Discussion
inflammation, T2D, microvascular dysfunction, CAD
BLOOD, INFLAMMATION, EVENTS, DISEASES, CAD
The beneficial effects of SGLT-2i in reducing the incidence of CV events and HF are well documented, but the mechanisms by which they exert these effects are still debated [The present study yielded important new findings: (1) the results demonstrate that 4 week treatment with dapagliflozin significantly reduced both thickness and FDG uptake in EAT (19% and 21.6% respectively); (2) this is the first study to demonstrate a selective effect of SGLT-2i on EAT compared to other visceral and subcutaneous adipose tissue depots; (3) the 21.6% reduction in EAT FDG uptake parallels the 30% improvement in myocardial flow reserve previously described [In line with previous studies, we saw a significant 19% reduction in EAT thickness [The EAT is the most metabolically active adipose tissue [Moreover, we are the first to find a 21.6% reduction in EAT SUV, which parallels the 30% improvement in myocardial flow reserve previously described [Adipose tissue and its proinflammatory state are known risk factors for CV diseases in T2D. In particular, inflammation of EAT, which anatomically is in direct contact with the myocardium [We recently demonstrated that a 4 week treatment with the SGLT-2i dapagliflozin can significantly reduce resting myocardial blood flow leading to an increase in myocardial flow reserve in patients with T2D and stable CAD [Since EAT and the myocardium share the same microcirculation [Further, the interpretation of these results should consider that FDG PET/CT scan was performed during a hyperinsulinemic euglycemic clamp. Blood supply (i.e., myocardial blood flow in our study) has been described as an important factor for the regulation of in vivo insulin-mediated glucose uptake in both subcutaneous and visceral fat [We can speculate that SGLT-2i treatment improves the anti-inflammatory role of EAT, alleviating microvascular dysfunction, which may explain the improvement in myocardial flow reserve described in our previous report [