Elevated von Willebrand factor antigen predicts deterioration in diabetic peripheral nerve function

Plater, M. E.; Ford, Isobel; Dent, M. T.; Preston, F. E.; Ward, John D.

doi:10.1007/s001250050450

Cited by 7 publications

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“…It is noteworthy that renal and nerve damage have been found to be associated in diabetes [50]. Our finding of higher levels of vWF in females with diabetic neuropathy is also of interest, in view of the recent suggestion that plasma vWF concentration predicts progression of neuropathy in IDDM [51].…”

Section: Discussionsupporting

confidence: 60%

Fibrinogen and von Willebrand factor in IDDM: relationships to lipid vascular risk factors, blood pressure, glycaemic control and urinary albumin excretion rate: the EURODIAB IDDM complications study

et al. 1997

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The pathogenic mechanisms underlying the development of microvascular complications in insulin-dependent diabetes mellitus (IDDM) remain obscure despite the fact that retinopathy develops in the majority [1][2][3], and nephropathy in around 30 % [3,4]. Although duration of diabetes and poor glycaemic control are established risk factors, they appear to account for only a proportion of an individual's risk [5]. We have recently demonstrated that, in subjects with retinopathy but not those without, mean urinary albumin excretion rate increases steeply when the mean diastolic blood pressure rises above 75 mmHg. It thus appears that members of a subgroup of diabetic subjects may have abnormal renal vulnerability Diabetologia (1997) Summary The interrelationships between fibrinogen, von Willebrand factor, a marker of vascular endothelial cell damage, and serum lipids were explored in well-characterised subjects with insulin-dependent diabetes mellitus. The 2091 subjects were enrolled into a cross-sectional, clinic-based study of complications, from 16 European countries: the EURODIAB IDDM Complications study. The anticipated significant relationships between both plasma fibrinogen and plasma von Willebrand factor concentrations and age and glycaemic control, and between fibrinogen and body mass index, were noted. Fibrinogen, adjusted for age and glycated haemoglobin concentration, was also related to smoking habits and was higher in the quartiles with highest systolic and diastolic blood pressures. There was a clustering of vascular risk factors, with a positive relationship between plasma fibrinogen and serum triglyceride concentrations in both genders and between fibrinogen and total cholesterol in males. An inverse relationship between fibrinogen and high density lipoprotein cholesterol was also apparent in males. A prominent feature was a positive relationship between both fibrinogen and von Willebrand factor and albumin excretion rate (p < 0.001 and p < 0.003 respectively) in those with retinopathy but not in those without this complication. In view of previous observations on blood pressure and albuminuria in these subjects the findings are consistent with the hypothesis that microalbuminuria and increased plasma von Willebrand factor are due to endothelial cell perturbation in response to mildly raised blood pressure in subjects with retinopathy. Fibrinogen may also contribute to microvascular disease and its relationships to lipid vascular risk factors suggest a possible pathogenic role in arterial disease in diabetes. [Diabetologia (1997) to mildly raised blood pressure and that retinopathy is a close correlate of this risk [6].von Willebrand factor (vWF) is synthesised by vascular endothelial cells and megakaryocytes and an increased concentration in plasma can serve as a marker of endothelial cell damage [7][8][9]. Such an increase is a feature of diabetic nephropathy [10]. Recent studies in small numbers of subjects with IDDM suggest that vWF is a sensitive marker of incipient nephropathy and that a r...

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Section: Discussionsupporting

confidence: 60%

Fibrinogen and von Willebrand factor in IDDM: relationships to lipid vascular risk factors, blood pressure, glycaemic control and urinary albumin excretion rate: the EURODIAB IDDM complications study

et al. 1997

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“…In the present study serum vWF level is almost similar which is in contrast with previous findings 12, 13 . It was also reported that serum vWF is associated with duration of diabetes not acute change of blood glucose 32, 33 .…”

Section: Discussioncontrasting

confidence: 99%

Neuropathic changes in young type 2 diabetes mellitus related to high serum t-PA

Bhowmik

Hassan

Parvin³

et al. 2014

Bangladesh J Med Sci

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Abstract:Background and Aims: A substantial number of diabetic patients, diagnosed at relatively younger age, who don't fit to typical type 2 and type 1 class of diabetes. These patients usually present with very high level of glycemia. The uniqueness of this group of patient provide the opportunity to explore the pathophysiology of nerve functional status at an early stage of diabetes. The present study was aimed to determine markers of endothelial dysfunction and evaluate nerve functional status of a group of newly diagnosed clinically uncomplicated young diabetic patients. Material and Methods: A total number of 32 (male-13 and female-19) newly diagnosed young (diabetes diagnosed under 30 yrs) were consecutively recruited from BIRDEM Out-patient department and 30 age-, BMI-matched healthy subjects with no family history of diabetes up to second generation served as controls. Serum fructosamine was measured by reduction test with NBT method. Serum C-peptide, endothelin-1 and tissue plasminogen activator (t-PA) by ELISA and von Willibrand factor (vWF) by Radial Immunodiffusion (RID) methods. Urinary albumin measured by immunoturbidimetry method. Nerve functional status was evaluated by nerve conduction velocities (NCV), distal latencies (DL), compound muscle action potential (CAMP), F wave latencies (FWL), nerve action potential (SNAP) for motor and sensory nerve as appropriate following the standard protocol. Results: Severe hyperglycemia in the diabetic group was reflected in their mean (SD) fasting C-peptide and fructosamine level. Altered endothelial dysfunction, as evidenced by significantly high tissue plasminogen activator (t-PA) (p<0.001) in the diabetic group. Albumin creatinine ratio (ACR) was almost similar in the two groups. Ulnar distal latency was similar in both the groups. But its CAMP and NCV were significantly lower in the diabetic group (p<0.02-0.001). Ulnar F wave latency were significantly higher (p=0.016) in the diabetic group. Ulnar sensory conduction parameters did not show any difference between two groups. Peroneal motor and sural sensory functional status of the diabetic subjects showed similar trend like that of ulnar motor and sensory status. Peroneal nerve motor NCV was significantly negtively correlated with fasting glucose [r=-0.456, p=0.001]. Peroneal motor distal latency was significantly correlated with fasting fractosamine [r=0. 439, p=0.012]. Fasting fructosamine showed significant negative correlation with motor peroneal NCV [r=-0.572, p=0.001], motor ulnar NCV [r=-0.468, p=0.007], both ulnar and sural sensory NAP (p=0.02 for both]. On the basis of F wave latency 53% of diabetic subjects had diabetic neuropathy and markedly higher t-PA compared to nonneuropathy groups (p=0.001). Conclusions: The data suggest that (i) Young type 2 diabetic subjects had endothelial dysfunction at the time of diagnosis even in the presence of normoalbuminuria state; (ii) Motor nerve conduction parameters are affected more than the sensory component; (iii) F wave latencies are more frequently a...

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“…Diabetes is also described as a hypercoagulable state and rheological parameters and endothelial products have been shown to be abnormal in diabetic subjects with microangiopathy [31,32]. Plater et al [33] specifically demonstrated elevated von Willebrand factor antigen (vWFag) at baseline as a predictor of deterioration in diabetic nerve function [33], although Ford et al [16] could not demonstrate elevated vWFag when measured by ELISA. In addition no difference was found in PAI, plasminogen, fibrinogen and plasma viscosity.…”

Section: Discussionmentioning

confidence: 99%

The potential role of cell adhesion molecules in the pathogenesis of diabetic neuropathy

et al. 1998

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Peripheral neuropathy is one of the commonest complications of diabetes mellitus with a prevalence of around 30±45 % [1±3]. The majority of patients will have developed neuropathy 10±20 years after the onset of diabetes [4] and it is an important cause of foot ulceration, Charcot joints and amputation, with increasing morbidity and mortality. There is therefore an urgent need for prevention of diabetic neuropathy and its sequelae.The exact pathogenesis of diabetic neuropathy is unclear, with both metabolic and vascular factors having been implicated [5]. Microvascular disease may play an important role in the causation and exacerbation of diabetic neuropathy [6]. Histopathological studies have shown thickening of endoneurial and perineurial vessel walls, hyperplasia of capillary endothelial cells and increased plugging of vessels in neuropathic patients [7±9].Cell adhesion molecules (CAMs) have been demonstrated to be increased in diabetes mellitus, both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) [10±13]. They have been implicated in the development of microvascular complications Diabetologia (1998) Summary Cross-sectional studies have shown plasma cell adhesion molecules (CAMs) to be increased in patients with diabetes-related complications. In the first prospective study of CAMs, we have shown that plasma CAMs may be a predictor of the development of diabetic neuropathy. We followed up 28 diabetic patients (13 neuropathic) over a 5 year period, starting from 1991. All patients had peroneal nerve conduction velocity (PNCV), vibration perception threshold and plasma CAMs measured at baseline and follow-up. We found P-selectin and intercellular adhesion molecule ±1 (ICAM-1) to be increased at baseline in patients with neuropathy compared to non-neuropathic patients. P-selectin and Eselectin were also found to be significantly higher at baseline in patients who at follow-up showed deterioration in PNCV of more than 3 m/s (p < 0.05; p = 0.01; respectively). P-selectin and ICAM-1 strongly correlated with PNCV. Univariate and multivariate regression analyses showed a significant inverse association between increasing log P-selectin, log E-selectin and log ICAM-1 with decreasing PNCV, and remained significant even after adjustment for glycaemic control. P-selectin and E-selectin, odds ratios of 8.8 (95 %CI: 1.1±68.8; p = 0.038) and 12.5 (95 % CI: 1.2±132.1; p = 0.036), respectively, were significantly associated with the risk of deterioration of PNCV after 5 years. This study suggests that plasma cell adhesion molecules may play an important role in the development and progression of peripheral neuropathy in diabetes mellitus. [Diabetologia (1998) 41: 330±336]

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Elevated von Willebrand factor antigen predicts deterioration in diabetic peripheral nerve function

Cited by 7 publications

References 0 publications

Fibrinogen and von Willebrand factor in IDDM: relationships to lipid vascular risk factors, blood pressure, glycaemic control and urinary albumin excretion rate: the EURODIAB IDDM complications study

Fibrinogen and von Willebrand factor in IDDM: relationships to lipid vascular risk factors, blood pressure, glycaemic control and urinary albumin excretion rate: the EURODIAB IDDM complications study

Neuropathic changes in young type 2 diabetes mellitus related to high serum t-PA

The potential role of cell adhesion molecules in the pathogenesis of diabetic neuropathy

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