4.6 Article

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

Journal

PLOS ONE
Volume 7, Issue 10, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0047830

Keywords

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Funding

  1. Medical Research Council UK
  2. Wellcome Trust
  3. British Heart Foundation
  4. Glasgow Royal Infirmary Research Endowment Fund and NHS Grampian Endowments
  5. Glasgow Centre for Population Health
  6. Scottish Government
  7. British Heart Foundation [FS/08/035/25309] Funding Source: researchfish

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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 c-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.

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