6.1 LOW-GRADE INFLAMMATION AND ENDOTHELIAL DYSFUNCTION PRECEDE THE INCREASE IN PULSE PRESSURE IN TYPE 1 DIABETES:A 20-YEAR LONGITUDINAL STUDY

Abstract

Purpose: To investigate, longitudinally, whether increases in markers of inflammation (CRP, sICAM-1) and endothelial dysfunction (sICAM-1, sVCAM-1) are associated with and precede the increase in pulse pressure (PP) in individuals with type-1 diabetes (DM1). Methods: Inception cohort of 277 DM1 patients (114 women; mean age at diagnosis: 27.5±13.8 yrs) who were consecutively admitted, upon diagnosis, between Sep’79–Aug’84 to an outpatient diabetic clinic (Gentofte, Denmark). Throughout a follow-up period of >20 yrs, patients’ PP, other risk factors, and CRP, sICAM-1 and sVCAM-1 were measured repeatedly (at 3–4 months intervals). Associations were analysed with generalized estimating equations (GEEs) and adjusted for sex, age at diagnosis, smoking, anti-hypertensive treatment and MAP. Results: PP increased by 0.53 mmHg/yr, CRP by 0.033mg/L/yr, sICAM-1 by 1.8 ng/ml/yr and sVCAM-1 by 1.8 ng/ml/yr over the 20-yr longitudinal period (all p<0.001). Higher levels of ln-CRP, sICAM-1 and sVCAM-1 were all significantly associated with higher levels of PP: 0.53 mmHg (95%CI: 0.05–1.00), 1.09 mmHg (0.53–1.66) and 0.94 mmHg (0.40–1.48) per SD increase in marker, respectively. In addition, levels of sICAM-1 and sVCAM-1, but not ln-CRP, at any time point, were also associated with increases in PP occurring in the 2 yrs thereafter: 0.56 mmHg (0.18–0.94), 0.53 mmHg (0.17–0.90) and −0.01 mmHg (−0.38 −0.35) per SD increase in marker, respectively. Adjustments for other risk factors did not change these associations. Conclusion: Life-course increases in low-grade inflammation/endothelial dysfunction are associated with and precede increases in PP, supporting the view of their involvement in the development of premature arterial stiffening in diabetes.