Østergaard, Jakob A6; Thiel, Steffen7; Hovind, Peter4; Holt, Charlotte B6; Parving, Hans-Henrik4; Flyvbjerg, Allan8; Rossing, Peter4; Hansen, Troels K6
1 Department of Clinical Medicine - The Department of Endocrinology and Diabetes, Department of Clinical Medicine, Health, Aarhus University2 Department of Biomedicine - Forskning og uddannelse, Øst, Department of Biomedicine, Health, Aarhus University3 Department of Clinical Medicine - Medical Research Laboratory, Department of Clinical Medicine, Health, Aarhus University4 unknown5 Faculty Secretariat, The Faculty of Health Sciences, Health, Aarhus University6 Department of Clinical Medicine - The Department of Endocrinology and Diabetes, Department of Clinical Medicine, Health, Aarhus University7 Department of Biomedicine - Forskning og uddannelse, Øst, Department of Biomedicine, Health, Aarhus University8 Faculty Secretariat, The Faculty of Health Sciences, Health, Aarhus University
an 18 year follow-up study
AIMS/HYPOTHESIS: Increasing evidence links complement activation through the lectin pathway to diabetic nephropathy. Adverse complement recognition of proteins modified by glycation has been suggested to trigger complement auto-attack in diabetes. H-ficolin (also known as ficolin-3) is a pattern recognition molecule that activates the complement cascade on binding to glycated surfaces, but the role of H-ficolin in diabetic nephropathy is unknown. We aimed to investigate the association between circulating H-ficolin levels and the incidence of microalbuminuria in type 1 diabetes. METHODS: We measured baseline H-ficolin levels and tracked the development of persistent micro- and macroalbuminuria in a prospective 18 year observational follow-up study of an inception cohort of 270 patients with newly diagnosed type 1 diabetes. RESULTS: Patients were followed for a median of 18 years (range 1-22 years). During follow-up, 75 patients developed microalbuminuria, defined as a persistent urinary albumin excretion rate (UAER) above 30 mg/24 h. When H-ficolin levels were divided into quartile groups an unadjusted Cox proportional hazards regression model showed a significant association with risk of incident microalbuminuria during follow-up (HR, fourth vs first quartile, 2.45; 95% CI 1.24, 4.85) (p = 0.01). This remained significant after adjusting for HbA1c, systolic blood pressure, smoking and baseline UAER (HR 2.09; 95% CI 1.03, 4.25) (p = 0.04). CONCLUSIONS/INTERPRETATION: Our data suggest that high levels of the complement activating molecule H-ficolin are associated with an increased risk of future progression to microalbuminuria in patients with newly diagnosed type 1 diabetes.