Investigation into changes in inflammatory and immune cell markers in pre-diabetic patients from Durban, South Africa.

The prevalence of pre-diabetes is increasing in rapidly urbanizing cities, especially in individuals aged 25 - 45 years old. Studies also indicate that this condition is associated with aberrant immune responses that are also influenced by environmental factors. This study sought to investigate changes in the concentration of immune cells and select inflammatory markers in patients with pre-diabetes in Durban, South Africa. Blood samples collected from King Edward Hospital, after obtaining ethics approval, were divided into non-diabetic (ND), pre-diabetic (PD) and type 2 diabetic (T2D) using ADA criteria. In each sample, the concentration of immune cells and select inflammatory markers were determined. The results showed a significant increase in eosinophil and basophil levels in the PD group as compared to the ND group. Compared to ND, the PD and T2D groups had significant increases in serum TNFα, CD40L and fibrinogen concentrations. Additionally, there were decreases in serum CRP, IL-6, and P-selectin in the PD group while these markers increased in the T2D group. These findings were indicative of immune activation and highlight the impact of pre-diabetes in this population. More studies are recommended with a higher number of samples that are stratified by gender and represent the gender ratio in the city.

The Changes in Red Blood Cell Indices That Occur in Pre-Diabetic Patients of all Ethnicities from the 25-45 Years of Age: A Protocol for a Systematic Review and Meta-Analysis.

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.

The Changes That Occur in the Immune System During Immune Activation in Patients With Prediabetes From All Ethnicities, Aged 25-45 Years: Protocol for a Systematic Review and Meta-analysis.

BACKGROUND: Prediabetes is an asymptomatic, intermediate state between normoglycemia and the onset of type 2 diabetes mellitus. Recent reports indicate that during prediabetes, there are subclinical changes to immune cells and inflammatory markers. Therefore, this systematic review will provide a synthesis of the available data on the changes in the concentration of immune cells and selective inflammatory markers. It will also give evidence of a demographic impact on changes or complications in the prediabetes state. OBJECTIVE: The objectives of this study are to create a protocol that will be used to analyze the collected data of previously published research based on immune cells such as neutrophils, lymphocytes, monocytes, eosinophils, and basophils, as well as inflammatory markers such as C-reactive protein, tumor necrosis factor-alpha, interleukin-6, P-selectin, cluster of differentiation 40 ligand, and fibrinogen. Additionally, an impact of demographics will be determined using the previously published data collected. METHODS: This protocol was prepared through adhering to the PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analysis) 2015 guidelines for reporting protocols. Published clinical studies that involve observational (cross-sectional, comparative cross-sectional, case-control, or cohort) study designs that include normal or nondiabetic and prediabetes reports will be used in this systematic review and meta-analysis. This will be accomplished by using clinical Medical Subject Headings to search on MEDLINE, Cochrane library, and African Journal Online. Reviewers (NCM, AMS, and AK) will screen all the results and select the studies that meet the eligibility criteria. Downs and Black Checklist will be used to check the risk of bias, and then a Review Manager v5.4 forest plot will be used for meta-analysis. Additionally, the forest 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 (GRADE) approach. RESULTS: Since July 5, 2020, there are no participants recruited. Publicly available data will be used in the review and will be collected after this protocol publication. No ethics approval is required as no subjects will be used, and analysis will be based on reported data. Authors will be contacted if there was a misunderstanding related to reading their reported data. CONCLUSIONS: The findings will clarify changes that might be observed in a study of interest based in the eThekwini district in South Africa. TRIAL REGISTRATION: International Prospective Registry of Systematic Reviews (PROSPERO) CRD42020184828; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=184828. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/31619.

The changes that occur in the immune system during immune activation in pre-diabetic patients of all ethnicities, from the age of 25- to 45-years: A systematic review and meta-analysis.

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.

Prevalence and correlates of pre-diabetes in adults of mixed ethnicities in the South African population: a systematic review and meta-analysis protocol.

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.

The changes in immune cell concentration during the progression of pre-diabetes to type 2 diabetes in a high-fat high-carbohydrate diet-induced pre-diabetic rat model.

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.