title: Circulating levels of microRNA from children with newly diagnosed type 1 diabetes and healthy controls: evidence that miR-25 associates to residual beta-cell function and glycaemic control during disease progression.
abstract: This study aims to identify key miRNAs in circulation, which predict ongoing beta-cell destruction and regeneration in children with newly diagnosed Type 1 Diabetes (T1D). We compared expression level of sera miRNAs from new onset T1D children and age-matched healthy controls and related the miRNAs expression levels to beta-cell function and glycaemic control. Global miRNA sequencing analyses were performed on sera pools from two T1D cohorts (n = 275 and 129, resp.) and one control group (n = 151). We identified twelve upregulated human miRNAs in T1D patients (miR-152, miR-30a-5p, miR-181a, miR-24, miR-148a, miR-210, miR-27a, miR-29a, miR-26a, miR-27b, miR-25, miR-200a); several of these miRNAs were linked to apoptosis and beta-cell networks. Furthermore, we identified miR-25 as negatively associated with residual beta-cell function (est.: -0.12, P = 0.0037), and positively associated with glycaemic control (HbA1c) (est.: 0.11, P = 0.0035) 3 months after onset [corrected]. In conclusion this study demonstrates that miR-25 might be a "tissue-specific" miRNA for glycaemic control 3 months after diagnosis in new onset T1D children and therefore supports the role of circulating miRNAs as predictive biomarkers for tissue physiopathology and potential intervention targets.
authors: Department of Pediatrics, Herlev Hospital, 2730 Herlev, Denmark. lnie0342@regionh.dk
authors: Lotte B
authors: LB
authors: Nielsen
authors: Cheng
authors: C
authors: Wang
authors: Kaspar
authors: K
authors: Sørensen
authors: Claus H
authors: CH
authors: Bang-Berthelsen
authors: Lars
authors: L
authors: Hansen
authors: Marie-Louise M
authors: ML
authors: Andersen
authors: Philip
authors: P
authors: Hougaard
authors: Anders
authors: A
authors: Juul
authors: Chen-Yu
authors: CY
authors: Zhang
authors: Flemming
authors: F
authors: Pociot
authors: Henrik B
authors: HB
authors: Mortensen
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D003718:Denmark; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D012074:Remission Induction; D017422:Sequence Analysis, DNA; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; C543351:MIRN25 microRNA, human; D035683:MicroRNAs