Social isolation, loneliness, and incident type 2 diabetes mellitus: results from two large prospective cohorts in Europe and East Asia and Mendelian randomization

Yanjun Song; Chen Zhu; Boqun Shi; Chenxi Song; Kongyong Cui; Zhen'ge Chang; Guofeng Gao; Lei Jia; Rui Fu; Qiuting Dong; Lei Feng; Chenggang Zhu; Dong Yin; JoAnn E Manson; Kefei Dou

doi:10.1016/j.eclinm.2023.102236

Social isolation, loneliness, and incident type 2 diabetes mellitus: results from two large prospective cohorts in Europe and East Asia and Mendelian randomization

EClinicalMedicine. 2023 Sep 21:64:102236. doi: 10.1016/j.eclinm.2023.102236. eCollection 2023 Oct.

Authors

Yanjun Song^{1

2}, Chen Zhu³, Boqun Shi^{1

2

4}, Chenxi Song^{1

2}, Kongyong Cui^{1

2}, Zhen'ge Chang⁵, Guofeng Gao^{1

2}, Lei Jia^{1

2}, Rui Fu^{1

2}, Qiuting Dong^{1

2}, Lei Feng^{1

2}, Chenggang Zhu^{1

2}, Dong Yin^{1

2}, JoAnn E Manson^{6

7

8}, Kefei Dou^{1

2}

Affiliations

¹ Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² State Key Laboratory of Cardiovascular Disease, Beijing, China.
³ College of Economics and Management, China Agricultural University, Beijing, 100083, China.
⁴ Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
⁵ Department of Cardiology, Civil Aviation General Hospital, Peking University, Beijing, China.
⁶ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁷ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Abstract

Background: Social isolation and loneliness pose significant public health challenges globally. The objective of this study is to investigate the association between social isolation, loneliness, and the risk of type 2 diabetes mellitus (T2DM).

Methods: 423,503 UK adults from the UK Biobank (UKB) and 13,800 Chinese adults from the China Health and Retirement Longitudinal Study (CHARLS) were analyzed. The exposures of interest were social isolation and loneliness. Social isolation was evaluated based on the number of household members, frequency of social activities, contact with others, and marriage status (CHARLS only). Loneliness was evaluated by the subjective feeling of loneliness and the willingness to confide in others (UKB only). The primary endpoint was incident T2DM. The two-sample Mendelian randomization (MR) analysis was based on the genome-wide association studies of UKB (n = 463,010) and the European Bioinformatics Institute (n = 655,666).

Findings: The UKB cohort study documented 15,072 T2DM cases during a mean follow-up of 13.5 years, and the CHARLS cohort study recorded 1,249 T2DM cases during a mean follow-up of 5.8 years. Social isolation and loneliness showed significant associations with an elevated risk of T2DM in both UKB (social isolation [most vs least]: HR 1.17, 95% CI 1.11-1.23; loneliness [yes vs no]: HR 1.21, 95% CI 1.13-1.30) and CHARLS cohorts (social isolation [yes vs no]: HR 1.22, 95% CI 1.06-1.40; loneliness [yes vs no]: HR 1.21, 95% CI 1.07-1.36). These associations remained significant after accounting for baseline glucose status and genetic susceptibility to T2DM. Two-sample MR analyses determined that feeling lonely (OR 1.04, 95% CI 1.02-1.06) and engaging in fewer leisure/social activities (OR 1.03, 95% CI 1.02-1.05) were associated with increased T2DM risk, whereas more contact with friends or family (OR 0.99, 95% CI 0.98-0.99) was associated with reduced T2DM risk.

Interpretation: Social isolation and loneliness are each associated with an elevated risk of T2DM, with MR analyses suggesting potential causal links. These associations remain significant after considering genetic susceptibility to T2DM. The findings highlight the importance of promoting initiatives to address social isolation and loneliness as part of T2DM prevention strategies.

Funding: CAMS Innovation Fund for Medical Sciences (No. 2021-I2M-1-008) and National Natural Science Foundation of China (No. 72103187).

Keywords: Cohort study; Loneliness; Mendelian randomization; Public health; Social isolation; Type 2 diabetes mellitus.