The influence of circadian rhythms on carbohydrate metabolism in health and in diabetes mellitus
https://doi.org/10.14341/DM13241
Abstract
Most processes in the human body and other living organisms are governed by biorhythms. The term biorhythms refers to periodically recurring changes in biological processes. Biological rhythms are genetically fixed and are crucial factors in natural selection and adaptation of organisms. In humans, circadian rhythms are regulated by central and peripheral clocks. The central clock is located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus, while peripheral clocks are found in various tissues and organs of the human body, including the brain, pancreas, liver, adipose tissue, gastrointestinal tract, and muscles. External and internal signals are in constant synchronization, ensuring homeostasis. A mismatch between internal biological clocks and external signals can lead to desynchronization of circadian rhythms. Desynchronization of the circadian rhythm may result in the onset of metabolically associated diseases, including the development of type 2 diabetes, obesity, and poorer glycemic control. This article examines the impact of circadian rhythms on biological processes and hormone secretion, as well as the relationship between circadian rhythms and glucose metabolism in individuals with type 2 diabetes and normoglycemia.
About the Authors
I. V. Misnikova
Moscow Regional Research Clinical Institute named after M.F. Vladimirsky
Russian Federation
Competing Interests:
Russian Federation
Inna V. Misnikova - MD, PhD; ScopusAuthor ID: 559756; eLibrary SPIN: 3614-3011.
Moscow
Competing Interests:
none
D. E. Zoloeva
Moscow Regional Research Clinical Institute named after M.F. Vladimirsky
Russian Federation
Competing Interests:
Russian Federation
Dzerassa Е. Zoloeva – MD.
61/2 Shchepkina street, 129110 Moscow
Competing Interests:
none
References
1. Lu X, Xie Q, Pan X, et al. Type 2 diabetes mellitus in adults: pathogenesis, prevention and therapy. Signal Transduct Target Ther. 2024;9(1):262. Doi: https://doi.org/10.1038/s41392-024-01951-9
2. Zimmet P, Alberti KGMM, Stern N, et al. The Circadian Syndrome: is the Metabolic Syndrome and much more! J Intern Med. 2019;286(2):181-191. Doi: https://doi.org/10.1111/joim.12924
3. Shi Z, Tuomilehto J, Kronfeld-Schor N, et al. The circadian syndrome predicts cardiovascular disease better than metabolic syndrome in Chinese adults. J Intern Med. 2021;289(6):851-860. Doi: https://doi.org/10.1111/joim.13204
4. Poggiogalle E, Jamshed H, Peterson CM. Circadian regulation of glucose, lipid, and energy metabolism in humans. Metabolism. 2018;84:11-27. Doi: https://doi.org/10.1016/j.metabol.2017.11.017
5. Sakai S, Tanaka Y, Tsukamoto Y, et al. D -Alanine Affects the Circadian Clock to Regulate Glucose Metabolism in the Kidney. Kidney360. 2024;5(2):237-251. Doi: https://doi.org/10.34067/KID.0000000000000345
6. Gamble KL, Berry R, Frank SJ, Young ME. Circadian clock control of endocrine factors. Nat Rev Endocrinol. 2014;10(8):466-475. Doi: https://doi.org/10.1038/nrendo.2014.78
7. Harfmann BD, Schroder EA, Esser KA. Circadian rhythms, the molecular clock, and skeletal muscle. J Biol Rhythms. 2015;30(2):84-94. Doi: https://doi.org/10.1177/0748730414561638
8. Mohawk JA, Green CB, Takahashi JS. Central and peripheral circadian clocks in mammals. Annu Rev Neurosci. 2012;35:445-462. Doi: https://doi.org/10.1146/annurev-neuro-060909-153128
9. Takahashi JS, Hong HK, Ko CH, mcdearmon EL. The genetics of mammalian circadian order and disorder: implications for physiology and disease. Nat Rev Genet. 2008;9(10):764-775. Doi: https://doi.org/10.1038/nrg2430
10. den Boon FS, Sarabdjitsingh RA. Circadian and ultradian patterns of HPA-axis activity in rodents: Significance for brain functionality. Best Pract Res Clin Endocrinol Metab. 2017;31(5):445-457. Doi: https://doi.org/10.1016/j.beem.2017.09.001
11. Baron KG, Reid KJ. Circadian misalignment and health. Int Rev Psychiatry. 2014;26(2):139-154. Doi: https://doi.org/10.3109/09540261.2014.911149
12. Li W, Wang Z, Cao J, Dong Y, Chen Y. Perfecting the Life Clock: The Journey from PTO to TTFL. Int J Mol Sci. 2023;24(3):2402. Doi: https://doi.org/10.3390/ijms24032402
13. Sorokin MY, Pinkhasov BB, Selyatitskaya VG. Circadian rhythm of carbohydrate metabolism in health and disease. Acta Biomedica Scientifica. 2023;8(2):124-137 (In Russ.) Doi: https://doi.org/10.29413/ABS.2023-8.2.12
14. Hudec M, Dankova P, Solc R, et al. Epigenetic Regulation of Circadian Rhythm and Its Possible Role in Diabetes Mellitus. Int J Mol Sci. 2020;21(8):3005. Doi: https://doi.org/10.3390/ijms21083005
15. Cheng H, Zhong D, Tan Y, et al. Advancements in research on the association between the biological CLOCK and type 2 diabetes. Front Endocrinol (Lausanne). 2024;15:1320605. Doi: https://doi.org/10.3389/fendo.2024.1320605
16. Miyamoto Y, Sancar A. Vitamin B2-based blue-light photoreceptors in the retinohypothalamic tract as the photoactive pigments for setting the circadian clock in mammals. Proc Natl Acad Sci USA. 1998;95(11):6097-6102. Doi: https://doi.org/10.1073/pnas.95.11.6097
17. Institute of Medicine (US) Committee on Sleep Medicine and Research. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem. / Ed. By Colten HR, Altevogt BM, editors. National Academies Press (US); Washington (DC): 2006
18. Vieira E, Merino B, Quesada I. Role of the clock gene Rev-erbα in metabolism and in the endocrine pancreas. Diabetes Obes Metab. 2015;17(Suppl 1):106-114. Doi: https://doi.org/10.1111/dom.12522
19. Walker WH, Hecmarie MF, Becker-Krail O, et al. Biological Clocks and Immune Function. In: Konsman, J.P., Reyes, T.M. (eds) Neuroendocrine-Immune System Interactions. Masterclass in Neuroendocrinology. 2023;13. Doi: https://doi.org/10.1007/978-3-031-21358-8_11
20. Stenvers DJ, Scheer FAJL, Schrauwen P, et al. Circadian clocks and insulin resistance. Nat Rev Endocrinol. 2019;15(2):75-89. Doi: https://doi.org/10.1038/s41574-018-0122-1
21. Jakubowicz D, Wainstein J, Tsameret S, Landau Z. Role of High Energy Breakfast «Big Breakfast Diet» in Clock Gene Regulation of Postprandial Hyperglycemia and Weight Loss in Type 2 Diabetes. Nutrients. 2021;13(5):1558. Doi: https://doi.org/10.3390/nu13051558
22. Morris CJ, Yang JN, Garcia JI, et al. Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans. Proc Natl Acad Sci U S A. 2015;112(17):E2225-E2234. Doi: https://doi.org/10.1073/pnas.1418955112
23. Saad A, Dalla Man C, Nandy DK, et al. Diurnal pattern to insulin secretion and insulin action in healthy individuals. Diabetes. 2012;61(11):2691-2700. Doi: https://doi.org/10.2337/db11-1478
24. Boden G, Ruiz J, Urbain JL, Chen X. Evidence for a circadian rhythm of insulin secretion. Am J Physiol. 1996;271(2 Pt 1):E246-E252. Doi: https://doi.org/10.1152/ajpendo.1996.271.2.E246
25. Adam EK, Quinn ME, Tavernier R, et al. Diurnal cortisol slopes and mental and physical health outcomes: A systematic review and meta-analysis. Psychoneuroendocrinology. 2017;83:25-41. Doi: https://doi.org/10.1016/j.psyneuen.2017.05.018
26. Morais JBS, Severo JS, Beserra JB, et al. Association Between Cortisol, Insulin Resistance and Zinc in Obesity: a Mini-Review. Biol Trace Elem Res. 2019;191(2):323-330. Doi: https://doi.org/10.1007/s12011-018-1629-y
27. Gómez-Abellán P, Díez-Noguera A, Madrid JA, Luján JA, Ordovás JM, Garaulet M. Glucocorticoids affect 24 h clock genes expression in human adipose tissue explant cultures. Plos One. 2012;7(12):e50435. Doi: https://doi.org/10.1371/journal.pone.0050435
28. bahammam AS, Pirzada A. Timing Matters: The Interplay between Early Mealtime, Circadian Rhythms, Gene Expression, Circadian Hormones, and Metabolism-A Narrative Review. Clocks Sleep. 2023;5(3):507-535. Doi: https://doi.org/10.3390/clockssleep5030034
29. Xiao Q, Bauer C, Layne T, Playdon M. The association between overnight fasting and body mass index in older adults: the interaction between duration and timing. Int J Obes (Lond). 2021;45(3):555-564. Doi: https://doi.org/10.1038/s41366-020-00715-z
30. Chawla S, Beretoulis S, Deere A, Radenkovic D. The Window Matters: A Systematic Review of Time Restricted Eating Strategies in Relation to Cortisol and Melatonin Secretion. Nutrients. 2021;13(8):2525. Doi: https://doi.org/10.3390/nu13082525
31. Vasey C, mcbride J, Penta K. Circadian Rhythm Dysregulation and Restoration: The Role of Melatonin. Nutrients. 2021;13(10):3480. Doi: https://doi.org/10.3390/nu13103480
32. Hudec M, Dankova P, Solc R, et al. Epigenetic Regulation of Circadian Rhythm and Its Possible Role in Diabetes Mellitus. Int J Mol Sci. 2020;21(8):3005. Doi: https://doi.org/10.3390/ijms21083005
33. Buonfiglio D, Parthimos R, Dantas R, et al. Melatonin Absence Leads to Long-Term Leptin Resistance and Overweight in Rats. Front Endocrinol (Lausanne). 2018;9:122. Doi: https://doi.org/10.3389/fendo.2018.00122
34. Peng F, Li X, Xiao F, Zhao R, Sun Z. Circadian clock, diurnal glucose metabolic rhythm, and dawn phenomenon. Trends Neurosci. 2022;45(6):471-482. Doi: https://doi.org/10.1016/j.tins.2022.03.010
35. Serin Y, Acar Tek N. Effect of Circadian Rhythm on Metabolic Processes and the Regulation of Energy Balance. Ann Nutr Metab. 2019;74(4):322-330. Doi: https://doi.org/10.1159/000500071
36. Davis R, Rogers M, Coates AM, et al. The Impact of Meal Timing on Risk of Weight Gain and Development of Obesity: a Review of the Current Evidence and Opportunities for Dietary Intervention. Curr Diab Rep. 2022;22(4):147-155. Doi: https://doi.org/10.1007/s11892-022-01457-0
37. Garaulet M, Gómez-Abellán P. Timing of food intake and obesity: a novel association. Physiol Behav. 2014;134:44-50. Doi: https://doi.org/10.1016/j.physbeh.2014.01.001
38. Palomar-Cros A, Srour B, Andreeva VA, et al. Associations of meal timing, number of eating occasions and night-time fasting duration with incidence of type 2 diabetes in the nutrinet-Santé cohort. Int J Epidemiol. 2023;52(5):1486-1497. Doi: https://doi.org/10.1093/ije/dyad081
39. Nas A, Mirza N, Hägele F, et al. Impact of breakfast skipping compared with dinner skipping on regulation of energy balance and metabolic risk. Am J Clin Nutr. 2017;105(6):1351-1361. Doi: https://doi.org/10.3945/ajcn.116.151332
40. Peschke E, Peschke D, Hammer T, Csernus V. Influence of melatonin and serotonin on glucose-stimulated insulin release from perifused rat pancreatic islets in vitro. J Pineal Res. 1997;23(3):156-163. Doi: https://doi.org/10.1111/j.1600-079x.1997.tb00349.x
41. Damiola F, Le Minh N, Preitner N, et al. Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes Dev. 2000;14(23):2950-2961. Doi: https://doi.org/10.1101/gad.183500
42. Kohsaka A, Laposky AD, Ramsey KM, et al. High-fat diet disrupts behavioral and molecular circadian rhythms in mice. Cell Metab. 2007;6(5):414-421. Doi: https://doi.org/10.1016/j.cmet.2007.09.006
43. Akbar Z, Shi Z. Dietary Patterns and Circadian Syndrome among Adults Attending NHANES 2005-2016. Nutrients. 2023;15(15):3396. Doi: https://doi.org/10.3390/nu15153396
44. Zisapel N. New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation. Br J Pharmacol. 2018;175(16):3190-3199. Doi: https://doi.org/10.1111/bph.14116
45. van der Velde JHP, Rutters F, Rosendaal FR, et al. Associations between chronotype waist circumference, visceral fat, liver fat, and incidence of type 2 diabetes. 60th EASD Annual Meeting of the European Association for the Study of Diabetes [abstract]. 2024;283:S146. Doi: https://doi.org/10.1007/s00125-024-06226-0
46. Kudielka BM, Federenko IS, Hellhammer DH, Wüst S. Morningness and eveningness: the free cortisol rise after awakening in «early birds» and «night owls». Biol Psychol. 2006;72(2):141-146. Doi: https://doi.org/10.1016/j.biopsycho.2005.08.003
47. Nelaeva YV, Rymar OD, Petrov IM, et al. The role of individual organization of circadian rhythms in the formation of carbohydrate metabolism disorders. Diabetes mellitus. 2023;26(3):224-235. (In Russ.). Doi: https://doi.org/10.14341/DM12909
48. Karlsson B. Commentary: Metabolic syndrome as a result of shift work exposure?. Int J Epidemiol. 2009;38(3):854-855. Doi: https://doi.org/10.1093/ije/dyp190
49. De Bacquer D, Van Risseghem M, Clays E, et al. Rotating shift work and the metabolic syndrome: a prospective study. Int J Epidemiol. 2009;38(3):848-854. Doi: https://doi.org/10.1093/ije/dyn360
50. Knutsson A. Health disorders of shift workers. Occup Med (Lond). 2003;53(2):103-108. Doi: https://doi.org/10.1093/occmed/kqg048
51. White AJ, Kresovich JK, Xu Z, et al. Shift work, DNA methylation and epigenetic age. Int J Epidemiol. 2019;48(5):1536-1544. Doi: https://doi.org/10.1093/ije/dyz027
52. Cedernaes J, Schönke M, Westholm JO, et al. Acute sleep loss results in tissue-specific alterations in genome-wide DNA methylation state and metabolic fuel utilization in humans. Sci Adv. 2018;4(8):eaar8590. Doi: https://doi.org/10.1126/sciadv.aar8590
53. Fatima N, Rana S. Metabolic implications of circadian disruption. Pflugers Arch. 2020;472(5):513-526. Doi: https://doi.org/10.1007/s00424-020-02381-6
54. Hariri A, Mirian M, Zarrabi A, et al. The circadian rhythm: an influential soundtrack in the diabetes story. Front Endocrinol (Lausanne). 2023;14:1156757. Doi: https://doi.org/10.3389/fendo.2023.1156757
55. Engin A. Circadian Rhythms in Diet-Induced Obesity. Adv Exp Med Biol. 2017;960:19-52. Doi: https://doi.org/10.1007/978-3-319-48382-5_2
56. Meng X, Li Y, Li S, et al. Dietary Sources and Bioactivities of Melatonin. Nutrients. 2017;9(4):367. Doi: https://doi.org/10.3390/nu9040367
57. Sutanto CN, Loh WW, Kim JE. The impact of tryptophan supplementation on sleep quality: a systematic review, meta-analysis, and meta-regression. Nutr Rev. 2022;80(2):306-316. Doi: https://doi.org/10.1093/nutrit/nuab027
58. Surme S, Ergun C, Gul S, et al. TW68, cryptochromes stabilizer, regulates fasting blood glucose levels in diabetic ob/ob and high fat-diet-induced obese mice. Biochem Pharmacol. 2023;218:115896. Doi: https://doi.org/10.1016/j.bcp.2023.115896
59. Barnea M, Haviv L, Gutman R, et al. Metformin affects the circadian clock and metabolic rhythms in a tissue-specific manner. Biochim Biophys Acta. 2012;1822(11):1796-1806. Doi: https://doi.org/10.1016/j.bbadis.2012.08.005
60. Vieira E, Marroquí L, Figueroa AL, et al. Involvement of the clock gene Rev-erb alpha in the regulation of glucagon secretion in pancreatic alpha-cells. Plos One. 2013;8(7):e69939. Doi: https://doi.org/10.1371/journal.pone.0069939
61. Alex A, Luo Q, Mathew D, Di R, Bhatwadekar AD. Metformin Corrects Abnormal Circadian Rhythm and Kir4.1 Channels in Diabetes. Invest Ophthalmol Vis Sci. 2020;61(6):46. Doi: https://doi.org/10.1167/iovs.61.6.46
62. Yang SC, Tseng HL, Shieh KR. Circadian-clock system in mouse liver affected by insulin resistance. Chronobiol Int. 2013;30(6):796-810. Doi: https://doi.org/10.3109/07420528.2013.766204
63. Fedchenko T, Izmailova O, Shynkevych V, et al. PPAR-γ Agonist Pioglitazone Restored Mouse Liver mrna Expression of Clock Genes and Inflammation-Related Genes Disrupted by Reversed Feeding. PPAR Res. 2022;2022:7537210. Doi: https://doi.org/10.1155/2022/7537210
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Misnikova I.V., Zoloeva D.E. The influence of circadian rhythms on carbohydrate metabolism in health and in diabetes mellitus. Diabetes mellitus. 2025;28(4):367-375. (In Russ.) https://doi.org/10.14341/DM13241
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