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Meta-analysis of the effect of structured exercise training on cardiorespiratory fitness in type 2 diabetes mellitus

NG Boule, GP Kenny, E Haddad, GA Wells, and RJ Sigal.

Review published: 2003.

CRD summary

This review assessed aerobic exercise in patients with type 2 diabetes. The authors concluded that aerobic exercise can lead to clinically important improvements in maximal oxygen uptake, with higher intensity exercise leading to greater benefits. The conclusions appear to follow from the evidence presented. Results may have limited generalisability due to included studies selecting volunteers with minimal co-existing health problems.

Authors' objectives

To compare the effect of structured aerobic exercise with no exercise on the cardiorespiratory fitness of adults with type 2 diabetes.

Searching

MEDLINE, EMBASE, SPORTDiscus, HealthSTAR, Dissertation Abstracts and the Cochrane Controlled Trials Register were searched to March 2002; the textwords and MeSH terms were stated. Reference lists in identified studies, major textbooks and reviews were also checked. Experts in the field were contacted for details of additional and unpublished studies. Studies published in any language were eligible.

Study selection

Study designs of evaluations included in the review

Randomised controlled trials (RCTs) were eligible for inclusion.

Specific interventions included in the review

Studies that compared a structured aerobic exercise intervention with a control group were eligible for inclusion. The interventions had to last 8 weeks or more. The review defined an exercise intervention as 'a predetermined exercise programme of continuous aerobic physical activity'. The exercise sessions had to be directly supervised, or compliance had to be assessed using exercise diaries. Studies of interventions with a large resistance exercise component were excluded, as were studies that included cointerventions with drugs. In the included studies, the exercise interventions averaged 3.4 sessions per week, each session lasted an average of 49 minutes, and the interventions lasted an average of 20 weeks. Most of the studies used moderate intensity exercise, usually cycling or walking.

Participants included in the review

Studies of adults with type 2 diabetes were eligible for inclusion. Authors of studies in which it was unclear whether the patients had diabetes or impaired glucose tolerance were contacted for the relevant patient data. In the included studies, the mean age of the patients was 55.7 years, the mean duration of diabetes was 4.1 years, and 40% of the patients were women. The participants tended to be volunteers with few cardiovascular or orthopaedic limitations.

Outcomes assessed in the review

Studies that assessed the maximum amount of oxygen consumed during exercise (VO2max) were eligible for inclusion. The studies had to measure VO2max at baseline and post intervention, and also during a maximal exercise test using either a direct measure of oxygen consumption or a validated estimation of oxygen consumption. Most of the included studies did not report the use of specific criteria to determine the true VO2max, so the review authors stated that the VO2max values reported were actually likely to be VO2 peak values.

How were decisions on the relevance of primary studies made?

The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.

Assessment of study quality

Validity was assessed and scored using the 5-point Jadad scale, which considers randomisation, blinding and withdrawals. Allocation concealment was also assessed. The authors did not state who performed the validity assessment.

Data extraction

Two reviewers independently extracted the data. The authors of reports with missing or ambiguous data were contacted for additional information. Pre- and post-intervention means and standard deviations were extracted, or estimated where necessary. Post-intervention means were also extracted for patients with high glycated haemoglobin (HbA1c). Exercise intensity was calculated in terms of metabolic equivalents and used to calculate the exercise volume or total energy expenditure on exercise. The relative exercise intensity was extracted or estimated from exercise heart rates.

Methods of synthesis

How were the studies combined?

The studies were combined using a meta-analysis. The standardised weighted mean difference with 95% confidence intervals (CIs) was calculated for pre- and post-intervention VO2max using a random-effects model. The standardised mean difference (SMD) in VO2max between the exercise and control group pre- and post-intervention, together with its 95% CI, was calculated for each study. A meta-analysis, using a random-effects model, was used to estimate the overall weighted SMD in VO2max pre- and post-intervention. The post-intervention mean was subtracted from the pre-intervention mean to calculate the percentage change in VO2max for each study and overall.

How were differences between studies investigated?

Statistical heterogeneity was tested using the chi-squared statistic. Where significant heterogeneity was found, subgroup analyses were used to explore potential causes. A meta-regression was used to determine which factors were most strongly associated with the post-intervention difference in VO2max and HbA1c. The factors examined included exercise intensity, exercise frequency, duration of the intervention, length of the session and exercise volume.

Results of the review

Nine comparisons reported in 7 RCTs were included (266 patients).

The studies were of low to moderate quality. The average quality score was 2 out of a possible 5. Compliance with the exercise interventions was relatively high (greater than 90% in 4 RCTs).

Exercise significantly increased post-intervention VO2max. The SMD (212 patients) was 0.53 (95% CI: 0.18, 0.88, P=0.003). The results suggested that some heterogeneity was present (P=0.06). The heterogeneity was largely explained by one RCT that used a higher intensity of exercise and showed a larger increase in VO2max (VO2max increased by 40%). Studies with lower intensity exercise (8 comparisons) showed smaller increases in VO2max (mean 9.5%, range: 2.6 to 18.4; SMD 0.40, P=0.003). There was no difference between RCTs measuring VO2 directly and RCTs using validated equations.

In the meta-regression, only exercise intensity showed an association with VO2max; the association was of borderline significance (r=0.60, P=0.08).

The post-intervention HbA1c levels were lower in the exercise groups. The weighted mean difference (WMD) was 0.71 (95% CI: -1.10, -0.32, P=0.0004). Relative exercise intensity (% VO2max) showed the strongest association with the difference in HbA1c (see Other Publications of Related Interest for more details).

There was a significant association between the post-intervention SMD in VO2max and the WMD in HbA1c (r=-0.72, P=0.04), suggesting greater glycaemic control with increasing VO2max.

Authors' conclusions

Aerobic exercise can lead to clinically important improvements in maximal oxygen uptake in people with type 2 diabetes, and higher intensity exercise can lead to greater benefits. The authors stated that these improvements may translate into reduced risks of cardiovascular disease.

CRD commentary

The review question was clear in terms of the study design, participants, intervention and outcomes. Several relevant sources were searched, the search terms were stated, no language restrictions were applied, and attempts were made to locate unpublished studies. The methods used to select the studies and assess validity were not described; hence, any efforts made to reduce errors and bias cannot be judged. The data were, however, extracted in duplicate, thus reducing the potential for bias and errors. Although validity was assessed, an inappropriate tool was used. Characteristics of the included studies were tabulated. The data were appropriately combined in a meta-analysis, statistical heterogeneity was assessed, and the influence of specified factors was explored. The authors discussed some limitations of the review. For example, the limited generalisability of the results due to the trials selecting volunteers with minimal co-existing health problems that could limit exercise. The evidence presented appears to support the authors' conclusions, but the results may have limited generalisability.

Implications of the review for practice and research

Practice: The authors did not report any implications for practice.

Research: The authors stated that future RCTs comparing the effect of more intense with less intense aerobic exercise in patients with type 2 diabetes could help clarify the relationship between exercise intensity and glycaemic control.

Bibliographic details

Boule N G, Kenny G P, Haddad E, Wells G A, Sigal R J. Meta-analysis of the effect of structured exercise training on cardiorespiratory fitness in type 2 diabetes mellitus. Diabetologia 2003; 46(8): 1071-1081. [PubMed: 12856082]

Other publications of related interest

Boule NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials. JAMA 2001;286:1218-27.

Indexing Status

Subject indexing assigned by NLM

MeSH

Databases, Factual; Diabetes Mellitus, Type 2 /physiopathology; Exercise /physiology; Exercise Therapy; Humans; MEDLINE; Middle Aged; Oxygen Consumption; Physical Fitness; Randomized Controlled Trials as Topic; Respiratory Physiological Phenomena

AccessionNumber

12003001731

Database entry date

31/12/2004

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 12856082