Causal effects of lifestyle and socioeconomic factors on diabetes and its complications and comorbidities: A Mendelian randomization study

Aims: Diabetes poses a growing global health burden. This study investigated the causal effects of lifestyle and socioeconomic factors on diabetes risk and related complications and comorbidities. Materials and Methods: We applied two-sample univariable and multivariable Mendelian randomization to assess the causal impact of 26 lifestyle and socioeconomic factors on diabetes, 7 complications, and 13 comorbidities. Results: Genetically predicted protective factors included vigorous physical activity (odds ratio [OR], 0.98 [0.98–0.99]), computer use time (OR, 0.13 [0.05, 0.30]), carbohydrate intake (OR, 0.22 [0.15, 0.34]), short (OR, 0.04 [0.01, 0.16]) and long sleep duration (OR, 0.62 [0.47, 0.82]), moderate alcohol (OR, 0.13 [0.04, 0.50]) and caffeine (OR, 0.72 [0.64, 0.81]) consumption, education (OR, 0.25–0.67), and household income (OR, 0.52–0.65), which were associated with reduced risks of type 2 and gestational diabetes, stroke, coronary heart disease, heart failure, myocardial infarction, sleep apnea, and anxiety disorder (adjusted P-values <0.05). Conversely, genetically predicted factors, such as television watching (OR, 1.39 [1.23, 1.57]) and driving time (OR, 3.28 [1.27, 8.48]), insomnia (OR, 1.21–1.82), smoking behaviors (OR, 1.17–1.77), alcohol dependence (OR, 1.17–1.28), coffee consumption (OR, 1.01 [1.00, 1.02]), and the Townsend deprivation index (OR, 1.51–1.57), are associated with increased risks of diabetes-related outcomes (i.e., all diabetic types, neovascular glaucoma, heart failure, nonalcoholic fatty liver disease, sleep apnea, and eating disorder) (adjusted P-values <0.05). Conclusions: Our findings support causal roles of lifestyle and socioeconomic factors and diabetes-related outcomes, emphasizing the need for targeted public health strategies to promote healthier living and socioeconomic equity. © 2026 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.