Mannose-Binding Lectin as a Predictor of Microalbuminuria in Type 1 Diabetes

An Inception Cohort Study

  1. Peter Hovind1,
  2. Troels Krarup Hansen2,
  3. Lise Tarnow1,
  4. Steffen Thiel3,
  5. Rudi Steffensen4,
  6. Allan Flyvbjerg2 and
  7. Hans-Henrik Parving15
  1. 1Steno Diabetes Center, Gentofte, Denmark
  2. 2Medical Department M (Immunoendocrine Research Unit) and Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark
  3. 3Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark
  4. 4Department of Clinical Immunology, Aalborg Hospital, Aalborg, Denmark
  5. 5Faculty of Health Science, University of Aarhus, Aarhus, Denmark
  1. Address correspondencereprint requests to Peter Hovind, MD, Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark. E-mail: phovind{at}dadlnet.dk

Abstract

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 μg/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 μg/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.

Footnotes

    • Accepted February 7, 2005.
    • Received December 16, 2004.
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