Glycemic variability and the risk of nonalcoholic fatty liver disease: A nationwide population-based cohort study

Aim: Although few recent studies have reported the association between the glycemic variability and the development of type 2 diabetes mellitus and cardiovascular disease in individuals without diabetes mellitus, the impact of the long-term variability in fasting plasma glucose (FPG) levels on the incident nonalcoholic fatty liver disease (NAFLD) has not been evaluated. Methods: The study included 57,636 Korean men and women without NAFLD and diabetes mellitus from the Korean National Health Insurance System cohort. FPG variability was calculated using the coefficient of variation (FPG-CV), standard deviation (FPG-SD), variability independent of the mean (FPG-VIM), and average successive variability (FPG-ASV). Results: The cumulative incidence of NAFLD demonstrated progressively increasing trends according to the higher quartiles of FPG variability in Kaplan-Meier curves. A multivariable Cox proportional hazard analysis revealed that the hazard ratio for incident NAFLD was 1.15 (95% confidence interval, 1.06–1.24) in the highest quartile of FPG-CV compared with the lowest quartile of FPG-CV after adjusting for various confounding factors, including mean FPG levels. When using FPG-SD, FPG-VIM, and FPG-ASV, the results were similar. The 10-unit increase in FPG variability was associated with a 14% increased risk of NAFLD in the fully adjusted model. Moreover, this effect remained consistent in the subgroup and sensitivity analyses. Conclusion: Increased long-term FPG variability is associated with the development of NAFLD, independent of confounding risk variables including mean FPG levels.