Introduction: Type 1 diabetes (T1DM) is a chronic disease with multifactor pathogenesis. Large number of studies confirmed that epigenetic, microRNA (miRNA)- mediated, regulation mechanisms of gene expression are associated with both pathogenesis of T1DM and the progression of its complications. Cardiac autonomic neuropathy (CAN), the microvascular complication, is one of the strongest risk factor of cardiac mortality among T1DM patients. Circulating miRNA might be a prediction marker for development and progression of this diabetic complication but studies concerning connection between miRNA and CAN in T1DM patients are still missing.
Materials and methods: The study included 54 T1DM subjects with and without CAN and 27 healthy, age-correlated volunteers, as a control group. The CAN prevalence was assessed using Ewing test. Expression analysis of human miRNAs was performed using the TaqMan Low-Density Arrays (TLDAs) Panel v3.0 (Applied Biosystems). Differentially and significant (p<0.05) expressed miRNA were uploaded into the DIANA-mirPath v.3, for Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis.
Results: Our study revealed a significantly upregulated expression of miR-190b, miR-520d-3p and miR-30a-5p in both CAN and T1DM groups comparing to control. Nevertheless, the miRNAs expression within T1DM group between CAN and T1DM groups did not differ.
Discussion: All of significantly altered miRNA are involved in axon guidance pathway, playing a role in neuron regeneration and, as a result of impaired function, neuropathy. Additional significantly regulated miR-30a-5p downregulates the expression of Beta/NeuroD gene, which role in the pathogenesis of diabetes mellitus is well documented.
Conclusion: Our study, for the first time, showed the potential correlation between epigenetic mechanisms and CAN, stressing that mi-30a-5p might be a new tool for early diagnosis and potentially therapeutic target of T1DM.
E. Tobor: None. A. Polus: None. J. Gastol: None. B. Matejko: Other Relationship; Self; Dexcom, Inc., Roche Diabetes Care. L. Pawlinski: Other Relationship; Self; Boehringer Ingelheim International GmbH. B. Kiec-Wilk: None.
National Science Centre in Poland (2014/13/B/NZ4/00149)