Sleep variability, 6-sulfatoxymelatonin, and diabetic retinopathy
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Sleep variability, 6-sulfatoxymelatonin, and diabetic retinopathy Supamas Sirisreetreerux 1 & Tharikarn Sujirakul 2 & Hataikarn Nimitphong 1 & Sittichai Pinyopodjanard 1 & Sunee Saetung 1 & La-or Chailurkit 1 & Naricha Chirakalwasan 3,4 & Ben S. Gerber 5 & Sirimon Reutrakul 1,6 Received: 3 June 2020 / Revised: 29 July 2020 / Accepted: 8 August 2020 # Springer Nature Switzerland AG 2020
Abstract Purpose Recent evidence suggests that diabetic retinopathy (DR) is associated with abnormal melatonin regulation, possibly related to dysfunction of the melanopsin-expressing intrinsically photosensitive retinal ganglion cells. This study explored melatonin regulation in type 2 diabetes (T2D) patients with DR and its relation to sleep and circadian functioning. Methods Thirty-five participants (10 non-diabetic controls, 10 T2D without DR, and 15 T2D with DR) were recruited. Overnight urine 6-sulfatoxymelatonin (aMT6s) and objective sleep and wrist activity (7-day actigraphy) were obtained. Results After adjusting for covariates, having T2D with DR was significantly associated with lower urinary aMT6s (β = − 1.369, p = 0.004) compared with controls, while having T2D without DR was not (p = 0.418). T2D patients with DR reported poorer sleep quality (p = 0.014) and had greater variability of sleep duration (p = 0.017) than others, while no differences were found in sleep duration, efficiency, and rest-activity rhythm. After adjusting for covariates, lower nocturnal aMT6s was significantly associated with greater sleep variability. Conclusion T2D patients with DR exhibited low overnight production of aMT6s which likely contributed to sleep irregularities possibly due to weak circadian signaling. Whether or not melatonin supplementation could improve health in T2D patients with DR remains to be explored. Keywords 6-Sulfatoxymelatonin . Retinopathy . Diabetes . Sleep variability
Introduction Emerging evidence suggests that diabetic retinopathy (DR) is associated with neural retina dysfunction [1]. The function of
* Sirimon Reutrakul [email protected] 1
Division of Endocrinology and Metabolism, Mahidol University, Bangkok, Thailand
2
Department of Ophthalmology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
3
Excellence Center for Sleep Disorders, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
4
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
5
Division of Academic Internal Medicine and Geriatrics, University of Illinois at Chicago, Chicago, IL, USA
6
Division of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago, 835 S. Wolcott Street, suite 625E, Chicago, IL 60612, USA
the melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), located in the inner retina, was found to be reduced in type 2 diabetes (T2D) patients with DR [2]. IpRGCs are a crucial component of the human circad
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