Circulating microRNAs from early childhood and adolescence are associated with pre-diabetes at 18 years of age in women from the PMNS cohort

Abstract

A high (20%) prevalence of glucose intolerance at 18-years was seen in women from the Pune Maternal Nutrition Study (PMNS) birth cohort. Here, we provide preliminary longitudinal analyses of circulating microRNAs in normal glucose tolerant (NGT@18y, N=10) and glucose intolerant (N=8) women (ADA criteria) at 6-, 12- and 17-years of their age using discovery analysis (OpenArray™ platform). Machine-learning workflows involving Lasso with bootstrapping/leave-one-out cross-validation (LOOCV) identified microRNAs associated with glucose intolerance at 18-years of age. Several microRNAs, including miR-212-3p, miR-30e-3p and miR-638, stratified glucose-intolerant women from NGT at childhood. Our results suggest that circulating microRNAs in childhood could predict pre-diabetes at 18-years of age. Validation of these findings in males and remaining participants from the PMNS birth cohort will provide a unique opportunity to study novel epigenetic mechanisms in the life-course progression of glucose intolerance and enhance current clinical risk prediction of pre-diabetes and progression to type 2 diabetes.