High Hemoglobin Glycation Index Is Associated With Telomere Attrition Independent of HbA1c, Mediated by TNFα

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.