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.