In our study, 24-hours urine mindin levels were identified to be higher among patients with DM compared to a non-diabetic control group. Urine mindin levels were also found to increase in correlation with the severity of DR. There was a negative correlation between serum mindin level and retinopathy severity. Multivariate logistic regression analysis identified that 24-hour urine mindin level was the most important parameter for prediction of retinopathy after HbA1c.
Many factors play roles in the etiopathogenesis of DR. The most important mechanisms comprise oxidative stress  and inflammatory processes [13–19]. Inflammation and oxidative stress are very closely related. Inflammation may be assessed as tissue response to stress factors changing the hemostasis of oxidant tissues. Though oxidative stress and inflammatory pathways are described and therapeutic approaches affecting these pathways are determined and in spite of glycemic control blood pressure control and lipid-lowering treatments, the prevalence of DR is increasing. In spite of control of risk factors known for many diseases, retinopathy progression continues in patients. This situation leads to the consideration that other molecules may play a role in the pathogenesis.
Mindin was shown to be an important molecule in construction of inflammatory cytokines like TNF-alpha and IL-6 . For migration of leukocytes to the inflammation area, mutual interaction between many integrins on leukocytes and ligands on endothelial cells is required. Mindin is a new ligand for integrins that has been shown to have critical importance for migration of inflammatory cells . Mindin may be target molecule for many diseases. A study administering rats 3% dextran sulfate sodium to induce an acute colitis model have shown mindin increased the acute colitis model and stimulated NF-κ B promotor activation via TLR-9. Rats with induced defective mindin were identified to have serious defects in immune response formation properties . This situation reveals the role of mindin as a basic element of innate and adaptive immunity. Previous studies have shown the correlation between urine mindin levels and DN. Murakoshi et al.  in a study of rats with type 2 DM found podocyte injury was more intense in the high-calorie group and that urine mindin levels may be a marker of podocyte injury identified in urine before albumin/creatinine ratio. Another study by Kahvecioglu et al  have identified that serum mindin levels increased in DN patients in parallel with proteinuria levels. In this study, serum mindin levels increased in parallel with the loss of renal function. In our study, mindin was measured in both 24-hours urine and serum, as previous studies have emphasized that measurement of urine levels may be more significant . In our study, no statistically significant correlation was identified between serum and urine mindin levels. While urine mindin level was correlated with presence and severity of retinopathy, serum mindin level was identified to have a negative correlation with severity of retinopathy showing there may be different factors affecting mindin fractionation. At the same time, we identified a significant positive correlation between urine mindin level and HbA1c levels in DM patients. Regression analysis for retinopathy performed in our study identified HbA1c, proteinuria and urine mindin levels as independent variables.
There is a very close correlation between microalbuminuria and DR in type 2 DM patients. Rani et al have found that the prevalence of DR in patients with microalbuminuria is doubled while it is six times for those with macroalbuminuria . In our study, proteinuria was identified to be significantly high in the DR patient group compared to those without DR and the control group. Logistic regression analysis identified proteinuria as an independent risk factor for retinopathy. A recent study assessed mindin as an early marker of glomerular basal membrane injury . Mindin causes cell/matric adhesion in glomeruli and changes in the glomerular filtration barrier with its role in inflammation (10). Finally, podocyte cell loss and glomerulosclerosis cause proteinuria. In our study, in accordance with the literature, there was a significant correlation identified between proteinuria and urine mindin. This indicates that identification of increased mindin, with elevation identifiable in the early period of the underlying pathogenetic process for diabetic nephropathy, in 24-hours urine may be assessed as an early biomarker with stimulating properties for retinopathy, just as for nephropathy.
There are a range of limitations of our study. First, our study population was taken from a single center and comprises relatively low numbers of patients. Additionally, the mean age of our control group did not match the diabetic patient group, which is another limitation of the study.
In conclusion, urine mindin levels increase in parallel with the severity of DR. 24 hour urine mindin level may be assessed as an independent variable for the determination of DR. Additionally, 24-hours urine mindin levels are also correlated with proteinuria, a finding in diabetic nephropathy. Serum mindin levels were not correlated with 24-hours urine mindin levels. Additionally, the positive correlation between DR with HbA1c and proteinuria once more emphasizes the effect of these two factors in development of DR and the importance of strict diabetes regulation for the prevention of DR.
With the property of being the first in this field to assess DR with urine and serum mindin levels, there is a need for experimental studies researching pathways associated with mindin in diabetic retinopathy pathogenesis as a continuation of our study.