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 <0.001, 0.038 and <0.001, respectively). However, there was no significant interaction between psychological wellbeing score and genetic susceptibility to diabetes (P interaction 0.691). Conclusion: Lower psychologic wellbeing score (worse overall psychologic wellbeing) was associated with an increased risk of incident type 2 diabetes in a dose-response fashion, independent of traditional risk factors. The association was strengthened by the genetic diabetes susceptibility, even though the interaction was statistically nonsignificant. Funding: This study was supported by the Science and Technology Commission of Shanghai Municipality (19140902400, 20YF1423500), Shanghai Municipal Human Resources and Social Security Bureau (2020074), Clinical Research Plan of SHDC (SHDC2020CR4006), National Natural Science Foundation of China (91857117). Declaration of Interest: No potential conflicts of interest relevant to this article were reported for any author. Ethical Approval: The North West Multi-Center Research Ethics Committee Study approved the UKB study, and all participants provided a written informed consent.