impaired fasting glucose
  • Impaired glucose tolerance.
Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment

Invitation of patients with impaired fasting glucose or impaired glucose tolerance and angiographic evidence of CAD.

Design

Parallel-group, randomized controlled trial. 

Blinding Used

Ultrasound sonographer; implied with measurements.

Intervention

8mg rosiglitazone, structured physical exercise program or control for six months. Subjects assigned to the structured one-week in-hospital physical exercise program exercised four times a day for 30 minutes on a bicycle ergometer at 75% of maximum heart rate defined as the HR at VO2max during an initial ergospirometry. After discharge, patients did daily home-based sessions on a stationary bicycle (30 minutes each at 75% maximum HR) and additional supervised in- and outdoor group exercise sessions twice a week (90 minutes each).

Statistical Analysis

Mean ±SD for continuous normal distributed variables and as number and percentage for categorical data. One-way analysis of variance was used to assess the effect of treatment between groups at six months. Post-hoc analysis were carried out using Fisher's test of lowest significant difference with the use of the Bonferroni correction. For within-group comparisons, a paired-sample T-test was used. Analysis of covariance was carried out to compared final values of between-group differences in flow mediated dilation (FMD) with the homeostasis model assessment (HOMA) score as covariate. 

 

Data Collection Summary:

Timing of Measurements

Baseline and six months.

Dependent Variables

  • Longitudinal brachial artery ultrasound FMD assessed and calculated as the percentage change of the mean end diastolic diameter 60-second after cuff deflation relative to the baseline diameter
  • Clinical examination
  • Blood samples. 

Variables

  • 8mg rosiglitazone
  • Structured one week in-hospital exercise program. Patients exercised four times a day for 30 minutes on a bicycle ergometer at 75% of maximum heart rate defined as the HR at VO2max during an initial ergospirometry. After discharge, patients did daily home-based sessions on a stationary bicycle (30 minutes each at 75% maximum HR) and additional supervised in- and outdoor group exercise sessions twice a week (90 minutes each).
  • Control group.
Description of Actual Data Sample:
  • Initial N:  43 subjects, 16 in the rosiglitazone group, 15 in the structured physical exercise program group and 12 in the control group
  • Attrition (final N): 42 subjects (33 males, nine females)
  • Age: 61.3±7.1 years (medication),  62.3±6.2 years (exercise) and 62.3±6.5 years (control)
  • Anthropometrics: No differences in LV ejection fraction, hypertension, smoking status, previous myocardial infarction or medication usage
  • Location: Leipzig, Germany.
Summary of Results:

Key Findings

  • There was a significantly higher VO2max in exercise patients (23.7±5.6ml per minute per kg) compared with patients taking rosiglitazone (18.5±4.7ml per minute per kg) and control (17.4±3.1ml per minute per kg) patients (P=0.016 exercise vs. medication and 0.005 exercise vs. control).
  • There were no significant differences between and within groups for BMI, fasting glucose, A1C, HDL cholesterol or blood pressure
  • Rosiglitazone and exercise both led to significant improvements in insulin resistance at six months while no change was observed in controls
  • The FMD improved significantly in physical exercise patients (9.7% to 14.1%, P=0.047 vs. baseline), while no change was observed in rosiglitazone or control groups. Between-group comparisons showed a significant relative improvement in FMD in exercise patients, compared with rosiglitazone or control patients. The results did not change when adjusted for baseline HOMA score by analysis of covariance. Endothelium independent vasodilation induced by nitroglycerine remained unchanged in all treatment groups.    
Author Conclusion:

Six months of physical exercise led to an improvement in endothelial function as measured by FMD in CAD patients with prediabetes, whereas rosiglitazone or usual care had no significant effect.

Funding Source:
Other: Funding source not reported
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? 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) 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)? 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