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

 Ji-Yeon Lee  ;  Young-Eun Kim  ;  Kyungdo Han  ;  Eugene Han  ;  Byung Wan Lee  ;  Eun Seok Kang  ;  Bong-Soo Cha  ;  Seung-Hyun Ko  ;  Yong-Ho Lee 
 JAMA NETWORK OPEN, Vol.5(2) : e220262, 2022-02 
Journal Title
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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 1 946 581 individuals with type 2 diabetes, 1 125 187 (57.8%) were male. During a median (IQR) follow-up of 5.2 (4.1-6.1) years, 45 135 (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. Presence of NAFLD should be considered when evaluating vulnerability to hypoglycemia in patients with type 2 diabetes.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Eun Seok(강은석) ORCID logo https://orcid.org/0000-0002-0364-4675
Kim, Young-Eun(김영은)
Lee, Byung Wan(이병완) ORCID logo https://orcid.org/0000-0002-9899-4992
Lee, Yong Ho(이용호) ORCID logo https://orcid.org/0000-0002-6219-4942
Lee, Ji Yeon(이지연)
Cha, Bong Soo(차봉수) ORCID logo https://orcid.org/0000-0003-0542-2854
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