Glycemic Measures and Development and Resolution of Nonalcoholic Fatty Liver Disease in Nondiabetic Individuals

Context: Type 2 diabetes (T2D) is closely associated with nonalcoholic fatty liver disease (NAFLD); however, evidence regarding the link between blood glucose, especially below the threshold for T2D, and NAFLD is scarce. Objective: The objective of this work is to examine the associations of fasting glucose, oral glucose tolerance test (OGTT) 2-hour glucose, and hemoglobin A(1c) (HbA(1c)), and changes in these measures with development and resolution of NAFLD in nondiabetic individuals. Methods: This longitudinal cohort study comprised 4273 Chinese adults age 40 years or older and free of baseline T2D from 2010 to 2015. Blood sampling was performed during the OGTT test. NAFLD was ascertained by hepatic ultrasonography. Risk ratios (RRs) were calculated using modified Poisson regression models. Results: During a mean 4.4 years of follow-up, NAFLD occurred in 573 (17.9%) of the 3209 participants without baseline NAFLD and resolved in 304 (28.6%) of the 1064 participants with baseline NAFLD. OGTT 2-h glucose was positively associated with NAFLD incidence (RR per 1-SD increase: 1.16, 95% CI: 1.08-1.25), whereas fasting (RR: 0.86, 95% CI: 0.78-0.94) and 2-hour glucose (RR: 0.85, 95% CI: 0.77-0.93) were inversely associated with resolution of NAFLD. Glycemic deterioration conferred increased risk of developing NAFLD and decreased likelihood of resolution of NAFLD than maintaining normal glycemic regulation (NGR). The strongest associations were observed for individuals who developed T2D. Meanwhile, baseline or incident NAFLD significantly increased the risk of deterioration in glucose metabolism. Conclusions: Increased glycemic levels within the nondiabetic range, as well as progression from NGR to T2D or prediabetes, were adversely associated with development and improvement of NAFLD.