Impact of visit-to-visit fasting plasma glucose variability on the development of diabetes: The mediation by insulin resistance

Background: Little is known about the risk of diabetes due to higher glycemic variability and the underlying mechanisms. We aimed to examine the association of visit-to-visit variability (VVV) in fasting plasma glucose (FPG) with incident diabetes in Chinese adults and whether the association was mediated by changes in insulin resistance (IR).

Methods: We included 1856 community residents without a history of diabetes and having attended 3 examinations in 2008, 2009, and 2013 respectively. The SD, the average successive variability (ASV), the coefficient of variation (CV), and the variability independent of the mean (VIM) of three recorded FPG measurements were calculated for each participant, and SD, ASV, CV, and VIM were used as a measure of VVV in FPG. Incident diabetes was defined according to the 1999 World Health Organization criteria. IR was evaluated using the homeostatic model assessment (HOMA).

Results: A total of 153 (8.2%) participants developed incident diabetes at the third visit. Compared with the lowest tertile (0-5.83 mg/dl) of FPG-SD, the highest tertile (9.55-74.17 mg/dl) was associated with a 148% increased risk of diabetes (odds ratio [OR], 2.48; 95% confidence interval [CI], 1.36-4.49), after adjustment for covariates including mean FPG at 3 visits. Mediation analyses suggested that changes in IR (ΔHOMA-IR) might mediate 17.3% of the association between increased FPG-SD and elevated diabetes risk. Similar results were found for FPG-CV, FPG-ASV, and FPG-VIM.

Conclusions: The VVV in FPG was significantly associated with risks of diabetes in Chinese adults, which was partially mediated by changes in IR.