Abstract
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.
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Abbreviations
- eGFR:
-
Estimated glomerular filtration rate
- MACs:
-
Membrane-attack complexes
- MBL:
-
Mannan-binding lectin
- UAER:
-
Urinary albumin excretion rate
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Acknowledgements
The Danish Diabetes Academy is thanked for supporting this study.
Funding
This work was supported by the Novo Nordisk Foundation and research grants from the Danish Diabetes Academy supported by the Novo Nordisk Foundation.
Duality of interest
No potential conflicts of interest relevant to this article were reported. PR reports having received lecture fees from Novartis Sanofi, Bristol Myers Squibb, Astra Zeneca and Boehringer Ingelheim, and a research grant from Novo Nordisk and Novartis; he has also served as a consultant for Merck, Astra Zeneca BMS and has equity interest in Novo Nordisk.
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All authors contributed to the conception and design of the study; the collection, research and interpretation of the data; and to the review and editing of the manuscript. JAØ wrote the manuscript draft. All authors approved the final version. JAØ and TKH are the guarantors of this work.
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Østergaard, J.A., Thiel, S., Hovind, P. et al. Association of the pattern recognition molecule H-ficolin with incident microalbuminuria in an inception cohort of newly diagnosed type 1 diabetic patients: an 18 year follow-up study. Diabetologia 57, 2201–2207 (2014). https://doi.org/10.1007/s00125-014-3332-7
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DOI: https://doi.org/10.1007/s00125-014-3332-7