Increased blood glucose levels, even within the nondiabetic range, are associated with increased risk for nonalcoholic fatty liver disease (NAFLD) and lower likelihood of resolution of existing NAFLD, according to study results published in the Journal of Clinical Endocrinology & Metabolism.

Several studies have reported a higher risk for NAFLD among patients with type 2 diabetes, but limited data are available on the association between blood glucose levels within the nondiabetic range and NAFLD risk. The goal of the current study was to explore the association between glucose homeostasis, measured by oral glucose tolerance test (OGTT) 2-hour glucose level and hemoglobin A1c (HbA1c), and risk for NAFLD, as well as the effect of changes in glycemic regulation on resolution of NAFLD in adults without diabetes.

The study cohort included individuals from 10 communities in the Jiading District of Shanghai, China. After exclusion of patients with known liver diseases, excessive alcohol consumption, and previous diagnosis of type 2 diabetes, the study cohort included 4273 Chinese adults aged ≥40 years with complete hepatic ultrasound data.

At baseline, the prevalence of NAFLD was 24.9%. Among 3209 individuals without baseline NAFLD, 573 (17.9%) incident cases of NAFLD were identified during a mean follow-up of 4.4 years. Patients who developed NAFLD tended to have higher body mass index, waist circumference, blood pressure, total cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting insulin, OGTT 2-hour glucose, and HbA1c levels compared with those who did not develop NAFLD.

Elevated 2-hour glucose level on OGTT and elevated HbA1c levels were positively associated with incident NAFLD. The relative risk that corresponded to each 1-standard deviation (SD) increment in 2-hour glucose level on OGTT was 1.16 (95% CI, 1.08-1.25). In addition, among those with NAFLD, 2-hour glucose level on OGTT was associated with a higher probability of advanced fibrosis (relative risk per SD increase, 1.07; 95% CI, 1.02-1.12).

Among the 1064 patients with NAFLD at baseline, NAFLD resolved in 304 (28.6%) during the follow-up period. Individuals who achieved resolution of NAFLD were older and more likely to be men and had healthier metabolic parameters, including lower levels of fasting insulin and fasting and OGTT 2-hour glucose levels, than patients whose NAFLD did not resolve.

Fasting and OGTT 2-hour glucose levels were negatively associated with resolution of NAFLD. The relative risks for resolution of NAFLD corresponding to each SD increment in fasting glucose and OGTT 2-hour glucose level were 0.86 (95% CI, 0.78-0.94) and 0.85 (95% CI, 0.77-0.93), respectively. The dose response association between HbA1c and NAFLD resolution was less clear.

The relative risk for resolution of NAFLD was lowest in patients who progressed from impaired glucose tolerance or impaired fasting glucose to type 2 diabetes (relative risks, 0.34 [95% CI, 0.21-0.54] and 0.45 [95% CI, 0.25-0.83], respectively) compared with those with sustained normal values regulation. The strongest associations were observed for individuals who developed diabetes.

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In analyses of bidirectionality, the researchers noted that baseline NAFLD was associated with a higher risk for progression to type 2 diabetes and transition from normal to impaired glucose tolerance. The development of NAFLD showed a more pronounced association with glycemic deterioration, whereas resolution of NAFLD was inversely associated with glycemic deterioration.

The researchers noted that NAFLD cases in this study were ascertained through onsite testing by hepatic ultrasonography, which largely reduced the possibility of underdiagnosis of asymptomatic NAFLD, a potential limitation to the study.

“Our findings support the intervention strategies that target prevention and treatment of NAFLD by managing long-term healthy glycemic status and vice versa,” concluded the researchers.

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Reference

Wang B, Li M, Zhao Z, et al. Glycemic measures and development and resolution of nonalcoholic fatty liver disease in nondiabetic individuals [published online March 7, 2020]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgaa112