Plasma level of Von willebrand factor in type 2 diabetics with cerebrovascular stroke, with and without microalbuminuria

ABSTRACT

The risk of cerebrovascular stroke is known to be markedly elevated in patients with long duration of type 2 diabetes mellitus[1] . Diabetes mellitus is a risk factor for ischemic stroke, and is assosciated with higher mortality and worse functional outcome[2]. Microalbuminuria is associated with cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus[3] Links between endothelial dysfunction [elevated level of Von Willebrand Factor], atherosclerosis and diabetes mellitus have been increasingly recognized. One of the earliest discernible atherogenic changes in diabetes is endothelial dysfunction. The aim of the present study is to examine the concept suggesting that microaluminuria in combination with high level of plasma Von Willebrand factor [as a marker of endothelial dysfunction] is a strong predictor for macrovascular disease [evidence by stroke] than microalbuminuria alone in type 2 diabetic patients. The study group consisted of thirty normotensive, non smoking diabetic patients with normal renal function selected from the internal medicine outpatient clinic of Kasr El A ini hospital. They were divided into two groups group [l] included 10 type 2 diabetic patients with cerebrovascular stroke [6 males and 4 females], with a mean age 56 +/- 8.39 years [range 43-69 years],mean diabetic duration 11.6 +/- 3.7 years . Group [2] included 20 type 2 diabetic patients without cerebrovascular stroke [9 males and 11 females] with a mean age 55.5 +/- 8.57 years [range 43-69 years], mean diabetic duration 5.7 +/- 2.6years .Ten age, sex and weight matched healthy subjects [4male and 6 female] with a mean age 52 +/- 7.1 years [range 43-62 years] were included as a control group. Urinary albumin excretion, was assessed qualitatively using the micral test [Boehringer Manheim, Germany] and quantitatively using double antibody albumin procedure.Plasma level of von- Willebrand factor using ELISA procedures to measure vWfAg generally expressed in relative percent [%] as compared to pooled normal plasma . Carotid IMT was evaluated using high resolution B-modeUltrasonography. Ten diabetic patients with cerebrovascular stroke had a significant higher fasting [p= 0.0001], postprandial blood glucose [p=0.0001], cholesterol [0.001], triglycerides [p-0.02], low denisty lipoprotein [p=0.01], microalbuminuria [74.689 +/- 66.24 vs 4.166 +/- 5.6 U gm /min, p=0.003], plasma level of vWf [190.0 +/- 22.60 vs 85.50 +/- 23.74%, p=0.002] and carotid artery IMT [1.14 +/- 0.388 vs 0.4 +/- 0.06 mm, p=0.001] compared to the control group [10 subjects]. Diabetic patients with cerebrovascular-stroke [group 1] had significantly higher vWF [190.0 +/- 22.60 vs 153.35 +/- 22.7%,p=0.05], carotid IMT [1.14 +/- 0.388 vs 0.9 +/- 0.45 mm, p= p=0.04], low density lipoprotein [79.1 +/- 53.19 vs 53 .05 +/- 23.11 mg/dl, p=0.002] as well as fasting [p=0.05] and post prandial blood glucose [p=0.009], compared to twenty uncomplicated diabetic patients [group 2].Six diabetic patients with stroke and microaluminuria had a significant higher level of vWf [190.83 +/- 21.07 vs 93.750 +/- 14.36, p= 0.003], carotid IMT [p=0.009] low density lipoprotein [p=0.001], as well as fasting [p= 0.008], post prandial blood glucose [p=0.001], Cholesterol [p=0.03] and triglyceride level [p=0.04] compared to four diabetic patients with stroke but without microalbumiuria .Diabetic patients with stroke and microalbuminuria [6 patients] had a significant higher vWf level [190.83 +/- 21.07 vs 102.45 +/- 17.8%, p=0.04], low dinesty lipoprotiens [114.67 +/- 35.66 vs 67.64 +/- 13.17 mg/dl, p=0.002] fasting [0.008] and post prandial blood glucose [0.003] compared to 11 microalbuminuric type 2 diabetic patients. Diabetic patients with stroke and microalbuminuria [6 patients] had a significant higher vWf [190.83 +/- 21.07 vs 98.55 +/- 19.6% p=0.027], low dinesty lipoproteins [114.67 +/- 35.66 vs 35.22 +/- 20 mg/dl, p=0.0001], fasting, post prandial blood glucose, cholesterol and triglycerides levels compared to type 2 diabetic patients without stroke or microalbuminuria [9 patients]. Correltion between vWf and other risk factors in type 2 diabetic patients showed a positive correlation to Fasting, posprandial blood glucose, low denidty lipoprotein, microalbuminuria and intima media thickness. The results of this study indicate that among type 2 diabetic patients with MA, those with higher plasma levels of vWf have greater risk of macrovascular disease, so the risk of cerebrovascular stroke among microalbuminuric type 2 diabetic patients is much higher in association with high level of plasma Von Willebrand factor and low denisty lipoprotein than when these factors are absent, and we recommend measurement of plasma Von Willebrand factor in type 2 diabetic patients as a predictor of macrovascular complication . We also recommend mandatory measurement of low density lipoprotein cholesterol level in type 2 diabetic patients to help in prevention of cerebrovascular stroke