JMIR Publications

ABSTRACT

Introduction T2DM is a metabolic disorder marked by chronic hyperglycaemia due to insufficient insulin production and/or insulin resistance in target tissues. The onset of T2DM, however, is often preceded by a condition known as prediabetes. Prediabetes is an intermediate condition of hyperglycaemia in which blood glucose indices are higher than normal but not high enough to reach the threshold for a diagnosis of T2DM. Studies have shown that complications associated with type 2 diabetes mellitus begin to develop during the prediabetes stage, including calcium homeostasis dysregulation. Recent animal studies have shown that prediabetes is linked with disrupted calcium homeostasis in rats; however, there have been no studies to investigate this in humans. Hence, the current systematic review aims to identify, evaluate, and summarise the literature investigating the changes in selected markers associated with calcium homeostasis in patients with both type 2 diabetes mellitus and prediabetes. Methods and Analysis This systematic review protocol will be developed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2020 guidelines. The databases to be screened are Google Scholar, PubMed and ScienceDirect. This review will include peer-reviewed studies involving adults (≥18) of all genders and ethnicities, comparing serum calcium and vitamin D levels across glycaemic groups, in T2DM, prediabetes, and normoglycemic controls. It will cover various study designs (observational and clinical trials), assessing both total/ionised calcium and vitamin D subtypes (D2 and D3), and will have no limits on publication year or location. Only English-language full-text articles will be considered. Studies will be excluded if they involve animal subjects, focus on unrelated conditions (e.g., type 1 or gestational diabetes), or include participants with disorders affecting calcium or vitamin D metabolism, unless subgroup data are clearly separated. Reviews, commentaries, case reports, and non-English or inaccessible full-text articles will also be excluded. Only studies with clear data on serum calcium or vitamin D and relevant group comparisons will be deemed eligible. Microsoft Excel will be used for data extraction. The extracted data will be reviewed by a second reviewer to ensure quality. Any disagreements will be discussed and resolved with the involvement of a third reviewer. The modified version of the Downs and Black risk of bias checklist will be used to assess for bias. Data extracted from these studies will be synthesised and meta-analysed using Review Manager v5.4 and IBM SPSS Statistics version 30. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach will then be used to grade the quality of the evidence. Results and Conclusion This systematic review will utilize only publicly available data, which will be collected following the publication of this protocol. Since the analysis is based exclusively on accessible published sources, ethical approval is not required. The review will examine variations in calcium and vitamin D levels among individuals with type 2 diabetes mellitus (T2DM), prediabetes, and those with normal glucose levels. This review will also look at how these alterations differ as the disease progresses from prediabetes to T2DM.