Diabetic retinopathy risk correlates with intracellular concentrations of the glycoxidation product Nε-(carboxymethyl) lysine independently of glycohaemoglobin concentrations
Diabetic retinopathy risk correlates with intracellular concentrations of the glycoxidation product Nε-(carboxymethyl) lysine independently of glycohaemoglobin concentrations
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DOI：
10.1007/s001250051201
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发表时间：
1999-05-01
期刊：
影响因子：
8.2
通讯作者：
Bretzel, RG
中科院分区：
文献类型：
--
作者：
Hammes, HP;Brownlee, M;Bretzel, RG
目标/假设。我们研究了糖尿病引起的细胞内氧化应激的量或高血糖引起的晚期糖基化终产物的浓度是否与糖尿病视网膜病变的风险相关。方法。我们测量了 21 名患有或不患有糖尿病视网膜病变的 I 型（胰岛素依赖性）糖尿病患者的 CD45RA（+）T 细胞中糖氧化产物 N-ε-（羧甲基）赖氨酸和两种非氧化依赖性晚期糖基化终末产物（甲基乙二醛衍生的和 3-脱氧葡萄糖酮衍生的）的浓度。 年龄匹配的非糖尿病对照受试者，结果。糖尿病患者的记忆 T 细胞中，氧化依赖性 N-ε-（羧甲基）赖氨酸和氧化非依赖性晚期糖基化终产物的细胞内浓度均增加。 N-ε-(羧甲基)赖氨酸：糖尿病中位数为 24176 任意单位/毫克蛋白质（95% 置信区间 18690-34099 任意单位/毫克蛋白质）；非糖尿病-9088 任意单位/毫克蛋白质（置信区间 6994-10696 任意单位/毫克蛋白质；p < 0.0001）。甲基乙二醛衍生的晚期糖基化终产物：糖尿病-5430任意单位/毫克蛋白质（置信区间3458-13610）；非糖尿病 - 271 任意单位/毫克蛋白质（置信区间 61-760 任意单位/毫克蛋白质；p < 0.0001）。 3-脱氧葡萄糖酮衍生的晚期糖基化终末产物：糖尿病-8070任意单位/毫克蛋白质（置信区间7049-16551任意单位/毫克蛋白质）；非糖尿病-1479 任意单位/毫克蛋白质（置信区间 1169-3170；p < 0.0001）。然而，只有 N-ε-（羧甲基）赖氨酸浓度与无视网膜病变糖尿病的持续时间呈负相关（r = -0.51；p < 0.02）。糖尿病依赖性 N-ε-（羧甲基）赖氨酸积累与年龄、糖尿病病程或平均糖化血红蛋白浓度无关。甲萘醌和淋巴细胞的体外实验证实，N-ε-（羧甲基）赖氨酸浓度反映了细胞内氧化应激。结论/解释。通过N-ε-(羧甲基)赖氨酸等标记物监测长寿CD45RA(+)淋巴细胞中氧化应激增加的细胞内浓度，可能会识别出微血管并发症高风险患者的亚组。
Aims/hypothesis. We investigated whether either the amount of diabetes-induced intracellular oxidative stress or the concentration of hyperglycaemia-induced advanced glycation endproducts is associated with the risk of diabetic retinopathy.Methods. We measured concentrations of the glycoxidation product N-epsilon-(carboxymethyl)lysine and two non-oxidation-dependent advanced glycation endproducts (methylglyoxal-derived and 3-deoxyglucosone-derived) in CD45RA(+) T-cells from 21 Type I (insulin-dependent) diabetic patients with and without diabetic retinopathy and from age-matched nondiabetic control subjects,Results. Intracellular concentrations of both oxidation-dependent N-epsilon-(carboxymethyl)lysine and oxidation-independent advanced glycation endproducts were increased in memory T-cells from diabetic patients. N-epsilon-(carboxymethyl)lysine: diabetic median-24176 arbitrary units/mg protein (95% confidence interval 18690-34099 arbitrary units/mg protein); nondiabetic-9088 arbitrary units/mg protein (confidence interval 6994-10696 arbitrary units/mg protein; p < 0.0001). Methylglyoxal-derived advanced glycation end products: diabetic-5430 arbitrary units/mg protein (confidence interval 3458-13610); non-diabetic-271 arbitrary units/mg protein (confidence interval 61-760 arbitrary units/mg protein; p < 0.0001). 3-Deoxyglucosone-derived advanced glycation end products: diabetic-8070 arbitrary units/mg protein (confidence interval 7049-16551 arbitrary units/mg protein); nondiabetic-1479 arbitrary units/mg protein (confidence interval 1169-3170; p < 0.0001). Only N-epsilon-(carboxymethyl)lysine concentrations, however, inversely correlated with the duration of retinopathy-free diabetes (r = -0.51; p < 0.02). Diabetes-dependent N-epsilon-(carboxymethyl)lysine accumulation did not correlate with age, diabetes duration, or averaged glycohaemoglobin concentrations. In vitro experiments wih menadione and lymphocytes confirmed that N-epsilon-(carboxymethyl)lysine concentrations reflect intracellular oxidative stress.Conclusion/interpretation. Monitoring intracellular concentrations of increased oxidative stress in long-lived CD45RA(+) lymphocytes by markers such as N-epsilon-(carboxymethyl)lysine possibly identifies a subgroup of patients at high risk for microvascular complications.