Division of Endocrinology, Medical University of South Carolina, Charleston, South Carolina, USA.
Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
J Diabetes Res. 2023 Aug 10;2023:8537693. doi: 10.1155/2023/8537693. eCollection 2023.
We aimed to determine whether plasma advanced glycation end products or oxidation products (AGE/oxidation-P) predict altered renal function and/or preeclampsia (PE) in pregnant women with type 1 diabetes.
Prospectively, using a nested case-control design, we studied 47 pregnant women with type 1 diabetes, of whom 23 developed PE and 24 did not. Nineteen nondiabetic, normotensive pregnant women provided reference values. In plasma obtained at ~12, 22, and 32 weeks' gestation (visits 1, 2, and 3; V1-V3), we measured five AGE products (carboxymethyllysine (CML), carboxyethyl-lysine (CEL), methylglyoxal-hydroimidazolone (MGH1), 3-deoxyglucosone hydroimidazolone (3DGH), and glyoxal-hydroimidazolone (GH1)) and four oxidation products (methionine sulfoxide (MetSO), 2-aminoadipic acid (2-AAA), 3-nitrotyrosine (3NT), and dityrosine (DT)), by liquid chromatography/mass spectroscopy. Clinical outcomes were "estimated glomerular filtration rate" (eGFR) at each visit and onset of PE.
In diabetic women, associations between AGE/oxidation-P and eGFR were found only in those who developed PE. In this group, CEL, MGH1, and GH1 at V2 and CML, CEL, MGH1, and GH1 at V3 were inversely associated with contemporaneous eGFR, while CEL, MGH1, 3DGH, and GH1 at V2 were inversely associated with eGFR at V3 (all < 0.05). There were no associations of plasma AGE or oxidation-P with pregnancy-related development of proteinuria or PE.
Inverse associations of second and early third trimester plasma AGE with eGFR among type 1 diabetic women who developed PE suggest that these patients constitute a subset susceptible to AGE-mediated injury and thus to cardiorenal complications later in life. However, AGE/oxidation-P did not predict PE in type 1 diabetic women.
我们旨在确定血浆晚期糖基化终产物或氧化产物（AGE/氧化产物-P）是否可预测 1 型糖尿病孕妇肾功能改变和/或先兆子痫（PE）。
前瞻性地，采用巢式病例对照设计，我们研究了 47 例 1 型糖尿病孕妇，其中 23 例发生 PE，24 例未发生。19 例非糖尿病、血压正常的孕妇提供参考值。在妊娠 12、22 和 32 周时（访视 1、2 和 3；V1-V3）获得的血浆中，我们测量了 5 种 AGE 产物（羧甲基赖氨酸（CML）、羧乙基赖氨酸（CEL）、甲基乙二醛-酰基咪唑啉酮（MGH1）、3-脱氧葡萄糖醛酮酰基咪唑啉酮（3DGH）和乙二醛-酰基咪唑啉酮（GH1））和 4 种氧化产物（甲硫氨酸亚砜（MetSO）、2-氨基己二酸（2-AAA）、3-硝基酪氨酸（3NT）和二酪氨酸（DT）），采用液相色谱/质谱联用技术进行检测。临床结局为每次访视的“估算肾小球滤过率”（eGFR）和 PE 的发生。
在糖尿病女性中，仅在发生 PE 的女性中，AGE/氧化产物-P 与 eGFR 之间存在关联。在该组中，V2 时的 CEL、MGH1 和 GH1 以及 V3 时的 CML、CEL、MGH1 和 GH1 与同期 eGFR 呈负相关，而 V2 时的 CEL、MGH1、3DGH 和 GH1 与 V3 时的 eGFR 呈负相关（均<0.05）。血浆 AGE 或氧化产物-P 与妊娠相关蛋白尿或 PE 的发生均无关联。
在发生 PE 的 1 型糖尿病女性中，第二和早期第三孕期血浆 AGE 与 eGFR 的负相关提示这些患者构成易受 AGE 介导损伤的亚组，因此易发生心血管和肾脏并发症。然而，AGE/氧化产物-P 不能预测 1 型糖尿病女性的 PE。
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