Separate and combined effect of visit‐to‐visit glycaemic variability and mean fasting blood glucose level on all‐cause mortality in patients with type 2 diabetes: A population‐based cohort study

Aims: To assess the independent and joint impact of visit-to-visit fasting blood glucose variability (VVV-FBG) and mean fasting glucose level (M-FBG) on all-cause mortality.Materials and methods: This prospective cohort study included 48,843 Chinese with type 2 diabetes. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) to evaluate the association of VVV-FBG and M-FBG with all-cause mortality. The potential nonlinear associations were examined by restricted cubic splines, and additive interaction was evaluated by the relative excess risk due to interaction (RERI). Cox generalized additive models (CGAM) and bivariate response surface models were further used to assess the joint effects of VVV-FBG and M-FBG.Results: A total of 4087 deaths was observed during a median follow-up of 6.99 years. Compared with patients with values at the 5th percentile of ARV and M-FBG, we observed a 23% and 38% increased risk of premature deaths among those with values at the 95th percentile of ARV (HR: 1.23, 95% CI 1.10,1.37) and M-FBG (HR: 1.38, 95% CI 1.26,1.51), respectively. The interaction between glycemic variability (ARV) and M-FBG was significant on both the additive scale [RERI: 0.80 (0.29, 1.32)] and multiplicative scale [HR: 1.90 (1.10, 3.28)]. Subjects with high VVV-FBG and high M-FBG conferred the highest risk of all-cause mortality (HR: 1.89, 95% CI: 1.64,2.17), compared to low VVV-FBG and low M-FBG. The CGAM revealed significant synergistic effects between glycemic variability and M-FBG (P < 0.05). Moreover, bivariate surface plot revealed that the risk of death increased more rapidly in type 2 diabetes patients at the lower M-FBG level combined with lower glycemic variability level.Conclusions: The coexistence of great glycemic variability and high level of glucose might exacerbate the independent risk of premature mortality in type 2 diabetes patients, highlighting the importance of achieving normal and stable glucose levels simultaneously in the management of glucose. This article is protected by copyright. All rights reserved.