Pancreas-enriched miRNAs are altered in the circulation of subjects with diabetes: a pilot cross-sectional study

Abstract

The clinical presentation of diabetes sometimes overlaps, contributing to ambiguity in the diagnosis. Thus, circulating pancreatic islet-enriched microRNAs (miRNAs) might be useful biomarkers of β-cell injury/dysfunction that would allow more accurate subtyping of diabetes. We measured plasma levels of selected miRNAs in subjects with prediabetes (n = 12), type 2 diabetes (T2D, n = 31), latent autoimmune diabetes of adults (LADA, n = 6) and type 1 diabetes (T1D, n = 16) and compared them to levels in healthy control subjects (n = 27). The study was conducted at the Translational Research Institute for Metabolism and Diabetes (TRI-MD), Florida Hospital. MiRNAs including miR-375 (linked to β-cell injury), miR-21 (associated with islet inflammation), miR-24.1, miR-30d, miR-34a, miR-126, miR-146, and miR-148a were significantly elevated in subjects with various forms of diabetes compared to healthy controls. Levels of several miRNAs were significantly correlated with glucose responses during oral glucose tolerance testing, HbA1c, β-cell function, and insulin resistance in healthy controls, prediabetes, and T2D. These data suggest that miRNAs linked to β-cell injury and islet inflammation might be useful biomarkers to distinguish between subtypes of diabetes. This information could be used to predict progression of the disease, guide selection of optimal therapy and monitor responses to interventions, thus improving outcomes in patients with diabetes.

A Systematic Study of Dysregulated MicroRNA in Type 2 Diabetes Mellitus

“…The main characteristics extracted from various datasets are summarized in Table 1, which includes the number of patients investigated, the measurement platform, type of sample used and the identity of miRNAs in the study [23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81]. Comparing results from multiple tissues provides an overall view of the impact of miRNAs in T2DM pathology.…”

MiRNAs in β-Cell Development, Identity, and Disease

“…Interestingly, both miR-34a and miR-146 may impact β-cell apoptosis (Nesca et al, 2013) and miR-146b has also been implicated in the effect of cytokines on pancreatic β-cells (Roggli et al, 2010). Seyhan et al (2016) found that both miR-34a and miR-146a are up-regulated in the circulation of patients with various forms of diabetes in comparison with healthy controls, establishing a link between those miRNAs and the development of the disease.…”

Circulating microRNAs: promising biomarkers in aplastic anemia

“…In general, JAK2, CALR and MPL are considered driver mutations, though there are elegant studies examining how acquisition order dictates phenotypic destiny. 4 Additional somatic mutations found in the disease include LNK, CBL, TET2, ASXL1, IDH1/2, IKZF1, EZH2, DNMT3A, TP53, SF3B1, SRSF2, and U2AF1, a list that is likely not exhaustive. While we await additional research on the mechanistic consequences of these aberrations, retrospective studies are already looking into the prognostic importance of mutations, or groups of mutations, in patients.…”

“…2 Furthermore, miRNAs released into the circulation after cell death, or in extracellular vesicles, have been identified in a number of different diseases. 3,4 These circulating miRNAs can be measured in the blood, and represent promising new biomarkers for both the diagnosis of disease and the assessment of treatment responses.…”