Increased levels of mannan-binding lectin in type 1 diabetic patients with incipient and overt nephropathy.
OBJECTIVE
Diabetic nephropathy is associated with insulin resistance, and low-grade inflammation and activation of the complement system may contribute to this cascade. Mannan-binding lectin (MBL) activates the complement system, and elevated MBL concentrations have been observed in normoalbuminuric type 1 diabetic patients. The aim of this study was to assess whether MBL is associated with diabetic nephropathy in type 1 diabetes, and whether there is an association between MBL and low-grade inflammatory markers or insulin resistance.


METHODS
A total of 191 type 1 diabetic patients from the Finnish Diabetic Nephropathy Study were divided into three groups based upon their AER. Patients with normal AER (n=67) did not take antihypertensive medication, while patients with microalbuminuria (n=62) or macroalbuminuria (n=62) were all treated with an ACE inhibitor. As a measure of insulin sensitivity we used estimated glucose disposal rate. MBL was measured by an immunofluorometric assay, C-reactive protein by a radioimmunoassay and IL-6 by high-sensitivity enzyme immunoassay.


RESULTS
Patients with normal AER (median [interquartile range]: 1,154 microg/l [180-2,202 microg/l]) had lower levels of MBL than patients with microalbuminuria (1,713 microg/l [724-2,760 microg/l]; p=0.029) or macroalbuminuria (1,648 microg/l [568-3,394 microg/l]; p=0.019). There was a significant correlation between MBL and estimated glucose disposal rate, but not between MBL and C-reactive protein or IL-6 levels in univariate analysis. However, in a multiple regression analysis, HbA1c was the single variable independently associated with MBL (beta+/-SEM: 0.26+/-0.08; p=0.003).


CONCLUSIONS
MBL concentrations are increased in type 1 diabetic patients with diabetic nephropathy. MBL was not associated with low-grade inflammatory markers.
Saraheimo
M
M
Folkhälsan Research Center, University of Helsinki, Biomedicum Helsinki (C318b), P.O. Box 63, 00014, Finland.
Forsblom
C
C
Hansen
T K
TK
Teppo
A-M
AM
Fagerudd
J
J
Pettersson-Fernholm
K
K
Thiel
S
S
Tarnow
L
L
Ebeling
P
P
Flyvbjerg
A
A
Groop
P-H
PH
D000328:Adult; D017668:Age of Onset; D000419:Albuminuria / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D015992:Body Mass Index; D049628:Body Size; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003928:Diabetic Nephropathies / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood*
D015415:Biomarkers; D008055:Lipids; D037601:Mannose-Binding Lectin