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 was analyzed. The complexity of glucose time series index (CGI) based on continuous glucose monitoring (CGM) was measured at baseline with refined composite multi-scale entropy. Participants were stratified by the tertiles of CGI: < 2.15, 2.15-2.99, 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 non-linear (P for non-linearity = 0.041) relationship between CGI and all-cause mortality in subjects with HbA1c < 7.0% only.


CONCLUSIONS
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.