| Autor: |
Pofi R; Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy., Giannetta E; Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy., Feola T; Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.; Neuroendocrinology, Neuromed Institute, IRCCS, 86077 Pozzilli (IS), Italy., Galea N; Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy., Barbagallo F; Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy., Campolo F; Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy., Badagliacca R; Department of Cardiovascular and Respiratory Diseases, Sapienza University of Rome, 00161 Rome, Italy., Barbano B; Department of Translational and Precision Medicine, Sapienza University of Rome, 00161 Rome, Italy., Ciolina F; Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, 00161 Rome, Italy., Defeudis G; Unit of Endocrinology and Diabetes, Department of Medicine, University Campus Bio-Medico di Roma, 00161 Rome, Italy., Filardi T; Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy., Sesti F; Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy., Minnetti M; Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy., Vizza CD; Department of Cardiovascular and Respiratory Diseases, Sapienza University of Rome, 00161 Rome, Italy., Pasqualetti P; Medical Statistics and Information Technology, AFaR, Fatebenefratelli Hospital, 00161 Rome, Italy., Caboni P; Department of Life and Environmental Sciences, University of Cagliari, 09124 Cagliari, Italy., Carbone I; Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, 00161 Rome, Italy., Francone M; Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, 00161 Rome, Italy., Catalano C; Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, 00161 Rome, Italy., Pozzilli P; Unit of Endocrinology and Diabetes, Department of Medicine, University Campus Bio-Medico di Roma, 00161 Rome, Italy., Lenzi A; Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy., Venneri MA; Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy., Gianfrilli D; Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy., Isidori AM; Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy. |
| Abstrakt: |
Cyclic GMP-phosphodiesterase type 5 (PDE5) inhibition has been shown to counteract maladaptive cardiac changes triggered by diabetes in some but not all studies. We performed a single-center, 20-week, double-blind, randomized, placebo-controlled trial (NCT01803828) to assess sex differences in cardiac remodeling after PDE5 inhibition in patients with diabetic cardiomyopathy. A total of 122 men and women (45 to 80 years) with long-duration (>3 years) and well-controlled type 2 diabetes mellitus (T2DM; HbA1c < 86 mmol/mol) were selected according to echocardiographic signs of cardiac remodeling. Patients were randomly assigned (1:1) to placebo or oral tadalafil (20 mg, once daily). The primary outcome was to evaluate sex differences in cardiac torsion change. Secondary outcomes were changes in cardiovascular, metabolic, immune, and renal function. At 20 weeks, the treatment-by-sex interaction documented an improvement in cardiac torsion (-3.40°, -5.96; -0.84, P = 0.011) and fiber shortening (-1.19%, -2.24; -0.14, P = 0.027) in men but not women. The primary outcome could not be explained by differences in cGMP concentrations or tadalafil pharmacodynamics. In both sexes, tadalafil improved hsa-miR-199-5p expression, biomarkers of cardiovascular remodeling, albuminuria, renal artery resistive index, and circulating Klotho concentrations. Immune cell profiling revealed an improvement in low-grade chronic inflammation: Classic CD14 ++ CD16 - monocytes reduced, and Tie2 + monocytes increased. Nine patients (14.5%) had minor adverse reactions after tadalafil administration. Continuous PDE5 inhibition could offer a strategy to target cardiorenal complications of T2DM, with sex- and tissue-specific responses. Further studies are needed to confirm Klotho and hsa-miR-199-5p as markers for T2DM complications. |
