Vascular effects of ACE inhibitors and statins in adolescents with type 1 diabetes: the Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT)

An increased albumin-creatinine ratio (ACR) within the normal range can identify adolescents at higher risk of developing adverse cardio-renal outcomes as they progress into adulthood. Utilizing a parallel randomized controlled trial and observational cohort study, we characterized the progression of vascular phenotypes throughout this important period and investigated the effect of ACE inhibitors and statins in high-risk adolescents. Endothelial function (flow-mediated dilation; FMD and reactive hyperemia index; RHI) and arterial stiffness (carotid-femoral pulse wave velocity; PWV) were assessed in 158 high-risk participants recruited to a randomized, double-blind placebo-controlled 2x2 factorial trial (RCT) of ACE inhibitors and/or statins in adolescents with type 1 diabetes (AdDIT). Identical measures were also assessed in 215 lower-risk individuals recruited to a parallel observational study. In the RCT, high-risk patients randomized to ACE inhibitors had improved FMD after 2-4 years of follow-up (mean [95%CI]: 6.6%[6.0,7.2] vs. 5.3%[4.7,5.9]; p=0.005), whereas no effect was observed following statin use (6.2%[5.5,6.8] vs. 5.8%[5.1,6.4]; p=0.358). In the observational study, high-risk ACR patients showed evidence of endothelial dysfunction at the end of follow-up (FMD= 4.8%[3.8,5.9] vs. 6.3% [5.8,6.7] for high-risk vs. low-risk groups; p=0.015). Neither RHI nor PWV were affected by either treatment (p > 0.05 for both), but both were found to increase over the duration of follow-up (0.07[0.03,0.12]; p=0.001 and 0.5m/s[0.4,0.6]; p