Journal
DIABETIC MEDICINE
Volume 28, Issue 10, Pages 1201-1205Publisher
WILEY
DOI: 10.1111/j.1464-5491.2011.03311.x
Keywords
acute cerebral infarction; acute myocardial infarction; epidemiology; risk factors; Type 2 diabetes
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Funding
- Diabetes Research and Wellness Foundation, UK
- HEFCE Clinical Senior Lecturer award
- Northern Regional Research Training Fellowship
- Manchester Academic Health Sciences Centre (MAHSC)
- NIHR Manchester Biomedical Research Centre
- Freeman Hospital Trustees
- GlaxoSmithKline
- Novo Nordisk
- Eli Lilly
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Aims To estimate the coronary heart disease and cardiovascular disease risk associated with novel biomarkers in Type 2 diabetes mellitus. Methods We measured baseline peripheral blood concentrations of soluble E-selectin, factor XIIa, thrombin-antithrombin III complex and plasminogen activator inhibitor-1 in 86 patients with Type 2 diabetes free of known coronary heart disease. We used Cox proportional hazard models to estimate multivariable-adjusted hazard ratios associated with biomarker levels for 10-year coronary heart disease risk (n = 33 events) or total cardiovascular disease risk (n = 45 events). Results At baseline, mean (SD) age was 62 years (7 years); 62 were men; and 43 had microalbuminuria. Soluble E-selectin demonstrated cross-sectional relationships with glucose and factor XIIa was related to plasminogen activator inhibitor-1 and triglycerides (all P < 0.05). Baseline log soluble E-selectin was significantly related to incident coronary heart disease and cardiovascular disease. Hazard ratios (95% CIs) associated with a 1-unit increase in log soluble E-selectin in age-and sex-adjusted models were: coronary heart disease : 4.6 (95% CI 1.9-11.3), P = 0.001; cardiovascular disease: 3.6 (95% CI 1.7-7.4, P = 0.001); and in multivariable-adjusted models were: coronary heart disease: 2.9 (95% CI 1.2-7.1, P = 0.02); cardiovascular disease: 2.3 (95% CI 1.1-4.8), P = 0.02. Factor XIIa was significantly related to incident cardiovascular disease. The hazard ratios associated with a 1-unit increase in factor XIIa in age-and sex-adjusted models was 1.5 (95% CI 1.1-1.9, P = 0.003) and in a multivariable-adjusted model was 1.3 (95% CI 1.0-1.6, P = 0.047). Plasminogen activator inhibitor-1 and thrombin-antithrombin III complex were not related to cardiovascular disease events. Conclusions In our study, soluble E-selectin and factor XIIa were significantly related to 10-year incident macrovascular events in patients with Type 2 diabetes. These preliminary findings call for replication in larger studies.
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