Postpartum Circulating MicroRNAs Can Predict the Development of Type 2 Diabetes in Women with Previous Gestational Diabetes

Type 2 diabetes (T2D) is a major cause of morbidity and death worldwide. Women with gestational diabetes mellitus (GDM) have a seven-fold higher risk of developing T2D later in life. However, accurate methods for post-partum T2D risk stratification of GDM women, are lacking. MicroRNAs are now well recognised as circulating biomarkers or mediators of metabolic disease. We aimed to determine if post-partum circulating microRNAs can predict the devolvement of T2D in women with previous GDM. Participants were part of the GDM follow-up program at the Mercy Hospital for Women, Australia. Plasma samples were collected at 12-week post-partum from 103 women following an index GDM pregnancy. Women were followed for 10 years to assess development of T2D. In a discovery approach, we measured 754 miRNAs in plasma from T2D non-progressors (N=11) and in T2D progressors (N=10) using TaqMan-based real time PCR on an OpenArray platform. Data were analysed using penalised logistic regression followed by bootstrapping. Top 15 miRNAs with high frequencies in this discovery bootstrap analysis were selected for validation in the remaining samples (N=82; 71 non-progressors and 11 progressors). Validation data were normalized to spike-in control (ath-miR-172a). Four miRNAs (miR-543, miR-410, miR-491 and miR-369-3p) were significantly dysregulated (p<0.05) between progressors and non-progressors to T2D, identifying these as risk factors. In a clinical model of prediction of T2D that included six traditional risk factors (age, BMI, pregnancy fasting glucose, post-OGTT change, cholesterol and triglycerides), the addition of these four circulating microRNA biomarkers measured at 12-weeks post-partum improved the prediction of future T2D from traditional AUC=0.8259 (95% CI: 0.68-0.9717) to an AUC= 0.9155 (95% CI: 0.8307-1). Replication of our findings in other cohorts is merited. Improved prediction will be beneficial in facilitating early intervention for T2D. Disclosure M. Joglekar: None. W.K. Wong: None. F. Ema: None. H.M. Georgiou: None. A. Hardikar: None. M. Lappas: None.