Increased serum levels of advanced glycation endproducts predict total, cardiovascular and coronary mortality in women with type 2 diabetes:: a population-based 18 year follow-up study

被引:135
作者
Kilhovd, B. K.
Juutilainen, A.
Lehto, S.
Ronnemaa, T.
Torjesen, P. A.
Hanssen, K. F.
Laakso, M. [1 ]
机构
[1] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland
[2] Aker & Ulleval Diabet Res Ctr, Oslo, Norway
[3] Univ Oslo, Fac Med, Aker Univ Hosp, Dept Endocrinol, N-0316 Oslo, Norway
[4] Kuopio Univ Hosp, SF-70210 Kuopio, Finland
[5] Univ Turku, Dept Med, SF-20500 Turku, Finland
[6] Turku Univ Hosp, FIN-20520 Turku, Finland
[7] Univ Oslo, Fac Med, Aker Univ Hosp, Hormone Lab, N-0316 Oslo, Norway
基金
芬兰科学院;
关键词
advanced glycation; cardiovascular diseases; coronary disease; diabetes mellitus; women;
D O I
10.1007/s00125-007-0687-z
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims/hypothesis AGEs, modification products formed by glycation or glycoxidation of proteins and lipids, have been linked to premature atherosclerosis in patients with diabetes. We investigated whether increased serum levels of AGEs predict total, cardiovascular (CVD) or CHD mortality in a population-based study. Subjects and methods Serum levels of AGEs were determined by immunoassay in a random sample of 874 Finnish diabetic study participants ( 488 men, 386 women), aged 45 - 64 years. These participants were followed for 18 years for total, CVD and CHD mortality. Results Multivariate Cox regression models revealed that serum levels of AGEs were significantly associated with total (p= 0.002) and CVD mortality ( p= 0.021) in women, but not in men. Serum levels of AGEs in the highest sex-specific quartile predicted all-cause ( hazards ratio [HR] 1.51; 95% confidence intervals [CI], 1.14 - 1.99; p= 0.004), CVD ( HR 1.56; 95% CI 1.12 - 2.19; p= 0.009), and CHD ( HR 1.68; 95% CI 1.11 - 2.52; p= 0.013) mortality in women, even after adjustment for confounding factors, including high-sensitivity C-reactive protein. Conclusions/interpretation Increased serum levels of AGEs predict total and CVD mortality in women with type 2 diabetes.
引用
收藏
页码:1409 / 1417
页数:9
相关论文
共 41 条
[1]   Advanced glycation end products in serum predict changes in the kidney morphology of patients with insulin-dependent diabetes mellitus [J].
Berg, TJ ;
Bangstad, HJ ;
Torjesen, PA ;
Osterby, R ;
Bucala, R ;
Hanssen, KF .
METABOLISM-CLINICAL AND EXPERIMENTAL, 1997, 46 (06) :661-665
[2]   The advanced glycation end product Nε-(carboxymethyl)lysine is increased in serum from children and adolescents with type 1 diabetes [J].
Berg, TJ ;
Clausen, JT ;
Torjesen, PA ;
Dahl-Jorgensen, K ;
Bangstad, HJ ;
Hanssen, KF .
DIABETES CARE, 1998, 21 (11) :1997-2002
[3]   AGEs bind to mesothelial cells via RAGE and stimulate VCAM-1 expression [J].
Boulanger, E ;
Wautier, MP ;
Wautier, JL ;
Boval, B ;
Panis, Y ;
Wernert, N ;
Danze, PM ;
Dequiedt, P .
KIDNEY INTERNATIONAL, 2002, 61 (01) :148-156
[4]   ADVANCED PROTEIN GLYCOSYLATION IN DIABETES AND AGING [J].
BROWNLEE, M .
ANNUAL REVIEW OF MEDICINE, 1995, 46 :223-234
[5]   Biochemistry and molecular cell biology of diabetic complications [J].
Brownlee, M .
NATURE, 2001, 414 (6865) :813-820
[6]   LIPID ADVANCED GLYCOSYLATION - PATHWAY FOR LIPID OXIDATION IN-VIVO [J].
BUCALA, R ;
MAKITA, Z ;
KOSCHINSKY, T ;
CERAMI, A ;
VLASSARA, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (14) :6434-6438
[7]   MODIFICATION OF LOW-DENSITY-LIPOPROTEIN BY ADVANCED GLYCATION END-PRODUCTS CONTRIBUTES TO THE DYSLIPIDEMIA OF DIABETES AND RENAL-INSUFFICIENCY [J].
BUCALA, R ;
MAKITA, Z ;
VEGA, G ;
GRUNDY, S ;
KOSCHINSKY, T ;
CERAMI, A ;
VLASSARA, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (20) :9441-9445
[8]   ADVANCED GLYCOSYLATION PRODUCTS QUENCH NITRIC-OXIDE AND MEDIATE DEFECTIVE ENDOTHELIUM-DEPENDENT VASODILATATION IN EXPERIMENTAL DIABETES [J].
BUCALA, R ;
TRACEY, KJ ;
CERAMI, A .
JOURNAL OF CLINICAL INVESTIGATION, 1991, 87 (02) :432-438
[9]   High levels of dietary advanced glycation end products transform low-density lipoprotein into a potent redox-sensitive mitogen-activated protein kinase stimulant in diabetic patients [J].
Cai, WJ ;
He, JCJ ;
Zhu, L ;
Peppa, M ;
Lu, CY ;
Uribarri, J ;
Vlassara, H .
CIRCULATION, 2004, 110 (03) :285-291
[10]   PREDICTION OF CREATININE CLEARANCE FROM SERUM CREATININE [J].
COCKCROFT, DW ;
GAULT, MH .
NEPHRON, 1976, 16 (01) :31-41