Loneliness and Social Isolation with Risk of Incident Non-alcoholic Fatty Liver Disease, UK Biobank 2006 to 2022

Ya Miao; Xiaoke Kong; Bin Zhao; Fang Fang; Jin Chai; Jiaqi Huang

doi:10.34133/hds.0220

Loneliness and Social Isolation with Risk of Incident Non-alcoholic Fatty Liver Disease, UK Biobank 2006 to 2022

Health Data Sci. 2024 Jan 7:5:0220. doi: 10.34133/hds.0220. eCollection 2025.

Authors

Ya Miao^{1

2

3

4}, Xiaoke Kong^{1

2

3

4}, Bin Zhao^{1

2

3

4}, Fang Fang⁵, Jin Chai⁶, Jiaqi Huang^{1

2

3

4}

Affiliations

¹ National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
² Xiangya School of Public Health, Central South University, Changsha, China.
³ CSU-Sinocare Research Center for Nutrition and Metabolic Health, Changsha, China.
⁴ Furong Laboratory, Changsha, China.
⁵ Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
⁶ Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing 400038, China.

Abstract

Background: Although loneliness and social isolation are proposed as important risk factors for metabolic diseases, their associations with the risk of non-alcoholic fatty liver disease (NAFLD) have not been elucidated. The aims of this study were to determine whether loneliness and social isolation are independently associated with the risk of NAFLD and to explore potential mediators for the observed associations. Methods: In this large prospective cohort analysis with 405,073 participants of the UK Biobank, the status of loneliness and social isolation was assessed through self-administrated questionnaires at study recruitment. The primary endpoint of interest was incident NAFLD. Multivariable-adjusted Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals for the associations between loneliness, social isolation, and risk of NAFLD. Results: During a median follow-up of 13.6 years, there were 5,570 cases of NAFLD identified. In the multivariable-adjusted model, loneliness and social isolation were both statistically significantly associated with an increased risk of NAFLD (HR = 1.22 and 1.13, respectively). No significant multiplicative or additive interaction was found between loneliness and social isolation on the risk of NAFLD. The mediation analysis estimated that 30.4%, 16.2%, 5.3%, 4.1%, 10.5%, and 33.2% of the loneliness-NAFLD association was mediated by unhealthy lifestyle score, obesity, current smoking, irregular physical activity, suboptimal sleep duration, and depression, respectively. On the other hand, 25.6%, 10.1%, 15.5%, 10.1%, 8.1%, 11.6%, 9.6%, 4.8%, and 3.0% of the social isolation-NAFLD association was mediated by unhealthy lifestyle score, obesity, current smoking, irregular physical activity, suboptimal sleep duration, depression, C-reactive protein, count of white blood cells, and count of neutrophils, respectively. Conclusions: Our study demonstrated that loneliness and social isolation were associated with an elevated risk of NAFLD, independent of other important risk factors. These associations were partially mediated by lifestyle, depression, and inflammatory factors. Our findings substantiate the importance of loneliness and social isolation in the development of NAFLD.