Dysregulated 24 h melatonin secretion associated with intrinsically photosensitive retinal ganglion cell function in diabetic retinopathy: a cross-sectional study

• Published in: Diabetologia 2024-06, Vol.67 (6), p.1114-1121
• Main Authors: Reutrakul, Sirimon, Park, Jason C., McAnany, J. Jason, Chau, Felix Y., Danielson, Kirstie K., Prasad, Bharati, Cross, Andrew, Sintetas, Stephanie, Law, Julie, Pannain, Silvana, Pratuangtham, Sarida, Van Cauter, Eve, Hanlon, Erin C.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Circadian Rhythm - physiology; Circadian rhythms; Cortisol; Cross-Sectional Studies; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; Diabetic retinopathy; Diabetic Retinopathy - blood; Diabetic Retinopathy - metabolism; Diabetic Retinopathy - physiopathology; Female; Hormones; Human Physiology; Humans; Hydrocortisone - blood; Hydrocortisone - metabolism; Internal Medicine; Male; Medicine; Medicine & Public Health; Melatonin; Melatonin - blood; Melatonin - metabolism; Metabolic Diseases; Middle Aged; Retina; Retinal Ganglion Cells - metabolism; Retinal Ganglion Cells - pathology; Retinopathy; Short Communication; Sleep; Sleep - physiology
• ISSN: 0012-186X; 1432-0428; 1432-0428
• DOI: 10.1007/s00125-024-06118-3

Aims/hypothesis The aim of this study was to explore whether diabetic retinopathy is associated with alterations of the circadian system, and to examine the role of reduced intrinsically photosensitive retinal ganglion cell (ipRGC) function. Methods Participants with type 2 diabetes, with diabetic retinopathy ( n =14) and without diabetic retinopathy ( n =9) underwent 24 h blood sampling for melatonin and cortisol under controlled laboratory conditions. ipRGC function was inferred from the post-illumination pupil response (PIPR). Habitual sleep duration, efficiency and variability were assessed by actigraphy. Results Participants with diabetic retinopathy compared to participants without diabetic retinopathy had smaller PIPR ( p =0.007), lower 24 h serum melatonin output ( p =0.042) and greater day-to-day sleep variability ( p =0.012). By contrast, 24 h cortisol profiles, sleep duration and efficiency were similar in both groups. Six individuals with diabetic retinopathy had no detectable dim-light melatonin onset. PIPR correlated with 24 h mean melatonin levels ( r =0.555, p =0.007). Conclusions/interpretation ipRCG dysfunction in diabetic retinopathy is associated with disruptions of the 24 h melatonin rhythm, suggesting circadian dysregulation in diabetic retinopathy. Graphical Abstract