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Thromb Haemost 2016; 116(06): 1089-1099
DOI: 10.1160/TH16-06-0471
Cellular Haemostasis and Platelets
Schattauer Publishers Schattauer

Increased circulating resistin is associated with insulin resistance, oxidative stress and platelet activation in type 2 diabetes mellitus

Francesca Santilli
1   Department of Medicine and Aging, Center of Excellence on Aging, “G. d’Annunzio” University of Chieti, Chieti, Italy
,
Rossella Liani
1   Department of Medicine and Aging, Center of Excellence on Aging, “G. d’Annunzio” University of Chieti, Chieti, Italy
,
Patrizia Di Fulvio
1   Department of Medicine and Aging, Center of Excellence on Aging, “G. d’Annunzio” University of Chieti, Chieti, Italy
,
Gloria Formoso
1   Department of Medicine and Aging, Center of Excellence on Aging, “G. d’Annunzio” University of Chieti, Chieti, Italy
,
Paola Simeone
1   Department of Medicine and Aging, Center of Excellence on Aging, “G. d’Annunzio” University of Chieti, Chieti, Italy
,
Romina Tripaldi
1   Department of Medicine and Aging, Center of Excellence on Aging, “G. d’Annunzio” University of Chieti, Chieti, Italy
,
Thor Ueland
2   Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
,
Pål Aukrust
2   Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
,
Giovanni Davì
1   Department of Medicine and Aging, Center of Excellence on Aging, “G. d’Annunzio” University of Chieti, Chieti, Italy
› Author Affiliations Financial support: This study was partially supported by a grant from the Italian Ministry of University and Research (PRIN n. 2010JS3PMZ to Santilli).
Further Information

Publication History

Received 27 June 2016

Accepted after major revision: 18 August 2016

Publication Date:
09 March 2018 (online)

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Summary

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-PGF2α 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 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-TXB2 and 8-iso-PGF2α 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-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.

Keywords

Diabetes mellitus - adipokine - insulin resistance - oxidative stress - platelet activation
 

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