JMIR Publications

ABSTRACT

Background:

BACKGROUND: Reduced cardiorespiratory fitness (CRF) is a well-recognized but under-integrated complication of type 2 diabetes mellitus (T2DM), contributing substantially to cardiovascular morbidity, mortality, and reduced quality of life. Evidence related to pulmonary function, functional exercise capacity, and autonomic dysfunction in T2DM remains fragmented and methodologically heterogeneous. OBJECTIVE: This protocol describes a systematic review and meta-analysis that aims to synthesize evidence on cardiorespiratory fitness in adults with T2DM, evaluate associated clinical and demographic determinants, and examine relationships with glycemic control and diabetes-related outcomes. METHODS: The protocol is registered with PROSPERO (CRD420251009300) and follows PRISMA-P guidelines. A comprehensive search of PubMed, Cochrane Library, Web of Science, ClinicalTrials.gov, WHO ICTRP, and grey literature will be conducted for studies published between 2013 and 2024. Randomized controlled trials, cohort studies, and cross-sectional and Case control studies involving adults with T2DM will be included. Primary outcomes include pulmonary function test parameters, six-minute walk test distance, and heart rate variability indices. Two reviewers will independently screen studies, extract data, and assess risk of bias using RoB 2.0, Newcastle–Ottawa Scale, and the JBI critical appraisal tools, as appropriate. Meta-analyses will be performed using random-effects models when sufficient homogeneity exists. The GRADE framework will be used to assess certainty of evidence. RESULTS: This review will provide pooled estimates of cardiorespiratory fitness impairments in individuals with T2DM and identify key determinants influencing these outcomes. CONCLUSIONS: The findings will support evidence-based clinical assessment and guide future research on integrative cardiopulmonary and autonomic evaluation in T2DM.

Objective:

1. To systematically evaluate the cardiorespiratory fitness in patients with type 2 diabetes mellitus compared to healthy individuals. 2. To identify factors (age, sex, diabetes duration, BMI, glycemic control (HbA1c), and physical activity levels) associated with cardiorespiratory fitness in T2DM patients. 3. To determine the association between the cardiorespiratory fitness and glycemic control (E.g.HbA1C levels) in patients with T2DM. 4. To investigate the relationship between cardiorespiratory fitness and all-cause mortality or diabetes-related complications (e.g., Neuropathy, Retinopathy) in T2DM. 5. To provide evidence-based recommendations for improving cardiorespiratory fitness in T2DM patients.

Methods:

STUDY DESIGN This systematic review and meta-analysis will adhere to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting standards. The review protocol is registered with PROSPERO (CRD420251009300), the International Prospective Register of Systematic Reviews. ELIGIBILITY CRITERIA Inclusion criteria Exclusion criteria Study • Cohort studies • Cross-sectional studies • Randomized Controlled Trials • Non-Randomized Controlled Trials • Pre-post studies without a control group • Case reports, case series, and qualitative studies. • Studies with inadequate reporting of methodology. • Duplicate publications of the same study. • Animal studies. Population Adults aged 30 to 75 years diagnosed with type 2 diabetes mellitus (T2DM). • Adults with Type 1 Diabetes Mellitus. • History of smoking and self-reported proof of any pulmonary and cardiac disease. • Cardiovascular diseases (e.g., heart failure, recent MI) • End-stage renal disease; etc. Outcomes assessed Cardiorespiratory fitness measurement methods Spirometry - for lung function test 6Minute Walk Test – Functional Capacity measurement. Heart Rate Variability – Autonomic function measurement. All-cause mortality: Diabetes-related complications (e.g., neuropathy, retinopathy): Other relevant details Source of funding: Potential conflict of interest statements from all included studies: No Any other relevant details : Non-English language INFORMATION SOURCES AND SEARCH STRATEGY Electronic searches We will conduct a thorough search of electronic databases, trial registries, and grey literature. Sources include MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials (Cochrane Library),SPORT Discus, Google Scholar, clinical trial registries, grey literature( Open grey, ProQuest Dissertations) hand-searching of key journals, and direct outreach to field experts, researchers, and organizations. The search spans all dates from January 2014 to December 2024. The search strategy Searches will combine MeSH terms, keywords, and related entries like "Cardiopulmonary Fitness," "Pulmonary Function," "6-Minute Walk," and "Heart Rate Variability," paired with "Type 2 Diabetes Mellitus." SCREENING AND SELECTION OF STUDIES The results of the search will be exported as a CSV file and then imported into Rayyan screening software. Each study will be initially screened based on the title and abstract. The studies found relevant in first phase of screening will be then assessed based on the full text. DATA EXTRACTION Two independent reviewers (GP, AG) will extract data from eligible studies using a pre-tested, standardized Microsoft Excel form. They will collect details on study characteristics; geographic factors like country and region; study design, type, and setting; and the unit of analysis. Any disagreements between the two reviewers during data extraction will be resolved through discussion to reach consensus. If consensus cannot be achieved, two other reviewer (AR, NK) will be consulted to make the final decision. Participant Details Participant characteristics include the number of participants, mean age, male-to-female ratio, and duration of diabetes, mean HbA1c levels, physical activity levels, and BMI. Study Selection After database searches and screening, studies that meet the predefined eligibility criteria will be included in the qualitative synthesis. The final selection will include case-control studies, analytical cross-sectional studies, and prospective cohort study, representing a diverse array of observational designs that evaluate the outcomes of interest. The study selection process is depicted in the PRISMA flow diagram. Study Characteristics Included studies will be summarized descriptively, in a table listing key features. Common elements will include study design (e.g., case-control, cohort), population demographics, interventions/exposures, outcomes measured, and geographic settings. This will provide an overview of the evidence base's scope and heterogeneity. RISK OF BIAS ASSESSMENT Risk of bias will be assessed using RoB 2.0 for randomized trials, Newcastle–Ottawa Scale for cohort studies, and JBI tools for Case –control and cross-sectional studies. Outcomes Assessed Outcomes measured cardiorespiratory fitness using Spirometry for lung function, the 6-minute walk test for functional capacity, and heart rate variability for autonomic function. Additional outcomes encompassed all-cause mortality and diabetes-related complications such as neuropathy and retinopathy.We will ensure that additional pertinent details, such as the funding sources and any potential conflict of interest statements from all included studies, are thoroughly addressed. If any data is missing, we will contact the authors via email to request the necessary information. The study selection process will be meticulously documented using a PRISMA flow chart. This chart will illustrate the number of research papers evaluated against the inclusion criteria and those ultimately incorporated into the systematic review, along with a comprehensive outline of the screening process that clarifies the reasons for excluding studies. SYNTHESIS OF RESULTS Meta-analysis will be conducted using STATA software (version 20) to perform the quantitative evaluation of the studies selected for inclusion. Meta-analytical techniques will be applied when adequate study homogeneity is present. For continuous variables (including PFT, HRV, walking distance, and VO2 max), data will be reported as Mean Differences (MDs) or standardized Mean Differences (SMDs) with corresponding 95% confidence intervals (CI) comparing participants with and without T2DM. A random-effects model will be utilized for data pooling to accommodate inter-study heterogeneity. SUBGROUP AND SENSITIVITY ANALYSES Subgroup analysis will be used when the number of available studies is insufficient for meta-regression (<10 studies per subgroup). Subgroup analyses will explore age, sex, BMI, glycemic control, and diabetes duration. Sensitivity analyses will assess robustness by excluding high-risk-of-bias studies. PUBLICATION BIAS Funnel plots and Egger and Begg tests will be used to assess publication bias when sufficient studies are available. GRADING THE QUALITY OF EVIDENCE The quality of evidence will be evaluated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach. This assessment will account for risk of bias, inconsistency of results, indirectness of evidence, imprecision, and publication bias.

Results:

This systematic review and meta-analysis aim to synthesize evidence regarding cardiorespiratory fitness (CRF) in adults diagnosed with type 2 diabetes mellitus (T2DM). Following comprehensive database searches and the removal of duplicates, studies that meet predefined eligibility criteria will be subjected to title/ abstract and full-text screening. Studies deemed eligible will be included in the qualitative synthesis, with quantitative pooling conducted where sufficient homogeneity is present. Pooled estimates of VO₂ max, pulmonary function parameters (FEV1, FVC, FVC/FEV1), six-minute walk test distance, and heart rate variability indices will be reported as mean differences or standardized mean differences, accompanied by 95% confidence intervals. Subgroup analyses will investigate the influence of age, sex, BMI, glycemic control, and diabetes duration on the outcomes.

Conclusions:

This protocol for a systematic review and meta-analysis details a comprehensive method for compiling evidence on cardiorespiratory fitness in people with type 2 diabetes mellitus. By thoroughly assessing and combining existing data across four primary outcome areas—pulmonary function test parameters (FEV1, FVC), six-minute walk test distance, heart rate variability indices, and VO₂ max—this review seeks to offer clinically significant, quantitative insights into the degree and factors of cardiorespiratory impairment in T2DM. The results are anticipated to inform evidence-based clinical assessment strategies and direct future research on integrated cardiopulmonary and autonomic evaluation in diabetes care. Clinical Trial: Protocol is registered with PROSPERO. Registration no.CRD420251009300