Increased serum concentration of von Willebrand factor in non-insulin dependent diabetic patients with and without diabetic nephropathyBMJ 1995; 311 doi: https://doi.org/10.1136/bmj.311.7017.1405 (Published 25 November 1995) Cite this as: BMJ 1995;311:1405
- J-W Chen, research fellowa,
- M-A Gall, research fellowa,
- M Deckert, aboratory techniciana,
- J S Jensen, research fellowb,
- H-H Parving, chief physiciana
- aSteno Diabetes Center, 2820 Gentofte, Denmark
- bThe Copenhagen City Heart Study, Rigshospitalet, University of Copenhagen, 2200 Copenhagen, Denmark
- aCorrespondence to: Dr Parving.
- Accepted 30 August 1995
Cardiovascular morbidity and mortality are increased in non-insulin dependent diabetic patients, particularly if microalbuminuria or macroalbuminuria is present.1 A systemic endothelial dysfunction may be the pathogenic factor linking albuminuria to atherosclerosis in these patients,2 as originally suggested in insulin dependent patients.3 Previous studies have suggested that serum von Willebrand factor concentration is an indicator of generalised endothelial damage and contributes to platelet aggregation to the vascular endothelium, the first step in thrombosis. We evaluated the validity of this concept by measuring the serum concentrations of von Willebrand factor in non-insulin dependent diabetic patients with or without diabetic nephropathy.
Patients, methods, and results
We studied a prevalence cohort of white non-insulin dependent diabetic patients under 76.1 Patients were stratified into three groups: those with normoalbuminuria (</=30 mg/24 h, n=323), microalbuminuria (31-299 mg/24 h, n=151), and persistent macroalbuminuria (>/=300 mg/24 h in two of three consective samples, n=75). Diabetic nephropathy was diagnosed in 47 of 75 macroalbuminuric patients on the basis of previously established clinical (n=20) or biopsy (n=27) based criteria.4 Sixty six healthy non-diabetic subjects served as controls. We analysed the results by using the statistics package SPSS for Windows version 6.0.
The table gives the results. The serum concentrations of von Willebrand factor, measured by microenzyme linked immunoabsorbent assay,3 were significantly higher in all of the diabetic groups than in the controls. Furthermore, the patients with a urinary albumin excretion rate above 30 mg/24 h had significantly higher serum von Willebrand factor concentrations than the normoalbuminuric patients. This was the case even after adjustment for the presence of cardiovascular disease (difference 1.15 (95% confidence interval 1.07 to 1.24) U/ml).
There was a positive association between the logarithmically transformed urinary albumin excretion rate and serum von Willebrand factor concentration, which was independent of age, sex, blood pressure, tobacco smoking, plasma total cholesterol concentration, haemoglobin A1c, and presence of cardiovascular disease (multiple linear regression analysis: r=0.20; P<0.0001). The presence of cardiovascular disease (World Health Organisation questionnaire, Minnesota coded electrocardiograms) was associated with higher rates of urinary albumin excretion, together with higher serum concentrations of von Willebrand factor (logistic regression analysis: r=0.16; P<0.0001 and r=0.11; P<0.005, respectively). The positive association between urinary albumin excretion and cardiovascular disease was independent of age, sex, blood pressure, tobacco smoking, plasma total cholesterol concentration, and haemoglobin A1c. Apart from the 47 patients with diabetic nephropathy, the normoalbuminuric and microalbuminuric subjects with cardiovascular disease had higher concentrations of von Willebrand factor than similar patients without these complications: median 1.66 (range 0.54-4.04) v 1.53 (0.44-6.16) U/ml (P<0.05), and 1.95 (0.67-4.45) v 1.69 (0.53-3.55) U/ml (P<0.05), respectively, though the 47 patients with diabetic nephropathy did not: 1.90 (0.59-7.53) v 2.30 (1.21-4.56) U/ml (NS).(The macroalbuminuric group (n=28) was excluded from this analysis.)
Our cross sectional study showed a progressive rise in serum concentration of von Willebrand factor with increasing urinary albumin excretion in non-insulin dependent diabetic patients. All diabetic groups had raised concentrations compared with healthy subjects. A lack of correlation between blood glucose concentration and von Willebrand factor has previously been shown. The presence of cardiovascular disease was associated with higher concentrations of von Willebrand factor in non-albuminuric patients. In agreement with previous studies, no association between diabetic retinopathy and von Willebrand factor was found.3
Recent studies have shown that a high serum concentration of von Willebrand factor is an independent predictor of subsequent acute coronary syndromes in patients with angina pectoris and in survivors of myocardial infarction.5 Furthermore, in non-insulin dependent diabetic patients an increased risk of new cardiovascular events is present only in patients with a von Willebrand factor concentration above the median, but not in patients with lower values.2
Our study supports generalised endothelial injury as a potential link between abnormally raised urinary albumin excretion and macroangiopathy in non-insulin dependent diabetic patients. The increased thrombogenic activity may also contribute to the cardiovascular events.
Conflict of interest None.