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

Abstract

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]

Erectile and endothelial dysfunction in Type II diabetes: a possible link

“…Soluble forms of CAMs are also considered to be an index of endothelial activation or even a molecular marker of early atherosclerosis [26]. In one study, plasma CAMs were associated with the risk of deterioration of peripheral neuropathy in diabetic patients [27]. Our findings suggest that diabetic patients with ED present an impairment of endothelial functions and indices of endothelial activation more marked than diabetic patients without ED.…”

Differential Association Between Biomarkers of Subclinical Inflammation and Painful Polyneuropathy: Results From the KORA F4 Study

“…Increasing plasma levels of soluble cell adhesion molecules (sICAM-1, E-selectin) were associated with decreasing peroneal nerve conduction velocity during a 5-year period in a small group of diabetic patients, which indeed indicated a vascular involvement in the development and progression of DSPN (28). Elevated concentrations of cell adhesion molecules such as sICAM-1 in the circulation result from increased expression and/or shedding of these proteins from the cell surface in response to endothelial activation.…”

The effects of short-term, rapid glycemic control on the peroneal nerve function and serum VCAM-1 and AGE in type 2 diabetic patients in Malaysia

“…An increase in the level of CAMs has been demonstrated in diabetic patients with microvascular disease. [13][14][15] In particular, a previous study on peroneal nerve function showed significant association between increasing levels of VCAM and worsening peroneal nerve function. [15] In our study, despite the lack of signiÞ cant changes in the serum VCAM-1 levels with glycemic improvement in either group, patients with neuropathy had significantly higher VCAM-1 values at baseline compared to those without.…”

“…[13][14][15] In particular, a previous study on peroneal nerve function showed significant association between increasing levels of VCAM and worsening peroneal nerve function. [15] In our study, despite the lack of signiÞ cant changes in the serum VCAM-1 levels with glycemic improvement in either group, patients with neuropathy had significantly higher VCAM-1 values at baseline compared to those without. [8][9][10][11][12][13][14][15] We also found that an increase in VCAM-1 levels correlated with an increase in AGE, supporting Þ ndings from other studies which showed that AGE products result in the release of CAMs through interaction with the receptors for AGE (RAGE).…”

“…[8][9][10][11][12][13][14] One study showed that these adhesion molecules were important long-term predictors of DPN. [15] Effects of glycemic control on the peripheral nerve function and these inß ammatory markers in the short-term have not been well studied.…”