Mannose-binding lectin as a predictor of microalbuminuria in type 1 diabetes: an inception cohort study.
Inflammation and complement activation via the mannose-binding lectin (MBL) pathway have been suggested to play a role in the pathogenesis of diabetic microvascular complications. The association between the complement-activating protein MBL and the development of persistent microalbuminuria was evaluated in an inception cohort of 286 newly diagnosed type 1 diabetic patients consecutively admitted to the Steno Diabetes Center between 1 September 1979 and 31 August 1984. Serum MBL was measured with an immunofluorometric assay in 270 of the patients (159 men) after 3 years of diabetes duration. During the median (range) follow-up period of 18.0 (1.0-21.8) years, 75 patients subsequently progressed to persistent micro- or macroalbuminuria (urinary albumin excretion rate >30 mg/24 h). In patients with MBL levels above the median (1,597 microg/l), the cumulative incidence of persistent micro- or macroalbuminuria was 41% (CI 31-50) as compared with 26% (CI 17-34) in patients with MBL levels below the median (log-rank test, P = 0.003). In a Cox proportional hazard model with sex and age as fixed covariates, MBL was independently associated with later development of persistent micro- or macroalbuminuria (hazard ratio 1.21 [CI 1.02-1.42] per 1,000 microg/l increase in MBL; P = 0.03) after adjusting for possible confounders. In our study, high levels of MBL early in the course of type 1 diabetes was significantly associated with later development of persistent micro- or macroalbuminuria, suggesting that complement activation initiated by MBL may be involved in the pathogenesis of diabetic microvascular complications.
Hovind
Peter
P
Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark. phovind@dadlnet.dk
Hansen
Troels Krarup
TK
Tarnow
Lise
L
Thiel
Steffen
S
Steffensen
Rudi
R
Flyvbjerg
Allan
A
Parving
Hans-Henrik
HH
D000328:Adult; D000419:Albuminuria / Q000453:epidemiology*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003167:Complement Activation; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000453:epidemiology*; D003928:Diabetic Nephropathies / Q000453:epidemiology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D015994:Incidence; D007249:Inflammation; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood*
D015415:Biomarkers; D037601:Mannose-Binding Lectin