Abstract

Spontaneous platelet aggregation (SPA) is enhanced in patients with type 2 diabetes. Adiponectin may inhibit platelet aggregation. The aims of the current study were to identify factors associated with in vitro SPA measured by a laser light scattering method and to investigate the effects of short-term glycemic control and adiponectin on SPA. In study 1, we investigated platelet aggregation in 20 healthy control subjects and 82 patients with type 2 diabetes. In study 2, we evaluated the changes of SPA and serum high-molecular-weight (HMW) adiponectin after 2 weeks of improved glycemic control in 20 hospitalized diabetic patients. In study 3, using washed platelets from 10 healthy subjects, in vitro SPA was measured over 15 min in the absence or presence of recombinant adiponectin (20 μg/mL). Platelet aggregation was assessed with a laser light scatter aggregometer that measured the size of platelet aggregates. SPA was defined as formation of small aggregates under constant stirring in the absence of any agonists. The area under the curve was calculated for SPA and also for agonist-induced small, medium, and large aggregates. SPA was increased in diabetic patients compared with control subjects. In diabetic patients, SPA was correlated positively with plasma fibrinogen, fasting plasma glucose, glycated albumin, and high-sensitivity C-reactive protein. A stepwise multivariate analysis showed that plasma fibrinogen was the strongest independent determinant of SPA in diabetic patients. In 20 diabetic patients, SPA decreased significantly after 2 weeks of glycemic control. A significant negative correlation was found between changes of SPA and those of HMW adiponectin during treatment. The in vitro study showed that adiponectin inhibited the spontaneous aggregation of washed platelets. In conclusion, hyperfibrinogenemia and hyperglycemia are associated independently with SPA in patients with type 2 diabetes. SPA is reduced after even short-term improvement of glycemic control and adiponectin also inhibits SPA directly.

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