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

Abstract

With type 2 diabetes presenting at younger ages, there is a growing need to identify biomarkers of future glucose intolerance. A high (20%) prevalence of glucose intolerance at 18 years was seen in women from the Pune Maternal Nutrition Study (PMNS) birth cohort. We investigated the potential of circulating microRNAs in risk stratification for future pre-diabetes in these women. 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 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, longitudinally assessed over 17 years of life, are dynamic biomarkers associated with and predictive of 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.

Neonatal Adiposity Is Associated with microRNAs in Adipocyte-Derived Extracellular Vesicles in Maternal and Cord Blood

“…have been associated with lipid accumulation and adipocyte differentiation in low-birth-weight adult humans 32 , and with increased subcutaneous adipose tissue in ammation 33 , respectively. In an earlier study we found that hsa-miR-212-3p is associated with increased risk of glucose intolerance in young adult PMNS female participants 34 . Fetal miRNAs hsa-miR-204-3p (FC=9.87 in adipose group) and hsa-miR-342-3p (FC=-0.098) have been shown to promote adipogenic differentiation of mesenchymal stem cells 35,36 and hsa-miR-15a (FC= -0.912) to regulate intramuscular adipogenesis 37 .…”

MicroRNAs in adipocyte-derived extracellular vesicles in maternal and cord blood are related to neonatal adiposity

“…Maternal miRNAs hsa-miR-483-3p (FC= 3.99 in adipose group) and hsa-miR-212-3p (FC=0.282 in adipose group) have been associated with lipid accumulation and adipocyte differentiation in low-birth-weight adult humans 32 , and with increased subcutaneous adipose tissue inflammation 33 , respectively. In an earlier study we found that hsa-miR-212-3p is associated with increased risk of glucose intolerance in young adult PMNS female participants 34 . Fetal miRNAs hsa-miR-204-3p (FC=9.87 in adipose group) and hsa-miR-342-3p (FC=-0.098) have been shown to promote adipogenic differentiation of mesenchymal stem cells 35,36 and hsa-miR-15a (FC= −0.912) to regulate intramuscular adipogenesis 37 .…”

Metabolic stress-induced human beta-cell death is mediated by increased intracellular levels of adenosine

“…Instead, we chose to study hsa-mir-30e-3p, a member of the miRNA-30 family, which is highly expressed in beta-cells, according to the same database. Interestingly, members of the miRNA-30 family have been reported to affect beta-cell insulin production, apoptosis and transdifferentiation to alpha-cells, and to function as biomarkers for pre-diabetes ( 30 – 32 ). We observed that blocking the binding of hsa-mir-30e-3p to ADA1 mRNA resulted in reduced intracellular adenosine levels, both at control conditions and in cells exposed to palmitate + high glucose ( Figure 8A ).…”