Østergaard, Jakob A2; Thiel, Steffen2; Hovind, Peter4; Holt, Charlotte B2; Parving, Hans-Henrik5; Flyvbjerg, Allan2; Rossing, Peter2; Hansen, Troels K2
1 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 unknown3 Section of Diagnostic Sciences, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet4 Section of Diagnostic Sciences, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet5 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
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.
Diabetologia, 2014, Vol 57, Issue 10, p. 2201-2207