Oxidative stress of erythrocytes in cats with diabetes mellitus.

In diabetic humans, erythrocytes have lower antioxidant capacity and increased protein and lipid oxidation byproducts as a consequence of hyperglycemia and hyperlipidemia. Similarly, erythrocytes from diabetic cats have increased Heinz bodies formation which may suggest increased oxidative stress, but this topic has not yet been thoroughly investigated. Furthermore, because remission of diabetes in cats has been shown to be associated with less marked hyperglycemia and normal serum cholesterol, it is possible that antioxidant capacity of cats achieving remission is higher than in those without remission. Thus, we assessed if erythrocyte oxidative stress is increased and antioxidant capacity decreased in diabetic cats, if antioxidant capacity differs between cases with and without remission, and if oxidative status is ameliorated by treatment. Healthy cats and cats with newly diagnosed diabetes not affected by obvious concurrent diseases were enrolled. Diabetic cats received insulin glargine and a low-carbohydrate diet and were followed-up for 3-4 months. Remission was defined as euglycemia without insulin for >4 weeks. Blood was collected at first admission, at 1-2 and 3-4 months. Erythrocytes were used to quantify carbonyls (protein oxidation byproducts) and thiols (group of antioxidants) in membranes, advanced oxidized protein products (AOPP, protein oxidation byproducts), thiobarbituric acid reactive substances (TBAR, lipid peroxidation byproducts) and thiols in cytoplasm. Nonparametric tests were used for comparisons. Eleven healthy cats and 27 diabetic cats were included; 15 diabetic cats achieved remission. Compared to controls, diabetic cats at diagnosis had higher median membrane carbonyls [4.6 nmol/mg (range: 0.1-37.7) vs. 0.7 nmol/mg (range: 0.1-4.7), p<0.001] and lower cytoplasmic thiols [0.4 μmol/mg (range: 0.2-0.6) vs. 0.6 μmol/mg (range: 0.4-0.8), p<0.01]. Cytoplasmic TBAR was lower in diabetic cats [1.9 nmol/mg (range: 0.5-2.4) vs. 2.4 nmol/mg (range: 1.4-3.5), p<0.01]. At 3-4 months, membrane carbonyls remained higher (p<0.01), cytoplasmic thiols and TBAR lower (p<0.05 and p<0.01, respectively). Differences between cats with and without remission were not documented, except for cytplasmic AOPP being lower in those with remission at 1-2 months (p<0.05). In conclusion, diabetic cats have erythrocytes with increased protein oxidation byproducts and reduced antioxidant capacity, suggesting increased oxidative stress. Because oxidative status was not ameliorated by treatment, it is possible that oxidative stress is persistent or needs longer treatment duration to decrease. The reason behind reduced TBAR in diabetic cats remains elusive. Lastly, oxidative status is not different between cats with and without remission.