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

Abstract

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.

Keywords: Circadian; Diabetic retinopathy; Melatonin.

Fig. 1

24 h profiles of melatonin and cortisol. (a) Mean 24 h melatonin profiles in participants with and without diabetic retinopathy. (b) Mean 24 h melatonin profiles in participants with diabetic retinopathy, and with and without DLMO. (c) Mean 24 h cortisol in participants with and without diabetic retinopathy. Vertical lines at each time point represent the SEM. DR, diabetic retinopathy

Fig. 1

24 h profiles of melatonin and cortisol. (a) Mean 24 h melatonin profiles in participants with and without diabetic retinopathy. (b) Mean 24 h melatonin profiles in participants with diabetic retinopathy, and with and without DLMO. (c) Mean 24 h cortisol in participants with and without diabetic retinopathy. Vertical lines at each time point represent the SEM. DR, diabetic retinopathy

Fig. 1

24 h profiles of melatonin and cortisol. (a) Mean 24 h melatonin profiles in participants with and without diabetic retinopathy. (b) Mean 24 h melatonin profiles in participants with diabetic retinopathy, and with and without DLMO. (c) Mean 24 h cortisol in participants with and without diabetic retinopathy. Vertical lines at each time point represent the SEM. DR, diabetic retinopathy