Objective: To investigate, in a prospective cohort of individuals with type 1 diabetes: 1) the association between an aggregated z-score of low-grade inflammation markers (CRP, IL-6, sPLA2 and sICAM-1) and pulse pressure (PP), as a marker of arterial stiffness, and 2) the association of low-grade inflammation with incident fatal and non-fatal cardiovascular disease (CVD) and the potential mediating role of PP herein.

Methods: We prospectively followed 339 individuals with type 1 diabetes who were free of CVD at study entry and in whom brachial PP and markers of low-grade inflammation were measured at baseline. Data were analysed with linear and Cox-regression models, and all results presented are adjusted for age, sex, duration of diabetes, eGFR, UAE, MAP, BMI, total cholesterol, smoking, endothelial dysfunction and the use of antihypertensive medication.

Results: PP increased with 3.2 mmHg (95%CI: 0.4–6.0, p=0.025) per SD increase in the inflammation score. During the course of follow-up [median duration: 12.3 yrs (IQR: 7.6–12.5)], 85 individuals suffered a fatal (n=48) and/or non-fatal (n=53) CVD event. Low-grade inflammation was associated with higher incidence of CVD [HR=1.56 (1.02–2.40), p=0.042], as was PP (per 10 mmHg increase): HR=1.27 (1.08–1.48), p=0.007. Additional adjustment for PP attenuated the association between inflammation and incident CVD with ∼20% to HR=1.45 (0.96–2.21), p=0.106.

Conclusions: Arterial stiffness, as expressed by PP, can partially explain the increased CVD associated with a higher low-grade inflammatory status in patients with type 1 diabetes. Treating inflammation may be a means to reduce the accelerated arterial stiffening that characterize these patients.