Circadian Biorhythms of Stress-limiting Hormones in Patients with Diabetic Retinopathy and Sarcopenic Obesity

The development of diabetic retinopathy is associated with the levels of melatonin, dehydroepiandrosterone and some other stress-limiting hormones, however, the circadian biorhythms of the latter were practically not analyzed in patients with diabetic retinopathy combined with sarcopenic obesity involved in the pathogenesis of diabetic retinopathy. The purpose: to study circadian biorhythms of stress-stimulating hormones in elderly patients with diabetic retinopathy and sarcopenic obesity. The study included an analysis of daily fluctuations of stresslimiting hormones in the morning and evening urine portions of 136 elderly patients with diabetic retinopathy combined with sarcopenic obesity and 125 patients of the same age with diabetic retinopathy without sarcopenic obesity. It was revealed that in patients with diabetic retinopathy and sarcopenic obesity, the content of all studied hormones, especially dehydroepiandrosterone (376,8 ± 5,2 mcg) and dopamine (323,8 ± 3,7 mcg), was statistically significantly lower compared to patients with diabetic retinopathy without sarcopenic obesity — 485,1 ± 6,3 mcg and 397,2 ± 5,4 mcg, respectively. Desynchronization of daily biorhythms in patients with diabetic retinopathy and sarcopenic obesity is expressed in a decrease in the content of cortisol in the morning and evening hours to 81,7 ± 2,2 mcg and 63,5 ± 2,5 mcg, melatonin to 8,4 ± 0,6 mcg and 19,5 ± 1,7 mcg, adrenaline to 10,9 ± 0,8 mcg and 4,2 ± 0,4 mcg, respectively. The gradient of changes in morning hormone values significantly (p < 0,001) exceeds that in the evening hours, amounting to –221,1 and –137,7, respectively, which indicates a decrease in the amplitude of daily fluctuations in circadian biorhythms of stress-limiting hormones among elderly patients with diabetic retinopathy combined with sarcopenic obesity, and the participation of desynchronization of the daily biorhythms of the hormones under discussion in the pathogenesis of diabetic retinopathy combined with sarcopenic obesity. Circadian biorhythms of stress-limiting hormones are recommended to be taken into account in case of combined diabetic retinopathy and sarcopenic obesity.

1. Ting DS, Cheung CY, Nguyen Q, Sabanayagam C, Lim G, Lim ZW. Deep learning in estimating prevalence and systemic risk factors for diabetic retinopathy: a multi ethnic study. NPJ Digit Media. 2019;2:24. doi: 10.1038/s41746-019-0097-x.

2. Murthy GV. Situational analysis of diabetic retinopathy screening in India: How has it changed in the last three years? Indian J Ophthalmol. 2021;69(11):2944–2950. doi: 10.4103/ijo.ijo_1242_21.

3. Mansour SE, Browning DJ, Wong K, Flynn HW, Bhavsar AR. The Evolving Treatment of Diabetic Retinopathy. Clin Ophthalmol. 2020;14:653–678. doi: 10.2147/opth.s236637.

4. Fukuda T, Bouchi R, Takeuchi T, Nakano Y, Murakami M. Association of diabetic retinopathy with both sarcopenia and muscle quality in patients with type 2 diabetes: a crosssectional study. BMJ Open Diabetes Res Care. 2017;5(1):е000404. doi: 10.1136/bmjdrc-2017-000404.

5. Zhu W, Wu Y, Meng YF, Xing Q, Tao JJ, Lu J. Association of obesity and risk of diabetic retinopathy in diabetes patients: A metaanalysis of prospective cohort studies. Medicine (Baltimore). 2018;97(32):е11807. doi: 10.1097/md.0000000000011807.

6. Andersen H, Nielsen S, Mogensen CE, Jakobsen J. Muscle strength in type 2 diabetes. Diabetes. 2004;53(6):1543–1548. doi: 10.2337/diabetes.53.6.1543.

7. Bhatwadekar AD, Rameswara V. Circadian rhythms in diabetic retinopathy: an overview of pathogenesis and investigational drugs. Expert Opin Investing Drugs. 2020;29(12):1431–1442. doi: 10.1080/13543784.2020.1842872.

8. Aydin E, Sahin S. Increased melatonin levelsin aqueous humor of patients with proliferative retinopathy in type 2 diabetes mellitus. Int J Ophthalmol. 2016;9(5):721– 724. doi: 10.18240/ijo.2016.05.15.

9. Wan WC, Long Y, Wan WW, Liu HZ, Zhang HH, Zhu W. Plasma melatonin levels in patients with diabetic retinopathy secondary to type 2 diabetes. World J Diabetes. 2021;12(2):138–148. doi: 10.4239/wjd.v12.i2.138.

10. Hendrick A, Smith J, Stelton C, Barb S, Yan J. Dopamine metabolite levels in the vitreous of diabetic and nondiabetic humans. Exp Eye Res. 2020;195:108040. doi: 10.1016/j.exer.2020.108040.

11. Zhang X, Huang Y, Xu N, Feng W, Qiao J, Liu M. Low serum dehydroepiandrosterone levels are associated with diabetic retinopathy in patients with type 2 diabetes mellitus. J Diabetes Investig. 2023;14(5):675–685. doi: 10.1111/jdi.13997.

12. Clinical recommendations “Diabetes mellitus: diabetic retinopathy, diabetic macular edema”. Moscow: AllRussian public organization “Association of Ophthalmologists”, 2020. 52 p. (In Russ.).

13. Wei S, Nguyen TT, Zhang Y, Ryu D, Gariani K. Sarcopenic obesity: epidemiology, pathophysiology, cardiovascular disease, mortality, and management. Front Endocrinol (Lausanne). 2023;14:1185221. doi: 10.3389/fendo.2023.1185221.