Abstract:
Background: Circadian rhythms are fundamental biological processes that regulate endocrine secretion, metabolic homeostasis, and immunological balance through tightly controlled molecular clocks. These rhythms are orchestrated by both central and peripheral oscillators that respond to environmental cues, particularly the light–dark cycle. Early morning wakefulness, especially within the time window of 04:00–05:00 AM, represents a critical transitional phase characterized by dynamic hormonal fluctuations, including the cortisol awakening response and the gradual suppression of melatonin. This temporal window may exert significant influence on systemic physiology, metabolic coordination, and the transcriptional activity of circadian-related genes, thereby potentially affecting overall human health.
Objective: This study aimed to systematically evaluate the biochemical and molecular effects of early morning wakefulness on circadian hormone regulation, metabolic synchronization, and systemic physiological health in a population of healthy adults.
Methods: A randomized experimental study design was employed from August 2023 to September 2024 across multiple regions in Indonesia, including Palopo, Luwu, Luwu Timur, Kolaka, and Kolaka Utara. A total of 210 healthy adult participants were recruited and randomly allocated into two groups: an intervention group instructed to wake consistently between 04:00–05:00 AM for a duration of four weeks, and a control group maintaining habitual sleep–wake patterns. Primary outcome measures included serum concentrations of cortisol, melatonin, insulin, fasting blood glucose, and beta-hydroxybutyrate (BHB). Additionally, molecular analyses were conducted to assess the expression levels of core circadian clock genes—BMAL1, PER2, CLOCK, and CRY1—using quantitative real-time polymerase chain reaction (qRT-PCR). Insulin resistance was evaluated using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR).
Results: Participants in the early wakefulness group demonstrated a statistically significant increase in morning cortisol levels by approximately 45%, accompanied by a 30% reduction in circulating melatonin levels (p < 0.001), indicating a pronounced shift in circadian hormonal dynamics. Metabolic parameters revealed significant reductions in fasting glucose and insulin levels, alongside a marked elevation in BHB concentrations (p < 0.05), suggesting enhanced metabolic flexibility and a shift toward increased lipid utilization. At the molecular level, gene expression analysis showed significant upregulation of BMAL1 and PER2 (approximately 1.5-fold increase, p < 0.01), while CLOCK and CRY1 exhibited stable but coordinated expression patterns. Notably, the upregulation of these core clock genes was inversely correlated with HOMA-IR scores, indicating improved insulin sensitivity.
Conclusion: Consistent early morning wakefulness exerts beneficial effects on circadian hormonal regulation, metabolic adaptation, and molecular clock gene expression. These findings suggest that early wakefulness may serve as a practical, non-pharmacological intervention to enhance circadian alignment and improve metabolic and endocrine health. Furthermore, the study provides robust biochemical and molecular evidence supporting the integration of behavioral chronotherapy strategies into preventive health frameworks.
Biography:
Dr. Agussalim, S.Kp., MSN, MST, DNS is an Associate Professor at the Parepare School of Nursing, Makassar Health Polytechnic, Ministry of Health of the Republic of Indonesia. He began his nursing career after graduating as a Primary Nurse from the Labuang Baji School of Nursing in 1996 and subsequently earned a Diploma in Nursing from the Anging Mammiri School of Nursing, Makassar (2000–2003). He completed his Bachelor of Nursing Science at Binawan University, Jakarta (2003–2006).
Dr. Agussalim pursued his postgraduate education at St. Paul University Philippines (SPUP), where he obtained a Master of Science in Nursing with a specialization in Adult Health Nursing (2007–2009), alongside a Master of Science in Teaching (2007). He later completed his Doctor of Nursing Science (DNS) at the same institution in 2015 under a competitive international scholarship program.
He has been actively engaged in international academic forums. In 2019, he was awarded a scholarship by the Directorate General of Higher Education of Indonesia to present his research at the Transcultural Nursing Society Conference in Richmond, Virginia, USA. In 2020, he was selected to participate in a short course program at Heidelberg University, Germany, although the program was postponed due to the COVID-19 pandemic.
Dr. Agussalim is frequently invited as a speaker at both national and international conferences, reflecting his recognized expertise in nursing science and healthcare research. He has an extensive publication record, with numerous research articles indexed on his Google Scholar profile, demonstrating sustained contributions to scientific knowledge. In addition, he serves as a peer reviewer for several reputable international journals, contributing to the advancement of scholarly standards in nursing and health sciences.
Beyond journal publications, he is a prolific author of academic books with ISBN registration, written in both Indonesian and English, covering diverse topics in nursing, healthcare, and education. His academic portfolio is further strengthened by multiple competitive research grants funded by the Government of Indonesia, including awards received in 2022.
In addition to his academic and research roles, Dr. Agussalim is actively involved in community service initiatives, applying evidence-based approaches to improve public health outcomes and strengthen healthcare capacity at the community level. His professional contributions encompass roles as a nurse educator, researcher, national accreditation team member, author, reviewer, and community service leader, reflecting a comprehensive commitment to advancing nursing practice, education, and research both nationally and globally.
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