EAL

PDM: Prediabetes (2013)

Citation:

Sixt S, Rastan A, Desch S, Sonnabend M, Schmidt A, Schuler G, Niebauer J. Exercise training but not rosiglitazone improves endothelial function in prediabetic patients with coronary disease. Eur J Cardiovasc Prev Rehabil. 2008; 15(4): 473-478.

PubMed ID: 18677174

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To assess the effects of intensive exercise training as compared to rosiglitazone or usual care on endothelial function in patients with coronary artery disease and impaired glucose tolerance.

Inclusion Criteria:

Impaired glucose tolerance
Coronary artery disease with at least one stenosis higher than 50%.

Exclusion Criteria:

Unstable angina
Pectoris
Stenosis of the left main stem higher than 25%
Left ventricular ejection fraction less than 40%
Known diabetes mellitus
Significant heart valvular disease
Smoking
Illness precluding participation in exercise program.

Description of Study Protocol:

Design

Randomized controlled trial.

Blinding Used

Staff was blinded to group assignment.

Intervention

34 patients were randomly assigned to either four weeks of exercise training, rosiglitazone (8mg) or usual care
During the first week, exercise training consisted of supervised ergometer training on electronically braked bicycles six times a day for 15 minutes each followed by three weeks of home-based sub-maximal ergometer training 30 minutes per day sub-maximal ergometer exercise. In addition, group exercise training of one hour was performed twice per week.

Statistical Analysis

Analysis of variance was performed to identify a significant difference between the mean values of a variable measured in more than two groups. When analysis of variance was significant, comparisons were made by unpaired Student's T-tests with Fisher's exact test correction. Correlations coefficients were calculated by Pearson's product-moment correlations.

Data Collection Summary:

Timing of Measurements

Measurements made at baseline and after four weeks of study.

Dependent Variables

Vascular function: Performed according to guidelines of American College of Cardiology, performed at 7:00 a.m. following overnight fast for at least eight hours
Conduit vessel function: B-mode and Doppler ultrasound images of the brachial artery of the dominant arm were obtained using a 10-MHz linear array transducer
Assessment of maximal exercise capacity: Heart rate, blood pressure, maximal oxygen uptake and respiratory quotient were determined by a graded maximal exercise test
Secondary endpoints were cardiometabolic risk factors, including exercise capacity, body weight, body mass index, glucose profile, dyslipidemia, high sensitivity C-reactive protein and fibrinogen.

Independent Variables

Exercise training: During first week, patients performed supervised ergometer training on electronically braked bicycles six times a day for 15 minutes each. Home-based ergometer training of 30 minutes a day was continued for another three weeks in addition to one-hour supervised group exercise sessions two times a week.
Rosiglitazone (8mg)
Usual care.

Description of Actual Data Sample:

Initial N: 34 male patients
Attrition (final N): 34 male patients (13 in the exercise training group, 11 in the rosiglitazone group and 10 in the control group)
Age: 64±6 years
Anthropometrics: No anthropometric differences were seen at baseline.
Location: Salzburg, Austria, Europe.

Summary of Results:

Key Findings

Metabolic Variables

After four weeks, triglycerides and uric acid were significantly lower in the exercise group whereas fasting glucose, HbA1c, LDL-cholesterol, HDL-cholesterol and body mass index did not differ between groups
Triglycerides were significantly lower in the exercise group (from 1.5±0.7, 2.3±1.2 and 2.2±1.4mmol per L to 1.2±0.6, 2.6±1.1 and 1.8±1.6mmol per L in the exercise training, rosiglitazone and usual care groups, respectively, P=0.03).

Inflammatory Markers

At baseline and after four weeks, the plasma levels of C-reactive protein and fibrinogen did not differ between groups at baseline and remained unchanged over the study period.

Exercise Training

At baseline, exercise capacity and oxygen (VO₂) update at peak exercise was comparable in all three groups
After four week, exercise capacity and VO_2max improved significantly in the training group as compared with baseline (P=0.03)
In the exercise group, exercise capacity (123±33 vs. 144±31 W; P=0.006) and endothelium-dependent, flow-mediated vasodilatation (P<0.01) increased significantly, whereas in the rosiglitazone group and in the control group no changes were seen
Both parameters remain unchanged in the rosiglitazone and the control group (P=0.15)
In comparison with the rosiglitazone and the control group, exercise capacity significantly improved (P=0.006), whereas there was no significant difference observed for VO_2max (P=0.06).

Author Conclusion:

The authors concluded that in patients with coronary artery disease (CAD) and impaired glucose tolerance, four weeks of exercise training led to an improvement of endothelium-dependent vasodilation, whereas this was not observed after rosiglitazone therapy or usual care.

Funding Source:

University/Hospital:

Paracelsus Medical University, Salzburg, Austria

Reviewer Comments:

Small numbers of subjects in groups. Only males were studied. Study duration was only four weeks.

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?	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?	???
	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)?	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?	Yes
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