{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:08:34Z","timestamp":1793318914108,"version":"4.5.0"},"reference-count":120,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Cardiometabolic diseases, including hypertension, type 2 diabetes, dyslipidemia, and obesity, along with their cardiovascular complications, remain leading causes of morbidity and mortality worldwide, imposing significant public health, economic, and societal burdens. Conventional pharmacological therapies often show limited efficacy and increased adverse effects because they do not account for the body\u2019s intrinsic circadian rhythms, which regulate organ function, drug absorption, and metabolism. Chronopharmacology, which aligns treatment timing with these biological rhythms, offers a strategy to enhance therapeutic outcomes. This review presents a comprehensive analysis of chronopharmacology principles applied to cardiometabolic disease management, integrating molecular, physiological, and clinical perspectives. It examines how core clock genes and tissue-specific circadian patterns influence drug action and absorption and summarizes evidence-based time-optimized interventions for hypertension, diabetes, dyslipidemia, obesity, and multimorbid patients. Furthermore, the review highlights emerging innovations, including artificial intelligence-guided dosing, circadian-biomarker-informed therapy selection, and wearable digital devices for real-time monitoring of biological rhythms. By synthesizing mechanistic and clinical insights, circadian-aligned treatment strategies are shown to improve drug efficacy, reduce adverse effects, and support the development of precision, rhythm-based therapeutics, offering a practical framework for personalized cardiometabolic disease care.<\/jats:p>","DOI":"10.3390\/biology15030241","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T15:56:12Z","timestamp":1769615772000},"page":"241","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Chronopharmacology-Driven Precision Therapies for Time-Optimized Cardiometabolic Disease Management"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5761-2073","authenticated-orcid":false,"given":"Shakta Mani","family":"Satyam","sequence":"first","affiliation":[{"name":"Department of Pharmacology, RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9919-4444","authenticated-orcid":false,"given":"Sainath","family":"Prabhakar","sequence":"additional","affiliation":[{"name":"Department of Perfusion Technology, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El-Tanani","sequence":"additional","affiliation":[{"name":"RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4057-7125","authenticated-orcid":false,"given":"Bhoomendra","family":"Bhongade","sequence":"additional","affiliation":[{"name":"RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1555-2820","authenticated-orcid":false,"given":"Adil Farooq","family":"Wali","sequence":"additional","affiliation":[{"name":"RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran Rashid","family":"Rangraze","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4999-2242","authenticated-orcid":false,"given":"Ismail Ibrahim Ali","family":"Matalka","sequence":"additional","affiliation":[{"name":"Department of Pathology, RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahia","family":"El-Tanani","sequence":"additional","affiliation":[{"name":"Royal Cornwall Hospital Trust, National Health Service (NHS), Truro TR1 3LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9549-8504","authenticated-orcid":false,"given":"Manfredi","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), School of Medicine, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sorina","family":"Ispas","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Ovidius University, 900470 Constanta, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5718-7441","authenticated-orcid":false,"given":"Ioannis","family":"Ilias","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Hippokration Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0058-2632","authenticated-orcid":false,"given":"Anna","family":"Paczkowska","sequence":"additional","affiliation":[{"name":"Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, 61-701 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana","family":"Maggio","sequence":"additional","affiliation":[{"name":"Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), School of Medicine, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6148-4094","authenticated-orcid":false,"given":"Karolina","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department and Clinic of Internal Diseases and Metabolic Disorders, Poznan University of Medical Sciences, 61-701 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rao, G.H. (2025). Cardiometabolic diseases: Risk factors and novel approaches for the management of risks. Cardiometabolic Diseases, Elsevier.","DOI":"10.1016\/B978-0-323-95469-3.00022-X"},{"key":"ref_2","first-page":"74","article-title":"Optimal control in a mathematical model of a spread of the obesity epidemic and its impact on diabetes","volume":"2023","author":"Smouni","year":"2023","journal-title":"Commun. Math. Biol. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S124","DOI":"10.1089\/acm.2018.0448","article-title":"Outcomes from a whole-systems ayurvedic medicine and yoga therapy treatment for obesity pilot study","volume":"25","author":"Rioux","year":"2019","journal-title":"J. Altern. Complement. Med."},{"key":"ref_4","first-page":"46","article-title":"Prevalence of Hypertension in Patients with Type-2 Diabetes Mellitus","volume":"4","author":"Islam","year":"2024","journal-title":"Med. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"103758","DOI":"10.1016\/j.amsu.2022.103758","article-title":"Prevalence of hypertension in Type-2 diabetes mellitus","volume":"78","author":"Naseri","year":"2022","journal-title":"Ann. Med. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1161\/HYPERTENSIONAHA.116.06588","article-title":"Keeping up with the clock: Circadian disruption and obesity risk","volume":"68","author":"Covassin","year":"2016","journal-title":"Hypertension"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e71011","DOI":"10.1096\/fj.202501289R","article-title":"External Cues as Transducers of Peripheral Tissue-Specific Molecular Clocks to Regulate Systemic Circadian Rhythms and Metabolism","volume":"39","author":"Zhang","year":"2025","journal-title":"FASEB J."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhao, M., Lu, D., Chen, M., and Wu, B. (2020). Introduction to Mammalian Circadian Clock System. Circadian Pharmacokinetics, Springer.","DOI":"10.1007\/978-981-15-8807-5_1"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41580-019-0179-2","article-title":"Molecular mechanisms and physiological importance of circadian rhythms","volume":"21","author":"Patke","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Alvarez, J. (2004). Genetic basis for circadian rhythms in mammals. Molecular Biology of Circadian Rhythms, John Wiley & Sons, Inc.","DOI":"10.1002\/0471459186.ch5"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Nuszkiewicz, J., Rzepka, W., Markiel, J., Porzych, M., Wo\u017aniak, A., and Szewczyk-Golec, K. (2025). Circadian rhythm disruptions and cardiovascular disease risk: The special role of melatonin. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47080664"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Shea, S.A., Scheer, F.A., Gumz, M.L., Eikenberry, S., Qian, J., Thosar, S.S., Sole, M.J., and Martino, T.A. (2026). Unlocking the Potential of Circadian Biology for Cardiovascular Health. Physiol. Rev., in press.","DOI":"10.1152\/physrev.00015.2025"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1161\/CIRCRESAHA.124.323515","article-title":"Hypertension: Causes and consequences of circadian rhythms in blood pressure","volume":"134","author":"Faraci","year":"2024","journal-title":"Circ. Res."},{"key":"ref_14","first-page":"HC12","article-title":"Influence of grape seed extract and zinc containing multivitamin-mineral nutritional food supplement on lipid profile in normal and diet-induced hypercholesterolemic rats","volume":"8","author":"Satyam","year":"2014","journal-title":"J. Clin. Diagn. Res. JCDR"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1007\/s12603-014-0020-8","article-title":"Grape seed extract and zinc containing nutritional food supplement prevents onset and progression of age-related cataract in Wistar rats","volume":"18","author":"Satyam","year":"2014","journal-title":"J. Nutr. Health Aging"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1007\/s13197-014-1305-y","article-title":"Grape seed extract and Zinc containing nutritional food supplement delays onset and progression of Streptozocin-induced diabetic cataract in Wistar rats","volume":"52","author":"Satyam","year":"2015","journal-title":"J. Food Sci. Technol."},{"key":"ref_17","first-page":"127","article-title":"Evaluation of burn wound healing activity of topical regular insulin in non-diabetic and streptozocin-induced diabetic rats","volume":"6","author":"Bairy","year":"2014","journal-title":"Int. J. Pharm. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Satyam, S.M., Bairy, L.K., Rehman, A., Attia, M., Ahmed, L., Emad, K., Jaafer, Y., and Bahaaeldin, A. (2024). Unlocking Synergistic Hepatoprotection: Dapagliflozin and Silymarin Combination Therapy Modulates Nuclear Erythroid 2-Related Factor 2\/Heme Oxygenase-1 Pathway in Carbon Tetrachloride-Induced Hepatotoxicity in Wistar Rats. Biology, 13.","DOI":"10.3390\/biology13070473"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Satyam, S.M., Bairy, L.K., Rehman, A., Farook, M., Khan, S., Nair, A.A., Binu, N.N., Yehya, M., and Khan, M.M. (2024). Dapagliflozin: A Promising Strategy to Combat Cisplatin-Induced Hepatotoxicity in Wistar Rats. Biology, 13.","DOI":"10.3390\/biology13090672"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4529","DOI":"10.52711\/0974-360X.2021.00788","article-title":"Methyl gallate mitigates doxorubicin-induced peripheral cytopenias: A preclinical experimental study","volume":"14","author":"Ahmed","year":"2021","journal-title":"Res. J. Pharm. Technol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"42395","DOI":"10.1038\/s41598-025-26559-z","article-title":"Development and validation of an integrated preclinical model mimicking cardiometabolic risk in postmenopausal female rats","volume":"15","author":"Sainath","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Rabbani, S.A., Patni, M.A., El-Tanani, M., Rangraze, I.R., Wali, A.F., Babiker, R., Satyam, S.M., El-Tanani, Y., and Almetwally, A.A.M.S. (2025). Impact of lifestyle modifications on cancer mortality: A systematic review and meta-analysis. Medicina, 61.","DOI":"10.3390\/medicina61020307"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"El-Tanani, M., Rabbani, S.A., Satyam, S.M., Rangraze, I.R., Wali, A.F., El-Tanani, Y., and Aljabali, A.A. (2025). Deciphering the role of cancer stem cells: Drivers of tumor evolution, therapeutic resistance, and precision medicine strategies. Cancers, 17.","DOI":"10.3390\/cancers17030382"},{"key":"ref_24","unstructured":"Mills, J. (1975). Aerospace Medicine and Biology. Aviat. Space Environ. Med., 1081."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1089\/rej.2018.2159","article-title":"Integration of melatonin related redox homeostasis, aging, and circadian rhythm","volume":"22","author":"Yanar","year":"2019","journal-title":"Rejuvenation Res."},{"key":"ref_26","first-page":"1","article-title":"Circadian Rhythms and Metabolism","volume":"449","author":"Grosbellet","year":"2023","journal-title":"Metab. Syndr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/cne.21146","article-title":"Development and morphology of the clock-gene-expressing lateral neurons of Drosophila melanogaster","volume":"500","author":"Shafer","year":"2007","journal-title":"J. Comp. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/S0960-9822(03)00167-2","article-title":"Circadian control of eclosion: Interaction between a central and peripheral clock in Drosophila melanogaster","volume":"13","author":"Myers","year":"2003","journal-title":"Curr. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1006\/bbrc.2001.6300","article-title":"Interactivating feedback loops within the mammalian clock: BMAL1 is negatively autoregulated and upregulated by CRY1, CRY2, and PER2","volume":"290","author":"Yu","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1007\/s00018-016-2378-8","article-title":"Molecular modulators of the circadian clock: Lessons from flies and mice","volume":"74","author":"Hegazi","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1111\/epi.16796","article-title":"Molecular regulation of brain metabolism underlying circadian epilepsy","volume":"62","author":"Chan","year":"2021","journal-title":"Epilepsia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1080\/07420528.2020.1771354","article-title":"Bedtime hypertension chronotherapy best reduces cardiovascular disease risk as documented by MAPEC and Hygia Chronotherapy outcomes trials","volume":"37","author":"Hermida","year":"2020","journal-title":"Chronobiol. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1080\/07420528.2020.1771356","article-title":"Current evidence on the circadian-time-dependent effects of hypertension medications and their combinations in relation to findings of MAPEC and Hygia Chronotherapy Trial","volume":"37","author":"Hermida","year":"2020","journal-title":"Chronobiol. Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1016\/S0140-6736(22)01900-6","article-title":"Best time for administration of antihypertensive medications: Morning or evening?","volume":"400","author":"Salah","year":"2022","journal-title":"Lancet"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/S0140-6736(22)01786-X","article-title":"Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): A prospective, randomised, open-label, blinded-endpoint clinical trial","volume":"400","author":"Mackenzie","year":"2022","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1177\/23727322231193967","article-title":"Health effects of disrupted circadian rhythms by artificial light at night","volume":"10","author":"Davis","year":"2023","journal-title":"Policy Insights Behav. Brain Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2174\/2212717806666190619120211","article-title":"Artificial Light Pollution at Night: A risk for normal circadian rhythm and physiological functions in humans","volume":"6","author":"Kumar","year":"2019","journal-title":"Curr. Environ. Eng."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Ribas-Latre, A., and Eckel-Mahan, K. (2022). Nutrients and the circadian clock: A partnership controlling adipose tissue function and health. Nutrients, 14.","DOI":"10.3390\/nu14102084"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"101235","DOI":"10.1016\/j.plipres.2023.101235","article-title":"Lipid metabolism around the body clocks","volume":"91","author":"Petrenko","year":"2023","journal-title":"Prog. Lipid Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1017\/S0007114512002139","article-title":"The role of the circadian clock system in nutrition and metabolism","volume":"108","author":"Cagampang","year":"2012","journal-title":"Br. J. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"144","DOI":"10.4093\/dmj.2018.0256","article-title":"Metabolic consequences of obstructive sleep apnea especially pertaining to diabetes mellitus and insulin sensitivity","volume":"43","author":"Song","year":"2019","journal-title":"Diabetes Metab. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1161\/CIRCRESAHA.120.316101","article-title":"Obesity phenotypes, diabetes, and cardiovascular diseases","volume":"126","author":"Tchernof","year":"2020","journal-title":"Circ. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1016\/j.metabol.2006.07.006","article-title":"Genetics of the sleep-wake cycle and its disorders","volume":"55","author":"Hamet","year":"2006","journal-title":"Metabolism"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41392-022-00899-y","article-title":"Molecular regulations of circadian rhythm and implications for physiology and diseases","volume":"7","author":"Fagiani","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1097\/FJC.0000000000001178","article-title":"Role of circadian rhythm and impact of circadian rhythm disturbance on the metabolism and disease","volume":"79","author":"Han","year":"2022","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1136\/oemed-2014-102292","article-title":"Night shift work at specific age ranges and chronic disease risk factors","volume":"72","author":"Ramin","year":"2015","journal-title":"Occup. Environ. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1027\/0269-8803\/a000267","article-title":"Circadian rhythms, sleep, and aging","volume":"35","author":"Garbarino","year":"2020","journal-title":"J. Psychophysiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"180","DOI":"10.5271\/sjweh.1324","article-title":"Sleep and autonomic nervous system changes\u2014Enhanced cardiac sympathetic modulations during sleep in permanent night shift nurses","volume":"35","author":"Chung","year":"2009","journal-title":"Scand. J. Work Environ. Health"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.52586\/5025","article-title":"Circadian rhythms, cardiac arrhythmias and sudden death","volume":"26","author":"Vicent","year":"2021","journal-title":"Front. Biosci.-Landmark"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1002\/j.2040-4603.2013.tb00505.x","article-title":"Circadian rhythms in liver physiology and liver diseases","volume":"3","author":"Tong","year":"2013","journal-title":"Compr. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/dom.12522","article-title":"Role of the clock gene Rev-erb\u03b1 in metabolism and in the endocrine pancreas","volume":"17","author":"Vieira","year":"2015","journal-title":"Diabetes Obes. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/jpi.12257","article-title":"Inter-relationships of the chronobiotic, melatonin, with leptin and adiponectin: Implications for obesity","volume":"59","author":"Reiter","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1007\/s00467-022-05802-z","article-title":"Endothelial dysfunction as a factor leading to arterial hypertension","volume":"38","year":"2023","journal-title":"Pediatr. Nephrol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.atherosclerosis.2017.08.001","article-title":"Insufficient sleep is associated with impaired nitric oxide-mediated endothelium-dependent vasodilation","volume":"265","author":"Bain","year":"2017","journal-title":"Atherosclerosis"},{"key":"ref_55","unstructured":"Assessment, P. (2025). Sleep and the Autonomic Nervous System. Fundamentals of Sleep and Circadian Science, Oxford University Press."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Rumanova, V.S., Okuliarova, M., Foppen, E., Kalsbeek, A., and Zeman, M. (2022). Exposure to dim light at night alters daily rhythms of glucose and lipid metabolism in rats. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.973461"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1080\/15384101.2017.1326768","article-title":"Circadian orchestration of insulin and glucagon release","volume":"16","author":"Petrenko","year":"2017","journal-title":"Cell Cycle"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Cano-Barquilla, P., Jim\u00e9nez-Ortega, V., Fern\u00e1ndez-Mateos, P., Virto, L., Maldonado Bautista, E., Perez-Miguelsanz, J., and Esquifino, A.I. (2025). Daily lipolysis gene expression in male rat mesenteric adipose tissue: Obesity and melatonin effects. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26020577"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Raza, G.S., Sodum, N., Kaya, Y., and Herzig, K.-H. (2022). Role of circadian transcription factor Rev-Erb in metabolism and tissue fibrosis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232112954"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/nrg.2016.150","article-title":"Transcriptional architecture of the mammalian circadian clock","volume":"18","author":"Takahashi","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1038\/s41580-022-00486-7","article-title":"Transcriptional control of energy metabolism by nuclear receptors","volume":"23","author":"Scholtes","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Zhang, T., Zhang, G., Liu, T.D., Gu, T., Yu, F., Xu, P., Mi, W., Zhao, X., Guo, Q., and Zheng, H. (2026). Circadian Immunity and Vascular Inflammation in Cardiovascular Disease Chronotherapy Windows: Time for a Re-Assessment. Med. Res.","DOI":"10.1002\/mdr2.70052"},{"key":"ref_63","first-page":"e27","article-title":"Pharmacokinetics: The dynamics of drug absorption, distribution, metabolism, and elimination","volume":"3","author":"Benet","year":"1996","journal-title":"Goodman Gilman\u2019s Pharmacol. Basis Ther."},{"key":"ref_64","unstructured":"Zentrum der Pharmakologie, J. (2013). Circadian variations in the effects of cardiovascular active drugs. Predisposing Cond. Acute Ischemic Syndr., 1."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1007\/s43440-025-00748-z","article-title":"Residence time in drug discovery: Current insights and future perspectives","volume":"77","author":"Kordylewski","year":"2025","journal-title":"Pharmacol. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.brainres.2007.08.061","article-title":"Effect of upregulated renin\u2013angiotensin system on per2 and bmal1 gene expression in brain structures involved in blood pressure control in TGR (mREN-2) 27 rats","volume":"1180","author":"Mravec","year":"2007","journal-title":"Brain Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Wang, S., and Gao, L. (2025). Circadian rhythm, glucose metabolism and diabetic complications: The role of glucokinase and the enlightenment on future treatment. Front. Physiol., 16.","DOI":"10.3389\/fphys.2025.1537231"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/s41419-022-04767-z","article-title":"The nuclear receptor REV-ERB\u03b1 is implicated in the alteration of \u03b2-cell autophagy and survival under diabetogenic conditions","volume":"13","author":"Brown","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2891","DOI":"10.1016\/S0021-9258(19)42714-2","article-title":"Dependence of the Circadian Rhythm of Hepatic \u03b2-Hydroxy-\u03b2-methylglutaryl Coenzyme A on Ribonucleic Acid Synthesis: A Possible Second Site of Inhibition by Dietary Cholesterol","volume":"249","author":"Edwards","year":"1974","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"F665","DOI":"10.1152\/ajprenal.00008.2018","article-title":"Predicted effect of circadian clock modulation of NHE3 of a proximal tubule cell on sodium transport","volume":"315","author":"Wei","year":"2018","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"20220170","DOI":"10.1098\/rstb.2022.0170","article-title":"Timing mechanisms to control heart rhythm and initiate arrhythmias: Roles for intracellular organelles, signalling pathways and subsarcolemmal Ca2+","volume":"378","author":"Terrar","year":"2023","journal-title":"Philos. Trans. R. Soc. B"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/S0002-8703(02)94797-6","article-title":"Circadian rhythm in the cardiovascular system: Chronocardiology","volume":"145","author":"Guo","year":"2003","journal-title":"Am. Heart J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1097\/00005344-199609000-00017","article-title":"Effects of antihypertensive drugs on the circadian blood pressure profile","volume":"28","author":"Voogel","year":"1996","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_74","first-page":"174","article-title":"Circadian variation in patients with acute heart failure with preserved ejection fraction","volume":"73","author":"Matsyshita","year":"2025","journal-title":"Minerva Cardiol. Angiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2174\/0115734021332079241226115916","article-title":"Understanding Efficacy of Using ACEIs and ARBs in Chronotherapeutic Treatment of Hypertension: Which Drug When?","volume":"21","author":"Yadav","year":"2025","journal-title":"Curr. Hypertens. Rev."},{"key":"ref_76","first-page":"765","article-title":"Nicotinamide: Oversight of metabolic dysfunction through SIRT1, mTOR, and clock genes","volume":"17","author":"Maiese","year":"2020","journal-title":"Curr. Neurovascular Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.yjmcc.2013.11.009","article-title":"The time-of-day variation in vascular smooth muscle contractility depends on a nitric oxide signalling pathway","volume":"66","author":"Denniff","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e3604","DOI":"10.31661\/gmj.v14i.3604","article-title":"Circadian Blood Pressure as An Indicator for Cardiovascular Complications","volume":"14","author":"Lutfi","year":"2025","journal-title":"Galen Med. J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4168","DOI":"10.7150\/thno.43834","article-title":"Targeting REV-ERB\u03b1 for therapeutic purposes: Promises and challenges","volume":"10","author":"Wang","year":"2020","journal-title":"Theranostics"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Wang, C., Yang, J., Yuan, J., Wang, X., Li, Q., Ren, C., Zhi, X., Lv, X., Liu, K., and Zhao, X. (2025). Role of circadian transcription factor REV-ERB in cardiovascular diseases: A review. Front. Cardiovasc. Med., 12.","DOI":"10.3389\/fcvm.2025.1516279"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1080\/07420528.2019.1570246","article-title":"Systemic oscillator-driven and nutrient-responsive hormonal regulation of daily expression rhythms for gluconeogenic enzyme genes in the mouse liver","volume":"36","author":"Taira","year":"2019","journal-title":"Chronobiol. Int."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Burgess, S.C. (2015). Regulation of glucose metabolism in liver. International Textbook of Diabetes Mellitus, Wiley.","DOI":"10.1002\/9781118387658.ch13"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1093\/ajhp\/55.21.2253","article-title":"Atorvastatin: A hydroxymethylglutaryl-coenzyme A reductase inhibitor","volume":"55","author":"Malinowski","year":"1998","journal-title":"Am. J. Health-Syst. Pharm."},{"key":"ref_84","first-page":"46","article-title":"Night shift-induced circadian disruption: Links to initiation of non-alcoholic fatty liver disease\/non-alcoholic steatohepatitis and risk of hepatic cancer","volume":"10","author":"Singh","year":"2024","journal-title":"Hepatoma Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1038\/s41591-018-0125-4","article-title":"Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo","volume":"24","author":"Madiraju","year":"2018","journal-title":"Nat. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"bqab089","DOI":"10.1210\/endocr\/bqab089","article-title":"Circadian regulation of the pancreatic beta cell","volume":"162","author":"Seshadri","year":"2021","journal-title":"Endocrinology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1007\/s11892-014-0474-4","article-title":"Does disruption of circadian rhythms contribute to beta-cell failure in type 2 diabetes?","volume":"14","author":"Rakshit","year":"2014","journal-title":"Curr. Diabetes Rep."},{"key":"ref_88","unstructured":"Bending, D.J. (2024). Utilising a Systems Pharmacology Approach to Model the Pathway For\u2019ex Nihilo\u2019glucose Exposure in Response to a Novel Somatostatin Agonist. [Master\u2019s Thesis, University of Warwick]."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Zeng, P., Hill, M.A., and Wu, J. (2025). Adipose Tissue Circadian Clocks: Implications for Metabolism and Metabolic Dysfunction. Obes. Rev., e70071.","DOI":"10.1111\/obr.70071"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/oby.2002.77","article-title":"Combining behavioral and pharmacological treatments for obesity","volume":"10","author":"Phelan","year":"2002","journal-title":"Obes. Res."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Cozma, D., V\u0103c\u0103rescu, C., and Stoicescu, C. (2025). Added Value to GLP-1 Receptor Agonist: Intermittent Fasting and Lifestyle Modification to Improve Therapeutic Effects and Outcomes. Biomedicines, 13.","DOI":"10.3390\/biomedicines13123079"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.clnesp.2025.08.033","article-title":"Time-restricted eating and its metabolic benefits in obesity and insulin resistance","volume":"69","author":"Jawamis","year":"2025","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1002\/j.2040-4603.2022.tb00198.x","article-title":"Circadian rhythm effects on the molecular regulation of physiological systems","volume":"12","author":"Crislip","year":"2022","journal-title":"Compr. Physiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"16523","DOI":"10.1073\/pnas.0904890106","article-title":"Molecular clock is involved in predictive circadian adjustment of renal function","volume":"106","author":"Zuber","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.2169\/internalmedicine.4243-19","article-title":"Chronotherapy with a renin-angiotensin system inhibitor ameliorates renal damage by suppressing intrarenal renin-angiotensin system activation","volume":"59","author":"Aoki","year":"2020","journal-title":"Intern. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/j.1751-7176.2011.00515.x","article-title":"\u03b2-adrenergic blockers","volume":"13","author":"Frishman","year":"2011","journal-title":"J. Clin. Hypertens."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/hr.2015.142","article-title":"Chronotherapy with conventional blood pressure medications improves management of hypertension and reduces cardiovascular and stroke risks","volume":"39","author":"Hermida","year":"2016","journal-title":"Hypertens. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"102111","DOI":"10.1016\/j.eujim.2022.102111","article-title":"Evening versus morning administration of drug therapy for hypertension: A meta-analysis of randomized controlled trials","volume":"50","author":"Zhao","year":"2022","journal-title":"Eur. J. Integr. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1007\/s00125-019-05042-1","article-title":"Metformin increases fasting glucose clearance and endogenous glucose production in non-diabetic individuals","volume":"63","author":"McCreight","year":"2020","journal-title":"Diabetologia"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1016\/j.jacl.2017.06.001","article-title":"Effects of morning vs evening statin administration on lipid profile: A systematic review and meta-analysis","volume":"11","author":"Awad","year":"2017","journal-title":"J. Clin. Lipidol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1080\/00325481.2016.1103640","article-title":"The importance of postprandial glycemic control: Optimizing add-on therapy to basal insulin","volume":"128","author":"Shaefer","year":"2016","journal-title":"Postgrad. Med."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Liu, C., Liu, Y., Xin, Y., and Wang, Y. (2022). Circadian secretion rhythm of GLP-1 and its influencing factors. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.991397"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s40675-025-00337-9","article-title":"Sleep and Circadian Effects on the Incretin System","volume":"11","author":"Yuan","year":"2025","journal-title":"Curr. Sleep Med. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"ooae027","DOI":"10.1093\/jamiaopen\/ooae027","article-title":"The Bitemporal Lens Model\u2014Toward a holistic approach to chronic disease prevention with digital biomarkers","volume":"7","author":"Barata","year":"2024","journal-title":"JAMIA Open"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Hesse, J., Malhan, D., Yal\u00e7in, M., Aboumanify, O., Basti, A., and Relogio, A. (2020). An optimal time for treatment\u2014Predicting circadian time by machine learning and mathematical modelling. Cancers, 12.","DOI":"10.3390\/cancers12113103"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Alam, J., Bansal, K.K., Kumar, V., Khalid, M., and Arfi, S. (2025). The Role of Artificial Intelligence in Optimizing Drug Timing. Chronopharmacology, CRC Press.","DOI":"10.1201\/9781003637745-9"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Kanakaprabha, S., Kumar, G.G., Reddy, B.P., Raju, Y.R., and Rai, P.C.M. (2024). Wearable devices and health monitoring: Big data and AI for remote patient care. Intell. Data Anal. Bioinform. Biomed. Syst., 291\u2013311.","DOI":"10.1002\/9781394270910.ch12"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Sirpal, P., and Yang, Y. (2025). Advancing Electroencephalogram in Tele-Neurorehabilitation: Integrating Wearable Technology and Multimodal Systems. Automation in Tele-Neurorehabilitation, CRC Press.","DOI":"10.1201\/9781003419235-2"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e71486","DOI":"10.1002\/hsr2.71486","article-title":"Wearable Technology and Its Potential Role in Cardiovascular Health Monitoring and Disease Management","volume":"8","author":"Nazir","year":"2025","journal-title":"Health Sci. Rep."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1039\/D5PM00089K","article-title":"Artificial intelligence in smart drug delivery systems: A step toward personalized medicine","volume":"2","author":"Panchpuri","year":"2025","journal-title":"RSC Pharm."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Park, H., Metwally, A.A., Delfarah, A., Wu, Y., Perelman, D., Rodgar, M., Mayer, C., Celli, A., McLaughlin, T., and Mignot, E. (2024). Lifestyle profiling using wearables and prediction of glucose metabolism in individuals with normoglycemia or prediabetes. medRxiv.","DOI":"10.1101\/2024.09.05.24312545"},{"key":"ref_112","unstructured":"Boureghda, A., Boukhari, H.K.E., Benderradji, T.Y., and Benmehamed, O. (2025). AI-Driven Prescription Safety System, University of Bordj Bou Arreridj."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/jim4.70003","article-title":"The role of artificial intelligence in pharmacy: Revolutionizing drug development and beyond","volume":"2","author":"Usman","year":"2025","journal-title":"J. Intell. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1177\/074873002129002474","article-title":"Comparisons of the variability of three markers of the human circadian pacemaker","volume":"17","author":"Klerman","year":"2002","journal-title":"J. Biol. Rhythm."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"281","DOI":"10.2147\/DMSO.S95120","article-title":"Role of sleep quality in the metabolic syndrome","volume":"9","author":"Koren","year":"2016","journal-title":"Diabetes Metab. Syndr. Obes. Targets Ther."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1161\/CIRCULATIONAHA.117.029617","article-title":"Cardiovascular and metabolic heterogeneity of obesity: Clinical challenges and implications for management","volume":"137","author":"Neeland","year":"2018","journal-title":"Circulation"},{"key":"ref_117","first-page":"e85580","article-title":"Harnessing Artificial Intelligence in Lifestyle Medicine: Opportunities, Challenges, and Future Directions","volume":"17","author":"Saeed","year":"2025","journal-title":"Cureus"},{"key":"ref_118","unstructured":"de Noronha Os\u00f3rio, D.F. (2022). Novel Approaches to Pervasive and Remote Sensing in Cardiovascular Disease Assessment. [Master\u2019s Thesis, Universidade NOVA de Lisboa]."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Gubin, D., Weinert, D., Stefani, O., Otsuka, K., Borisenkov, M., and Cornelissen, G. (2025). Wearables in Chronomedicine and interpretation of circadian health. Diagnostics, 15.","DOI":"10.3390\/diagnostics15030327"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Hesketh, S.J. (2025). Resetting Time: The Role of Exercise Timing in Circadian Reprogramming for Metabolic Health. Obesities, 5.","DOI":"10.3390\/obesities5030059"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/3\/241\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T16:18:27Z","timestamp":1769617107000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/3\/241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":120,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["biology15030241"],"URL":"https:\/\/doi.org\/10.3390\/biology15030241","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]}}}