Soluble ST2 associates with diabetes but not established cardiovascular risk factors: a new inflammatory pathway of relevance to diabetes?

Miller, A. M. et al. (2012) Soluble ST2 associates with diabetes but not established cardiovascular risk factors: a new inflammatory pathway of relevance to diabetes? PLoS ONE, 7(10), e47830. (doi:10.1371/journal.pone.0047830) (PMID:23112853) (PMCID:PMC3480428)

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Publisher's URL: http://dx.doi.org/10.1371/journal.pone.0047830

Abstract

Preliminary data mostly from animal models suggest the sST2/IL-33 pathway may have causal relevance for vascular disease and diabetes and thus point to a potential novel inflammatory link to cardiometabolic disease. However, the characterisation of sST2 levels in terms of metabolic or vascular risk in man is completely lacking. We sought to address this gap via a comprehensive analysis of risk factor and vascular correlates of sST2 in a cross-sectional study (pSoBid). We measured sST2 in plasma in 639 subjects and comprehensively related it to cardiovascular and diabetes risk factors and imaged atherosclerosis measures. Circulating sST2 levels increased with age, were lower in women and in highest earners. After adjusting for age and gender, sST2 levels associated strongly with markers of diabetes, including triglycerides [effect estimate (EE) per 1 standard deviation increase in sST2:1.05 [95%CI 1.01,1.10]), liver function (alanine aminotransaminase [ALT] and γ-glutamyl transferase [GGT]: EE 1.05 [1.01,1.09] and 1.13 [1.07,1.19] respectively), glucose (1.02 [1.00,1.03]) and sICAM-1 (1.05 [1.02,1.07]). However, sST2 levels were not related to smoking, cholesterol, blood pressure, or atheroma (carotid intima media thickness, plaque presence). These results suggest that sST2 levels, in individuals largely without vascular disease, are related principally to markers associated with diabetes and ectopic fat and add support for a role of sST2 in diabetes. Further mechanistic studies determining how sST2 is linked to diabetes pathways may offer new insights into the inflammatory paradigm for type 2 diabetes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and McConnachie, Dr Alex and Welsh, Dr Paul and Asquith, Dr Darren and Purves, Mr David and Miller, Dr Ashley and Ford, Professor Ian and Shiels, Professor Paul and Cavanagh, Professor Jonathan and Velupillai, Dr Yoganathan and McLean, Dr Jennifer and Packard, Professor Chris and Sattar, Professor Naveed
Authors: Miller, A. M., Purves, D., McConnachie, A., Asquith, D. L., Batty, G. D., Burns, H., Cavanagh, J., Ford, I., McLean, J. S., Packard, C. J., Shiels, P. G., Turner, H., Velupillai, Y. N., Deans, K. A., Welsh, P., McInnes, I. B., and Sattar, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Published Online:24 October 2012
Copyright Holders:Copyright © 2012 The Authors
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
483611Interleukin-33: A Novel Cytokine in the Inflammation of Atherosclerosis and ObesityAshley MillerBritish Heart Foundation (BHF)FS/08/035/25309III -IMMUNOLOGY
483612Interleukin-33: A Novel Cytokine in the Inflammation of Atherosclerosis and ObesityAshley MillerBritish Heart Foundation (BHF)FS/08/035/25309III -IMMUNOLOGY