Elevated levels of mannan-binding lectin in patients with type 1 diabetes

被引:115
作者
Hansen, TK
Thiel, S
Knudsen, ST
Gravholt, CH
Christiansen, JS
Mogensen, CE
Poulsen, PL
机构
[1] Aarhus Univ Hosp, Med Dept M, DK-8000 Aarhus, Denmark
[2] Aarhus Univ, Dept Med Microbiol & Immunol, DK-8000 Aarhus, Denmark
关键词
D O I
10.1210/jc.2003-030742
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 mug/liter (interquartile range, IQR 354- 2961 mug/liter) vs. 970 mug/liter (IQR 277- 1607 mug/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.
引用
收藏
页码:4857 / 4861
页数:5
相关论文
共 34 条
[1]   How hyperglycemia promotes atherosclerosis: molecular mechanisms [J].
Aronson, Doron ;
Rayfield, Elliot J. .
CARDIOVASCULAR DIABETOLOGY, 2002, 1 (1)
[2]   Complement activation after oxidative stress -: Role of the lectin complement pathway [J].
Collard, CD ;
Väkevä, A ;
Morrissey, MA ;
Agah, A ;
Rollins, SA ;
Reenstra, WR ;
Buras, JA ;
Meri, S ;
Stahl, GL .
AMERICAN JOURNAL OF PATHOLOGY, 2000, 156 (05) :1549-1556
[3]   Endothelial oxidative stress activates the lectin complement pathway - Role of cytokeratin 1 [J].
Collard, CD ;
Montalto, MC ;
Reenstra, WR ;
Buras, JA ;
Stahl, GL .
AMERICAN JOURNAL OF PATHOLOGY, 2001, 159 (03) :1045-1054
[4]   Complement activation following oxidative stress [J].
Collard, CD ;
Lekowski, R ;
Jordan, JE ;
Agah, A ;
Stahl, GL .
MOLECULAR IMMUNOLOGY, 1999, 36 (13-14) :941-948
[5]   PREDICTORS OF MICROALBUMINURIA IN INDIVIDUALS WITH IDDM [J].
COONROD, BA ;
ELLIS, D ;
BECKER, DJ ;
BUNKER, CH ;
KELSEY, SF ;
LLOYD, CE ;
DRASH, AL ;
KULLER, LH ;
ORCHARD, TJ .
DIABETES CARE, 1993, 16 (10) :1376-1383
[6]   MASP-3 and its association with distinct complexes of the mannan-binding lectin complement activation pathway [J].
Dahl, MR ;
Thiel, S ;
Matsushita, M ;
Fujita, T ;
Willis, AC ;
Christensen, T ;
Vorup-Jensen, T ;
Jensenius, JC .
IMMUNITY, 2001, 15 (01) :127-135
[7]   Glomerular deposition of mannose-binding lectin (MBL) indicates a novel mechanism of complement activation in IgA nephropathy [J].
Endo, M ;
Ohi, H ;
Ohsawa, I ;
Fujita, T ;
Matsushita, M ;
Fujita, T .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 1998, 13 (08) :1984-1990
[8]   Complement activation through the lectin pathway in patients with Henoch-Schonlein purpura nephritis [J].
Endo, M ;
Ohi, H ;
Ohsawa, I ;
Fujita, T ;
Matsushita, M ;
Fujita, T .
AMERICAN JOURNAL OF KIDNEY DISEASES, 2000, 35 (03) :401-407
[9]   Intensive insulin therapy exerts antiinflammatory effects in critically ill patients and counteracts the adverse effect of low mannose-binding lectin levels [J].
Hansen, TK ;
Thiel, S ;
Wouters, PJ ;
Christiansen, JS ;
Van den Berghe, G .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2003, 88 (03) :1082-1088
[10]   GH strongly affects serum concentrations of mannan-binding lectin: Evidence for a new IGF-I independent immunomodulatory effect of GH [J].
Hansen, TK ;
Thiel, S ;
Dall, R ;
Rosenfalck, AM ;
Trainer, P ;
Flyvbjerg, A ;
Jorgensen, JOL ;
Christiansen, JS .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (11) :5383-5388