高血红蛋白糖基化指数与端粒损耗有关，与 HbA1c 无关，其介导物为 TNFα。
High Hemoglobin Glycation Index Is Associated With Telomere Attrition Independent of HbA1c, Mediated by TNFα.
机构信息
Department of Endocrinology, NHC Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Department of Nutrition, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
出版信息
J Clin Endocrinol Metab. 2022 Jan 18;107(2):462-473. doi: 10.1210/clinem/dgab703.
CONTEXT
The hemoglobin glycation index (HGI) is correlated with metabolic diseases and inflammation. Whether the HGI is associated with the aging process and how inflammation and oxidative stress affect the relationship remain unclear.
OBJECTIVE
We aimed to analyze links between the HGI and aging biomarkers, and to explore a potential role of inflammation and oxidative stress in the correlations.
METHODS
A cross-sectional study of 434 subjects with different glucose intolerances in a rural community was enrolled. The HGI was calculated as the difference between the measured and predicted hemoglobin A1c (HbA1c). The population was categorized into tertiles of the HGI. Telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) determined by polymerase chain reaction assay. Tumor necrosis factor (TNF) α and interleukin (IL) 6, 8-oxo-2'-deoxyguanosine (8-oxo-dG), superoxide dismutase (SOD) activities, and glutathione reductase (GR) were measured.
RESULTS
Participants in the high HGI group were older and reported a shorter LTL, higher levels of TNFα, SOD activities, and HbA1c. Correlation analyses demonstrated that HGI was correlated with LTL (r = -0.25, P < .001) and TNFα (r = 0.19, P < .001) regardless of HbA1c levels. No relationship was found between HGI and mtDNAcn. HGI (β = -0.238, 95% CI -0.430, -0.046, P = .015) and TNFα (β = -0.02, 95% CI -0.030, -0.014, P < .001) were proved to be correlated with LTL independently, using multiple linear regression analysis. Ordinal logistic regression models showed that compared with subjects the high HGI group, the possibilities of a higher-level LTL was 5.29-fold in the low HGI group (OR 5.29, 95% CI (2.45, 11.41), P < .001), 2.41-fold in the moderate HGI group (OR 2.41, 95% CI 1.35, 4.30, P = .003) after controlling for confounding variables. Mediation analyses indicated that TNFα accounted for 30.39% of the effects of the HGI on LTL.
CONCLUSION
HGI was negatively related to telomere attrition, independent of HbA1c. TNFα acted as a mediator of the relationship between HGI and LTL.
背景
血红蛋白糖化指数（HGI）与代谢疾病和炎症有关。HGI 是否与衰老过程有关，以及炎症和氧化应激如何影响这种关系尚不清楚。
目的
本研究旨在分析 HGI 与衰老生物标志物之间的关系，并探讨炎症和氧化应激在这些相关性中的潜在作用。
方法
对农村社区中不同葡萄糖耐量的 434 名受试者进行横断面研究。HGI 计算为实测 HbA1c 与预测 HbA1c 之间的差值。根据 HGI 的三分位值将人群分为三组。聚合酶链反应检测端粒长度（LTL）和线粒体 DNA 拷贝数（mtDNAcn）。测定肿瘤坏死因子（TNF）α和白细胞介素（IL）6、8-氧代-2'-脱氧鸟苷（8-oxo-dG）、超氧化物歧化酶（SOD）活性和谷胱甘肽还原酶（GR）。
结果
HGI 较高组的参与者年龄较大，报告的 LTL 较短，TNFα、SOD 活性和 HbA1c 水平较高。相关性分析表明，无论 HbA1c 水平如何，HGI 均与 LTL（r = -0.25，P <.001）和 TNFα（r = 0.19，P <.001）相关。HGI 与 mtDNAcn 之间无相关性。多元线性回归分析显示，在校正混杂因素后，HGI（β = -0.238，95%CI -0.430，-0.046，P =.015）和 TNFα（β = -0.02，95%CI -0.030，-0.014，P <.001）与 LTL 独立相关。有序逻辑回归模型显示，与 HGI 较低组相比，HGI 较高组的 LTL 水平较高的可能性高 5.29 倍（OR 5.29，95%CI（2.45，11.41），P <.001），HGI 中等组高 2.41 倍（OR 2.41，95%CI 1.35，4.30，P =.003）。中介分析表明，TNFα占 HGI 对 LTL 影响的 30.39%。
结论
HGI 与端粒损耗呈负相关，独立于 HbA1c。TNFα是 HGI 与 LTL 之间关系的中介。
Zotero 插件