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The exponential increase in the prevalence of prediabetes has become a global concern due to the comorbidities and mortality rates that are positively associated with it. The incidence of prediabetes is directly proportional to the prevalence of comorbidities with risk factors such as insulin resistance, adiposity, lipotoxicity, obesity and the alteration of the renin-angiotensin-aldosterone system. Hence, the current study systematically reviewed and performed a meta-analysis of these risk factors, their clinical indicators and the RAAS components. This systematic review was developed in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-2020) standards. This was accomplished by searching clinical MeSH categories in MEDLINE with full texts, EMBASE, Web of Science, PubMed, Cochrane Library, Academic Search Complete, ICTRP and ClinicalTrial.gov. Reviewers examined all the findings and selected the studies that satisfied the inclusion criteria. The Downs and Black Checklist was used to assess for bias, followed by a Review Manager v5. A Forrest plot was used for the meta-analysis and sensitivity analysis. The protocol for this review was registered with PROSPERO CRD42022320252. The clinical studies ( n  = 2) comprised 1065 patients with prediabetes and 1103 normal controls. The RAAS measurements were completed in the adipose tissue. The RAAS components, renin and aldosterone were higher in the prediabetic (PD) compared to the control [mean difference (MD) = 0.16, 95% CI 0.16 (−0.13, 0.45),  p  = 0.25]. Furthermore, the PD group demonstrated higher triglycerides mean difference [MD = 7.84, 95% CI 7.84 (−9.84, 25.51),  p  = 0.38] and increased BMI [MD = 0.13, 95% CI 0.13 (−0.74, 0.99),  p  = 0.77] compared to the control. The overall quality of the studies was fair with a median score and range of 17 (16–18). The current study highlights the relationship between increased BMI, RAAS and insulin resistance which is a predictor of prediabetes. The renin is slightly higher in the prediabetes group without any statistical significance, aldosterone is rather negatively associated with prediabetes which may be attributed to the use of anti-hypertensive treatment.

The relationship between adipose tissue RAAS activity and the risk factors of prediabetes: a systematic review and meta-analysis