ABSTRACT
BACKGROUND: Standard diagnostic and monitoring methods for glycemic status involve invasive sample collection through venous puncture or fingerstick. Recent attention has been focused on exploring noninvasive methods through oral biofluids. Specifically, serum fructosamine has been established as a short-term (2- to 3-wk) marker of disease status in patients with diabetes. Fructosamine measured through noninvasive means such as saliva has shown promise, but its clinical applicability is unknown. OBJECTIVE: Evaluate the available evidence on using salivary fructosamine as a reliable noninvasive marker to screen and diagnose patients with diabetes mellitus in the clinical setting. A comparative analysis of the correlative accuracy of salivary fructosamine measurements with established blood glycemic biomarkers such as serum fructosamine, blood glucose, and HbA1c will be conducted. METHODS: Six electronic databases (PubMed, PubMed Central, MEDLINE, EMBASE, Scopus, Cochrane Library) were searched for original research papers (clinical and animal studies) that were relevant to the objective of this systematic review. The search was initiated on May 28, 2020. The systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Bias risk assessment, overall quality, and level of evidence were based on the Oxford Centre for Evidence-Based Medicine, Appraisal Tool for Cross-Sectional Studies, and Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies tool. Heterogeneity was assessed using the National Institutes of Health quality assessment tool for cross-sectional studies. RESULTS: A total of 174 records were identified. Full-text articles screened for eligibility (n = 21) identified only 6 original research articles relevant to the research question and were thus included in the systematic review. The types of studies identified were cross-sectional and in vivo studies. Three studies (3/6) showed positive correlation of salivary fructosamine with blood glucose levels, while 1 study (1/6) demonstrated a positive correlation with glycated hemoglobin (HbA1c). Limitations related to sample size and selection were identified along with a fair level of interstudy heterogeneity. CONCLUSION: Based on the evidence evaluated, the utility of salivary fructosamine as a noninvasive marker to screen and diagnose patients with diabetes is doubtful. The overall level of evidence was low (IIIB) and the risk of bias was determined to be high. KNOWLEDGE TRANSFER STATEMENT: Further evidence in the form of large-scale well-controlled studies is needed prior to recommending salivary fructosamine as a noninvasive diagnostic tool for glycemic status in patients with diabetes mellitus.