Increased levels of mannan-binding lectin in type 1 diabetic patients with incipient and overt nephropathy

Aims/hypothesis: 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]: 1,154mug/l [180 - 2,202 mug/l]) had lower levels of MBL than patients with microalbuminuria ( 1,713 mug/l [ 724 - 2,760 mug/l]; p= 0.029) or macroalbuminuria ( 1,648 mug/l [ 568 - 3,394 mug/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/interpretation: MBL concentrations are increased in type 1 diabetic patients with diabetic nephropathy. MBL was not associated with low-grade inflammatory markers.