Impact of the Complexity of Glucose Time Series on All-Cause Mortality in Patients With Type 2 Diabetes

CONTEXT: Previous studies suggest that the complexity of glucose time series may serve as a novel marker of glucose homeostasis. OBJECTIVE: We aimed to investigate the relationship between the complexity of glucose time series and all-cause mortality in patients with type 2 diabetes. METHODS: Prospective data of 6000 adult inpatients with type 2 diabetes from a single center were analyzed. The complexity of glucose time series index (CGI) based on continuous glucose monitoring (CGM) was measured at baseline with refined composite multiscale entropy. Participants were stratified by CGI tertiles of: < 2.15, 2.15 to 2.99, and ≥ 3.00. Cox proportional hazards regression models were used to assess the relationship between CGI and all-cause mortality. RESULTS: During a median follow-up of 9.4 years, 1217 deaths were identified. A significant interaction between glycated hemoglobin A1c (HbA1c) and CGI in relation to all-cause mortality was noted (P for interaction = 0.016). The multivariable-adjusted hazard ratios for all-cause mortality at different CGI levels (≥ 3.00 [reference group], 2.15-2.99, and < 2.15) were 1.00, 0.76 (95% CI, 0.52-1.12), and 1.47 (95% CI, 1.03-2.09) in patients with HbA1c < 7.0%, while the association was nonsignificant in those with HbA1c ≥ 7.0%. The restricted cubic spline regression revealed a nonlinear (P for nonlinearity = 0.041) relationship between CGI and all-cause mortality in subjects with HbA1c < 7.0% only. CONCLUSION: Lower CGI is associated with an increased risk of all-cause mortality among patients with type 2 diabetes achieving the HbA1c target. CGI may be a new indicator for the identification of residual risk of death in well-controlled type 2 diabetes.