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Erschienen in: Diabetologia 8/2017

12.05.2017 | Article

Association of serum microRNAs with islet autoimmunity, disease progression and metabolic impairment in relatives at risk of type 1 diabetes

verfasst von: Isaac V. Snowhite, Gloria Allende, Jay Sosenko, Ricardo L. Pastori, Shari Messinger Cayetano, Alberto Pugliese

Erschienen in: Diabetologia | Ausgabe 8/2017

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Abstract

Aims/hypothesis

MicroRNAs (miRNAs) are key regulators of gene expression and novel biomarkers for many diseases. We investigated the hypothesis that serum levels of some miRNAs would be associated with islet autoimmunity and/or progression to type 1 diabetes.

Methods

We measured levels of 93 miRNAs most commonly detected in serum. This retrospective cohort study included 150 autoantibody-positive and 150 autoantibody-negative family-matched siblings enrolled in the TrialNet Pathway to Prevention Study. This was a young cohort (mean age = 11 years), and most autoantibody-positive relatives were at high risk because they had multiple autoantibodies, with 39/150 (26%, progressors) developing type 1 diabetes within an average 8.7 months of follow-up. We analysed miRNA levels in relation to autoantibody status, future development of diabetes and OGTT C-peptide and glucose indices of disease progression.

Results

Fifteen miRNAs were differentially expressed when comparing autoantibody-positive/negative siblings (range −2.5 to 1.3-fold). But receiver operating characteristic (ROC) analysis indicated low specificity and sensitivity. Seven additional miRNAs were differentially expressed among autoantibody-positive relatives according to disease progression; ROC returned significant AUC values and identified miRNA cut-off levels associated with an increased risk of disease in both cross-sectional and survival analyses. Levels of several miRNAs showed significant correlations (r values range 0.22–0.55) with OGTT outcomes. miR-21-3p, miR-29a-3p and miR-424-5p had the most robust associations.

Conclusions/interpretation

Serum levels of selected miRNAs are associated with disease progression and confer additional risk of the development of type 1 diabetes in young autoantibody-positive relatives. Further studies, including longitudinal assessments, are warranted to further define miRNA biomarkers for prediction of disease risk and progression.
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Metadaten
Titel
Association of serum microRNAs with islet autoimmunity, disease progression and metabolic impairment in relatives at risk of type 1 diabetes
verfasst von
Isaac V. Snowhite
Gloria Allende
Jay Sosenko
Ricardo L. Pastori
Shari Messinger Cayetano
Alberto Pugliese
Publikationsdatum
12.05.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Diabetologia / Ausgabe 8/2017
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-017-4294-3

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