Division of Endocrinology & Metabolism, Nemours Children's Health, Jacksonville, FL, 32207.
Department of Biostatistics, University of Delaware, DE.
Nutr Res. 2023 Sep;117:83-90. doi: 10.1016/j.nutres.2023.05.010. Epub 2023 May 25.
In earlier studies, we showed that adolescents with type 1 diabetes mellitus (T1DM) have significant glutathione (GSH) depletion and that GSH is reciprocally related to glycemic control. In both the general population and in those with diabetes, the use of over-the-counter antioxidant supplements is widespread. We hypothesized that improved glycemic control, alone or in combination with dietary antioxidants, would restore blood GSH pool. The study included 41 participants who were 15.8 ± 2.4 years of age (mean ± standard deviation) and with poorly controlled T1DM (hemoglobin A1c [HbA1c] 8.2 ± 0.6%). Erythrocyte GSH, and 3-nitrotyrosine, F2-isoprostane, and 8-hydroxy-2'-deoxy-guanosine (as markers of protein, lipid, and DNA oxidative stress, respectively) were determined in the postabsorptive state after blood glucose was maintained overnight near euglycemia. Participants were then randomized to a mix of antioxidants (vitamin C, selenium, zinc, vitamin E, β-carotene) or placebo for 3 to 6 months, and diabetes management was intensified using CSII (n = 30) or multiple daily injections (n = 11) coupled with CDE phone calls and visits with a Nutritionist. A second, identical study was performed when/if a drop in HbA1c ≥0.5% was achieved. HbA1c levels dropped similarly in both groups (from 8.9 ± 1.0% to 7.9 ± 0.9% and 8.5 ± 0.6% to 7.7 ± 0.7% in placebo and antioxidant group, respectively). Neither total nor reduced GSH was altered by improved metabolic control. Markers of protein, lipid, and DNA oxidation remained unaltered. We conclude that, in youngsters with T1DM, neither a significant improvement in diabetes control over a 3-month period nor the regimen of dietary antioxidant supplied in the current study can mitigate oxidative stress. These findings suggest that, in adolescents with T1DM, (1) more sustained improvement of diabetes control may be needed to alleviate oxidative stress and (2) the putative benefit of antioxidant supplements remains to be proven.
在之前的研究中，我们发现 1 型糖尿病（T1DM）青少年患者谷胱甘肽（GSH）明显耗竭，并且 GSH 与血糖控制呈反向相关。在普通人群和糖尿病患者中，使用非处方抗氧化补充剂的现象非常普遍。我们假设，血糖控制的改善（单独或与饮食抗氧化剂联合）将恢复血液 GSH 池。该研究包括 41 名年龄为 15.8 ± 2.4 岁（平均值 ± 标准差）且血糖控制不佳的 T1DM 患者（血红蛋白 A1c [HbA1c] 8.2 ± 0.6%）。在夜间将血糖维持在接近正常血糖水平后，测定空腹状态下的红细胞 GSH 和 3-硝基酪氨酸、F2-异前列腺素、8-羟基-2'-脱氧鸟苷（分别作为蛋白质、脂质和 DNA 氧化应激的标志物）。然后，将参与者随机分为抗氧化剂（维生素 C、硒、锌、维生素 E、β-胡萝卜素）或安慰剂组，持续 3 至 6 个月，同时使用胰岛素泵（n = 30）或多次每日胰岛素注射（n = 11）联合 CDE 电话咨询和营养师访视，强化糖尿病管理。如果 HbA1c 降低≥0.5%，则进行第二次相同的研究。两组的 HbA1c 水平均相似下降（安慰剂组从 8.9 ± 1.0%降至 7.9 ± 0.9%，抗氧化剂组从 8.5 ± 0.6%降至 7.7 ± 0.7%）。无论代谢控制改善与否，总 GSH 和还原型 GSH 均未改变。蛋白质、脂质和 DNA 氧化的标志物仍未改变。我们得出结论，在 T1DM 青少年中，（1）3 个月内显著改善糖尿病控制，或当前研究中提供的饮食抗氧化剂方案，都不能减轻氧化应激。这些发现表明，在 T1DM 青少年中，（1）可能需要更持续的糖尿病控制改善，以减轻氧化应激，（2）抗氧化补充剂的潜在益处仍有待证明。
