COPEPTIN LEVEL IN PATIENTS WITH DIABETIC NEPHROPATHY WITH ACE GENE POLYMORPHISM

Abstract

Aim of the study was to determine the copeptin level in the blood serum of patients with type 2 diabetes mellitus (T2DM) depending on the kidney’s function and accounting for the Alu Ins/Del (rs4646994) polymorphism of the angiotensin-converting enzyme (ACE) gene. Materials and methods: 146 patients with T2DM complicated by diabetic nephropathy (DN) were examined. Patients were divided into 4 groups according to the chronic kidney disease stage. Control group – 30 healthy subjects. Serum levels of copeptin and insulin were determined by ELISA using appropriate kits in accordance with the manufacturers' instructions. Genotyping was performed using TagMan allelic discrimination assay. Results. Our study has shown that the development of DN in T2DM is accompanied by a significant increase of copeptin level in blood serum compared with the control group and with diabetic patients without signs of nephropathy. The highest copeptin levels were found in patients with albuminuria and impaired glomerular filtration rate. In patients with T2DM, a significant linear correlation founded between copeptin level and serum creatinine (r = 0.247, p < 0.03). We found more significant violations of glucose metabolism in DN patients with high serum levels of copeptin compared with patients with normal values of this factor. In particular significant increase in serum, copeptin was accompanied by an increase in the HOMA index and insulin level. In patients with T2DM – carriers of the homozygous I/I genotype were founded a reliable association with increasing copeptin levelы in blood serum, in contrast to D/D and I/D genotypes. Conclusions. The highest copeptin levels were founded in carriers of the homozygous I/I genotype of the Alu Ins/Del polymorphism of the ACE gene. An increase in the copeptin level has a certain genetic determinism, and its high level correlates with impaired glucose metabolism and the development of nephropathy in T2DM. Serum copeptin can be considered as a diagnostic marker of renal and metabolic lesions in T2DM. Keywords: diabetic nephropathy, copeptin, arginine-vasopressin system, diabetes mellitus, angiotensin-converting enzyme, ACE gene polymorphism.