PMID- 35704597
OWN - NLM
STAT- MEDLINE
DCOM- 20220617
LR  - 20220803
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Linking)
VI  - 14
IP  - 649
DP  - 2022 Jun 15
TI  - Sex-specific effects of daily tadalafil on diabetic heart kinetics in RECOGITO, a 
      randomized, double-blind, placebo-controlled trial.
PG  - eabl8503
LID - 10.1126/scitranslmed.abl8503 [doi]
AB  - 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 degrees , -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.
FAU - Pofi, Riccardo
AU  - Pofi R
AUID- ORCID: 0000-0001-7808-5735
AD  - Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, 
      Italy.
FAU - Giannetta, Elisa
AU  - Giannetta E
AD  - Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, 
      Italy.
FAU - Feola, Tiziana
AU  - Feola T
AUID- ORCID: 0000-0003-1066-0064
AD  - Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, 
      Italy.
AD  - Neuroendocrinology, Neuromed Institute, IRCCS, 86077 Pozzilli (IS), Italy.
FAU - Galea, Nicola
AU  - Galea N
AUID- ORCID: 0000-0003-4708-5120
AD  - Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, 
      Italy.
FAU - Barbagallo, Federica
AU  - Barbagallo F
AUID- ORCID: 0000-0002-2972-370X
AD  - Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, 
      Italy.
FAU - Campolo, Federica
AU  - Campolo F
AD  - Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, 
      Italy.
FAU - Badagliacca, Roberto
AU  - Badagliacca R
AD  - Department of Cardiovascular and Respiratory Diseases, Sapienza University of 
      Rome, 00161 Rome, Italy.
FAU - Barbano, Biagio
AU  - Barbano B
AD  - Department of Translational and Precision Medicine, Sapienza University of Rome, 
      00161 Rome, Italy.
FAU - Ciolina, Federica
AU  - Ciolina F
AUID- ORCID: 0000-0001-5284-3569
AD  - Department of Radiological Sciences, Oncology and Pathology, Sapienza University 
      of Rome, 00161 Rome, Italy.
FAU - Defeudis, Giuseppe
AU  - Defeudis G
AD  - Unit of Endocrinology and Diabetes, Department of Medicine, University Campus 
      Bio-Medico di Roma, 00161 Rome, Italy.
FAU - Filardi, Tiziana
AU  - Filardi T
AUID- ORCID: 0000-0001-5002-0753
AD  - Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, 
      Italy.
FAU - Sesti, Franz
AU  - Sesti F
AUID- ORCID: 0000-0003-3850-627X
AD  - Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, 
      Italy.
FAU - Minnetti, Marianna
AU  - Minnetti M
AUID- ORCID: 0000-0002-9091-2809
AD  - Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, 
      Italy.
FAU - Vizza, Carmine D
AU  - Vizza CD
AUID- ORCID: 0000-0002-3540-4983
AD  - Department of Cardiovascular and Respiratory Diseases, Sapienza University of 
      Rome, 00161 Rome, Italy.
FAU - Pasqualetti, Patrizio
AU  - Pasqualetti P
AUID- ORCID: 0000-0001-5560-1979
AD  - Medical Statistics and Information Technology, AFaR, Fatebenefratelli Hospital, 
      00161 Rome, Italy.
FAU - Caboni, Pierluigi
AU  - Caboni P
AUID- ORCID: 0000-0003-2448-3767
AD  - Department of Life and Environmental Sciences, University of Cagliari, 09124 
      Cagliari, Italy.
FAU - Carbone, Iacopo
AU  - Carbone I
AUID- ORCID: 0000-0003-3108-7527
AD  - Department of Radiological Sciences, Oncology and Pathology, Sapienza University 
      of Rome, 00161 Rome, Italy.
FAU - Francone, Marco
AU  - Francone M
AD  - Department of Radiological Sciences, Oncology and Pathology, Sapienza University 
      of Rome, 00161 Rome, Italy.
FAU - Catalano, Carlo
AU  - Catalano C
AUID- ORCID: 0000-0003-4208-9691
AD  - Department of Radiological Sciences, Oncology and Pathology, Sapienza University 
      of Rome, 00161 Rome, Italy.
FAU - Pozzilli, Paolo
AU  - Pozzilli P
AUID- ORCID: 0000-0001-5090-636X
AD  - Unit of Endocrinology and Diabetes, Department of Medicine, University Campus 
      Bio-Medico di Roma, 00161 Rome, Italy.
FAU - Lenzi, Andrea
AU  - Lenzi A
AD  - Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, 
      Italy.
FAU - Venneri, Mary Anna
AU  - Venneri MA
AUID- ORCID: 0000-0002-0687-8135
AD  - Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, 
      Italy.
FAU - Gianfrilli, Daniele
AU  - Gianfrilli D
AUID- ORCID: 0000-0002-2682-8266
AD  - Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, 
      Italy.
FAU - Isidori, Andrea M
AU  - Isidori AM
AUID- ORCID: 0000-0002-9037-5417
AD  - Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, 
      Italy.
LA  - eng
SI  - ClinicalTrials.gov/NCT01803828
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20220615
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
RN  - 0 (Carbolines)
RN  - 0 (MicroRNAs)
RN  - 0 (Phosphodiesterase 5 Inhibitors)
RN  - 742SXX0ICT (Tadalafil)
RN  - EC 3.1.4.35 (Cyclic Nucleotide Phosphodiesterases, Type 5)
SB  - IM
MH  - Carbolines/pharmacology/therapeutic use
MH  - Cyclic Nucleotide Phosphodiesterases, Type 5
MH  - *Diabetes Mellitus, Type 2/complications/drug therapy
MH  - Double-Blind Method
MH  - *Erectile Dysfunction/drug therapy/etiology
MH  - Female
MH  - Humans
MH  - Kinetics
MH  - Male
MH  - *MicroRNAs
MH  - Penile Erection
MH  - Phosphodiesterase 5 Inhibitors/pharmacology/therapeutic use
MH  - Tadalafil/pharmacology/therapeutic use
MH  - Treatment Outcome
MH  - Ventricular Remodeling
EDAT- 2022/06/16 06:00
MHDA- 2022/06/18 06:00
CRDT- 2022/06/15 14:04
PHST- 2022/06/15 14:04 [entrez]
PHST- 2022/06/16 06:00 [pubmed]
PHST- 2022/06/18 06:00 [medline]
AID - 10.1126/scitranslmed.abl8503 [doi]
PST - ppublish
SO  - Sci Transl Med. 2022 Jun 15;14(649):eabl8503. doi: 10.1126/scitranslmed.abl8503. 
      Epub 2022 Jun 15.