The receptor for advanced glycation end products and risk of peripheral arterial disease, amputation or death in type 2 diabetes: a population-based cohort study.
The receptor for advanced glycation end products and risk of peripheral arterial disease, amputation or death in type 2 diabetes: a population-based cohort study.
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DOI：
10.1186/s12933-015-0257-5
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发表时间：
2015-07-28
影响因子：
9.3
通讯作者：
Brismar K
中科院分区：
文献类型：
--
作者：
Malmstedt J;Kärvestedt L;Swedenborg J;Brismar K
2型糖尿病患者早期和广泛发生外周动脉疾病（PAD）的风险较高，这种过度风险不能用传统动脉粥样硬化风险因素的负担增加来解释。晚期糖基化终末产物受体（AGEs）的激活可能是加速PAD和增加截肢和死亡风险的另一种机制。我们调查了2型糖尿病患者血浆中的甘油三酯成分与PAD、截肢和死亡风险之间的关系。我们还估计了无截肢生存率和无PAD生存率。我们研究了血浆羧甲基赖氨酸、S100 A12和内分泌抑制剂（esophagus）水平是否与两个终点相关：在146例2型糖尿病患者中进行的12年前瞻性队列研究中，无PAD的生存率和无截肢的生存率。在Cox回归分析中，评价了基线血浆水平对两个终点的影响（单独和通过RAGE评分组合）。随访期间，106例患者存活，无截肢，93例存活，无PAD体征。较高水平的S100 A12和RAGE评分与截肢或死亡风险增加相关，风险比（HR）为1.29; 95%置信区间（CI）为[1.04，1.59]和1.79; 95% CI为[1.07，2.99]，与PAD或死亡风险增加相关，HR为1.22;校正年龄和性别后的95% CI [1.00，1.49]和1.56; [1.00，2.44]。在调整Frachial心血管疾病评分后，效应降低：截肢或死亡风险，HR 1.17; 95% CI [0.94，1.46]和1.54; [0.95，2.49]，PAD或死亡风险，HR 1.12; 95% CI [0.91，1.38]和1.38; S100 A12和RAGE评分分别为[0.91，2.11]。截肢或死亡的发生率为2.8/100人年; 95% CI [2.0，3.7]，PAD或死亡的发生率为3.6/100人年; 95% CI [2.7，4.8]。较高的血浆S100 A12水平和艾司氯胺酮、羧甲基赖氨酸和S100 A12的联合作用（RAGE评分）似乎与2型糖尿病患者较短的无PAD和无截肢生存期相关。这可能表明S100 A12在PAD中通过激活ESTA系统的作用。本文的在线版本（doi：10.1186/s12933-015-0257-5）包含补充材料，可供授权用户使用。
Patients with type 2 diabetes have a high risk for early and extensive development of peripheral arterial disease (PAD) and this excess risk is not explained by increased burden of traditional atherosclerotic risk factors. Activation of the receptor for advanced glycation end products (RAGE) could be one additional mechanism for accelerated PAD and increased risk for amputation and death. We investigated the association between RAGE plasma components and the risk for PAD, amputation and death in patients with type 2 diabetes. We also estimated the rate of amputation-free survival and survival without PAD. We investigated if plasma levels of carboxymethyl-lysine, S100A12 and endosecretory RAGE (esRAGE) were associated with two endpoints: survival without development of PAD and survival without amputation in a 12 years prospective population-based cohort of 146 patients with type 2 diabetes, free from PAD at inclusion. Influence of baseline plasma levels of RAGE ligands (individually and combined by a RAGE-score) were evaluated for both endpoints in the Cox-regression analysis. 106 patients survived without amputation and 93 survived without signs of PAD during follow up. Higher levels of S100A12 and RAGE-score were associated with increased risk for amputation or death, hazard ratios (HR) 1.29; 95% confidence interval (CI) [1.04, 1.59] and 1.79; 95% CI [1.07, 2.99] and with increased risk for PAD or death, HR 1.22; 95% CI [1.00, 1.49] and 1.56; [1.00, 2.44] after adjustment for age and sex. The effect was decreased after adjustment for Framingham cardiovascular disease score: risk for amputation or death, HR 1.17; 95% CI [0.94, 1.46] and 1.54; [0.95, 2.49], and risk for PAD or death, HR 1.12; 95% CI [0.91, 1.38] and 1.38; [0.91, 2.11] for S100A12 and RAGE-score respectively. The incidence for amputation or death was 2.8 per 100 person-years; 95% CI [2.0, 3.7] and the incidence rate for PAD or death was 3.6 per 100 person-years; 95% CI [2.7, 4.8]. Higher plasma levels of S100A12 and the combined effect (RAGE-score) of esRAGE, carboxymethyl-lysine and S100A12 seem to be associated with shorter PAD- and amputation-free survival in patients with type 2 diabetes. This may indicate a role for S100A12 in PAD by activation of the RAGE system. The online version of this article (doi:10.1186/s12933-015-0257-5) contains supplementary material, which is available to authorized users.