Association between stress-related exposures and risk of pre-diabetes and type 2 diabetes: results from the population-based Lifelines cohort study.

introductionTo examine the associations between chronic and acute stress-related exposures and incident pre-diabetes and type 2 diabetes (T2D) and to explore how stress domains cluster with socioeconomic and lifestyle factors. RESEARCH DESIGN AND

methodsWe conducted a prospective population-based cohort study using data from the Lifelines cohort study in the Netherlands, with baseline assessments conducted between 2006 and 2013 and follow-up between 2014 and 2018. The study included 152 861 adults without diabetes at baseline. Chronic stress was measured by the Life Difficulties Inventory (LDI), and acute stress was measured by the List of Threatening Experiences (LTE). Stress exposures were assessed at baseline and follow-up and modeled as time-varying exposures. Outcomes were incident pre-diabetes, defined as fasting plasma glucose 6.1 to <7.0 mmol/L and/or glycated hemoglobin (HbA1c) 6.0% to 6.5%, and incident T2D, defined by self-report, fasting plasma glucose ≥7.0 mmol/L and/or HbA1c ≥6.5%. Cox proportional hazards models were sequentially adjusted for demographic, socioeconomic and lifestyle factors. False discovery rate correction was applied. Exploratory network analyses examined structural relationships between stress domains, socioeconomic factors and lifestyle factors.

resultsDuring follow-up, 7499 participants developed pre-diabetes and 3127 developed T2D. In lifestyle-adjusted models, cumulative LDI and LTE scores showed limited associations with outcomes. The LDI sum score was modestly associated with T2D (HR 1.03, 95% CI 1.01 to 1.04), but not with pre-diabetes. Domain-specific analyses showed that moderate financial strain (LDI) was associated with pre-diabetes (HR 1.17, 95% CI 1.10 to 1.25) and T2D (HR 1.28, 95% CI 1.17 to 1.41). Restricted free time was associated with pre-diabetes, while health-related stress was associated with T2D. Major financial crisis (LTE) was also associated with both outcomes. Network analyses demonstrated clustering of stress domains with socioeconomic factors, particularly marital status and income, and structural links to behavioral factors.

conclusionsStress-related exposures were modestly and selectively associated with incident pre-diabetes and T2D, with domain-specific rather than cumulative patterns. Stress clustered with socioeconomic and lifestyle factors, suggesting that its contribution to diabetes risk may operate primarily through interconnected social and lifestyle pathways rather than as a strong independent determinant.