Oh Dae Jong, Jeong Chaiho, Kim Junhyung, Kim Eun Soo, Oh Kang-Seob, Shin Young Chul, Shin Dong-Won, Jeon Sang-Won, Cho Sung Joon
Workplace Mental Health Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Lancet Reg Health West Pac. 2025 Aug 20;62:101672. doi: 10.1016/j.lanwpc.2025.101672. eCollection 2025 Sep.
Despite emerging evidence, the causal relationship between insulin resistance and depression remains controversial. This study aimed to investigate whether insulin resistance is associated with increased risk of incident depression and whether the association is affected by potential moderators.
This multi-centered prospective cohort study analyzed health screening data from 233,452 Korean adults participating in the Kangbuk Samsung Health Study from 2011 to 2022. At baseline, all participants indicated no major psychiatric or neurologic disorders and had not used antidepressant or diabetes medications. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). Incident depression was defined as having a Center for Epidemiologic Studies Depression Scale score of ≥16.
Participants (age = 36.1 ± 8.6 years, 54.1% male) were followed up for 4.8 ± 2.9 years. During the 1,124,268 person-years of follow-up duration, 38,801 cases of incident depression were identified. Multivariate Cox proportional hazards analysis revealed a positive dose-dependent association between HOMA-IR level and the risk of incident depression (hazard ratio [HR] for highest vs. lowest quartile = 1.15, 95% confidence interval [CI] = 1.11-1.19). This association was particularly strong in younger adults under 40 years and in individuals with euglycemia, overweight, and low muscle-to-fat ratio.
Insulin resistance may be a modifiable risk factor for depression, underscoring the importance of early screening and management of insulin resistance to potentially reduce the burden of depression, especially among at-risk subgroups.
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尽管有新的证据出现，但胰岛素抵抗与抑郁症之间的因果关系仍存在争议。本研究旨在调查胰岛素抵抗是否与新发抑郁症风险增加相关，以及这种关联是否受潜在调节因素的影响。
这项多中心前瞻性队列研究分析了2011年至2022年参加江北三星健康研究的233452名韩国成年人的健康筛查数据。在基线时，所有参与者均表示无重大精神或神经疾病，且未使用过抗抑郁药或糖尿病药物。使用胰岛素抵抗稳态模型评估（HOMA-IR）来评估胰岛素抵抗。新发抑郁症定义为流行病学研究中心抑郁量表得分≥16。
参与者（年龄=36.1±8.6岁，男性占54.1%）随访了4.8±2.9年。在1124268人年的随访期间，共识别出38801例新发抑郁症病例。多变量Cox比例风险分析显示，HOMA-IR水平与新发抑郁症风险之间存在正剂量依赖性关联（最高四分位数与最低四分位数的风险比[HR]=1.15，95%置信区间[CI]=1.11-1.19）。这种关联在40岁以下的年轻人、血糖正常、超重和肌肉与脂肪比例低的个体中尤为明显。
胰岛素抵抗可能是抑郁症的一个可改变的风险因素，这突出了早期筛查和管理胰岛素抵抗以潜在减轻抑郁症负担的重要性，特别是在高危亚组中。
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