Association between circulating cell adhesion molecules and risk of type 2 diabetes: A meta-analysis

Background and aims: Cell adhesion molecules (CAMs) are implicated in the initiation and progression of atherosclerosis, but their association with risk of type 2 diabetes remains inconsistent. This meta-analysis aimed to quantify this association with dose-response analysis in the general population without type 2 diabetes at baseline. Methods: Prospective studies, investigating the association of circulating (plasma/serum) CAMs, such as intercellular adhesion molecule-1 (ICAM-1), E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and P-selectin, with risk of type 2 diabetes, were included. The overall relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Results: Sixteen datasets from 15 studies were included. The overall RR was 1.88 (95% CI 1.59 to 2.23) per 1-ln mu g/ml increase in ICAM-1, and 2.44 (95% CI 1.90 to 3.12) per 1-ln mu g/ml increase in E-selectin. These associations were log-linearly shaped (both pnon-linearity> 0.05) and independent of traditional cardiovascular risk factors (all p < 0.05). ICAM-1 had comparable predictive ability as E-selectin (2.22 versus 2.66, p = 0.40). However, no significant association was observed for VCAM-1 (RR 1.20, 95% CI 0.73 to 1.98) or P-selectin (RR 1.01, 95% CI 0.64 to 1.59), and the added predictive value of circulating CAMs assessed by Integrated Discrimination Improvement to the basic prediction models was small (0.01 for ICAM-1, 0.003 for E-selectin, and 0.007 for VCAM-1). Conclusions: Elevated circulating CAMs, especially ICAM-1 and E-selectin, led to increased risk of type 2 diabetes in a dose-dependent manner, supporting the assumption that endothelial dysfunction contributes to the development of diabetes.