Pre-diabetes is a long-lasting condition that precedes type 2 diabetes (T2D). T2D has been shown to suppress the immune response. However, it remains unclear if immune activation occurs before the onset of T2D during the progression of the pre-diabetic state. This study sought to characterize the changes in general immunity occurring during the progression from pre-diabetes to T2D. Male rats were fed a high-fat high-carbohydrate diet for 20 weeks (pre-diabetes induction period) and kept on the same diet being monitored for a further 12 weeks (experimental period). Blood was collected for haemocytometer analysis on week 0, 4, 8, and 12 of the experimental period after which the animals were sacrificed. Plasma was collected from centrifuged blood for ELISA (TNF-α, CRP, P-selectin, CD40 L, fibrinogen, and IL-6). Blood neutrophils percentage significantly decreased at week 12 possibly due to recruited neutrophils migrating to an inflamed area such as visceral adipose tissue as further observed. Due to hyperglycaemia, there was significant increase in blood lymphocytes percentage at week 12. Blood monocytes percentage significantly increased at week 12. Monocytes recruited and circulated in blood due to hyperglycaemia for glucose uptake to decrease it from circulation. Blood eosinophils percentage significantly decreased at week 12. Eosinophils migrated to inflamed areas such as visceral adipose tissue as further observed. Blood basophils percentage significantly increased due to their recruitment and activation. TNF-α, CRP, and IL-6 increased significantly after 12 weeks. There was also upregulation of fibrinogen, P-selectin, and CD40L. The results of this study show that there are changes in immune cells concentration and that immune cells such as neutrophils and eosinophils migrate to inflamed areas such as adipose tissue. There is also upregulation of various inflammatory cytokines. Based on these findings, immune activation begins during the pre-diabetic state as there is upregulation of inflammatory markers.

Introduction: Pre-diabetes is a metabolic condition characterised by moderate glycaemic dysregulation and is a frontline risk factor for multiple metabolic complications such as type 2 diabetes mellitus. To the best of our knowledge, this will be the first systematic review and meta-analysis focusing on generating a comprehensive pooling of studies reporting on pre-diabetes prevalence in South Africa. Therefore, the review’s purpose will be to screen and select reports that can be used to synthesise and provide the best estimate prevalence of pre-diabetes and its associated correlates in the South African population. Methods and analysis: To determine the prevalence and correlates of pre-diabetes in South Africa, we searched PubMed, Web of Science, Google scholar and African Journal online for published or unpublished studies reporting the prevalence of pre-diabetes in South Africa starting from the year 2000 to 2020. Studies were assessed for eligibility by checking if they met the inclusion criteria. Results & conclusion: The total number of studies deemed eligible is 13 and from these studies, an overall prevalence of pre-diabetes was reported to be 15,56% in the South African population. Hypertension, obesity and sedentary lifestyle were the common correlates recorded for the population of interest. Therefore, the review highlights the disturbingly high prevalence of pre-diabetes in South Africa and necessitates further investigations into the possible genetics, biochemical and hormonal changes in pre-diabetes. Ethics and dissemination: The review will not require ethics clearance because non-identifiable data will be used. The review outcomes will give insight into the current burden that pre-diabetes has in South Africa. PROSPERO registration number: CRD42020182430

Introduction: Pre-diabetes is an intermediate, asymptomatic state between normoglycaemia and the onset of type 2 diabetes mellitus (T2D). Recent reports indicate that there are sub-clinical changes observed in red blood cells during pre-diabetes. This systematic review protocol will provide an outline of all procedures in the synthesis of the available data on the changes in red blood cell indices. Methods and Analysis: This protocol was prepared by adhering to the PRISMA 2015 guidelines for reporting protocols. Published clinical studies that involve observation, whether it is cross-sectional, comparative cross-sectional, case-control or cohort study designs that involve normal/non-diabetic and pre-diabetes reports were used. Additionally, this was accomplished by using clinical MeSH headings to search on MEDLINE, COCHRANE library and African Journal Online. Three reviewers (NCM, AMS & AK) screened all the results for eligibility criteria. Then, Downs and Black checklist was used to check the risk of bias. Review Manager v5.4 Forrest plot was used for meta-analysis and sensitivity analysis. Strength of evidence was then assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach (GRADE). Results and Conclusion: This protocol will give direction on the exploration of articles that report on changes in red blood cell indices in the pre-diabetic state. The results obtained from this protocol will further give direction on the research to be done at in the eThekwini district of South Africa. Ethics and Dissemination: The data that will be analyzed will be data that has already been published thus there will be no data collection from subjects. Therefore, no ethical clearance is required. Registration Details: This protocol has been registered with the International Prospective Registry of Systematic Reviews (PROSPERO) registration number “CRD42020189080” dated 05-07-2020.

Introduction Pre-diabetes is a metabolic condition characterised by moderate glycaemic dysregulation and is a front-line risk factor to multiple metabolic complications such as overt diabetes. To the best of our knowledge, this will be the first systematic review and meta-analysis that focuses on generating a comprehensive pooling of studies that report on the pre-diabetes prevalence in South Africa. Therefore, the review’s purpose will be to screen and elect reports that can be used to synthesise and provide the best estimate prevalence and correlate of pre-diabetes in the South African population. Methods and analysis To determine the prevalence and correlates of pre-diabetes in South African, we will search PubMed, Embase and African Journal online for published or unpublished studies reporting the prevalence of pre-diabetes in South Africa starting from the year 2000 to 2020. Studies will be assessed for eligibility by checking if they meet the inclusion criteria. Eligible studies will undergo data extraction and risk of bias assessment. We will perform a subgroup analysis to detect probable causes of heterogeneity. Ethics and dissemination The review will not require ethics clearance because non-identifiable data will be used. The review outcomes will give more insight into the current burden that pre-diabetes has in South Africa. PROSPERO registration number CRD42020182430.

Background: Pre-diabetes is an intermediate state between normoglycaemia and type 2 diabetes (T2D). This condition has been shown to be asymptomatic thus making it hard to investigate the changes that occur in the body during this state. Recent findings stipulate that in this state, there are changes that are often associated with T2D. These include changes in concentration of immune cells and inflammatory markers. This systematic review will provide a synthesis of the data that is available reporting on the changes in the concentration of immune cells and selected markers during prediabetes. It will also give clarity of the variation of the complications of the condition among the various demographic groups. Methods: The assembly of this systematic review was through strict adherance to the PRISMA 2020 guidelines for reporting systematic reviews. This systematic review has been registered with the International Prospective Registry of Systematic Reviews (PROSPERO), registration number “CRD42020184828” dated 05-07-2020). In this systematic review, published clinical studies articles that involve observational reports, whether it is case-control, cross-sectional, and comparative cross-sectional will be used. Cohort study designs that involve normal/non-diabetic and pre-diabetes reports will be used in this systematic review and meta-analysis. Clinical MeSH headings to search on MEDLINE, COCHRANE library, EMBASE, and ICTRP and African Journal Online will be a tool used to achieve the required report. Reviewers (NCM, AMS, and AK) will screen all the results and select the studies that will be eligible by guidance according to eligibility criteria. Downs and Black Checklist will be used to check the risk of bias and then for meta-analysis Review Manager v5.4 Forrest plot will be used. Additionally, the Forrest plot will also be used for sensitivity analysis. The strength of evidence will then be assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results: Only 4 reports were eligible and risk of bias checked. The results indicated the outcomes even though there were only few reports. Discussion and conclusion: This systematic review will give an indication on the available data on this research area and lay a foundation for future studies.

Background Prediabetes 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 analysis The 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 Conclusion This 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 Dissemination No 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 Details The International Prospective Registry of Systematic Reviews (PROSPERO) has been used to register this protocol, registration number (CRD42023407084) dated 05/04/2023.