Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands; NIHR Great Ormond Street Biomedical Research Centre, Great Ormond Street Hospital and UCL Great Ormond Street Institute of Child Health, London, UK.
Clin Nutr. 2021 Jun;40(6):4192-4200. doi: 10.1016/j.clnu.2021.01.039. Epub 2021 Feb 3.
BACKGROUND & AIMS: Damage induced by lipid peroxidation has been associated with impaired glucose homeostasis. Vitamin E (α-tocopherol, α-TOH) competitively reacts with lipid peroxyl radicals to mitigate oxidative damage, and forms oxidized vitamin E metabolites. Accordingly, we aimed to investigate the associations between α-TOH metabolites (oxidized and enzymatic) in both circulation and urine and measures of glucose homeostasis in the general middle-aged population.
This cross-sectional study was embedded in the population-based Netherlands Epidemiology of Obesity (NEO) Study. α-TOH metabolites in blood (α-TOH and α-CEHC-SO) and urine [sulfate (SO) and glucuronide (GLU) of both α-TLHQ (oxidized) and α-CEHC (enzymatic)] were quantified by liquid chromatography coupled with tandem mass spectrometry (LC/MS-MS). Measures of glucose homeostasis (HOMA-B, HOMA-IR, Insulinogenic index and Matsuda index) were obtained from fasting and postprandial blood samples. Multivariable linear regression analyses were performed to assess the associations of α-TOH metabolites and measures of glucose homeostasis.
We included 498 participants (45% men) with mean (SD) age of 55.8 (6.1) years who did not use glucose-lowering medication. While blood α-TOH was not associated with measures of glucose homeostasis, urinary oxidized metabolites (α-TLHQ-SO/GLU) were associated with HOMA-IR and Matsuda index. For example, a one-SD higher α-TLHQ-SO was associated with 0.92 (95% CI: 0.87, 0.97) fold lower HOMA-IR and 1.06 (1.01, 1.11) fold higher Matsuda index, respectively. Similar results were obtained for the urinary α-TLHQ to α-CEHC ratio as a measure of oxidized-over-enzymatic conversion of α-TOH.
Higher urinary levels of oxidized α-TOH metabolites as well as higher oxidized-to-enzymatic α-TOH metabolite ratio, but not circulating α-TOH or enzymatic metabolites, were associated with lower insulin resistance. Rather than circulating α-TOH, estimates of the conversion of α-TOH might be informative in relation to health and disease.
脂质过氧化损伤与葡萄糖稳态受损有关。维生素 E（α-生育酚，α-TOH）与脂质过氧自由基竞争反应，减轻氧化损伤，并形成氧化的维生素 E 代谢物。因此，我们旨在研究中老年人群中循环和尿液中 α-TOH 代谢物（氧化和酶）与葡萄糖稳态测量值之间的关联。
本横断面研究嵌入在基于人群的荷兰肥胖症流行病学研究（NEO）中。通过液相色谱串联质谱法（LC/MS-MS）定量测定血液中的 α-TOH 代谢物（α-TOH 和 α-CEHC-SO）和尿液中的代谢物[硫酸盐（SO）和葡萄糖醛酸苷（GLU），均为 α-TLHQ（氧化）和 α-CEHC（酶）]。从空腹和餐后血样中获得葡萄糖稳态的测量值（HOMA-B、HOMA-IR、胰岛素生成指数和 Matsuda 指数）。采用多元线性回归分析评估 α-TOH 代谢物与葡萄糖稳态测量值之间的关联。
我们纳入了 498 名参与者（45%为男性），平均（SD）年龄为 55.8（6.1）岁，且未使用降血糖药物。虽然血液 α-TOH 与葡萄糖稳态的测量值无关，但尿液中的氧化代谢物（α-TLHQ-SO/GLU）与 HOMA-IR 和 Matsuda 指数有关。例如，α-TLHQ-SO 增加一个标准差与 HOMA-IR 降低 0.92（95%CI：0.87，0.97）倍和 Matsuda 指数升高 1.06（1.01，1.11）倍相关。作为 α-TOH 氧化与酶促转化比值的尿液中 α-TLHQ 与 α-CEHC 的比值也得到了类似的结果。
尿液中氧化的 α-TOH 代谢物水平升高，以及氧化与酶促的 α-TOH 代谢物比值升高，与胰岛素抵抗降低有关，但与循环中的 α-TOH 相比，α-TOH 转化的估计值可能与健康和疾病有关。
