Journal Article

Dapagliflozin treatment is associated with a reduction of epicardial adipose tissue thickness and epicardial glucose uptake in human type 2 diabetes

Sorice, Gian Pio, Giordano, Alessandro, Cinti, Francesca, Leccisotti, Lucia, Lorusso, Margherita, Giaccari, Andrea, Capotosti, Amedeo, Mezza, Teresa, Indovina, Luca, Iozzo, Patricia, Guarneri, Andrea, Capece, Umberto, Crea, Filippo, Ferraro, Pietro Manuel, Gugliandolo, Shawn, Guzzardi, Maria Angela, Morciano, Cassandra, D’Amario, Domenico

2023

Overview

Objective We recently demonstrated that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) leads to an increase in myocardial flow reserve in patients with type 2 diabetes (T2D) with stable coronary artery disease (CAD). The mechanism by which this occurs is, however, unclear. One of the risk factors for cardiovascular disease is inflammation of epicardial adipose tissue (EAT). Since the latter is often increased in type 2 diabetes patients, it could play a role in coronary microvascular dysfunction. It is also well known that SGLT-2i modify adipose tissue metabolism. We aimed to investigate the effects of the SGLT-2i dapagliflozin on metabolism and visceral and subcutaneous adipose tissue thickness in T2D patients with stable coronary artery disease and to verify whether these changes could explain observed changes in myocardial flow. Methods We performed a single-center, prospective, randomized, double-blind, controlled clinical trial with 14 T2D patients randomized 1:1 to SGLT-2i dapagliflozin (10 mg daily) or placebo. The thickness of visceral (epicardial, mediastinal, perirenal) and subcutaneous adipose tissue and glucose uptake were assessed at baseline and 4 weeks after treatment initiation by 2-deoxy-2-[ 18 F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography during hyperinsulinemic euglycemic clamp. Results The two groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, BMI, renal and heart function). Dapagliflozin treatment significantly reduced EAT thickness by 19% (p = 0.03). There was a significant 21.6% reduction in EAT glucose uptake during euglycemic hyperinsulinemic clamp in the dapagliflozin group compared with the placebo group (p = 0.014). There were no significant effects on adipose tissue thickness/metabolism in the other depots explored. Conclusions SGLT-2 inhibition selectively reduces EAT thickness and EAT glucose uptake in T2D patients, suggesting a reduction of EAT inflammation. This could explain the observed increase in myocardial flow reserve, providing new insights into SGLT-2i cardiovascular benefits.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Adipose tissue / Angiology / Angioplasty / Antidiabetics / Body fat / Cardiology / Cardiovascular disease / Cardiovascular diseases / Clinical trials / Computed tomography / Coronary artery disease / Coronary vessels / Diabetes / Diabetes mellitus (non-insulin dependent) / Epicardial adipose tissue / Glucose / Heart diseases / Inflammation / Medical imaging / Medicine / Medicine & Public Health / Metabolism / Microvascular dysfunction / Microvasculature / Nonparametric statistics / Pathogenesis / Patients / PET / Placebos / Positron emission tomography / Renal function / Risk factors / SGLT-2i / Sodium-glucose cotransporter / Statistical analysis / Tomography / Vein & artery diseases