Zhijie Wang Mengai Wu ^* Haidong Li ^* Bin Zheng ^*

• School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang Province, China

The disruption of circadian rhythm has been reported to aggravate the progression of diabetic retinopathy (DR). Rest-activity rhythm (RAR) is a widely used method for measuring individual circadian time influencing behavior. In this study, we sought to explore the potential association between RAR and the risk of DR.Methods: Diabetic participants aged over 40 from 2011-2014 National Health and Nutrition Examination Survey (NHANES) were enrolled. Data from the wearable device ActiGraph GT3X was used to generate RAR metrics, including interdaily stability (IS), intradailty variability (IV), most active 10-hour period (M10), least active 5-hour period (L5), and Relative amplitude (RA). Weighted multivariable logistic regression analysis and restricted cubic spline analysis were conducted to examine the association between RAR metrics and DR risk. Sensitivity analysis was also conducted to examine the robustness of the findings. An unsupervised K-means clustering analysis was conducted to identify patterns in IV and M10.Results: A total of 1,096 diabetic participants were enrolled, with a DR prevalence of 20.53%. The mean age of participants was 62.3 years, with 49.57% being male. After adjusting covariates, IV was positively associated with DR (β: 3.527, 95%CI: 1.371-9.073). Compared with the lowest quintile of IV, the highest quintile of IV had 136% higher odds of DR. In contrast, M10 was negatively associated with DR (β: 0.902, 95%CI: 0.828-0.982), with participants in the highest M10 quintile showing 48.8% lower odds of DR. Restricted cubic spline analysis confirmed that these associations were linear. Meanwhile, sensitivity analysis confirmed the robustness. K-means clustering identified three distinct clusters, with participants in Cluster C (high-IV, low-M10) had a significantly higher risk of DR comparing with Cluster A (low-IV, high-M10).A more fragmented rhythm and lower peak activity level might be associated with an increased risk of DR. These findings indicate that maintaining a more rhythmic sleep-activity behavior might mitigate the development of DR. Further research is necessary to establish causality and understand the underlying mechanisms, and focus on whether interventions designed to enhance daily rhythm stability and increase diurnal activity level can effectively mitigate the risk of progression of DR.