Circulating Inflammatory Markers and The Risk of Vascular Complications and Mortality in People With Type 2 Diabetes Mellitus and Cardiovascular Disease or Risk Factors: The Advance Study
- Gordon Lowe1⇑,
- Mark Woodward2,
- Graham Hillis2,
- Ann Rumley1,
- Qiang Li2,
- Stephen Harrap3,
- Michel Marre4,
- Pavel Hamet5,
- Anushka Patel2,
- Neil Poulter6 and
- John Chalmers2
- 1From the Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
- 2The George Institute for Global Health, University of Sydney, Australia
- 3University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia
- 4Hôpital Bichat-Claude Bernard and Université Paris 7, Paris
- 5Centre Hospitalier de I’Université de Montreal and Université de Montreal, Montreal
- 6Imperial College and St Marys Hospital, London
- Corresponding Author: Prof Gordon Lowe, E-mail:
C-reactive protein (CRP), fibrinogen, and interleukin-6 (IL-6), are associated with cardiovascular disease and death in general populations. However, studies in type 2 diabetes are limited. We studied their associations with risk of major macrovascular events, microvascular complications and mortality in patients with type 2 diabetes who participated in the ADVANCE trial. Plasma CRP, fibrinogen and IL-6 levels were determined in a case-cohort study (n=3,865) nested within the 11,140 men and women with type 2 diabetes and baseline cardiovascular disease or risk factors in the ADVANCE trial. All three biomarkers of inflammation were associated with an increased risk of macrovascular events and death in analyses adjusting for age, sex and treatment groups. After further adjustment, only IL-6 was an independent predictor of macrovascular events (hazard ratio [HR] per SD increase 1.37, 95% confidence interval [CI] 1.24-1.51); and death (HR 1.35, 95% CI 1.23-1.49). IL-6 significantly improved the prediction of macrovascular events and death. After adjustment, none of the markers predicted microvascular complications. We conclude that IL-6 levels, but not CRP or fibrinogen levels, add significantly to the prediction of macrovascular events and mortality in individuals with type 2 diabetes who have baseline cardiovascular disease or risk factors.
- Received November 22, 2012.
- Accepted November 7, 2013.
- © 2013 by the American Diabetes Association.
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