Soluble ST2 associates with diabetes but not established cardiovascular risk factors

a new inflammatory pathway of relevance to diabetes?

Ashley M. Miller, David Purves, Alex McConnachie, Darren L. Asquith, G. David Batty, Harry Burns, Jonathan Cavanagh, Ian Ford, Jennifer S. McLean, Chris J. Packard, Paul G. Shiels, Helen Turner, Yoga N. Velupillai, Kevin A. Deans, Paul Welsh, Iain B. McInnes, Naveed Sattar

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article numbere47830
Number of pages7
JournalPLoS ONE
Volume7
Issue number10
DOIs
Publication statusPublished - 24 Oct 2012

Fingerprint

Medical problems
Vascular Diseases
Blood Vessels
diabetes
risk factors
Carotid Intima-Media Thickness
Atherosclerotic Plaques
Transferases
Alanine
Type 2 Diabetes Mellitus
Atherosclerosis
vascular diseases
Triglycerides
Animal Models
Cross-Sectional Studies
Smoking
Fats
Cholesterol
Blood Pressure
blood vessels

Keywords

  • soluble ST2
  • diabetes
  • cardiovascular risk factors

Cite this

Miller, Ashley M. ; Purves, David ; McConnachie, Alex ; Asquith, Darren L. ; Batty, G. David ; Burns, Harry ; Cavanagh, Jonathan ; Ford, Ian ; McLean, Jennifer S. ; Packard, Chris J. ; Shiels, Paul G. ; Turner, Helen ; Velupillai, Yoga N. ; Deans, Kevin A. ; Welsh, Paul ; McInnes, Iain B. ; Sattar, Naveed. / Soluble ST2 associates with diabetes but not established cardiovascular risk factors : a new inflammatory pathway of relevance to diabetes?. In: PLoS ONE. 2012 ; Vol. 7, No. 10.
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title = "Soluble ST2 associates with diabetes but not established cardiovascular risk factors: a new inflammatory pathway of relevance to diabetes?",
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.",
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author = "Miller, {Ashley M.} and David Purves and Alex McConnachie and Asquith, {Darren L.} and Batty, {G. David} and Harry Burns and Jonathan Cavanagh and Ian Ford and McLean, {Jennifer S.} and Packard, {Chris J.} and Shiels, {Paul G.} and Helen Turner and Velupillai, {Yoga N.} and Deans, {Kevin A.} and Paul Welsh and McInnes, {Iain B.} and Naveed Sattar",
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Miller, AM, Purves, D, McConnachie, A, Asquith, DL, Batty, GD, Burns, H, Cavanagh, J, Ford, I, McLean, JS, Packard, CJ, Shiels, PG, Turner, H, Velupillai, YN, Deans, KA, Welsh, P, McInnes, IB & Sattar, N 2012, 'Soluble ST2 associates with diabetes but not established cardiovascular risk factors: a new inflammatory pathway of relevance to diabetes?', PLoS ONE, vol. 7, no. 10, e47830. https://doi.org/10.1371/journal.pone.0047830

Soluble ST2 associates with diabetes but not established cardiovascular risk factors : a new inflammatory pathway of relevance to diabetes? / Miller, Ashley M.; Purves, David; McConnachie, Alex; Asquith, Darren L.; Batty, G. David; Burns, Harry; Cavanagh, Jonathan; Ford, Ian; McLean, Jennifer S.; Packard, Chris J.; Shiels, Paul G.; Turner, Helen; Velupillai, Yoga N.; Deans, Kevin A.; Welsh, Paul; McInnes, Iain B.; Sattar, Naveed.

In: PLoS ONE, Vol. 7, No. 10, e47830, 24.10.2012.

Research output: Contribution to journalArticle

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T1 - Soluble ST2 associates with diabetes but not established cardiovascular risk factors

T2 - a new inflammatory pathway of relevance to diabetes?

AU - Miller, Ashley M.

AU - Purves, David

AU - McConnachie, Alex

AU - Asquith, Darren L.

AU - Batty, G. David

AU - Burns, Harry

AU - Cavanagh, Jonathan

AU - Ford, Ian

AU - McLean, Jennifer S.

AU - Packard, Chris J.

AU - Shiels, Paul G.

AU - Turner, Helen

AU - Velupillai, Yoga N.

AU - Deans, Kevin A.

AU - Welsh, Paul

AU - McInnes, Iain B.

AU - Sattar, Naveed

PY - 2012/10/24

Y1 - 2012/10/24

N2 - 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.

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