Analysis of Severe Hypoglycemia Among Adults With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease

Yong Ho Lee, Ji Yeon Lee, Young Eun Kim, Kyungdo Han, Eugene Han, Byung Wan Lee, Eun Seok Kang, Bong Soo Cha, Seung Hyun Ko

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3 Citations (Scopus)


Importance: Previous studies have indicated that liver cirrhosis is associated with hypoglycemia, but there have been no studies investigating the association between nonalcoholic fatty liver disease (NAFLD) and hypoglycemia in noncirrhotic populations with type 2 diabetes. Objective: To explore the association of NAFLD with severe hypoglycemia among patients with type 2 diabetes. Design, Setting, and Participants: This nationwide population-based retrospective cohort study using the National Health Insurance System of South Korea included individuals aged 20 years or older who had undergone a medical health examination between January 1, 2009, and December 31, 2012, and were diagnosed with type 2 diabetes. Participants were followed up until December 31, 2015. Data analyses were performed between January 1, 2019, and February 2, 2021. Exposures: The baseline fatty liver index (FLI) was used as a surrogate marker for NAFLD. Main Outcomes and Measures: The outcome of interest, severe hypoglycemia, was measured using hospital admission and emergency department visit records with a primary diagnosis of hypoglycemia. Results: Among 1946581 individuals with type 2 diabetes, 1125187 (57.8%) were male. During a median (IQR) follow-up of 5.2 (4.1-6.1) years, 45135 (2.3%) experienced 1 or more severe hypoglycemia events. Participants with severe hypoglycemia, vs those without severe hypoglycemia, were older (mean [SD] age, 67.9 [9.9] years vs 57.2 [12.3] years; P <.001) and had lower mean (SD) body mass index (24.2 [3.43] vs 25.1 [3.4]; P <.001). 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; 95% CI, 0.83-0.90; 9th decile: aHR, 1.02; 95% CI, 0.96-1.08; 10th decile: aHR, 1.29; 95% CI, 1.22-1.37), and the estimated risk of hypoglycemia was higher in participants with NAFLD (aHR, 1.26; 95% CI, 1.22-1.30). The association was more prominent in female participants (aHR, 1.29; 95% CI, 1.23-1.36) and those with underweight (aHR, 1.71; 95% CI, 1.02-2.88). Conclusions and Relevance: In this study, NAFLD was associated with a higher risk of severe hypoglycemia in patients with type 2 diabetes independent of obesity status.

Original languageEnglish
Pages (from-to)E220262
JournalJAMA network open
Issue number2
Publication statusPublished - 2022 Feb 23

Bibliographical note

Funding Information:
Funding/Support: This research was supported by the grant 2018R1D1A1B07050005 from the Basic Science Research Program through the National Research Foundation of Korea by grant NRF-2016R1A5A1010764 funded by the Korean Government.

Publisher Copyright:
© 2022 Elsevier Ltd. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Medicine(all)


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