Association of cumulative blood glucose load with cardiovascular risk and all-cause mortality

Background: Incorporation both the magnitude and duration of exposure to elevated fasting blood glucose (FBG) into a single risk parameter (cumulative FBG load) for future diseases is intuitively appealing, although a databased demonstration of the utility of this metric is not available. This study aimed to investigate the associations with cumulative FBG load with the risk of cardiovascular diseases (CVD) and all-cause mortality in the general population. Methods: This prospective cohort study included 41,728 participants who were free of CVD and underwent four health examinations from 2006 to 2012. Cumulative FBG load during 2006-2012 was calculated as the area under curve for FBG values >= 5.6 mmol/L divided by the total area curve. We also compared the predicting value cumulative FBG load with other FBG metrics. Results: During a median follow-up of 6.75 years, we identified 2323 cases of CVD and 1724 cases of all-cause mortality. Per 1-standard deviation increase in cumulative FBG load was associated with a 16 % higher risk of CVD (hazard ratio [HR]: 1.16; 95 % confidence interval [CI], 1.13-1.20) and 20 % higher risk of all-cause mortality (HR, 1.20; 95 % CI, 1.16-1.25). For the prediction of cardiovascular outcomes and all-cause mortality, cumulative FBG load outperformed FBG time-in-target, visit-to-visit FBG variability, and mean FBG in terms of C-statistics and reclassification indexes. Conclusions: Cumulative FBG load may provide a better prediction of cardiovascular outcomes compared with other FBG metrics in the general population. These findings emphasized the important role of cumulative FBG load in assessing cardiovascular and mortality risk.