**2.1 Hematological parameters of ZDF rats**

In general, diabetic patients have increased values of some hematological parameters as platelet count, mean platelet volume (MPV), and platelet distribution width (PDWc). Platelet activation can result in the generation of vascular disease [67]. Hematological parameters can be altered as a result of infection that occurs during DM [65]. In the human study, the total granulocyte count was increased in diabetic patients. It was confirmed that granulocyte count is associated with T2DM [68]. In our experiment significant increase in granulocyte count was also observed in diabetic ZDF rats in comparison with the control animals [54]. It was also published that increased count of one part of granulocytes (neutrophils) correlated with the rising risk of vascular disease in T1DM [69] with consequences as diabetic angiopathy [70]. Mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were decreased in the diabetic ZDF rats when compared to the lean control [54]. Similar results are published by Mahmoud [71] in white albino rats with experimentally induced DM and Oyedemi et al. [65] in streptozotocin-induced diabetic Wistar rats. Generally, the decrease of these hematological parameters during the diabetes could be an indicator of abnormal hemoglobin synthesis, failure of blood osmoregulation, and plasma osmolality [72].

Platelets play a critical role in atherogenesis and thrombosis-mediated myocardial ischemia accelerated in diabetic state [73]. They are source of inflammatory mediators [74]. We observed increased values of platelets in diabetic ZDF rats against the lean control [54]. Through inflammatory process during the DM, the platelets are highly activated. Activated platelets presumably support neutrophil activation and recruitment through expressing selectins, inflammatory cytokines, and chemokines [75]. It was proven that platelets and neutrophils regulate and affect each other's functions by platelet-leukocyte contact and releasing soluble effector mediators [76].

The marker of platelet function and activation is hematological parameter— MPV [77]. Increased MPV can be an independent risk factor for arterial thrombotic events such as myocardial infarction and cerebral thromboembolism [78]. Usually diabetic patients have increased MPV values [79] correlated with a large thrombocyte size that are more reactive and aggregable [77] which can upset hemostatic system during the diabetic state [80]. In diabetes the risk of retinopathy onset increases with higher MPV [79, 81]. In our study diabetic ZDF rats had increased MPV values in comparison with the healthy lean control [54]. In diabetic patients there is usually higher value of PDWc—the hematological parameter that presents an indicator of variation in platelets' size and activity [79, 82]. In our previous research [83], we observed that the rise in the secondary symptoms of T2DM complications caused by high-energy diet was accompanied with disturbed hematological parameters. It could be also a potential marker of angiopathy.
