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Nutrients 2018, 10(12), 1872; https://doi.org/10.3390/nu10121872

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

1
Department of Medicine and Aging and Center of Aging Science and Translational Medicine (CESI-Met), University of Chieti, 66100 Chieti, Italy
2
Department of Epidemiology and Prevention, IRCCS NEUROMED, Via dell’Elettronica, 86077 Pozzilli, Italy
3
Department of Neuroscience & Imaging, University of Chieti, 66100 Chieti, Italy
4
Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
5
Division of Endocrinology and Metabolic Diseases, Azienda Ospedaliera Universitaria of Parma, 43126 Parma, Italy
6
Clinical Pathology, Chieti Hospital, 66100 Chieti, Italy
This paper is dedicated to the memory of the late Professor Giovanni Davì.
*
Author to whom correspondence should be addressed.
Received: 2 November 2018 / Revised: 20 November 2018 / Accepted: 26 November 2018 / Published: 2 December 2018
(This article belongs to the Special Issue Diet, lifestyle and cardiometabolic health in vulnerable populations)
Full-Text   |   PDF [933 KB, uploaded 2 December 2018]   |  

Abstract

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)F, 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 (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- (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. View Full-Text
Keywords: obesity; diabetes mellitus; weight loss; oxidative stress; platelet activation; adipose tissue distribution; liraglutide obesity; diabetes mellitus; weight loss; oxidative stress; platelet activation; adipose tissue distribution; liraglutide
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Simeone, P.; Liani, R.; Tripaldi, R.; Di Castelnuovo, A.; Guagnano, M.T.; Tartaro, A.; Bonadonna, R.C.; Federico, V.; Cipollone, F.; Consoli, A.; Santilli, F. Thromboxane-Dependent Platelet Activation in Obese Subjects with Prediabetes or Early Type 2 Diabetes: Effects of Liraglutide- or Lifestyle Changes-Induced Weight Loss. Nutrients 2018, 10, 1872.

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