AUTHOR=Santos-Bezerra Daniele P. , Santos Aritania S. , Guimarães Gabriel C. , Admoni Sharon N. , Perez Ricardo V. , Machado Cleide G. , Pelaes Tatiana S. , Passarelli Marisa , Machado Ubiratan F. , Queiroz Marcia S. , da Silva Maria Elizabeth R. , Correa-Giannella Maria Lucia 

TITLE=Micro-RNAs 518d-3p and 618 Are Upregulated in Individuals With Type 1 Diabetes With Multiple Microvascular Complications

JOURNAL=Frontiers in Endocrinology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00385

DOI=10.3389/fendo.2019.00385

ISSN=1664-2392

ABSTRACT=<p><bold>Objective:</bold> To compare the serum micro-RNAs (miRNAs) profile of individuals with type 1 diabetes without microvascular complications vs. those with multiple severe microvascular complications, in order to identify epigenetically modulated pathways in these two groups of individuals.</p><p><bold>Research Design and Methods:</bold> A total of 10 subjects were selected among individuals followed in the Diabetes Outpatient Clinic and sorted according to the absence or presence of all microvascular complications. Samples from these participants were used for evaluation of serum miRNA expression profile employing a qRT-PCR assay with hydrolysis probes based on the Taqman Low Density Arrays (TLDA) system. The top six most differentially expressed miRNAs between the aforementioned groups were validated by qRT-PCR in additional 47 type 1 diabetes individuals sorted according to the absence or presence of all microvascular complications and matched for age, sex, degree of metabolic control, diabetes duration, and age at diagnosis.</p><p><bold>Results:</bold> Twenty one out of three hundred and seventy seven miRNAs were upregulated in the group of individuals with all microvascular complications vs. the group without complications. The following miRs were validated: 518-3p, 34a-5p, 126-5p, 425-5p, 618, and 139-5p and logistic regression analyses showed that miRNA-518-3p and miRNA-618 were positively associated with multiple microvascular complications after adjustment for age, sex, diabetes duration, HbA<sub>1</sub>c and use of statin, angiotensin-converting enzyme inhibitors and amlodipine.</p><p><bold>Conclusions:</bold> In this cohort of type 1 diabetes individuals, serum miR-518d-3p and miR-618 were upregulated in those with diabetes kidney disease, diabetes retinopathy, peripheral neuropathy, and cardiovascular autonomic neuropathy in comparison to individuals with no microvascular complications.</p>