Are elevated circulating intercellular adhesion molecule 1 levels more strongly predictive of diabetes than vascular risk? Outcome of a prospective study in the elderly

Abstract

Aims/hypothesis The aim of this prospective study was to determine whether circulating intercellular adhesion molecule (ICAM) 1, as a potential surrogate of 'endothelial activation', is more strongly associated with risk of vascular events than with incident diabetes. MethodsWe related baseline ICAM-1 levels to vascular events (866 CHD and stroke events in 5,685 participants) and incident diabetes (292 in 4,945 without baseline diabetes) in the elderly over 3.2 years of follow-up. Results ICAM-1 levels correlated positively with triacylglycerol but negatively with LDL-and HDL-cholesterol. ICAM-1 levels were higher in those who developed diabetes (388.6±1.42 vs 369.4±1.39 ng/ml [mean±SD], p=0.011) and remained independently associated with newonset diabetes (HR 1.84, 95% CI 1.26-2.69, p=0.0015 per unit increase in log[ICAM-1] after adjusting for classical risk factors and C-reactive protein). By contrast, ICAM-1 levels were not significantly (p=0.40) elevated in those who had an incident vascular event compared with those who remained event-free, and corresponding adjusted risk associations were null (HR 0.98, 95% CI 0.80-1.22, p= 0.89) in analyses adjusted for other risk factors. Conclusions/interpretation We show that elevated ICAM-1 levels are associated with risk of incident diabetes in the elderly at risk, despite no association with incident cardiovascular disease risk. We suggest that perturbations in circulating ICAM-1 levels are aligned more towards diabetes risk.

Soluble ST2 Associates with Diabetes but Not Established Cardiovascular Risk Factors: A New Inflammatory Pathway of Relevance to Diabetes?

“…A large body of evidence points towards the involvement of subclinical, low-grade inflammation and increased systemic levels of acute phase proteins, cytokines and adhesion molecules in patients with T2D [4]. Previous studies show that sICAM-1 predicts diabetes [30], and sICAM-1 associates more strongly with diabetic risk than cardiovascular risk [31]. Furthermore, it has been shown that endothelial cells can secrete sST2 in response to treatment with various inflammatory mediators [32].…”

Microvascular Dysfunction Is Associated With a Higher Incidence of Type 2 Diabetes Mellitus

“…All articles were published in English after 1994. We found 15 prospective population-based cohort studies, [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] 3 prospective nested case-control studies, [31][32][33] and 5 prospective case-cohort studies. [34][35][36][37][38] The studies examined mainly white participants from Europe, the United States, and Australia.…”

“…Eleven studies 17,22,26,28,31,32,[34][35][36][37][38] investigated the association of microvascular dysfunction as measured by plasma markers of endothelial dysfunction and incident T2DM. Table I in the online-only Data Supplement shows a higher incidence of T2DM at higher levels of sE-selectin, sICAM-1, and vWF at baseline.…”

“…The prospective study of pravastatin in the elderly at risk 26 1.22 (1.08-1.38) 1 .4 ng/ml* The women's health initiative observational study 32 1.20 (1.06-1.34) 8 9.3 ng/ml 1.21 (1.11-1.31) Test for overall effect: Z = 4.53 (P < 0.001)…”

“…) The remaining 4 studies 22,26,32,36 were included in the meta-analysis. With regard to peripheral vascular reactivity, only 1 study 25 was available ( Figure 2).…”