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

doi:10.1002/dmrr.2895

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

Diabetes Metab Res Rev. 2017 Jul;33(5). doi: 10.1002/dmrr.2895. Epub 2017 Apr 11.

Authors

J A Østergaard^{1

2}, S Thiel³, I T Hoffmann-Petersen¹, P Hovind⁴, H-H Parving⁵, L Tarnow^{6

7

8}, P Rossing^{6

8

9}, T K Hansen¹

Affiliations

¹ Department of Endocrinology and Internal Medicine, Aarhus University Hospital and Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
² The Danish Diabetes Academy, Odense, Denmark.
³ Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
⁴ Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
⁵ Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
⁶ Steno Diabetes Center, Gentofte, Denmark.
⁷ Nordsjaellands Hospital, Hillerød, Denmark.
⁸ Faculty of Health, Aarhus University, Aarhus, Denmark.
⁹ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

PMID: 28303635
DOI: 10.1002/dmrr.2895

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_1c , 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.

Keywords: complement; diabetes; kidney; lectin; microalbuminuria; nephropathy.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Albuminuria / diagnosis*
Albuminuria / epidemiology
Albuminuria / metabolism
Denmark / epidemiology
Diabetes Mellitus, Type 1 / complications*
Female
Follow-Up Studies
Humans
Incidence
Male
Mannose-Binding Protein-Associated Serine Proteases / metabolism*
Prospective Studies
Young Adult

Substances

MASP2 protein, human
Mannose-Binding Protein-Associated Serine Proteases