THU315 Sleep And Circadian Regulation, And Intrinsically Photosensitive Retinal Ganglion Cells Function In Diabetic Retinopathy

Abstract

Abstract Disclosure: S. Reutrakul: None. J.J. McAnany: None. J.C. Park: None. F.Y. Chau: None. K.K. Danielson: None. P. Bharati: None. S. Pannain: None. E. Van Cauter: None. E.C. Hanlon: None. Background: Diabetic retinopathy (DR) is associated with a dysfunction of intrinsically photosensitive retinal ganglion cells (ipRGCs), a crucial component of the entrainment of the circadian system and of the photic entrainment of melatonin secretion. We explored ipRGC function, sleep, 24-h melatonin and cortisol profiles in patients with and without DR. Methods: Type 2 diabetes patients with DR (n=10) and without DR (n=7,) participated. ipRGC function was inferred from the post illumination pupil response (PIPR). Sleep was assessed by 14-day actigraphy. Serum was sampled at hourly intervals for 24hrs for melatonin and cortisol measurement. Results: Mean (SD) age (53.8 (8.1) vs (54.0 (8.6) yr) and mean A1C (7.5 (1.7) vs. 7.1 (0.9)%) did not differ between DR and no-DR patients. PIPR was significantly smaller in DR than no-DR patients (0.14 (0.16) vs. 0.33 (0.10), p=0.001). Nightly sleep duration and efficiency were similar, but sleep variability (standard deviation of daily sleep duration over 7 nights) tended to be larger in DR than no-DR patients (84.1 (29.8) vs. 59.5 (21.8) minutes), p=0.08. Twenty four-hour serum melatonin output was significantly lower in DR than no-DR patients (103.1 (95.4) pg/ml vs. 231.1 (131.3) pg/ml, p=0.034). All no-DR patients exhibited the classical 24-h profile of melatonin with consistently low levels during the day time and a clear nocturnal rise peaking around the middle of the night. In contrast, a normal melatonin rhythm was observed only in 3 of the 10 patients with DR. Six DR patients had 24-h mean melatonin level under 3 pg/ml, five without any evident day-night pattern. One DR patient had a shift in melatonin timing. There was a significant correlation between PIPR and 24-h melatonin output, r= 0.726, p<0.001, but not with sleep variability. In contrast, mean 24-h cortisol profiles and levels, however, were not significantly different between the two groups (mean levels DR 6.18 (1.23) vs no-DR 6.18 (0.73) μg/dL), Conclusion: DR is associated with ipRCGs dysfunction, irregular sleep, and with major disruptions of the 24-hour melatonin rhythm while cortisol rhythm was maintained, suggesting circadian dysfunction in those with type 2 diabetes and retinopathy. Whether melatonin supplementation is beneficial in type 2 diabetes with DR should be explored. Presentation: Thursday, June 15, 2023