Markers of inflammation are cross-sectionally associated with microvascular complications and cardiovascular disease in type 1 diabetes - the EURODIAB Prospective Complications Study

Aims/hypothesis: The pathogenesis of vascular complications in type 1 diabetes is poorly understood, but may involve chronic, low-grade inflammation. We investigated the association of markers of inflammation with vascular complications in type 1 diabetes. Methods: A cross-sectional nested case- control study of the follow- up data of the EURODIAB Prospective Complications Study. This study included 543 individuals ( 278 men) with type 1 diabetes diagnosed at < 36 years of age. Cases ( n= 348) had complications of diabetes, controls ( n= 195) had no complications. Results: C- reactive protein, interleukin- 6 and tumour necrosis factor-alpha levels, which were combined in an inflammatory marker Z- score, were associated with albuminuria, retinopathy and cardiovascular disease. Calculated means ( 95% confidence intervals) of the marker Z-score were - 0.15 (- 0.22 to - 0.07), 0.10 (- 0.05 to 0.25), and 0.28 ( 0.15 to 0.41), p for trend < 0.0001, in individuals with normo-, micro- and macroalbuminuria; - 0.23 (- 0.33 to - 0.13), 0.14 ( 0.02 to 0.25) and 0.20 ( 0.07 to 0.32), p for trend < 0.0001, in individuals with no, non- proliferative and proliferative retinopathy; and - 0.28 (- 0.39 to - 0.18) and 0.06 (- 0.08 to 0.20), p< 0.001, in individuals without and with cardiovascular disease. Per 1 SD increase of the inflammatory marker Z-score, GFR decreased by - 4.6 (- 6.6 to - 2.6) ml per min per 1.73 m(2) ( p< 0.001). Conclusions/ interpretation: We have shown that markers of inflammation are strongly and independently associated with microvascular complications and cardiovascular disease in type 1 diabetes. These data suggest that strategies to decrease inflammatory activity may help to prevent the development of vascular complications in type 1 diabetes.