Circulating miRNA Signatures Associated with Insulin Resistance in Adolescents with Obesity.

PURPOSE: MicroRNAs (miRNAs) are implicated in metabolic changes accompanying progression of obesity, insulin resistance (IR), and metabolic disorders in children. Identifying circulating miRNAs that uniquely associate with these disorders may be useful in early identification and prevention of obesity-related complications. We aimed to identify circulating miRNA signatures that distinguish adolescents with obesity and IR from those with obesity unaccompanied by IR. METHODS: Adolescents (aged 10-17 years) with obesity were recruited from a weight management clinic. Fasting serum samples were obtained from 33 participants. A total of 179 miRNAs were queried by a quantitative RT-PCR-based miRNA focus panel. Differentially expressed miRNAs were compared between groups using Student's t-test or one-way ANOVA analysis, and the association between IR evaluated by homeostatic model assessment model (HOMA-IR > 4) and body mass index (BMI) status was assessed using Pearson's correlation analysis. RESULTS: We found an expression pattern consisting of 12 elevated miRNAs linked to IR in obese adolescents. miR-30d, -221, and -122 were significantly correlated with clinical and biochemical markers of obesity and IR, suggestive of IR in adolescents at risk. CONCLUSION: Specific signatures of circulating miRNAs reflected metabolic phenotypes and predicted the presence of IR in adolescents with obesity, suggesting that miRNA indicators may identify obesity-associated complications in childhood. Further studies will be needed to understand cause versus effect and the mechanisms by which IR status links to changes in blood miRNA profiles.