Serum 1,5‐Anhydroglucitol Identifies Residual Mortality Risk Beyond Time in Range in Type 2 Diabetes: A Cohort Study
Jiaying Ni, Lei Chen, Hang Su, Jingyi Guo, Chunfang Wang, Yufei Wang, Jingyi Lu, Jian Zhou, Tian Xia, Feng JiangABSTRACT
Background
The combined prognostic value of continuous glucose monitoring (CGM) metrics and circulating glucose biomarkers for predicting mortality in type 2 diabetes has not been fully established, particularly regarding residual risk in patients achieving glycemic targets.
Methods
This cohort study included 3677 patients with type 2 diabetes for a median of 7.4 years follow‐up. Cox proportional hazards models evaluated the associations of baseline CGM‐derived time in range (TIR) (target 70%) and serum 1,5‐anhydroglucitol (1,5‐AG) (threshold 6.0 μg/mL) with all‐cause and cardiovascular mortality in the overall population. We further examined the relationship between 1,5‐AG and mortality within TIR subgroups and compared its performance with metrics of glycemic variability derived from CGM.
Results
During follow‐up, 522 all‐cause deaths and 181 cardiovascular deaths occurred. TIR and 1,5‐AG were moderately correlated and independently predicted mortality, with concurrent low TIR (≤ 70%) and low 1,5‐AG (< 6.0 μg/mL) yielding the highest risk (hazard ratio [HR] 1.82, 95% CI 1.40–2.37). In stratified analyses, reduced 1,5‐AG was significantly associated with increased mortality risk in patients with TIR > 70% (HR 1.69, 95% CI 1.25–2.28), whereas no significant association was observed in those with TIR ≤ 70%. Adding 1,5‐AG improved traditional risk prediction in the former subgroup. Compared with 1,5‐AG, CGM‐derived glycemic variability indices such as mean amplitude of glycemic excursions, coefficient of variation, and standard deviation of glucose showed no significant association with mortality.
Conclusions
TIR and serum 1,5‐AG offer independent and complementary value, with low 1,5‐AG identifying residual mortality risk despite achieving TIR targets.