[Association of Serum Levels and Gene Polymorphism of Vascular Endothelium Growth Factor With Ischemic Heart Disease in Type 2 Diabetic Patients].

AIM: to study serum levels of vascular endothelium growth factor family peptides (VEGF-A, VEGF-C and VEGF-D) and functional gene polymorphisms of VEGFA gene (rs699947 and rs3025039) in patients with type 2 diabetes (T2D) depending on the presence of ischemic heart disease (IHD). MATERIALS AND METHODS: The study involved 196 Caucasian patients with T2D (age 43-70 years, 76 with IHD). The concentrations of VEGF-A, VEGF-C and VEGF-D in blood serum were determined by Multiplex assay. Twenty-four persons without diabetes and IHD served as controls. The genotyping of VEGFA polymorphism -2578A/C (rs699947) and +936C/ (rs3025039) was performed by TaqMan. RESULTS: Concentrations of VEGF-A and VEGF-C in patients with T2D were significantly lower than those in controls (p=0.03 and p=0.006, respectively). The level of VEGF-D showed a tendency to decrease (p=0.14). Patients with IHD, as compared to other patients, had higher levels of VEGF-A (p=0.04) and a tendency to VEGF-D increase (p=0.06). The concentration of VEGF-C was not different between groups. No relationships were found between VEGF-A, VEGF-C and VEGF-D levels, HbA1c or glucose variability parameters. C-allele and CC-genotype at +936 position of VEGFA were more frequent among patients with IHD (odds ratio 2.14 and 2.41, respectively, p=0.02). The rs699947 polymorphism was not related to IHD and VEGF-A levels. CONCLUSION: Patients with T2D have decreased serum levels of angiogenic factors VEGF-A and VEGF-C. VEGFA rs3025039 polymorphism is associated with presence of IHD and levels of circulating VEGF-A in these patients.

[Acute-phase serum proteins and adipocytokines in women with type 2 diabetes mellitus: Relationships with body composition and blood glucose fluctuations]. / Belki ostroi fazy vospaleniya i adipotsitokiny v syvorotke krovi u zhenshchin s sakharnym diabetom 2-go tipa: vzaimosvyazi s sostavom tela i kolebaniyami urovnya glyukozy v krovi.

AIM: To estimate the relationships between the serum concentrations of acute-phase proteins (APPs) and adipocytokines, body composition (BC), and blood glucose (BG) fluctuations in women with type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: A total of 165 women with T2DM and 22 with a normal body mass index (BMI) at the age of 40 to 70 years were examined. The concentrations of high-sensitivity C-reactive protein (hs-CRP) and acid α1-glycoprotein (α1-AGP) were determined by ELISA. The levels of interleukins 6, 8, and 18 (IL-6, IL-8, IL-18), tumor necrosis factor-α (TNF-α), and plasminogen activator inhibitor type 1 (PAI-1) were measured by a multiplex analysis. Dual energy X-ray absorptiometry was used to estimate BC parameters. BG fluctuations were estimated via continuous glucose monitoring. RESULTS: The levels of hs-CRP, α1-AGP, IL-6, IL-8, IL-18, TNF-α, and PAI-1 were significantly higher in the obese women with T2DM than those in the control group. In the diabetic normal weight women, only hs-CRP, α1-AGP, and IL-8 concentrations exceeded those in the controls. The level of hs-CRP (other than α1-AGP) correlated positively with BMI, the mass of adipose tissue, body trunk (android), and gynoid fats. A multivariate regression analysis showed that adipose tissue mass and trunk fat proportion were independent predictors of hs-CRP levels. The concentrations of IL-6, IL-8, IL-18, PAI-1, and TNF-α correlated positively with waist-to-hip ratio, but demonstrated no associations with BMI and BC. Only the serum α1-AGP level showed a positive association with mean BG and its variability parameters. CONCLUSION: In the women with T2DM, the serum concentrations of APPs and adipocytokines correlate differently with the mass of adipose tissue, its distribution, and BG fluctuations. The findings indicate the multifactorial genesis of chronic inflammation in these patients.

Effect of Linagliptin on Structural Changes in the Kidney in Experimental Type 2 Diabetes Mellitus.

Effect of the dipeptidyl peptidase-4 inhibitor linagliptin on structural manifestations of diabetic nephropathy was studied in BKS.Cg-Dock7m+/+Leprdb/J mice (experimental model of type 2 diabetes mellitus). Linagliptin (10 mg/kg per day) or vehicle was administered by gavage over 8 weeks. Mesangial expansion, thickening of the basement membrane in glomerular capillaries and proximal tubules, and retraction of cytopodia were less pronounced in mice receiving linagliptin. The protective effect of linagliptin on the kidney structure was not associated with its hypoglycemic action.

[Increased serum concentrations of inflammatory cytokines in type 2 diabetic patients with chronic kidney disease].

AIM: To study the relationship between serum inflammatory cytokine levels in chronic kidney disease patients with type 2 diabetes. SUBJECTS AND METHODS: Sixty-four patients aged 43 to 70 years with a glomerular filtration rate (GFR) of > 30 ml/min/1.73 m2 were examined. A control group consisted of 15 healthy individuals. The serum concentration of macrophage colony-stimulating factor (M-CSF), macrophage inflammatory protein 1α (MIP-1α), macrophage migration inhibitory factor (MIF), interleukin 6 (IL-6), as well as the urinary excretion of albumin and type IV collagen was determined by enzyme immunoassay. RESULTS: In patients with a GFR of > 60 ml/min/1.73 m2, M-CSF and MIF concentrations proved to be significantly higher than those in the control group (p = 0.0003 and p = 0.001, respectively). In those with a GFR of 30-59 ml/min/1.73 m2, there was an increase in the levels of M-CSF (p < 0.0001), MIP-1α (p = 0.002), MIF (p = 0.02), and IL-6 (p = 0.02). The decline in GFR was associated with the higher levels of M-CSF (p = 0.02) and MIP-1α (p = 0.02) and with the higher urinary excretion of type IV collagen (p = 0.01). M-CSF, MIP-1α, and IL-6 correlated positively with the urinary excretion of albumin (r = 0.34, r = 0.28, and r = 0.28, respectively; all p < 0.05) and type IV collagen (r = 0.31, r = 0.4, and r = 0.43, respectively; all p < 0.05). CONCLUSION: The findings confirm the concept that chronic inflammation is involved in the development of diabetic kidney disease.