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J Clin Res Pediatr Endocrinol. 2018 Nov 6. doi: 10.4274/jcrpe.0221. [Epub ahead of print]

Urine Levels of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Children with Type 1 Diabetes Mellitus.

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Istanbul University, Istanbul Faculty of Medicine, Pediatric Nephrology Department, Istanbul, Turkey.
Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Biochemistry Department, Istanbul, Turkey.
Istanbul University, Istanbul Faculty of Medicine, Department of Pediatrics, Istanbul, Turkey.
Istanbul University, Istanbul Faculty of Medicine, Istanbul, University, Biostatistics Department, Istanbul, Turkey.
Istanbul University, Istanbul Faculty of Medicine, Pediatric Endocrinology Department, Istanbul, Turkey.



Histopathological changes of the kidney in type 1 diabetes mellitus (T1DM) begin before the microalbuminuria. Therefore, efforts are focused on finding a biomarker for the detection of early diabetic kidney injury. The aim of the study is to determine whether urine levels of indicators of fibrosis alter in diabetic children and if they may predict a progressive renal injury in T1DM.


Urinary matrix metalloproteinase 2 and 9 (MMP2 and MMP9), tissue inhibitor of metalloproteinase 1 and 2 (TIMP1 and TIMP2), Transforming growth factor βeta-1 (TGF-β1) were assessed in 33 patients with T1DM with normal renal functions as well as in 24 healthy children. Microalbuminuria was not present in the patient group except three. The results were adjusted to urine creatinine and the comparison between patients and controls was evaluated. Also, same measurements were repeated after one year and were compared to the first year results.


Urine MMP2/Creatinine (Cr), MMP9/Cr, TIMP1/Cr, TIMP2/Cr, TGF-β1/Cr were not different between the patient and control groups (p>0.05). There was also no significant difference between the results of first and second year according to these biomarkers (p>0.05). All these parameters were not correlated to HbA1c, body mass index (BMI) and duration of T1DM. Interestingly, all parameters were negatively correlated to the age of onset of T1DM (p<0.05) Conclusion: Our findings suggest that urinary biomarkers of fibrosis do not increase in diabetic children without microalbuminuria. As the age of onset of T1DM decreases, the risk of early fibrosis may increase according to our results.


Biomarker; Children; Diabetic Nephropathy; MMP TIMP.; Type 1 Diabetes Mellitus

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