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Elevated Levels of Mannan-Binding Lectin in Patients with Type 1 Diabetes

Medical Department M (T.K.H., S.T.K., C.H.G., J.S.C., C.E.M., P.L.P.), Aarhus University Hospital, and Department of Medical Microbiology and Immunology (S.T.), Aarhus University, DK-8000 Aarhus, Denmark

Address all correspondence and requests for reprints to: Troels Krarup Hansen, M.D., Ph.D., Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Norrebrogade 42-44, DK-8000 Aarhus C, Denmark. E-mail: tkh{at}dadlnet.dk.

The hepatic protein mannan-binding lectin (MBL) activates the complement system on binding to carbohydrate patterns and is involved in first-line defense against invading microorganisms. Emerging evidence indicates that in some situations MBL may cause inexpedient complement activation and tissue injury through binding to endothelial glycosylations. MBL levels are suppressed by insulin treatment in critically ill patients, and, hypothetically, hepatic portal hypoinsulinemia could lead to increased levels of MBL in patients with type 1 diabetes. We measured MBL and C-reactive protein (CRP) levels in 132 normoalbuminuric type 1 diabetic patients and 66 healthy age- and sex-matched controls. The median MBL concentration was higher in diabetic patients than in healthy controls [1290 µg/liter (interquartile range, IQR 354-2961 µg/liter) vs. 970 µg/liter (IQR 277-1607 µg/liter), P = 0.025], whereas CRP concentrations were similar among patients and controls [1.42 mg/liter (IQR 0.95–2.21) vs. 1.21 mg/l (IQR 0.74–2.13), NS]. In diabetic subjects, CRP levels correlated with poor glycemic control as indicated by hemoglobin A_1c and daily insulin dose, which was not the case with MBL. MBL concentrations were positively correlated with urinary albumin excretion (r = 0.22; P = 0.013) and increased with increasing urinary albumin excretion tertile (P = 0.036). In conclusion, our data demonstrate that circulating MBL concentrations are significantly elevated in patients with type 1 diabetes and suggest a possible role of MBL in the pathogenesis of renovascular complications in diabetes.

Abbreviations: CRP, C-reactive protein; Hb, hemoglobin; IQR, interquartile range; MBL, mannan-binding lectin; UAE, urinary albumin excretion.

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