C-reactive protein (CRP),
fibrinogen, and
interleukin-6 (IL-6) are associated with
cardiovascular disease (CVD) and death in general populations. However, studies of these factors in
type 2 diabetes are limited. We studied their associations with the risk of major macrovascular events, microvascular complications, and mortality in patients with
type 2 diabetes who participated in the Action in Diabetes and
Vascular Disease:
Preterax and
Diamicron Modified Release Controlled Evaluation (ADVANCE) Study. 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 CVD or risk factors in the ADVANCE Study. All three
biomarkers of
inflammation were associated with an increased risk of macrovascular events and death in analyses adjusted for age, sex, and treatment groups. After further adjustment, only
IL-6 was an independent predictor of macrovascular events (hazard ratio per SD increase 1.37 [95% CI 1.24-1.51]) and death (1.35 [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 CVD or risk factors.