Ivan Pchelin

Uninephrectomized High-Fat-Fed Nicotinamide-Streptozotocin-Induced Diabetic Rats: A Model for the Investigation of Diabetic Nephropathy in Type 2 Diabetes

Type 2 diabetes (DM2) could be reproduced in rats with alimentary obesity by using low doses of streptozotocin (LD-STZ) as well as STZ in high doses with preliminary nicotinamide (NA) administration. However, STZ could induce tubulotoxicity. Aim. To develop rat model of DN in NA-STZ-induced DM2 and compare it with LD-STZ-model in order to choose the most relevant approach for reproducing renal glomerular and tubular morphofunctional diabetic changes. Starting at 3 weeks after uninephrectomy, adult male Wistar rats were fed five-week high-fat diet and then received intraperitoneally either LD-STZ (40 mg/kg) or NA (230 mg/kg) followed by STZ (65 mg/kg). Control uninephrectomized vehicle-injected rats received normal chow. At weeks 10, 20, and 30 (the end of the study), metabolic parameters, creatinine clearance, albuminuria, and urinary tubular injury markers (NGAL, KIM-1) were evaluated as well as renal ultrastructural and light microscopic changes at weeks 20 and 30. NA-STZ-group showed higher reproducibility and stability of metabolic parameters. By week 10, in NA-STZ-group NGAL level was significantly lower compared to LD-STZ-group. By week 30, diabetic groups showed early features of DN. However, morphofunctional changes in NA-STZ-group appeared to be more pronounced than those in STZ-group despite lower levels of KIM-1 and NGAL. We proposed a new rat model of DM2 with DN characterized by stable metabolic disorders, typical renal lesions, and lower levels of tubular injury markers as compared to LD-STZ-induced diabetes.

PS 11-58 CLINICAL CORRELATES OF INFLAMMATION IN HYPERTENSIVE AND NORMOTENSIVE PATIENTS WITH ABDOMINAL OBESITY

Objective: Patients with abdominal obesity are at increased cardiovascular risk. However, it is evident that this clinical group is heterogeneous. The aim of the study was to assess clinical correlates of C-reactive protein level in hypertensive and normotensive patients with abdominal obesity. Design and Method: We investigated 55 middle-aged adults with abdominal obesity including 34 hypertensive and 21 normotensive subjects. Abdominal obesity was defined according to IDF definition (2009). In addition to routine clinical investigation we measured serum levels of high sensitive C-reactive protein and insulin. Glomerular filtration rate (GFR) was calculated with Cockroft-Gault formula. Spearmens correlation coefficient (rs) was used to assess the correlations between the clinical and laboratory parameters in each group. Results: Elevated serum level of C-reactive protein was found in 4 out of 34 hypertensive and in 1 out of 21 normotensive patients with abdominal obesity (11.8% vs. 4.8% respectively). In both groups this parameter had no significant correlations with age, body mass index, serum levels of urea, creatinine, LDL, HDL, triglycerides and left ventricular mass index. In hypertensive patients serum level of C-reactive protein correlated with serum insulin (rs = 0.422, p = 0.016), HOMA-IR index (rs = 0.439, p = 0.013), total cholesterol level (rs = 0.395, p = 0.023) and estimated GFR (rs = 0.344, p = 0.048). In normotensive patients it correlated with waist-to-hip ratio (rs = 0.511, p = 0.036) but not with serum insulin (p = 0.185), HOMA-IR index (p = 0.128), total cholesterol level (p = 0.642) or GFR (p = 0.566). Conclusions: The results of the study suggest that hypertensive and normotensive patients with abdominal obesity are characterized by different clinical correlates of C-reactive protein level. Further studies are needed to elucidate clinical implications of these findings.