Ricerc@Sapienza

Type 2 diabetes (T2D) mellitus is associated with an increased fracture risk, independently of bone mineral density (BMD). A reduction in bone quality might explain this discrepancy in T2D. Appropriate exercise results in bone mass maintenance, bone formation and improved bone strength. miRNAs play a role in the pathogenesis of T2DM and diabetic bone disease. Changes in miRNA levels may precede changes in bone turnover markers (BTMs), making them more sensitive markers of bone disease.
This study aims to identify miRNA signatures of exercise training that modulate the expression of specific genes regulating osteoclast and osteoblast function in T2D, thus impacting bone quality.
In step 1, 30 trained and 30 untrained T2D patients, will be selected from patients participating in the SWEET BONE Trial. Patients, previously randomized to either the Exercise group or the Control group, will be evaluated at the end of the 24-month follow-up of the trial. Patients¿ sera will be used in a screening analysis of the entire miRNome performed by Next Generation Sequencing (NGS). Relevant up/down-regulated miRNAs will then be tested and validated by quantitative Real Time-PCR (RT-PCR). The identified circulating c-miRNA will be correlated with measures of bone quality, BTMs, vertebral fractures, cardiorespiratory and muscular fitness, and body composition.
Should the identified c-miRNAs be associated with clinical outcomes, i.e. measures of bone quality and strength (and number of fractures), we would generate the hypothesis that c-miRNAs are mediators of the effects of exercise training on bone quality and fracture risk in T2D. Further, in vitro studies will be necessary to test this hypothesis in controlled, experimental conditions.