Increased platelet aggregation in vivo in the Zucker Diabetic Fatty rat: differences from the streptozotocin diabetic rat

BACKGROUND AND PURPOSE: Diabetes mellitus, especially type 2, is associated with increased arterial thrombosis. Our aims were (i) to characterize and compare platelet aggregation in vivo and in vitro in a type 2 diabetes model; and (ii) to determine whether these results differ from those in a type 1 diabetes model. EXPERIMENTAL APPROACH: Platelet aggregation to ADP in lean or obese Zucker Diabetic Fatty (ZDF) rats and in streptozotocin (STZ)-treated or control Wistar rats was measured in vitro, using Born aggregometry, and in vivo, by (111)Indium-labelled pulmonary platelet accumulation. KEY RESULTS: In vivo, ADP responses were higher in obese (type 2 model) than lean ZDF rats. However, in vitro, ADP aggregation did not differ between platelet-rich plasma from ZDF lean or obese rats; nor was any difference seen in ADP responses when platelets from either lean or obese ZDF rats were suspended in plasma from obese or lean ZDF rats, respectively. In vivo, ADP responses were similar in STZ treated (type 1 model) and control rats whereas, in vitro, isolated platelets from STZ diabetic rats were more responsive to ADP aggregation than controls. Platelets from control or STZ-treated rats suspended in plasma from STZ-treated rats exhibited reduced ADP aggregation, compared to when suspended in plasma from control rats. CONCLUSIONS AND IMPLICATIONS: The platelet aggregation results obtained in vitro do not reflect those in vivo, therefore in vitro aggregation data should be interpreted with caution. Moreover, both in vitro and in vivo, different diabetic models exhibit important differences in platelet responsiveness.