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Incident microalbuminuria and complement factor mannan‐binding lectin‐associated protein 19 in people with newly diagnosed type 1 diabetes
Author(s) -
Østergaard J.A.,
Thiel S.,
HoffmannPetersen I.T.,
Hovind P.,
Parving H.H.,
Tarnow L.,
Rossing P.,
Hansen T.K.
Publication year - 2017
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.2895
Subject(s) - microalbuminuria , medicine , hazard ratio , diabetes mellitus , endocrinology , mannan binding lectin , type 2 diabetes , immunology , gastroenterology , confidence interval , lectin
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.