Nephropathy, but not Angiographically Proven Retinopathy, is Associated with Neutrophil to Lymphocyte Ratio in Patients with Type 2 Diabetes.

BACKGROUND: Type 2 Diabetes Mellitus is a leading cause of end stage renal disease in the worldwide. Inflammation is regarded as one of the main reasons for the progression of diabetes complications. We aimed to evaluate the association of neutrophil to lymphocyte ratio (NLR) as indicator of systemic inflammation with diabetic retinopathy and nephropathy. PATIENTS AND METHODS: This is a cross-sectional study of 114 prevalent type 2 diabetic subjects. All of the patients underwent detailed examination for the presence of diabetic retinopathy and nephropathy. Diabetic retinopathy was approved and classified according to findings based on flouresceint fundal angiography results. Estimated glomerular filtration rate (eGFR) and microalbumin to creatinine ratio were calculated to establish the diabetic nephropathy. NLR was calculated as ratio of absolute neutrophil count to absolute lymphocyte count. RESULTS: Retinopathy was present in 55 (48.2%) out of 114 patients, whereas nephropathy was present in 62 patients (54.3%). NLR was significantly higher in patients with nephropathy than in patients without nephropathy. NLR was also positively correlated with CRP (p=0.017, r=0.224) and microalbuminuria (p=0.016, r=0.257) whereas negatively correlated with eGFR (p<0.001, r=-0.337) values in the whole cohort. NLR was independent predictors for diabetic nephropathy, whereas it did not appear as an independent associate of diabetic retinopathy. CONCLUSION: NLR and diabetic nephropathy have an independent association between them whereas there was no independent association between NLR with retinopathy in type 2 diabetic patients.

α1-Adrenoceptor-mediated contraction of rat aorta is partly mediated via transactivation of the epidermal growth factor receptor.

BACKGROUND AND PURPOSE: High level of plasma catecholamines is a risk factor for vascular diseases such as hypertension and atherosclerosis. Catecholamines induce hypertrophy of vascular smooth muscle through α(1) -adrenoceptors, which in cell culture involves the transactivation of epidermal growth factor receptor (EGFR). We hypothesized that EGFR transactivation was also involved in contractions of rat aorta mediated by α(1) -adrenoceptors. EXPERIMENTAL APPROACH: Thoracic aorta was isolated from 12-14 week old male Wistar rats. In vitro aortic contractile responses to cumulative doses of phenylephrine were characterized in the absence and presence of the EGFR kinase inhibitors, AG1478 and DAPH, in intact and endothelium-denuded rings. Involvement of signal transduction pathways was investigated by using heparin and inhibitors of Src, matrix metalloproteinase (MMP), extracellular signal-regulated kinase (ERK)1/2 and phosphatidyl inositol 3-kinase (PI3K). Phosphorylation of EGFR and ERK1/2 was measured after short-term phenylephrine or EGF stimulation in aorta segments in the presence of AG1478 and the PI3K inhibitor, wortmannin. KEY RESULTS: AG1478 and DAPH concentration dependently attenuated phenylephrine-induced contractile responses in intact or endothelium-denuded aortic rings. Inhibition of PI3K (wortmannin and LY294002) but not heparin or inhibitors of Src or MMP, prevented the effect of AG1478 on the responses to phenylephrine. Phenylephrine induced phosphorylation of EGFR, which was partially blocked by AG1478. Phenylephrine also increased phosphorylation of ERK1/2, time-dependently and was blocked by AG1478 and wortmannin. CONCLUSIONS AND IMPLICATIONS: Contractions of rat thoracic aorta mediated by α(1) -adrenoceptors involved transactivation of EGFR, mediated via a PI3K and ERK1/2 dependent pathway.