Introduction Type 2 diabetes is a chronic metabolic disorder that has been associated with alterations in the status of trace elements, including zinc, copper, iron and manganese. However, clinical studies reporting statuses of these trace elements in type 2 diabetes patients compared to controls have shown conflicting results. Objective This meta-analysis aimed to summarize the existing literature on the statuses of zinc, copper, iron, and manganese in Type 2 diabetes mellitus patients. Methods A literature search of Embase, PubMed, EBSCOHost, ScienceDirect, Scopus, Cochrane library and Web of Science electronic databases was conducted to find studies published from 1970 to November 2016 that compared the trace elements of interest between type 2 diabetic patients and healthy controls. Keywords used were type 2 diabetes, diabetes, hyperglycemia, insulin, glucose, HbA1c, trace elements, micronutrients, zinc, manganese, copper, ceruloplasmin, iron and ferritin. The bias corrected Hedges’ g, was utilized as the effect sizes. Due to the biological interaction between trace elements, it is important to collectively evaluate the statuses of these minerals in type 2 diabetes. Thus, the robust variance estimation method was chosen to handle dependency between multiple outcomes. Results A total of 52 studies met the inclusion criteria, amounting to 98 effect sizes. Diabetic patients (n=20183) had significantly lower zinc status when compared to controls (effect size = −1.73, p<0.01); whereas copper (effect size = 1.10, p<0.05) and ferritin levels (effect size = 1.05, p<0.01) were significantly higher. Although not significant, ceruloplasmin (effect size = 1.85, p=0.06) and iron (effect size = 1.42, p=0.06) levels were higher, and manganese (effect size = 0.27, p=0.34) was lower in patients. Conclusion Results from this meta-analysis indicate lower zinc status accompanied by increased copper and ferritin levels in patients with type 2 diabetes when compared to controls.

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Oral submucous fibrosis (OSF) is a potentially malignant disorder which causes fibrosis and inflammation of the oral mucosa. Studies have reported altered levels of trace elements in oral submucous fibrosis subjects, but findings have been inconsistent. The objective of this research is to perform a meta-analysis to summarize studies that report zinc (Zn), copper (Cu), and iron (Fe) in patients, with and without OSF. A literature search of Embase, PubMed, Cochrane Library, and Web of Science electronic databases was conducted for studies up to January 2017. A total of 34 reports met the inclusion criteria. The standardized mean difference was utilized as the effect size. The robust variance estimation method was chosen to handle dependency of multiple related outcomes in meta-analysis. There was a significant increase in the levels of Cu (effect size = 1.17, p value < 0.05, 95% confidence interval (CI): 0.164–2.171) and a significant decrease in levels of Zn (effect size = −1.95, p value < 0.05, 95% CI: −3.524 to −0.367) and Fe (effect size = −2.77, p value < 0.01, 95% CI: −4.126 to −1.406) in OSF patients. The estimation of Zn, Cu, and Fe levels may serve as additional biomarkers in the diagnosis and prognosis of OSF along with the clinical features.

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