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

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.

Diurnal blood pressure pattern may predict the increase of urinary albumin excretion in normotensive normoalbuminuric type 1 diabetes mellitus patients.

To characterise the relationship between diurnal blood pressure and the subsequent increase of urinary albumin excretion (UAE) in normotensive normoalbuminuric type 1 diabetic patients, ambulatory blood pressure monitoring (ABPM) was performed in 53 patients, who were then followed for 5 years. Albumin excretion rate changed from 12.4 (8.9-17.2) to 29.3 (15.2-47.0) mg/day. Macroalbuminuria developed in 2 (3.8%), microalbuminuria in 22 (41.5%) patients, 29 (54.7%) remained normoalbuminuric. Night-time diastolic blood pressure was significantly higher (64.3+/-6.5 vs. 60.9+/-5.5 mmHg, P<0.05), diastolic diurnal index significantly lower (15.5+/-9.7 vs. 22.3+/-6.2%, P<0.01) in patients who later progressed to micro- or macroalbuminuria. Diastolic diurnal index (r=-0.40; P<0.01) and nocturnal diastolic pressure (r=0.35; P<0.01) were correlated to the change in albumin excretion. In a multivariate analysis model with the change of albumin excretion as dependent, and means and diurnal indices of systolic and diastolic blood pressure, baseline UAE, cholesterol, triglycerides, HbA1c and retinopathy as independent parameters (r=0.68; P=0.001), diurnal index for diastolic blood pressure (beta=-0.30; r=0.013), baseline HbA1c (beta=0.32; P=0.010) and retinopathy (beta=0.44; P=0.001) were significant independent correlates. We conclude that the relative increase of nocturnal blood pressure is associated with the subsequent increase of albuminuria, which in turn is predictive of overt diabetic nephropathy.