title: Increased circulating resistin is associated with insulin resistance, oxidative stress and platelet activation in type 2 diabetes mellitus.
abstract: Resistin is an adipokine that promotes inflammation and insulin resistance by targeting several cells including platelets. We hypothesised that in type 2 diabetes (T2DM), resistin may foster in vivo oxidative stress, thromboxane-dependent platelet activation and platelet-derived inflammatory proteins release, key determinants of atherothrombosis. A cross-sectional comparison of circulating resistin, sCD40L, as a marker of platelet-mediated inflammation, asymmetric dimethylarginine (ADMA), endothelial dysfunction marker, Dickkopf (DKK)-1, reflecting the inflammatory interaction between platelets and endothelial cells, and urinary 8-iso-PGF2αand 11-dehydro-TxB2, reflecting in vivo lipid peroxidation and platelet activation, respectively, was performed between 79 T2DM patients and 30 healthy subjects. Furthermore, we investigated the effects of the α-glucosidase inhibitor acarbose and the PPARγ agonist rosiglitazone, targeting hyperglycaemia or insulin resistance, versus placebo, in 28 and 18 T2DM subjects, respectively. Age- and gender-adjusted serum resistin levels were significantly higher in patients than in controls. HOMA (β=0.266, p=0.017) and 11-dehydro-TXB2(β=0.354, p=0.002) independently predicted resistin levels. A 20-week treatment with acarbose was associated with significant reductions (p=0.001) in serum resistin, DKK-1, urinary 11-dehydro-TXB2and 8-iso-PGF2αwith direct correlations between the change in serum resistin and in other variables. A 24-week rosiglitazone treatment on top of metformin was associated with significant decreases in resistin, DKK-1, 11-dehydro-TXB2and 8-iso-PGF2α, in parallel with HOMA decrease. In conclusion, resistin, antagonising insulin action in part through PPARγ activation, may favour insulin resistance and enhance oxidative stress, endothelial dysfunction and platelet activation. The adipokine-platelet interactions may be involved in platelet insulin resistance and their consequent pro-aggregatory phenotype in this setting.
authors.forename: Francesca
authors.initials: F
authors.lastname: Santilli
authors.forename: Rossella
authors.initials: R
authors.lastname: Liani
authors.forename: Patrizia
authors.initials: P
authors.lastname: Di Fulvio
authors.forename: Gloria
authors.initials: G
authors.lastname: Formoso
authors.forename: Paola
authors.initials: P
authors.lastname: Simeone
authors.forename: Romina
authors.initials: R
authors.lastname: Tripaldi
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Prof. Giovanni Davì, Internal Medicine and Center of Excellence on Aging, "G. D'Annunzio" University Foundation, Via Colle dell'Ara, 66013 Chieti, Italy, E-mail: gdavi@unich.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Davì
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D006943:Hyperglycemia; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D015539:Platelet Activation; D052243:Resistin / Q000097:blood*
chemical_list: D052243:Resistin
keywords: Diabetes mellitus; adipokine; insulin resistance; oxidative stress; platelet activation