Thromboxane-Dependent Platelet Activation in Obese Subjects with Prediabetes or Early Type 2 Diabetes: Effects of Liraglutide- or Lifestyle Changes-Induced Weight Loss

• Published in: Nutrients Vol. 10; no. 12; p. 1872
• Main Authors: Simeone, Paola, Liani, Rossella, Tripaldi, Romina, Di Castelnuovo, Augusto, Guagnano, Maria Teresa, Tartaro, Armando, Bonadonna, Riccardo C., Federico, Virginia, Cipollone, Francesco, Consoli, Agostino, Santilli, Francesca
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.12.2018; MDPI
• Subjects: adipose tissue; agonists; Antidiabetics; Biosynthesis; Blood platelets; Body fat; Body mass index; C-reactive protein; counseling; Diabetes; excretion; Family medical history; glucagon-like peptide receptors; Glucose; glycemic control; glycosylation; hemoglobin; Hyperglycemia; Inflammation; Insulin resistance; Intervention; islets of Langerhans; lifestyle; Lifestyles; Lipid peroxidation; Lipids; Magnetic resonance imaging; Metabolism; Metabolites; noninsulin-dependent diabetes mellitus; Obesity; Oxidative stress; patients; platelet activation; therapeutics; tissue distribution; Tumor necrosis factor-TNF; Weight control; weight loss; liraglutide; adipose tissue distribution; weight loss; diabetes mellitus; obesity; oxidative stress; platelet activation
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu10121872

Thromboxane (TX)-dependent platelet activation and lipid peroxidation, as reflected in vivo by the urinary excretion of 11-dehydro-TXB2 and 8-iso-prostaglandin (PG)F2α, 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-PGF2α (Beta = 0.31, p = 0.0088), glycosylated hemoglobin (HbA1c) (Beta = 2.64, p = 0.0011) Ln-TNF-α (Beta = 0.58, p = 0.0075) and SAT (Beta = 0.14, p = 0.044) were significant independent predictors of 11-dehydro-TXB2. After achievement of the weight loss target, a comparable reduction in U-11-dehydro-TXB2 (between-group p = 0.679) and 8-iso-PGF-2α (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.