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Serum 1,5-Anhydroglucitol Identifies Residual Mortality Risk Beyond Time in Range in Type 2 Diabetes: A Cohort Study
Jiaying Ni1, Lei Chen2, Hang Su1,3
1Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China.
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.
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