Association Between Mannose-Binding Lectin and Vascular Complications in Type 1 Diabetes

Abstract

Complement activation and inflammation have been suggested in the pathogenesis of diabetic vascular lesions. We investigated serum mannose-binding lectin (MBL) levels and polymorphisms in the MBL gene in type 1 diabetic patients with and without diabetic nephropathy and associated macrovascular complications. Polymorphisms in the MBL gene and serum MBL levels were determined in 199 type 1 diabetic patients with overt nephropathy and 192 type 1 diabetic patients with persistent normoalbuminuria matched for age, sex, and duration of diabetes, as well as in 100 healthy control subjects. The frequencies of high- and low-expression MBL genotypes were similar in patients with type 1 diabetic and healthy control subjects. High MBL genotypes were significantly more frequent in diabetic patients with nephropathy than in the normoalbuminuric group, and the risk of having nephropathy given a high MBL genotype assessed by odds ratio (OR) was 1.52 (1.02-2.27, P = 0.04). Median serum MBL concentrations were significantly higher in patients with nephropathy than in patients with normoalbuminuria: 2,306 microg/l (interquartile range [IQR] 753-4,867 microg/l) vs. 1,491 microg/l (577-2,944 microg/l), P = 0.0003. In addition, even when comparing patients with identical genotypes, serum MBL levels were higher in the nephropathy group than in the normoalbuminuric group. Patients with a history of cardiovascular disease had significantly elevated MBL levels independent of nephropathy status (3,178 microg/l [IQR 636-5,231 microg/l] vs. 1,741 microg/l [656-3,149 microg/l], P = 0.02). The differences in MBL levels between patients with and without vascular complications were driven primarily by pronounced differences among carriers of high MBL genotypes (P < 0.0001). Our findings suggest that MBL may be involved in the pathogenesis of micro- and macrovascular complications in type 1 diabetes, and that determination of MBL status might be used to identify patients at increased risk of developing these complications.