Increased circulating resistin is associated with insulin resistance, oxidative stress and platelet activation in type 2 diabetes mellitus.
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 PGF2a and 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 a glucosidase inhibitor acarbose and the PPARg 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 (b=0.266, p=0.017) and 11 dehydro TXB2 (b=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 TXB2 and 8 iso PGF2a with 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 TXB2 and 8 iso PGF2a, in parallel with HOMA decrease. In conclusion, resistin, antagonising insulin action in part through PPARg 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.
Thrombosis and haemostasis