Renal tublar dysfunction in patients with type 2 diabetes mellitus

ABSTRACT

1] To determine the activity of urinary enzymes [N-acetyl-beta-D-glucosaminidase [NAG], a lysosomal enzyme, gamma-glutamyltranspeptidase [GGT], alkaline phosphatase [ALP], brush border enzymes and beta2 microglobulin [beta2-MG] as one of the tubular proteins] as markers of tubular damage which may reflect early stage of diabetic nephropathy. 2] To clarify the importance of estimation of these enzymes as noninvasive cheap tools in monitoring the course of diabetic nephropathy [DN]. 3] To evaluate serum levels of angiotensin converting enzyme [ACE] as a marker of endothelial cell disorder in diabetic patients. Patients The study included 75 subjects, 60 were non-smokers type 2 diabetic patients and 15 healthy, nonsmoker, age and sex matched controls. The patients were classified into 3 groups, the 1st group was 20 normoalbuminuric diabetic patients, the 2nd group was 20 patients with microalbuminuria [urinary albumin is >30 mg - <300 mg/day], and the 3rd group was 20 patients with macroalbuminuria [>300 mg/day]. Setting: Departments of Biochemistry and Internal Medicine, Faculty of Medicine, Assiut University, EGYPT. There were significant increased levels of the urinary NAG, ALP and beta2-MG, serum ACE and glycated haemoglobin [HbA1c], in addition to significant decreased levels of GGT, in the three diabetic groups compared to the corresponding levels of controls. These changes were encountered in the microalbuminuric group compared to the normoalbumjnuric group and in the macroalbuminuric group compared to both the normoalbuminuric and microalbuminuric groups. Patients with either nephropathy alone or multi-diabetic complications showed that serum ACE, and urinary NAG, ALP and beta2-MG were significantly higher, while, urinary GGT was significantly lower than those without complications and in those with multi-diabetic complications than those with DN alone. In the normoalbuminuric group, microalbuminuria [MA] showed significant positive correlations with the urinary beta2-MG and serum ACE and a significant negative correlation with the urinary GGT. Serum ACE showed also significant negative correlation with the urinary GGT and a significant positive correlation with the urinary beta2-MG. In the microalbuminuric group, MA showed significant positive correlations with urinary beta2 MG, serum ACE and HbA1c and a significant negative correlation with urinary GGT. Serum ACE showed a significant negative correlation with urinary GGT and significant positive correlations with urinary beta2-MG and HbA1c For early detection of diabetic nephropathy, it would now seem recommended to include markers of tubular dysfunction such as urinary NAG, serum ACE and urinary ALP in addition to measuring albumin excretion