Association between mannose-binding lectin and vascular complications in type 1 diabetes

被引:150
作者
Hansen, TK
Tarnow, L
Thiel, S
Steffensen, R
Stehouwer, CD
Schalkwijk, CG
Parving, HH
Flyvbjerg, A
机构
[1] Aarhus Univ Hosp, Immunoendocrine Res Unit, Med Dept M Endocrinol & Diabet, DK-8000 Aarhus, Denmark
[2] Aarhus Univ Hosp, Med Res Labs, DK-8000 Aarhus, Denmark
[3] Steno Diabet Ctr, Gentofte, Denmark
[4] Univ Aarhus, Dept Med Microbiol & Immunol, Aarhus, Denmark
[5] Aalborg Hosp, Reg Ctr Blood Transfus & Clin Immunol, Aalborg, Denmark
[6] Free Univ Amsterdam, Med Ctr, Cardiovasc Res Inst, Amsterdam, Netherlands
[7] Aarhus Univ, Fac Hlth Sci, Aarhus, Denmark
关键词
D O I
10.2337/diabetes.53.6.1570
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 AML 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 mug/l (interquartile range [IQR] 753-4,867 mug/l) vs. 1,491 mug/l (577-2,944 mug/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 mug/l [IQR 636-5,231 mug/l] vs. 1,741 mug/l [656-3,149 mug/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.
引用
收藏
页码:1570 / 1576
页数:7
相关论文
共 40 条
[1]   Molecular basis for a link between complement and the vascular complications of diabetes [J].
Acosta, J ;
Hettinga, J ;
Flückiger, R ;
Krumrei, N ;
Goldfine, A ;
Angarita, L ;
Halperin, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (10) :5450-5455
[2]   How hyperglycemia promotes atherosclerosis: molecular mechanisms [J].
Aronson, Doron ;
Rayfield, Elliot J. .
CARDIOVASCULAR DIABETOLOGY, 2002, 1 (1)
[3]   Prospective analysis of mannose-binding lectin genotypes and coronary artery disease in American Indians - The Strong Heart Study [J].
Best, LG ;
Davidson, M ;
North, KE ;
MacCluer, JW ;
Zhang, Y ;
Lee, ET ;
Howard, BV ;
DeCroo, S ;
Ferrell, RE .
CIRCULATION, 2004, 109 (04) :471-475
[4]  
BROWNLEE M, 1988, NEW ENGL J MED, V318, P1315
[5]   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
[6]   Complement activation following oxidative stress [J].
Collard, CD ;
Lekowski, R ;
Jordan, JE ;
Agah, A ;
Stahl, GL .
MOLECULAR IMMUNOLOGY, 1999, 36 (13-14) :941-948
[7]   FAMILIAL CLUSTERING OF CARDIOVASCULAR-DISEASE IN PATIENTS WITH INSULIN-DEPENDENT DIABETES AND NEPHROPATHY [J].
EARLE, K ;
WALKER, J ;
HILL, C ;
VIBERTI, G .
NEW ENGLAND JOURNAL OF MEDICINE, 1992, 326 (10) :673-677
[8]   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
[9]   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
[10]   Genetic heterogeneity of mannose-binding proteins: The Jekyll and Hyde of innate immunity? [J].
Ezekowitz, RAB .
AMERICAN JOURNAL OF HUMAN GENETICS, 1998, 62 (01) :6-9