Circadian Rhythm Amplification in Diabetic Retinopathy: A Pilot Study
Sirimon Reutrakul, J Jason McAnany, Jason C Park, Andrew Cross, Kirstie K Danielson, Eve Van Cauter, Erin C Hanlon, Julie Law, Sarida Pratuangtham, Felix Y Chau, Kelly G Baron, Medha Priyadarshini, Jennifer DuffecyAbstract
Study Objectives
Data suggested that diabetic retinopathy (DR) may be associated with a dysregulated melatonin rhythm and disturbed sleep. This pilot study explored the effects of a novel behavioral intervention “Amplify-RHYTHM” in type 2 diabetes (T2D) with DR.
Methods
Eight T2D persons (5 M/3F, mean age 57.2 years) with DR participated in a 6-week “Amplify-RHYTHM” intervention, consisting of sleep stability (remote weekly coaching and educational content), and timed light exposure (morning bright light exposure, evening blue light reduction, and nightly light-blocking sleep mask). Data were collected before and after the intervention. Primary outcomes were insomnia symptoms and 14-day actigraphy-derived sleep parameters. Circadian related parameters included rest-activity rhythm parameters, dim light melatonin onset (DLMO, n = 5), and overnight urinary 6-sulfatoxymelatonin (aMT6s). Cardiometabolic parameters included glucose levels from a 14-day continuous glucose monitor (CGM), high sensitivity C-reactive protein (hs-CRP), resting blood pressure and heart rate. Statistical analysis was performed using paired t-tests or Wilcoxon signed rank tests.
Results
Compared to baseline, after Amplify-RHYTHM intervention, insomnia symptoms significantly decreased (p = 0.041), variability of sleep midpoint reduced [0.90 (0.27) vs. 1.33 (0.39) h, p = 0.018], and intradaily variability decreased [0.82 (0.13) vs. 0.95 (0.21), p = 0.049]. Urinary aMT6s remained low and the DLMO was unchanged. Hs-CRP significantly decreased, 1.58 (2.29) vs. 2.36 (3.3) mg/L, p = 0.011, but heart rate change was non-significant (p = 0.065). CGM glucose levels and blood pressure did not change.
Conclusion
Amplify-RHYTHM resulted in less insomnia symptoms, more regular sleep, reduced behavioral circadian fragmentation, and reduced systemic inflammation. These pilot data should be confirmed in a larger, randomized study.
Clinical Trials
The study was registered at www.clinicaltrials.gov, NCT06183476.