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Diabetologia. 2017 Aug;60(8):1409-1422. doi: 10.1007/s00125-017-4294-3. Epub 2017 May 12.

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

Author information

1
Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, 1450 NW 10th Avenue, Miami, FL, 33136, USA.
2
Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA.
3
Department of Epidemiology and Public Health Sciences, Division of Biostatistics, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA.
4
Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, 1450 NW 10th Avenue, Miami, FL, 33136, USA. apuglies@med.miami.edu.
5
Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA. apuglies@med.miami.edu.
6
Department of Microbiology and Immunology, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA. apuglies@med.miami.edu.

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.

KEYWORDS:

Clinical science; Microarray; Prediction and prevention of type 1 diabetes

PMID:
28500393
PMCID:
PMC5839115
DOI:
10.1007/s00125-017-4294-3
[Indexed for MEDLINE]
Free PMC Article

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