PMID- 30513818 OWN - NLM STAT- MEDLINE DCOM- 20190131 LR - 20221207 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 10 IP - 12 DP - 2018 Dec 2 TI - Thromboxane-Dependent Platelet Activation in Obese Subjects with Prediabetes or Early Type 2 Diabetes: Effects of Liraglutide- or Lifestyle Changes-Induced Weight Loss. LID - 10.3390/nu10121872 [doi] LID - 1872 AB - Thromboxane (TX)-dependent platelet activation and lipid peroxidation, as reflected in vivo by the urinary excretion of 11-dehydro-TXB(2) and 8-iso-prostaglandin (PG)F(2alpha), play a key role in atherothrombosis in obesity and type 2 diabetes mellitus (T2DM) since the earlier stages. Thirty-five metformin-treated obese subjects with prediabetes or newly-diagnosed T2DM were randomized to the glucagon-like peptide receptor agonist (GLP-RA) liraglutide (1.8 mg/day) or lifestyle counseling until achieving a comparable weight loss (-7% of initial body weight), to assess whether changes in subcutaneous (SAT) and visceral (VAT) adipose tissue distribution (MRI), insulin sensitivity (Matsuda Index) and beta-cell performance (multiple sampling OGTT beta-index), with either intervention, might affect TX-dependent platelet activation, lipid peroxidation and inflammation. At baseline, Ln-8-iso-PGF(2alpha) (Beta = 0.31, p = 0.0088), glycosylated hemoglobin (HbA1c) (Beta = 2.64, p = 0.0011) Ln-TNF-alpha (Beta = 0.58, p = 0.0075) and SAT (Beta = 0.14, p = 0.044) were significant independent predictors of 11-dehydro-TXB(2). After achievement of the weight loss target, a comparable reduction in U-11-dehydro-TXB(2) (between-group p = 0.679) and 8-iso-PGF-(2alpha) (p = 0.985) was observed in both arms in parallel with a comparable improvement in glycemic control, insulin sensitivity, SAT, high-sensitivity C-reactive protein (hs-CRP). In obese patients with initial impairment of glucose metabolism, the extent of platelet activation is related to systemic inflammation, isoprostane formation and degree of glycemic control and abdominal SAT. Successful weight loss, achieved with either lifestyle changes or an incretin-based therapy, is associated with a significant reduction in lipid peroxidation and platelet activation. FAU - Simeone, Paola AU - Simeone P AD - Department of Medicine and Aging and Center of Aging Science and Translational Medicine (CESI-Met), University of Chieti, 66100 Chieti, Italy. paolagsimeone@gmail.com. FAU - Liani, Rossella AU - Liani R AD - Department of Medicine and Aging and Center of Aging Science and Translational Medicine (CESI-Met), University of Chieti, 66100 Chieti, Italy. rossellaliani@yahoo.it. FAU - Tripaldi, Romina AU - Tripaldi R AD - Department of Medicine and Aging and Center of Aging Science and Translational Medicine (CESI-Met), University of Chieti, 66100 Chieti, Italy. romina.tripaldi@hotmail.it. FAU - Di Castelnuovo, Augusto AU - Di Castelnuovo A AD - Department of Epidemiology and Prevention, IRCCS NEUROMED, Via dell'Elettronica, 86077 Pozzilli, Italy. dicastel@ngi.it. FAU - Guagnano, Maria Teresa AU - Guagnano MT AD - Department of Medicine and Aging and Center of Aging Science and Translational Medicine (CESI-Met), University of Chieti, 66100 Chieti, Italy. guagnano@unich.it. FAU - Tartaro, Armando AU - Tartaro A AD - Department of Neuroscience & Imaging, University of Chieti, 66100 Chieti, Italy. armando.tartaro@gmail.com. FAU - Bonadonna, Riccardo C AU - Bonadonna RC AD - Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy. bonadonna.riccardo@fastwebnet.it. AD - Division of Endocrinology and Metabolic Diseases, Azienda Ospedaliera Universitaria of Parma, 43126 Parma, Italy. bonadonna.riccardo@fastwebnet.it. FAU - Federico, Virginia AU - Federico V AD - Clinical Pathology, Chieti Hospital, 66100 Chieti, Italy. virgin83@virgilio.it. FAU - Cipollone, Francesco AU - Cipollone F AD - Department of Medicine and Aging and Center of Aging Science and Translational Medicine (CESI-Met), University of Chieti, 66100 Chieti, Italy. francesco.cipollone@unich.it. FAU - Consoli, Agostino AU - Consoli A AD - Department of Medicine and Aging and Center of Aging Science and Translational Medicine (CESI-Met), University of Chieti, 66100 Chieti, Italy. consoli@unich.it. FAU - Santilli, Francesca AU - Santilli F AD - Department of Medicine and Aging and Center of Aging Science and Translational Medicine (CESI-Met), University of Chieti, 66100 Chieti, Italy. francesca.santilli@unich.it. LA - eng GR - 2010JS3PMZ/Ministero dell'Istruzione, dell'Universita e della Ricerca/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20181202 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin A) RN - 0 (Thromboxanes) RN - 27415-26-5 (8-epi-prostaglandin F2alpha) RN - 54397-85-2 (Thromboxane B2) RN - 67910-12-7 (11-dehydro-thromboxane B2) RN - 839I73S42A (Liraglutide) RN - B7IN85G1HY (Dinoprost) SB - IM MH - Blood Glucose/analysis MH - Diabetes Mellitus/blood/*therapy MH - Diabetes Mellitus, Type 2/blood/therapy MH - Diet MH - Dinoprost/analogs & derivatives/urine MH - Exercise MH - Female MH - Glycated Hemoglobin/analysis MH - Humans MH - *Life Style MH - Lipid Peroxidation MH - Liraglutide/*therapeutic use MH - Longitudinal Studies MH - Male MH - Middle Aged MH - Obesity/blood/complications/*therapy MH - Platelet Activation/*physiology MH - Prediabetic State/blood/therapy MH - Thromboxane B2/analogs & derivatives/urine MH - Thromboxanes/*physiology MH - Weight Loss PMC - PMC6315606 OTO - NOTNLM OT - adipose tissue distribution OT - diabetes mellitus OT - liraglutide OT - obesity OT - oxidative stress OT - platelet activation OT - weight loss COIS- Consoli received lecture fees and fees for serving on advisory boards from Novo Nordisk, Eli Lilly, AstraZeneca, Sanofi Aventis, Merck Sharp & Dohme, and Takeda and grant support to his institution from Novo Nordisk. No other potential conflicts of interest relevant to this article were reported. EDAT- 2018/12/06 06:00 MHDA- 2019/02/01 06:00 PMCR- 2018/12/01 CRDT- 2018/12/06 06:00 PHST- 2018/11/02 00:00 [received] PHST- 2018/11/20 00:00 [revised] PHST- 2018/11/26 00:00 [accepted] PHST- 2018/12/06 06:00 [entrez] PHST- 2018/12/06 06:00 [pubmed] PHST- 2019/02/01 06:00 [medline] PHST- 2018/12/01 00:00 [pmc-release] AID - nu10121872 [pii] AID - nutrients-10-01872 [pii] AID - 10.3390/nu10121872 [doi] PST - epublish SO - Nutrients. 2018 Dec 2;10(12):1872. doi: 10.3390/nu10121872.