Skip to main content
SpringerLink
Log in

Sleep variability, 6-sulfatoxymelatonin, and diabetic retinopathy

  • Psychiatrics • Short Communication
  • Published:
Sleep and Breathing Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Data availability

Data are available upon request

References

  1. Lynch SK, Abramoff MD (2017) Diabetic retinopathy is a neurodegenerative disorder. Vision Res 139:101–107. https://doi.org/10.1016/j.visres.2017.03.003

    Article  PubMed  PubMed Central  Google Scholar 

  2. Park JC, Chen YF, Blair NP, Chau FY, Lim JI, Leiderman YI, Shahidi M, McAnany JJ (2017) Pupillary responses in non-proliferative diabetic retinopathy. Sci Rep 7:44987. https://doi.org/10.1038/srep44987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Chen W, Cao H, Lu QY, Wang N, Zhao SZ, Xu X et al (2014) Urinary 6-sulfatoxymelatonin level in diabetic retinopathy patients with type 2 diabetes. Int. J. Clin. Exp. Pathol 7(7):4317–4322

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Reutrakul S, Siwasaranond N, Nimitphong H, Saetung S, Chirakalwasan N, Chailurkit LO, Srijaruskul K, Ongphiphadhanakul B, Thakkinstian A (2017) Associations between nocturnal urinary 6-sulfatoxymelatonin, obstructive sleep apnea severity and glycemic control in type 2 diabetes. Chronobiol. Int 34(3):382–392. https://doi.org/10.1080/07420528.2016.1278382

    Article  CAS  PubMed  Google Scholar 

  5. Hikichi T, Tateda N, Miura T (2011) Alteration of melatonin secretion in patients with type 2 diabetes and proliferative diabetic retinopathy. Clin. Ophthalmol 5:655–660. https://doi.org/10.2147/OPTH.S19559

    Article  PubMed  PubMed Central  Google Scholar 

  6. Reutrakul S, Crowley SJ, Park JC, Chau FY, Priyadarshini M, Hanlon EC, Danielson KK, Gerber BS, Baynard T, Yeh JJ, McAnany JJ (2020) Relationship between intrinsically photosensitive ganglion cell function and circadian regulation in diabetic retinopathy. Sci Rep 10:1560. https://doi.org/10.1038/s41598-020-58205-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ba-Ali S, Brondsted AE, Andersen HU, Sander B, Jennum PJ, Lund-Andersen H (2019) Assessment of diurnal melatonin, cortisol, activity, and sleep-wake cycle in patients with and without diabetic retinopathy. Sleep Med 54:35–42. https://doi.org/10.1016/j.sleep.2018.10.018

    Article  PubMed  Google Scholar 

  8. Chew M, Tan NYQ, Lamoureux E, Cheng CY, Wong TY, Sabanayagam C (2020) The associations of objectively measured sleep duration and sleep disturbances with diabetic retinopathy. Diabetes Res Clin Pract 159:107967. https://doi.org/10.1016/j.diabres.2019.107967

    Article  CAS  PubMed  Google Scholar 

  9. Skene DJ, Bojkowski CJ, Arendt J (1994) Comparison of the effects of acute fluvoxamine and desipramine administration on melatonin and cortisol production in humans. Br J Clin Pharmacol 37(2):181–186. https://doi.org/10.1111/j.1365-2125.1994.tb04258.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Davis MD, Fisher MR, Gangnon RE, Barton F, Aiello LM, Chew EY et al (1998) Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: early treatment diabetic retinopathy study report #18. Invest Ophthalmol Vis Sci. 39(2):233–252

    CAS  PubMed  Google Scholar 

  11. Sitasuwan T, Bussaratid S, Ruttanaumpawan P, Chotinaiwattarakul W (2014) Reliability and validity of the Thai version of the Pittsburgh Sleep Quality Index. J. Med. Assoc. Thai 97(Suppl 3):S57–S67

    PubMed  Google Scholar 

  12. Buysse DJ, Reynolds CF III, Monk TH, Berman SR, Kupfer DJ (1989) The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 28(2):193–213 doi:0165-1781(89)90047-4

    Article  CAS  Google Scholar 

  13. van Someren EJ, Hagebeuk EE, Lijzenga C, Scheltens P, de Rooij SE, Jonker C et al (1996) Circadian rest-activity rhythm disturbances in Alzheimer's disease. Biological psychiatry 40(4):259–270. https://doi.org/10.1016/0006-3223(95)00370-3

    Article  PubMed  Google Scholar 

  14. Blume C, Santhi N, Schabus M (2016) 'nparACT' package for R: A free software tool for the non-parametric analysis of actigraphy data. MethodsX 3:430–435. https://doi.org/10.1016/j.mex.2016.05.006

    Article  PubMed  PubMed Central  Google Scholar 

  15. R Core Team. R (2020) A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. available at https://www.R-project.org/.

  16. Baron KG, Reid KJ, Malkani RG, Kang J, Zee PC (2017) Sleep variability among older adults with insomnia: associations with sleep quality and cardiometabolic disease risk. Behav Sleep Med 15(2):144–157. https://doi.org/10.1080/15402002.2015.1120200

    Article  PubMed  Google Scholar 

  17. Chontong S, Saetung S, Reutrakul S (2016) Higher sleep variability is associated with poorer glycaemic control in patients with type 1 diabetes. J Sleep Res 25(4):438–444. https://doi.org/10.1111/jsr.12393

    Article  PubMed  Google Scholar 

  18. McMullan CJ, Curhan GC, Schernhammer ES, Forman JP (2013) Association of nocturnal melatonin secretion with insulin resistance in nondiabetic young women. Am. J. Epidemiol 178(2):231–238. https://doi.org/10.1093/aje/kws470

    Article  PubMed  PubMed Central  Google Scholar 

  19. McMullan CJ, Schernhammer ES, Rimm EB, Hu FB, Forman JP (2013) Melatonin secretion and the incidence of type 2 diabetes. JAMA 309(13):1388–1396. https://doi.org/10.1001/jama.2013.2710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Doosti-Irani A, Ostadmohammadi V, Mirhosseini N, Mansournia MA, Reiter RJ, Kashanian M et al (2018) The effects of melatonin supplementation on glycemic control: a systematic review and meta-analysis of randomized controlled trials. Hor Metab Res 50(11):783–790. https://doi.org/10.1055/a-0752-8462

    Article  CAS  Google Scholar 

  21. Chang JY, Yu F, Shi L, Ko ML, Ko GY (2019) Melatonin affects mitochondrial fission/fusion dynamics in the diabetic retina. J Diabetes Res 2019:8463125–8463117. https://doi.org/10.1155/2019/8463125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Garaulet M, Qian J, Florez JC, Arendt J, Saxena R, Scheer F (2020) Melatonin effects on glucose metabolism: time to unlock the controversy. Trends Endocrinol Metab 31(3):192–204. https://doi.org/10.1016/j.tem.2019.11.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank all the subjects for their participation.

Funding

The study was supported by a grant from Faculty of Medicine Ramathibodi Hospital, Bangkok, Thailand

Author information

Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Mahidol University, Bangkok, Thailand

    Supamas Sirisreetreerux, Hataikarn Nimitphong, Sittichai Pinyopodjanard, Sunee Saetung, La-or Chailurkit & Sirimon Reutrakul

  2. Department of Ophthalmology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    Tharikarn Sujirakul

  3. Excellence Center for Sleep Disorders, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand

    Naricha Chirakalwasan

  4. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Naricha Chirakalwasan

  5. Division of Academic Internal Medicine and Geriatrics, University of Illinois at Chicago, Chicago, IL, USA

    Ben S. Gerber

  6. Division of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago, 835 S. Wolcott Street, suite 625E, Chicago, IL, 60612, USA

    Sirimon Reutrakul

Authors
  1. Supamas Sirisreetreerux
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tharikarn Sujirakul
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hataikarn Nimitphong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sittichai Pinyopodjanard
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sunee Saetung
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. La-or Chailurkit
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Naricha Chirakalwasan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ben S. Gerber
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sirimon Reutrakul
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.S., T.S., H.N., S.P., Su.S., and L.C. researched the data and reviewed and edited the manuscript. B.S.G. analyzed the data and reviewed and edited the manuscript. S.R. researched and analyzed the data and reviewed and edited the manuscript.

Corresponding author

Correspondence to Sirimon Reutrakul.

Ethics declarations

Conflict of interest

Dr. Reutrakul reports personal fees from Becton Dickinson outside the submitted work. All other authors have nothing to disclose.

Ethics approval

The protocol was approved by the Faculty of Medicine Ramathibodi Hospital.

Consent to participate

All participants gave a written informed consent.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sirisreetreerux, S., Sujirakul, T., Nimitphong, H. et al. Sleep variability, 6-sulfatoxymelatonin, and diabetic retinopathy. Sleep Breath 25, 1069–1074 (2021). https://doi.org/10.1007/s11325-020-02165-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11325-020-02165-3

Keywords

Search

Navigation