Association of serum microRNAs with islet autoimmunity, disease progression and metabolic impairment in relatives at risk of type 1 diabetes
| العنوان: | Association of serum microRNAs with islet autoimmunity, disease progression and metabolic impairment in relatives at risk of type 1 diabetes |
|---|---|
| المؤلفون: | Gloria Allende, Alberto Pugliese, Isaac Snowhite, Jay M. Sosenko, Shari Messinger Cayetano, Ricardo L. Pastori |
| المصدر: | Diabetologia. 60:1409-1422 |
| بيانات النشر: | Springer Science and Business Media LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Adolescent, Microarray, Endocrinology, Diabetes and Metabolism, Autoimmunity, 030209 endocrinology & metabolism, Disease, Biology, medicine.disease_cause, Article, Islets of Langerhans, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Child, Autoantibodies, Retrospective Studies, Type 1 diabetes, Autoantibody, Infant, Retrospective cohort study, Glucose Tolerance Test, medicine.disease, MicroRNAs, Diabetes Mellitus, Type 1, 030104 developmental biology, ROC Curve, Child, Preschool, Immunology, Cohort, Female |
| الوصف: | 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. 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. 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. 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. |
| تدمد: | 1432-0428 0012-186X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a1c91eb769c85b49ddff551a16c5d919Test https://doi.org/10.1007/s00125-017-4294-3Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a1c91eb769c85b49ddff551a16c5d919 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14320428 0012186X |
|---|