title: Circulating miR-192 and miR-193b are markers of prediabetes and are modulated by an exercise intervention.
abstract: BACKGROUND
  Diabetes is frequently diagnosed late, when the development of complications is almost inevitable, decreasing the quality of life of patients. However, early detection of affected individuals would allow the implementation of timely and effective therapies.
  
  
  OBJECTIVE
  Here we set to describe the profile of circulating microRNAs (miRNAs) in prediabetic patients with the intention of identifying novel diagnostic and therapeutic tools.
  
  
  METHODS
  We used real-time RT-PCR to measure the abundance of 176 miRNAs in serum of a cohort of 92 control and prediabetic individuals with either impaired fasting glucose or impaired glucose tolerance, as well as newly diagnosed diabetic patients. We validated the results in a second cohort of control and prediabetic subjects undergoing a therapeutic exercise intervention, as well as in a mouse model of glucose intolerance.
  
  
  RESULTS
  We identified two miRNAs, miR-192 and miR-193b, whose abundance is significantly increased in the prediabetic state but not in diabetic patients. Strikingly, these miRNAs are also increased in plasma of glucose-intolerant mice. Moreover, circulating levels of miR-192 and miR-193b return to baseline in both prediabetic humans and glucose-intolerant mice undergoing a therapeutic intervention consisting in chronic exercise, which succeeded in normalizing metabolic parameters.
  
  
  CONCLUSIONS
  Our data show that the pattern of circulating miRNAs is modified by defects in glucose metabolism in a similar manner in mice and humans. This circulating miRNA signature for prediabetes could be used as a new diagnostic tool, as well as to monitor response to intervention.
authors.affiliation: Diabetes and Obesity Research Laboratory (M.P., L.B., Y.E., A.G.-F., S.C., S.M., P.M.G.-R., J.-M.S., A.N.), Institut d'Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain; Biomedical Research Center in Diabetes and Associated Metabolic Disorders (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas) (M.P., L.B., Y.E., A.G.-F., S.C., S.M., P.M.G.-R., J.-M.S., A.N.), 08036 Barcelona, Spain; Department of Endocrinology (E.G.-B.), Hospital Clínic, 08036 Barcelona, Spain; and Department of Physiological Sciences (R.C.), and National Institute of Physical Education of Catalonia (J.A.C.), University of Barcelona, 08038 Barcelona, Spain.
authors.forename: Marcelina
authors.initials: M
authors.lastname: Párrizas
authors.forename: Laura
authors.initials: L
authors.lastname: Brugnara
authors.forename: Yaiza
authors.initials: Y
authors.lastname: Esteban
authors.forename: Alba
authors.initials: A
authors.lastname: González-Franquesa
authors.forename: Sílvia
authors.initials: S
authors.lastname: Canivell
authors.forename: Serafín
authors.initials: S
authors.lastname: Murillo
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gordillo-Bastidas
authors.forename: Roser
authors.initials: R
authors.lastname: Cussó
authors.forename: Joan A
authors.initials: JA
authors.lastname: Cadefau
authors.forename: Pablo M
authors.initials: PM
authors.lastname: García-Roves
authors.forename: Joan-Marc
authors.initials: JM
authors.lastname: Servitja
authors.forename: Anna
authors.initials: A
authors.lastname: Novials
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D015444:Exercise / Q000502:physiology; D005081:Exercise Therapy; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011236:Prediabetic State / Q000097:blood* / Q000235:genetics / Q000628:therapy*; D059467:Transcriptome
chemical_list: D015415:Biomarkers; C546783:MIRN192 microRNA, human; C546818:MIRN193 microRNA, human; D035683:MicroRNAs