Salivary immunoglobulins (A, G, and M) in type 1 diabetes mellitus patients: A PROSPERO-registered systematic review and meta-analysis

Abstract Objective To assess the difference in the salivary levels of immunoglobulins between patients with type 1 diabetes mellitus (DM1) and healthy controls. Design This systematic review was registered on the PROSPERO (CRD42020159198) database. All references were cross-checked and the risk of bias assessment was conducted using the Newcastle-Ottawa Scale. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to appraise the quality of evidence. The standardized mean difference and Cohen's d as the effect size were used in the meta-analysis. I-square statistics was used to estimate heterogeneity. Analysis was performed using the RevMan® software (p  Results Of the total 92 articles, 9 were selected for this study. The meta-analysis included 333 DM1 patients and 325 healthy controls. DM1 patients showed a significant reduction in salivary flow (p = 0.0008; Cohen’s d= -0.19, CI 95%= -0.33, -0.05), although not significant enough to modify the IgA concentration (p = 0.120; Cohen’s d = 0.58, CI 95%= -0.15, 1.32). However, DM1 increased IgA concentration by reducing salivary flow (Cohen’s d = 0.84; CI 95% = 0.36, 1.32), with a strong estimate of effect (p = 0.0006). Regarding IgG, no significant change was noted with DM1 in the patient’s saliva (p = 0.420). Furthermore, there was no significant variation in the salivary IgM levels (p = 0.300). Conclusions The data suggest that the salivary levels of the evaluated immunoglobulins do not seem to be altered in DM1 patients when compared to that in healthy controls. However, the increase in IgA salivary concentration was dependent on total protein estimation.