In this study, serum and vitreous ADMA levels in patients with diabetic retinopathy were investigated and compared with the control group with the same demographic characteristics. Serum ADMA levels were higher in patients with diabetic retinopathy compared to the control group, but there was no elevation in the vitreous ADMA level. In the literature, there are many studies on plasma ADMA levels in patients with Type 2 diabetes mellitus [11, 14-16]. Krzyzanowska et al.[16] measured the level of plasma ADMA and homocysteine in 136 patients with type 2 diabetes. Fifty-five of these patients were being diagnosed some macrovascular disease such as stroke, myocardial infarction, coronary artery disease, and peripheral artery disease. The relationship among with macrovascular disease, ADMA and homocysteine was investigated. ADMA and homocysteine levels were significantly higher in the group diagnosed with macrovascular disease. One year later, Krzyzanowska et al.[17] reported that elevated ADMA levels in patients with type 2 diabetes were a strong indicator of cardiovascular events such as myocardial infarction, cerebrovascular event, and death from all causes. In addition, in terms of diabetic complications, it has been reported that there is a strong relationship between ADMA and microvascular complications such as macrovascular and retinopathy [12, 17-19]. There are also studies showing increased plasma ADMA levels in patients with diabetic retinopathy. Malecki et al.[12] examined the relation between plasma ADMA levels and Type 2 diabetic retinopathy in 182 diabetes Type 2 patients and 52 healthy control groups. They identified that the ADMA levels were the highest in patients with diabetic retinopathy (0.60±0.06 μmol/l), moderate in diabetic patients without diabetic retinopathy (0.51±0.06 μmol/l), and the lowest in the control group (0.45±0.05 μmol/l). In our study, mean serum ADMA level was found 0.59±0.10 μmol/L in diabetic patient group and 0.54±0.08 μmol/L in control group. Serum ADMA levels were similar to those found by Malecki et al.[12] In our study too, there was statistically significant difference in serum ADMA levels between the patient group and the control group.
In the literature, no study has been found about vitreous ADMA levels in patients with Type 2 diabetes. Sugai et al.[13] investigated ADMA levels in serum and aqueous humor in 17 diabetic and 21 nondiabetic patients and reported that ADMA levels were higher in diabetic patients, especially in patients with advanced diabetic retinopathy, in both serum and aqueous humor. Serum ADMA levels were 0.67±0.26 μmol/L in the advanced diabetic retinopathy group and 0.53±0.08 μmol/L in the nondiabetic group. ADMA levels in aqueous humor were 0.55±0.20 μmol/L in the diabetic patient group and 0.32±0.16 μmol/L in the nondiabetic group. However, there was no relationship between serum and aqueous humor ADMA levels in both groups. Du et al.[20] reported that ADMA levels increased in the aqueous humor of diabetic rats and ADMA contributes to the neovascularization of retina in diabetes mellitus. In our study, vitreous ADMA levels in group 1 and group 2 were 0.25 ± 0.09 μmol / L and 0.26 ± 0.08 μmol / L, respectively. There was no increase in the vitreous ADMA level as in the aqueous humor. The aqueous humor is continuously in circulation and renewed. It is estimated that the aqueous humor completes this cycle in about 2 hours [21]. But the vitreous gel is not renewed. It has also been reported that the glucose concentration of the aqueous humor and the serum are almost the same [22]. When glucose concentrations of vitreous and serum were compared, vitreous glucose concentration was found to be lower than serum glucose concentration [23]. Increased plasma levels of glucose, are associated with decreased levels of DDAH that plays a role in the metabolism of ADMA [24]. Due to hyperglycemia in the aqueous humor, ADMA production is stimulated in the anterior chamber. Because the same hyperglycemia is not in the vitreous gel, ADMA production in the vitreous is not the same. Therefore, the concentration of ADMA in the vitreous may not be related to the serum level.
In our study, a decrease in vitreous ADMA level was observed in diabetic group as the duration of diabetes increased. Ersoy et al.[25] found a decrease in serum ADMA levels as the duration of diabetes increased in 83 disease groups. In our study, the same finding was found for the vitreous ADMA level. But there was no significant correlation between serum ADMA level and the duration of diabetes. This may be due to a small number of patients in our diabetic group. Marcovecchio et al.[26] also found a decrease in serum ADMA level with an increase in the duration of diabetes. The authors could not give a complete explanation to this inverse relationship and they hypothesized that chronic hyperglycemia could lead to damage that would adversely affect ADMA production.