South Korea: Study on NAFLD and Hypoglycemia

A recent study in JAMA Network Open has revealed an association between nonalcoholic fatty liver disease (NAFLD) and a higher risk of severe hypoglycemia in patients with type 2 diabetes. This association was independent of obesity status and the knowledge of this association could help inform management.

Possible Mechanism

Explaining the possible mechanism behind the association of NAFLD with severe hypoglycemia, the authors wrote it could be due to altered glucose metabolism in NAFLD. "Glucagon level is found to be increased in the presence of NAFLD and hyperglucagonemia might induce downregulation of hepatic glucagon receptor or blunt the counter-regulatory response to hypoglycemic events in hepatic glucose production," they wrote. "NAFLD may be associated with glycemic variability through increased oxidative stress, which is an important determinant of hypoglycemia."

Study Background

Previous studies have shown liver cirrhosis to be associated with hypoglycemia but no studies have investigated the association between NAFLD and hypoglycemia in noncirrhotic populations with type 2 diabetes. To fill this knowledge gap, Ji-Yeon Lee, Yonsei University College of Medicine, Seoul, Republic of Korea, and colleagues aimed to explore the association of NAFLD with severe hypoglycemia in type 2 diabetes patients in a nationwide population-based retrospective cohort study.

The study included individuals aged 20 years or older who had undergone a medical health examination between January 1, 2009, and December 31, 2012, and was diagnosed with type 2 diabetes using the National Health Insurance System of South Korea. Follow-up of the participants was done until December 31, 2015. Data analysis was performed between January 1, 2019, and February 2, 2021.

Methodology

The baseline fatty liver index (FLI) was used as a surrogate marker for NAFLD. Hospital admission and emergency department visit records with a primary diagnosis of hypoglycemia were used to measure the outcome of interest, severe hypoglycemia.

Study Findings

• Among 1,946,581 individuals with type 2 diabetes, 1,125,187 (57.8%) were male.
• During a median follow-up of 5.2 years, 45,135 (2.3%) experienced 1 or more severe hypoglycemia events.
• Participants with severe hypoglycemia, vs those without severe hypoglycemia, were older (mean age, 67.9 years vs 57.2 years) and had lower mean body mass index (24.2 vs 25.1).
• Patients with NAFLD tended to have less severe hypoglycemia without consideration of obesity status. However, after adjustment of multiple clinical covariates, including body mass index, there was a J-shaped association between FLI and severe hypoglycemia (5th decile: adjusted hazard ratio [aHR], 0.86; 9th decile: aHR, 1.02; 10th decile: aHR, 1.29), and the estimated risk of hypoglycemia was higher in participants with NAFLD (aHR, 1.26).
• The association was more prominent in female participants (aHR, 1.29) and those with underweight (aHR, 1.71).

Conclusion

To conclude, knowing the association of NAFLD with severe hypoglycemia in adults with type 2 diabetes, independent of obesity status, could help to inform management.

Reference

Lee J, Kim Y, Han K, et al. Analysis of Severe Hypoglycemia Among Adults With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease. JAMA Netw Open. 2022;5(2):e220262. doi:10.1001/jamanetworkopen.2022.0262