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

Abstract

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 micro g/liter (interquartile range, IQR 354-2961 micro g/liter) vs. 970 micro g/liter (IQR 277-1607 micro g/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.

Protection from inflammatory disease in insulin resistance: the role of mannan-binding lectin

“…These observations seem to contradict recent articles describing increased MBL concentrations in patients with type 1 diabetes with microvascular complications [29][30][31][32][33]. However, MBL plays a dual role in modifying inflammatory responses to injury [34].…”

Mannose-binding lectin deficiency attenuates renal changes in a streptozotocin-induced model of type 1 diabetes in mice

“…In clinical trials, normoalbuminuric patients with type 1 diabetes have higher serum MBL levels than non-diabetic controls [4,5]. The groups had the same distribution of MBL genotypes [5].…”

“…Under normal conditions MBL does not bind to the body's own structures, but it does possess potential self-reactive properties. A significant association between serum MBL levels and renal function has been reported in normoalbuminuric, microalbuminuric and macroalbuminuric type 1 diabetic patients [4][5][6]. Furthermore, in a cohort study of type 1 diabetic patients followed for 18 years from diagnosis, serum MBL was a significant predictor of later renal impairment.…”

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

“…Patients with type 1 diabetes and normal AER show increased levels of MBL when compared with healthy subjects; further, the MBL concentration was associated with AER even within the normoalbuminuric range while no correlation between MBL and C-reactive protein (CRP) was observed [4].…”

“…However, low-grade inflammation and endothelial dysfunction may be a common denominator of microvascular and macrovascular complications [1][2][3], and it has been suggested that the activation of the complement system contributes to this cascade of inflammation [4].…”