Urinary albumin excretion is correlated to fibrinogen levels and protein S activity in patients with type 1 diabetes mellitus without overt diabetic nephropathy

Abstract

The aim of the study was to test the hypothesis that in diabetic patients without overt nephropathy there may be a correlation between the activity of natural anticoagulant proteins and glomerular dysfunction. Assays for functional activity of proteins S and C, measurements of urinary albumin excretion, lipid parameters and haemoglobin A1c were performed in 91 patients with type 1 diabetes mellitus and 85 patients with type 2. Patients with type 1 diabetes and microalbuminuria had significantly higher mean age (44.1 +/- 10.9 vs. 37.9 +/- 12.7 years; p<0.05), fibrinogen level (3.75 +/- 1.0 vs. 3.21 +/- 0.8 g/l; p<0.01), protein S activity (92.3 +/- 17.6 vs. 84.5 +/- 15.5%; p<0.05) and higher prevalence of retinopathy (p<0.01) and macrovascular disease (p<0.01) than those with normoalbuminuria. Albumin excretion was significantly correlated to age (r=0.25, p<0.05), fibrinogen level (r=0.39, p<0.01), protein S activity (r=0.27; p<0.05), total cholesterol (r=0.23; p<0.05), apoprotein B (r=0.22; p<0.05), retinopathy (r=0.33; p<0.01) and macrovascular disease (r=0.33; p<0.01). Patients with type 2 diabetes mellitus and microalbuminuria had significantly higher apoprotein B levels (1.17 +/- 0.3 vs. 1.06 +/- 1.2 mg/dl; p<0.05) than those with normoalbuminuria, and apoprotein B was significantly correlated to albumin excretion (r=0.22; p<0.05). In a multivariate model of type 1 diabetes mellitus with fibrinogen, protein S and C activity, cholesterol, triglycerides, haemoglobin A1c, retinopathy, and macrovascular disease as independent parameters (r=0.53; p<0.003), there was significant independent correlation of fibrinogen (beta=0.28; p<0.01), protein S activity (beta=0.27; p<0.05) and retinopathy (beta=0.21; p<0.01) with albumin excretion. We conclude that in type 1 diabetes, relative elevation of fibrinogen level and protein S activity appear in the early stages of development of diabetic nephropathy, and may be related to the pathogenesis of diabetic kidney disease.

Fibrinogen, Lp(a), Microalbuminuria and Left Ventricular Mass Index: Cardiovascular Disease Risk factors in Diabetes

“…Raised fibrinogen levels in diabetes contribute significantly to thrombus formation due to increased blood viscosity and sluggish blood flow. Higher fibrinogen levels in presence of MAU (group II) as compared to normoalbuminuric patients (group I) is in agreement with earlier studies [4,12]. High fibrinogen is result of increased synthesis not compensated by proportional increase in its clearance.…”

“…All this causes glomerular damage and endothelial dysfunction leading to increased systemic vascular permeability [2]. It modulate the metabolism of cardiovascular risk factors like fibrinogen, Lp(a) and left ventricular mass (LVM) [3][4][5].…”

The estimation of selected endogenous anticoagulation system parameters in patients with subclinical Cushing's syndrome

“…Sumida et al (40) did not reveal any differences in TM activity between the patients with insulindependent diabetes mellitus and healthy controls. Most studies seem to confirm an increased TM concentration or PS activity in patients with diabetic complications, especially diabetic nephropathy (41)(42)(43). Such patients were not included in our study.…”