Nutrient sensing pathway genes expression dysregulated in patients with T2DM and coronary artery disease

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder and its prevalence is rapidly increasing worldwide. Patients with T2DM suffer from an increased risk of vascular complications. Of these, the development of coronary artery disease (CAD) causes the most mortality in patients with T2DM, however, its underlying molecular mechanisms are not fully understood. Nutrient sensing pathways which play a key role in sensing cellular energy and nutrients levels are reported to dysregulated in metabolic disease like T2DM. The aim of this study was to investigate the expression levels of nutrient sensing genes including SIRT1, PRKAB1, PRKAB2 and mTOR in CAD⁺ versus CAD^-T2DM patients.

Sixty-five people with T2DM who referred to Tehran heart center were participated in this study. Based on coronary angiography data these individuals were classified into two groups: CAD⁺ T2DM (n = 34) and CAD^-T2DM (n = 31). Peripheral blood mononuclear cells were isolated from these patients and the expression levels of genes were evaluated by RT-qPCR.

Significant down-regulations of the SIRT1 (3.1-fold, p = 0.0013) and PRKAB1 (3.5-fold, p = 0.0001) mRNA expression were observed in CAD⁺ T2DM group in comparison with CAD^-T2DM patients. Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curve was 0.8529 (p = 0.0001) and 0.7078 (p = 0.004) for PRKAB1 and SIRT1 respectively.

Our results suggest that the dysregulation of genes involved in nutrient sensing pathway may be associated with the pathogenesis of CAD in patients with T2DM. Furthermore, the expression levels of these genes could be consider as potential biomarkers.