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 I 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 microor macroalbuminuria (urinary albumin excretion rate > 30 mg/24 h). In patients with MBL levels above the median (1,597 mu g/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 [Cl 1.02-1.42] per 1,000 mu g/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 I diabetes was significantly associated with later development of persistent microor macroalbuminuria, suggesting that complement activation initiated by MBL may be involved in the pathogenesis of diabetic microvascular complications.