Abstract
BackgroundAccumulation of epicardial fat (EF) is associated with increased cardio-metabolic risks and coronary events, independently of traditional cardiovascular risk factors. Therefore, the reduction of EF volume (EFV) may be associated with reduced cardio-metabolic risks and future cardiovascular events. Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce body fat including visceral fat and cardiovascular events in patients with type 2 diabetes. However, it has still been unknown whether SGLT2 inhibitors can reduce EFV.MethodsType 2 diabetic patients with HbA1c 6.5–9.0% and body mass index (BMI, kg/m2) ≥25.0 were enrolled in this single arm pilot study. Participants were administered luseogliflozin 2.5 mg daily and the dosage was tolerated to be increased up to 5.0 mg daily. EFV [median (interquartile range), cm3] was measured by magnetic resonance imaging. Primary endpoint was the decrease in EFV at 12 weeks. Visceral fat area (VFA, cm2) and liver attenuation index (LAI) measured by the abdominal computed tomography, and skeletal muscle index (SMI) and body fat (%) measured by the whole body dual-energy X-ray absorptiometry were also determined at baseline and at 12 weeks.ResultsNineteen patients (mean age: 55 ± 12 years; 26% female) completed this study. Luseogliflozin treatment significantly reduced EFV at 12 weeks [117 (96–136) to 111 (88–134), p = 0.048]. The body weight, BMI, systolic and diastolic blood pressure, HbA1c, fasting plasma glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, SMI, and body fat were significantly reduced by luseogliflozin at 12 weeks. The reduction of EFV was significantly correlated with the reduction of C-reactive protein (r = 0.493, p = 0.019). Neither VFA nor LAI were significantly reduced by the luseogliflozin treatment. No severe adverse events were observed.ConclusionsOur data suggest that luseogliflozin could reduce the EFV in parallel with the improvement of systemic micro-inflammation and the reduction of body weight in Japanese patients with type 2 diabetes. The reduction of muscle mass after the administration of SGLT2 inhibitors may require a particular attention.Trial registration umin.ac.jp, UMIN000019072
Highlights
Accumulation of epicardial fat (EF) is associated with increased cardio-metabolic risks and coronary events, independently of traditional cardiovascular risk factors
We have focused on the potential of luseogliflozin to improve the abnormal regional fat distribution, especially an excessive accumulation of EF volume (EFV) and we conducted this small-scale pilot study to investigate whether luseogliflozin could reduce the EFV in Japanese patients with type 2 diabetes
Correlation of EFV with markers for body composition and cardio‐metabolic risks As shown in Table 3, the EFV was significantly correlated with the body mass index (BMI), visceral fat area (VFA), total fat mass, and homeostasis model assessment-insulin resistance (HOMA-IR) and tended to be correlated with the subcutaneous fat area (SFA)
Summary
Accumulation of epicardial fat (EF) is associated with increased cardio-metabolic risks and coronary events, independently of traditional cardiovascular risk factors. Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce body fat including visceral fat and cardiovascular events in patients with type 2 diabetes It has still been unknown whether SGLT2 inhibitors can reduce EFV. EFV is associated with cardio-metabolic risks including insulin resistance [10, 11] and type 2 diabetes [12] and both fatal and nonfatal coronary events, independently of traditional cardiovascular risk factors [9]. The authors demonstrate that the degree of both hepatic and epicardial fat accumulations are associated with a cardiac contractile dysfunction in the patients with diabetes Give these findings, the evaluation of EFV may be important to predict future coronary events, especially in obese patients with diabetes
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