Associations of plasma metal levels with type 2 diabetes and the mediating effects of microRNAs.

The present study aims to determine the associations of multiple plasma metal levels and plasma microRNAs (miRNAs) with diabetes risk, and further explore the mediating effects of plasma miRNAs on the associations of plasma metal with diabetes risk. We detected plasma levels of 23 metals by inductively coupled plasma mass spectrometry (ICP-MS) among 94 newly diagnosed and untreated diabetic cases and 94 healthy controls. The plasma miRNAs were examined by microRNA Array screening and Taqman real-time PCR validation among the same study population. The multivariate logistic regression models were employed to explore the associations of plasma metal and miRNAs levels with diabetes risk. Generalized linear regression models were utilized to investigate the relationships between plasma metal and plasma miRNAs, and mediation analysis was used to assess the mediating effects of plasma miRNAs on the relationships between plasma metals and diabetes risk. Plasma aluminum (Al), titanium (Ti), copper (Cu), zinc (Zn), selenium (Se), rubidium (Rb), strontium (Sr), barium (Ba), and Thallium (Tl) levels were correlated with elevated diabetic risk while molybdenum (Mo) with decreased diabetic risk (P < 0.05 after FDR multiple correction). MiR-122-5p and miR-3141 were positively associated with diabetes risk (all P < 0.05). Ti, Cu, and Zn were positively correlated with miR-122-5p (P = 0.001, 0.028 and 0.004 respectively). Ti, Cu, and Se were positively correlated with miR-3141 (P = 0.003, 0.015, and 0.031 respectively). In addition, Zn was positively correlated with miR-193b-3p (P = 0.002). Ti was negatively correlated with miR-26b-3p (P = 0.016), while Mo and miR-26b-3p were positively correlated (P = 0.042). In the mediation analysis, miR-122-5p mediated 48.0% of the association between Ti and diabetes risk. The biological mechanisms of the association are needed to be explored in further studies.
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