Ricerc@Sapienza

Diabetes mellitus (DM) is associated with excess mortality, that is mainly, though not exclusively attributable to increased cardiovascular disease (CVD) risk. Unfortunately, such increased risk is not accurately estimated by the multivariable prediction models based upon traditional CVD risk factors. There is, therefore, the need to identify novel biomarkers able to improve the performance of existing algorithms. Recently, attention has been focused on circulating microRNAs (miRNAs).
This project is aimed at evaluating the association of circulating miRNAs with a composite endpoint (all-cause mortality, nonfatal acute myocardial infarction, nonfatal stroke) in patients with type 2 DM (T2DM) from the Sapienza University Mortality and Morbidity Event Rate (SUMMER) Study in Diabetes.
The SUMMER Study in Diabetes is an observational, prospective, multicenter, cohort study comprising 5,000 T2DM patients recruited in the years 2014-2018, who will be followed for at least 5 years. At baseline, traditional CVD risk factors have been assessed, together with prevalence of CVD events, nephropathy and retinopathy. Based on the present follow-up duration and a preliminary estimate of 3% yearly incidence rate of the composite outcome, by June 30, 2019 315 cases will be collected and matched with 315 controls using a propensity score matching for the UKPDS risk score variables. The entire mirnome will be analyzed in a "discovery" case-control sample (n=24 each) by nest generation sequencing. Then, the 10 most dysregulated miRNAs (plus 6 miRNA reported to be associated with myocardial infarction in the general population) will be validated in a "validation" nested case-control sample (n=315 each) by qRT-PCR.
This project is expected to provide evidence of an association between individual miRNAs and the composite CVD outcome. This information will allow improving CVD risk prediction in T2DM patients and eventually indicate new research directions and future therapeutic strategies.