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Circadian rhythm amplification in diabetic retinopathy: a pilot study
Sirimon Reutrakul1, J Jason McAnany2, Jason C Park2
1Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois Chicago, Chicago, IL, United States.
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.
Materials And Methods:
Eight T2D persons (5M/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 (n = 5), and overnight urinary 6-sulfatoxymelatonin. Cardiometabolic parameters included glucose levels from a 14-day continuous glucose monitor, high sensitivity C-reactive protein, 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 = .041), variability of sleep midpoint reduced (0.90 [0.27] vs. 1.33 [0.39] h, p = .018), and intradaily variability decreased (0.82 [0.13] vs. 0.95 [0.21], p = .049). Urinary 6-sulfatoxymelatonin remained low and the dim light melatonin onset was unchanged. High sensitivity C-reactive protein significantly decreased, 1.58 (2.29) versus 2.36 (3.3) mg/L, p = .011, but heart rate change was nonsignificant (p = .065). Continuous glucose monitor 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.

