Joint Exposure to Positive Affect, Life Satisfaction, Depressive Symptoms, and Neuroticism and Incident Type 2 Diabetes

Objectives: Using a comprehensive indicator to measure the association between psychological wellbeing score and type 2 diabetes and whether this association was modified by genetic predisposition. Methods: In UK Biobank, a total of 127,496 participants were included in this prospective cohort study without type 2 diabetes at baseline. The healthy psychological wellbeing score was calculated according four factors: happiness, life satisfaction, broad depression and neuroticism. Cox proportional hazard models were used to test the association between quartile of weighted psychological wellbeing score and type 2 diabetes risk. Interaction analysis between psychological wellbeing and weighted genetic risk score to diabetes was further performed. Results: During the median follow-up of 10.0 years (about 1.3 million person-years), 2,547 incident type 2 diabetes were documented. Moderate to extreme unhappiness, satisfaction score ≤3, presence of broad depression and neuroticism score ≥3 were all significantly associated with increased risk of incident diabetes when mutually adjusted. When considered as a comprehensive indicator, there was a significant association between weighted psychological wellbeing score quartiles and type 2 diabetes. Compared with individuals in the highest quartile, which means healthiest, the fully adjusted HRs (95% CI) of type 2 diabetes in lower quintile groups were 1.39(1.19-1.63), 1.44(1.23-1.67) and 1.86(1.60-2.17), respectively. In the stratified analysis, we observed the significant interactions among age, physical activity, HbA1c and type 2 diabetes (P interaction