Incident microalbuminuria and complement factor mannan-binding lectin-associated protein 19 in people with newly diagnosed type 1 diabetes.

J A Østergaard, S Thiel, I T Hoffmann-Petersen, P Hovind, H-H Parving, L Tarnow, P Rossing, T K Hansen

Journal: Diabetes/metabolism research and reviews 2018;33(5):

PMID: 28303635

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Abstract

BACKGROUND

Evidence links the lectin pathway of complement activation to diabetic kidney disease. Upon carbohydrate-recognition by pattern-recognition molecules, eg, mannan-binding lectin (MBL), the MBL-associated serine protease (MASP-2) is activated and initiates the complement cascade. The MASP2 gene encodes MASP-2 and the alternative splice product MBL-associated protein 19 (MAp19). Both MAp19 and MASP-2 circulate in complex with MBL. We tested the hypothesis that MAp19 and MASP-2 concentrations predict the risk of incident microalbuminuria.

METHODS

Baseline MAp19 and MASP-2 were measured in 270 persons with newly diagnosed type 1 diabetes tracked for incidence of persistent microalbuminuria in a prospective observational 18-year-follow-up study.

RESULTS

Seventy-five participants (28%) developed microalbuminuria during follow-up. MBL-associated protein 19 concentrations were higher in participants that later progressed to microalbuminuria as compared with those with persistent normoalbuminuria (268 ng/mL [95% CI, 243-293] vs 236 ng/mL [95% CI, 223-250], P = .02). Participants with MAp19 concentration within the highest quartile of the cohort had an increased risk of microalbuminuria as compared with participants with MAp19 concentration within the combined lower 3 quartiles in unadjusted Cox analysis, hazard ratio 1.86 ([95% CI, 1.17-2.96], P = .009). This remained significant in adjusted models, eg, adjusting for age, sex, HbA , systolic blood pressure, urinary albumin excretion, smoking, serum creatinine, and serum cholesterol. MBL-associated serine protease concentration was not associated with incidence of microalbuminuria.

CONCLUSIONS

In conclusion, the results show an association between baseline MAp19 concentration and the incidence of microalbuminuria in an 18-year-follow-up study on persons with newly diagnosed type 1 diabetes.

Address: Department of Endocrinology and Internal Medicine, Aarhus University Hospital and Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.; The Danish Diabetes Academy, Odense, Denmark.; Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark.; Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.; Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.; Steno Diabetes Center, Gentofte, Denmark.; Nordsjaellands Hospital, Hillerød, Denmark.; Faculty of Health, Aarhus University, Aarhus, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

DOI: 10.1002/dmrr.2895

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MeSH Terms: Adolescent, Adult, Albuminuria, Denmark, Diabetes Mellitus, Type 1, Female, Follow-Up Studies, Humans, Incidence, Male, Mannose-Binding Protein-Associated Serine Proteases, Prospective Studies, Young Adult