The potential role of cell adhesion molecules in the pathogenesis of diabetic neuropathy.
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 E-selectin 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.
Jude
E B
EB
Department of Medicine/Diabetes, Manchester Royal Infirmary, UK.
Abbott
C A
CA
Young
M J
MJ
Anderson
S G
SG
Douglas
J T
JT
Boulton
A J
AJ
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000502:physiology*; D003929:Diabetic Neuropathies / Q000097:blood / Q000209:etiology*; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008875:Middle Aged; D009431:Neural Conduction / Q000502:physiology; D019007:P-Selectin / Q000097:blood; D017933:Peripheral Nervous System / Q000502:physiology; D011446:Prospective Studies; D012016:Reference Values; D012044:Regression Analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D015415:Biomarkers; D001786:Blood Glucose; D015815:Cell Adhesion Molecules; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1