Investigating the Impact of Prediabetes on the Aging Process through Longitudinal Analysis of Blood-Based Biomarkers: A Systematic Review and Meta-Analysis Protocol
Authors: Mbatha Nonkululeko Avril , Mzimela Nomusa Christina , Mushebenge Aganze Gloire-Aimé , Khathi Andile 
Published: August 2023

ABSTRACTBackgroundPrediabetes is a disorder that affects the metabolic function of the body, and it can lead to heart disease, stroke, and type 2 diabetes (T2D). Previous studies have reported a correlation between T2D and exacerbated senescence, however, none have reported a link between prediabetes and senescence. Hence, this systematic review protocol and meta-analysis will be the first, to the best of our knowledge, to provide detailed guidance on all steps taken in the synthesis and meta-analysis of data reporting the correlation of prediabetes with senescence by identifying changes to biological aging indices.Methods and analysisThe PRISMA 2015 reporting protocol preparation standards were followed in the creation of this protocol. The search for pertinent studies will be undertaken by the framework for Arksey and O’Malley reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-ScR). Clinical studies published in English from January 2003 to March 2023 with observational methods will be used, including cross-sectional, comparative cross-sectional, case-control, and cohort study designs with normal/non-diabetic, prediabetic, and type 2 diabetic cases reporting on senescence and changes in blood-based biomarker levels in a multi-ethnic population aged 25-45 years. An extensive search of relevant studies will be conducted in the following databases: PubMed, Google Scholar, Cochrane Library, ScienceDirect, Web of Science, Scopus, WHO Global Health Library, and African Journals Online. In addition, all the results will be examined for eligibility by two reviewers (NAM, NCM). Any differences between the two authors will be settled by a third reviewer (GAM), to ensure the overall quality of the findings. To find additional relevant studies, authors will also look through reference lists, grey literature sources, and peer-reviewed journals. The risk of bias will be examined using the Downs and Black checklist. To assess statistical heterogeneity of the studies, a standard chi-square test will be used with a significance level of P 0.10 indicating that there is no true heterogeneity between the studies. For the meta-analysis and to analyse the sensitivity of the data, Review Manager (RevMan) software (version 5.4) will be used to populate forest plots that will display the effect estimates and confidence intervals from each study. The strength of the evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.Results and ConclusionThis protocol aims to provide guidance on how to investigate articles that reported on the correlation of prediabetes with exacerbated senescence by identifying common pathways utilized and changes induced to biomarkers of biological aging. The results from this protocol will highlight research gaps in the impact of prediabetes on aging and provide suggestions for future research. In addition, it will provide evidence-based information to give guidance to policymakers on treatment decisions to improve patient outcomes.Ethics and DisseminationNo ethical approval is required as the data under consideration have already been published and no additional data will be requested from participants. The results of this review will be disseminated through a peer-reviewed publication and presented at pertinent conferences.Registration DetailsThe International Prospective Registry of Systematic Reviews (PROSPERO) has been used to register this protocol, registration number (CRD42023407084) dated 05/04/2023.