High Hemoglobin glycation index is associated with telomere attrition independent of HbA1c, mediating by TNFα.

CONTEXT The hemoglobin glycation index(HGI) is correlated with metabolic diseases and inflammations. Whether the HGI is associated with the ageing process and how inflammation and oxidative stress affect the relationship remain unclear. OBJECTIVE We aim to analyze links between HGI and ageing 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 HGI. Telomere length(LTL) and mitochondrial DNA copy number(mtDNAcn) determined by PCR assay. Tumor necrosis factor α(TNFα) and interleukin 6(IL-6), 8-oxo-2'-deoxyguanosine(8-oxo-dG), superoxide dismutase(SOD) activities and glutathione reductase(GR) were measured. RESULT 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<0.001) and TNFα(r=0.19,p<0.001) regardless of HbA1c levels. No relationship was found between HGI and mtDNAcn. HGI(β=-0.238,95%CI(-0.430,-0.046),p=0.015) and TNFα(β=-0.02,95%CI(-0.030,-0.014),p<0.001) were proved to be correlated with LTL independently using multiple linear regression analysis. Ordinal logistic regression models showed that compared with subjects in High-HGI, the possibilities of a higher-level LTL was 5.29-fold in Low-HGI(OR5.29,95%CI(2.45,11.41),p<0.001), 2.41-fold in Moderate-HGI (OR2.41,95%CI(1.35,4.30),p=0.003) after controlling for confounding variables. Mediation analyses indicated that TNFα accounted for 30.39% effects of 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.