Urinary Albumin-to-Creatinine Ratio Tertiles Predict Risk of Diabetic Retinopathy Progression: A Natural History Study from The Adolescent Cardio-Renal Intervention Trial (AdDIT) observational cohort

Aims/hypothesis We hypothesised that adolescents with type 1 diabetes with a urinary albumin-to-creatinine ratio (ACR) in the upper tertile of the normal range (high-ACR) are at greater risk of 3-step diabetic retinopathy progression (3DR) independent of glycaemic control. Methods Prospective observational study in 710 normoalbuminuric adolescents with type 1 diabetes from the non-intervention cohorts of AdDIT (ISRCTN91419926). Participants were classified as ‘high-ACR’ or ‘low-ACR’ (lowest and middle ACR tertiles) using baseline standardised logACR. The primary outcome (3DR) was determined from centrally graded, standardised two-field retinal photographs. 3DR risk was determined using multivariable cox regression for the effect of high-ACR, with HbA1c, blood pressure (BP), LDL-cholesterol and BMI as covariates; diabetes duration was the time dependent variable. Results At baseline mean(SD) age was 14.3(1.6) years and diabetes duration 7.2(3.3) years. After a median 3.2 years, 83/710 (12%) had developed 3DR. In multivariable analysis, high-ACR (HR 2.03 95%CI: 1.29-3.20, p =0.002), higher mean HbA1c (1.34, 1.14-1.58, p=0.01) and higher baseline DBP SDS (1.43, 1.08-1.89, p=0.01) were independently associated with 3DR risk. Conclusions/interpretation High-ACR is associated with greater risk of 3DR in adolescents providing a target for future intervention studies.National Health and Medical Research Council of Australia (NHMRC) 632521, Juvenile Diabetes Foundation International, British Heart Foundation, Diabetes UK, Canadian Clinical Trial Network