Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, University Hospital, Coventry, UK.
Diabetes. 2010 Apr;59(4):1038-45. doi: 10.2337/db09-1455. Epub 2010 Jan 12.
The aim of this study was to investigate whether apolipoprotein B100 of LDL suffers increased damage by glycation, oxidation, and nitration in patients with type 2 diabetes, including patients receiving metformin therapy.
For this study, 32 type 2 diabetic patients and 21 healthy control subjects were recruited; 13 diabetic patients were receiving metformin therapy (median dose: 1.50 g/day). LDL was isolated from venous plasma by ultracentrifugation, delipidated, digested, and analyzed for protein glycation, oxidation, and nitration adducts by stable isotopic dilution analysis tandem mass spectrometry.
Advanced glycation end product (AGE) content of apolipoprotein B100 of LDL from type 2 diabetic patients was higher than from healthy subjects: arginine-derived AGE, 15.8 vs. 5.3 mol% (P < 0.001); and lysine-derived AGE, 2.5 vs. 1.5 mol% (P < 0.05). Oxidative damage, mainly methionine sulfoxide residues, was also increased: 2.5 vs. 1.1 molar equivalents (P < 0.001). 3-Nitrotyrosine content was decreased: 0.04 vs. 0.12 mol% (P < 0.05). In diabetic patients receiving metformin therapy, arginine-derived AGE and methionine sulfoxide were lower than in patients not receiving metformin: 19.3 vs. 8.9 mol% (P < 0.01) and 2.9 vs. 1.9 mol% (P < 0.05), respectively; 3-nitrotyrosine content was higher: 0.10 vs. 0.03 mol% (P < 0.05). Fructosyl-lysine residue content correlated positively with fasting plasma glucose. Arginine-derived AGE residue contents were intercorrelated and also correlated positively with methionine sulfoxide.
Patients with type 2 diabetes had increased arginine-derived AGEs and oxidative damage in apolipoprotein B100 of LDL. This was lower in patients receiving metformin therapy, which may contribute to decreased oxidative damage, atherogenicity, and cardiovascular disease.
本研究旨在探讨 2 型糖尿病患者，包括接受二甲双胍治疗的患者，其 LDL 中的载脂蛋白 B100 是否会因糖化、氧化和硝化而受到更大的损伤。
本研究共招募了 32 名 2 型糖尿病患者和 21 名健康对照者；其中 13 名糖尿病患者正在接受二甲双胍治疗（中位数剂量：1.50 g/天）。通过超速离心从静脉血浆中分离 LDL，去脂，消化，并通过稳定同位素稀释分析串联质谱法分析蛋白质糖化、氧化和硝化加合物。
2 型糖尿病患者 LDL 载脂蛋白 B100 的晚期糖基化终产物（AGE）含量高于健康对照组：精氨酸衍生的 AGE，15.8 vs. 5.3 mol%（P < 0.001）；赖氨酸衍生的 AGE，2.5 vs. 1.5 mol%（P < 0.05）。氧化损伤，主要是蛋氨酸亚砜残基，也增加了：2.5 vs. 1.1 摩尔当量（P < 0.001）。3-硝基酪氨酸含量降低：0.04 vs. 0.12 mol%（P < 0.05）。接受二甲双胍治疗的糖尿病患者，精氨酸衍生的 AGE 和蛋氨酸亚砜低于未接受二甲双胍治疗的患者：19.3 vs. 8.9 mol%（P < 0.01）和 2.9 vs. 1.9 mol%（P < 0.05）；3-硝基酪氨酸含量更高：0.10 vs. 0.03 mol%（P < 0.05）。果糖基赖氨酸残基含量与空腹血糖呈正相关。精氨酸衍生的 AGE 残基含量相互关联，并与蛋氨酸亚砜呈正相关。
2 型糖尿病患者 LDL 载脂蛋白 B100 中的精氨酸衍生 AGEs 和氧化损伤增加。接受二甲双胍治疗的患者水平较低，这可能有助于降低氧化损伤、致动脉粥样硬化性和心血管疾病的风险。
