Temporal Tactics: Leveraging Circadian Rhythms in Diabetes Treatment

Varun Chauhan; Deepak Sharma; Saurabh Srivastava

doi:10.33069/cim.2025.0020

Chronobiol Med > Volume 7(3); 2025 > Article

Chauhan, Sharma, and Srivastava: Temporal Tactics: Leveraging Circadian Rhythms in Diabetes Treatment

Review Article

Chronobiology in Medicine 2025;7(3):128-137.

Published online: September 30, 2025

DOI: https://doi.org/10.33069/cim.2025.0020

Temporal Tactics: Leveraging Circadian Rhythms in Diabetes Treatment

Varun Chauhan¹

, Deepak Sharma²

, Saurabh Srivastava²

¹Multi-Disciplinary Research Unit, Governmnet Institute of Medical Sciences (GIMS), Greater Noida, India

²Department of Medicine, Government Institute of Medical Sciences (GIMS), Greater Noida, India

Corresponding author: Saurabh Srivastava, MD, Department of Medicine, Government Institute of Medical Sciences (GIMS), Greater Noida 201310, India.
Tel: 91-9654233158, E-mail: saurabhsrivas@gmail.com

Received April 9, 2025 Revised July 13, 2025 Accepted August 1, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Diabetes mellitus (DM), a global metabolic disease, is closely associated with circadian rhythms (CRs), and the situation is quite multifaceted for clinicians. Chronobiological knowledge reveals the complex relationship between circadian cycle and DM. This review demonstrates that CRs controlled by the suprachiasmatic nucleus (SCN) play a complex role in glucose homeostasis, insulin sensitivity, and pancreatic β-cell function. Chronic disruption of CRs or chronodisruption worsens metabolic dysregulation; therefore, the timing of treatments should coincide with biological rhythms. Cycles and rhythms of diabetes incidence also emphasize the need for targeted interventions, as it is with chronotherapy and chronopharmacology. External factors such as shift work, irregular sleep, and jet lag are new contributors to chronodisruption, which further aggravate metabolic derangement in diabetes. Epidemiological data underline the necessity of interventions that are related to natural rhythms. This review maps the current state of knowledge of chronobiology in diabetes and uses clinical evidence to highlight the possibilities of chronobiological interventions. Deeper understanding of CRs may provide knowledge about the diabetes progression and point towards the development of more specific treatments. Measures such as light treatment, sleep hygiene, meal timing, and chronotherapy are potential approaches that may help to entrain CRs and enhance metabolic regulation in diabetic patients. Focusing on person-centerd strategies, healthcare providers can address specific aspects of patients’ lifestyles, thus improving glycaemic control and quality of life. Yet, more studies are needed to describe the specific processes and develop more specific approaches to treatment.

Keywords: Chronodisruption; Circadian rhythms; Diabetes mellitus; Suprachiasmatic nucleus; Clock genes

INTRODUCTION

Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycaemia due to dysfunction of the metabolic pathways and has recently been found to be associated with changes in circadian rhythms, including sleep-wake cycle and feeding time [1]. Circadian biology, the science that deals with the rhythm of life, has a great impact on physiological functions, such as metabolism and hormone secretion [2]. This interplay between the body’s internal clock and the external environment is very important in the regulation of homeostasis, especially in DM.

Previous studies defined the importance of timing in different physiological processes such as the control of cell division, sleep-wake cycle, and hormonal oscillations [3]. This led to the identification of a new term, circadian rhythms (CRs)—a system of intracellular oscillators regulating these processes [4]. CRs are involved in the precise control of glucose metabolism, insulin sensitivity, and pancreatic β-cell function, thereby maintaining efficient metabolic processes and responsiveness to energy requirements [5]. The master clock is situated in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus and co-ordinates CRs by entraining other oscillators in tissues such as the liver, pancreas, adipose tissue, and skeletal muscle [6]. SCN being the master clock synchronized with light can regulate physiological functions based on the 24-hour light-dark cycle [3].

The CR disruption, known as chronodisruption, is linked to metabolic diseases such as type 2 diabetes mellitus (T2DM), obesity, and metabolic syndrome [7]. Some research has shown that shift work and irregular sleep patterns cause chronodisruption, which in turn increases the risk of developing metabolic disorders and T2DM [8]. These findings underscore the pressing need for the creation of therapeutic interventions that are in harmony with natural rhythms.

Epidemiological research shows that diabetes occurrence exhibits a rhythm in time, which is why interventions should be synchronized with natural rhythms [9]. This insight is the foundation of chronotherapy and chronopharmacology, which seeks to establish the right time for the delivery of therapy in diabetes. This review aims to discuss the advances in chronobiology in diabetes with consideration of clinical research data. In this review, we will first try to disentangle the complex interconnection between circadian rhythms and diabetes with the hope of shedding light on the possibilities offered by chronobiological strategies for improving diabetes treatment (Figure 1).

CHRONOBIOLOGY AND CIRCADIAN RHYTHMS IN DIABETES

Overview of CRs and their link to glucose homeostasis and metabolism

CRs, intrinsic 24-hour biological cycles, synchronize an organism’s physiological and behavioral processes with the day-night cycle. The coordination is overseen by the master circadian clock situated in the SCN within the hypothalamus as discussed before. Beyond regulating sleep-wake cycles, CRs play a fundamental role in governing various physiological functions, encompassing metabolism, hormone secretion, and immune activity [2]. In clinical diabetes management, the role of circadian regulation in glucose metabolism receives much attention [10,11]. The maintenance of glucose homeostasis is one of the most complex aspects of circadian regulation, which is characterized by temporal oscillations in insulin sensitivity, glucose tolerance, and pancreatic β-cell function [12]. The circadian system is able to regulate blood glucose levels all through the day. It is important to note that during the active/feeding period, the plasma glucose concentration depends on dietary intake, while during the resting/fasting stage, the liver has a key role in glucose production [11]. Glucose is then transported to adipose and skeletal tissues, as such, glucose regulation is not just confined to the circadian cycle. This is where it matters to understand how the body’s processes may be more aligned with the different rhythms of the day so that the therapeutic and diabetes interventions can be done at the right time. It therefore becomes clear that knowledge of the molecular components that are involved in glucose homeostasis in the context of circadian biology is an important piece of the puzzle when trying to build a comprehensive picture of circadian biology and its relation to metabolic health.

Circadian rhythm and chronodisruption

The changes in the CR that have been defined as chronodisruption have been found to have an influence on the development of diabetes [13]. The most recent clinical studies have examined the reciprocal relationship between circadian disruption and glucose metabolism dysfunction, especially in relation to diabetes manifestation and progression [14,15]. During morning and evening meals, observations have been made on the impact of CRs on glucose control. The body’s own clock influences glucose metabolism, and it is known that glucose tolerance is worse in the evening and that if a person consumes a higher proportion of calories in the evening, the risk of developing conditions associated with metabolic syndrome is increased [16]. These fluctuations in insulin release are also linked to variations in glycaemic control and may lead to augmented hepato- and peripherally mediated insulin resistance [16]. Current findings suggest that pancreatic insulin secretion has a rhythmicity that is governed by an intrinsic circadian clock in pancreatic islets [17]. The rhythmic regulation of the circadian clock is essential for the proper functioning and survival of β-cells. Circadian misalignment disrupts the rhythmic activity of pancreatic islets, culminating in the reduction of β-cell mass or impairment of their function. This impairment contributes to the development of T2DM [18]. Gale et al. [19] demonstrated that disrupted CRs accelerate the decline of pancreatic β-cell performance and quantity in individuals with T2DM, heightening susceptibility to the condition. A study by Polonsky et al. [20] underscored irregular patterns of insulin release in untreated individuals diagnosed with T2DM, indicating compromised rhythmic control of the disease. Beyond insulin, numerous nutrient hormones essential for glucose homeostasis, such as glucagon, adiponectin, leptin, amylin, and glucose inhibitory peptides, exhibit circadian control. These hormones fluctuate in response to periods of activity/feeding and rest/starvation. The disturbances to these circadian patterns, encompassing variations in diet, shifts in meal schedules, and continuous exposure to artificial light, could negatively influence the functions and concentrations of these hormones [15]. Circadian clocks extend their influence beyond modulating insulin secretion to impact insulin action. The CR of skeletal muscle, facilitated by insulin-induced activation of glucose transporters like glucose transporter type 4 (GLUT4), is essential in facilitating the absorption of glucose into skeletal muscle tissues. Notably, the removal of circadian clocks within liver cells has been linked to adverse impacts on lipid and glucose metabolism, hindering the regulation of insulin-induced inhibition of hepatic glucose production [21]. Understanding the intricate web of interactions between circadian disruptions and diabetes pathophysiology is pivotal for devising targeted interventions and therapeutic strategies aimed at restoring circadian balance for improved metabolic health.

TEMPORAL PATTERNS OF DM

A large number of epidemiological investigations have reported different temporal trends in the incidence and development of diabetes. These studies focus on certain times of the day when people with diabetes are vulnerable to hyperglycaemia and its effects [22]. For example, it has been found that the probability of cardiovascular complications, which are typical for diabetes, may differ during the day. Of these, it is crucial to comprehend these temporal patterns to design interventions and preventive measures [23]. Circadian changes are fluctuations that occur on a daily basis. There are significant circadian rhythms in many aspects of diabetes including insulin sensitivity, glucose tolerance, and β-cell function. Here, we have discussed the diurnal variations in each of these parameters.

Insulin sensitivity

Insulin sensitivity is the ability of the body to respond to insulin, especially in the uptake of glucose from the blood by cells following insulin signals. It is known that insulin sensitivity fluctuates during the day, and studies show that it has a circadian nature. It is also important to note that insulin sensitivity is at its highest during the early morning hours, thus glucose uptake by peripheral tissues like skeletal muscles and adipose tissue is efficient. It is believed that this increased sensitivity helps in the utilization of glucose in the morning after fasting throughout the night and for the energy requirements of the day [24]. We also know that with the increase of the day, the sensitivity to insulin decreases and reaches its minimum in the evening and nighttime. This variability is due to factors such as changes in hormonal levels, timing of meals, physical activity, and the sleep-wake cycle. For example, cortisol concentration is high in the morning and increases insulin sensitivity, whereas in the evening it is low and reduces insulin sensitivity. Likewise, meal consumption leads to the secretion of insulin and glucose uptake, which reverses the phenomenon for a while, especially if the meals are taken in the right proportions in a day.

Other works have offered some explanation for the molecular regulation of insulin sensitivity in relation to diurnal rhythms. For instance, it has been revealed that the molecular clock gene Rev-erbα is involved in the regulation of insulin sensitivity in peripheral tissues including skeletal muscle and adipose tissue [25,26]. Rev-erbα expression also exhibits circadian oscillation, with the highest level during the time of inactivity (night in humans), thus regulating insulin sensitivity rhythms. Yang et al. [27], established that Rev-erbα mRNA and protein rhythmically accumulated in skeletal muscle, kidney, and thymus of mice, and mice lacking this nuclear receptor had a shorter period of behavioral rhythms, indicating that Rev-erbα is involved in stabilizing circadian oscillations [27].

Furthermore, the impact of meal timing on human’s circadian rhythm of insulin sensitivity has also been explored, and it has been found that the consumption of carbohydrates during the day may improve insulin sensitivity compared to that at night [28,29]. It is therefore important to recognize the differences in insulin sensitivity throughout the day in order to best address diseases like DM. The factors that affect insulin sensitivity include meal timing, physical activity, and sleep quality, and therefore, targeting these factors may help in improving glycemic control and preventing complications related to insulin resistance.

Glucose tolerance

Post-prandial glycemia is the ability of the body to maintain blood glucose levels after consuming carbohydrates. Like insulin sensitivity, glucose tolerance also has diurnal variation, but in an inverse manner. In other words, glucose tolerance is low in the morning and high in the evening. This pattern is partly due to the diurnal variation of insulin release and sensitivity, and variation in counter-regulatory hormones, cortisol, and glucagon. In the recent article by Mason et al. [14], circadian disruption was found to affect glucose tolerance among people with shift work. The study talks about how night-shift workers had a higher level of glucose intolerance than day-shift workers because their circadian rhythms are not synchronized with the external light-dark cycle.

However, the timing of exercise can also affect other physiological processes such as substrate utilization and CR. Timing of exercise can influence the body’s reaction to both exercise and food, even in relation to blood sugar. In a study, researchers compared the impact of morning exercise and afternoon exercise on glucose change with different indices. The authors of the study also discovered that glucose variability was slightly higher when the exercise was done in the afternoon as compared to the morning. This was evidenced by increased continuous overlapping net glycemic action (CONGA) and α2 of detrended fluctuation analysis (DFA) glucose variation indices during the afternoon exercise trial. Moreover, other indices showed reduced stability in glucose variation in the post-afternoon exercise condition compared to post-morning exercise or no exercise condition. In a rather surprising fashion, the meal tolerance was lower after both exercise trials, which indicates that exercise influences the way meals are tolerated. Glucose levels were reduced only during the afternoon exercise trial, making the blood glucose levels more fluctuating throughout the 24-hour period of the exercise. In other words, the time of day at which one exercise—in the morning or afternoon—affects the body’s ability to manage glucose changes, and afternoon exercise may cause a slightly less favorable outcome than morning exercise or no exercise at all (Figure 2) [30].

β-cell function

β-cell function is described as the ability of the pancreatic β-cells to secrete insulin in response to changes in blood glucose levels. These oscillations are essential for the control of glucose levels over the day [31]. There is evidence that β-cell function is cyclical with the maximum insulin release occurring just before the meal and the minimum during fasting or inactivity. According to Lee et al. [32], the clock gene Bmal1 plays an important role in maintaining normal β-cell function, as shown in mouse models. The study also revealed that if the internal biological clock is altered especially in the pancreatic β cells diabetes is experienced in mice. This is due to elevated reactive oxygen species (ROS) levels, which impaired mitochondrial function, thereby reducing glucose-stimulated insulin secretion. These mice had reduced antioxidant genes and consequently high ROS. Additionally, Nrf2, the master antioxidant regulator gene, was shown to be under the control of the clock gene Bmal1; this underlines the importance of circadian control in the proper functioning of the β-cells and protection against oxidative stress-induced diabetes, particularly in shift working conditions. Insulin and glucagon secretion, insulin sensitivity, and glucose tolerance were proven to have circadian rhythms only recently [7]. This underlines the general circadian regulation of the integrity of the β-cells and prevents the oscillations of glucose concentrations.

Therefore, diurnal changes in insulin sensitivity, glucose tolerance, and β-cell function are important in the development of DM. Knowledge of these mechanisms and their circadian rhythm is crucial for effective prevention and treatment of diabetes and its complications. Hence, knowledge of these diurnal variations is essential for the design of individualized diabetic care, including the chronopharmacology of diabetes medications, chrononutrition, and chronointerventions.

CHRONODISRUPTION

External factors contributing to chronodisruption in individuals with diabetes

These processes are regulated by internal oscillators, or “clocks,” with the master clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus, while other clocks exist in nearly all tissues of the body. The fact that these clocks are present almost in all parts of the body proves their importance for health in general. Synchronization is vital for health, which means the synchronization of the internal and external time and the synchronization of all the clocks within the organism. Our internal clock mainly entrains the external environment through light information that is conveyed to the SCN through the retinal ganglion cells [33]. The central clock, in turn, synchronizes peripheral clocks by controlling temperature rhythms, the activity of the autonomous nervous system, and the secretion of hormones, including cortisol and melatonin [34,35]. Peripheral clocks can also coordinate through other signals, such as feeding and fasting signals [36].

Zeitgeber is the external signals that affect the functioning of the CRs and is necessary for proper synchronization of an organism’s circadian rhythms with the external world. These include factors such as light exposure, timing of meals, and social interactions, which are crucial for biological clocks. However, the most dominant zeitgeber is light, which entrains the master clock, the SCN of the hypothalamus, which regulates the timing of most physiological processes [1]. Chrono disruption is the state in which internal biological rhythms are not synchronized with zeitgebers, which can be disrupted by shift work or eating at the wrong time. This misalignment, however, can have a significant impact on metabolic health, especially for those with diabetes [1]. For instance, shift work disrupts the light-dark cycle and meal timing leading to circadian disruption and metabolic changes [37]. Similarly, social jet lag, the variability in sleep-wake between workdays and free days, may disrupt CRs and result in metabolic disruption [38]. Here, we reviewed some external factors such as shift work, irregular sleep patterns, and jet lag which can cause chronodisruption in diabetic patients.

Circadian disruptors in modern lifestyles

Shift work

Shift work involves working outside the typical daytime hours of 9:00 am to 5:00 pm, providing 24/7 services in order to meet the needs of modern society [39]. Working at night is a major risk factor at the workplace and is associated with adverse health consequences in the long run (Figure 3) [40]. Shift work is working during nonstandard hours, which alters the circadian rhythm, thereby reducing melatonin production and disrupting the diet and the sleep-wake cycle, all of which have negative effects on physical and mental health [41]. In shift workers, this disruption in CR has been reported to be associated with elevated incidence of cardiovascular diseases, metabolic syndrome, obesity, cancer, psychological disorders, and T2DM [15,32,42–44]. Circadian disruption in shift workers is also attributed to environmental factors including irregular sleep-wake cycle and exposure to artificial light [37].

This disruption of the day-night cycle is one of the causes of metabolic disruption among the night shift workers; their postprandial glucose, insulin, and triacylglycerol levels are higher than those of the day shift workers [45]. Further, a meta-analysis found that shift workers had a 9% higher risk of developing T2DM, especially for those working in rotating shifts [44]. Studies in rat models of simulated shift work showed abdominal obesity and disruption of glucose level rhythmicity [46]. Accelerated beta cell dysfunction and loss have been shown in rats with disturbance of light-dark cycles, and impairing glucose-stimulated insulin secretion [47]. Studies in Bmal1 knockout mice demonstrated that the Bmal1 gene plays a critical role in dealing with circadian perturbations, as well as in protection against oxidative stress, and that its dysfunction is implicated in beta cell dysfunction and diabetes [32]. These findings, while observational, emphasize the detrimental impact of night or rotating shifts, later chronotypes, sleep irregularity, and meal timing on cardiometabolic outcomes [8]. Taken together, these observations highlight the critical role of CR alignment in preserving metabolic health.

Irregular sleep patterns

Sleep, a biologically essential and reversible state of inactivity, is ubiquitous across multicellular organisms and is crucial. Although ubiquitous, the exact function of sleep is unknown, and leading theories include brain energy restoration, facilitation of synaptic plasticity for memory and learning, and removal of neural waste [48]. Animal studies of sleep deprivation experiments have shown its critical nature; complete sleep loss leads to death within weeks [49]. Sleep is driven homeostatically, similar to hunger or thirst, and as an organism postpones sleep, it becomes progressively sleepier, until it is more likely to fall asleep [50]. The connections between sleep and health are obvious, but much about sleep remains mysterious. Sleep regularity is a key constituent of the multidimensional sleep health framework in the context of CRs. In contemporary lifestyles, insufficient sleep, irregular sleep-wake schedules, and frequent changes in sleep timing are common. Sleep and CRs are tightly coupled, and the master circadian clock in the SCN of the hypothalamus controls the sleep drive that regulates daily sleep patterns. Sleep timing is a rough marker of the circadian phase, and light, a potent CR shifter, affects both sleep and CRs [50]. Irregular sleep patterns are common in modern living and can lead to chronodisruption, a particularly important phenomenon for people with diabetes, as it may have metabolic implications [51]. A recent study in adolescents and young adults with type 1 diabetes mellitus (T1DM) found significant associations between poor subjective quality of sleep (as measured by the Pittsburgh Sleep Quality Index [PSQI]) and decreased endothelial function (%FMD). Furthermore, low sleep efficiency and high sleep duration variability were associated with increased HbA1C levels and thus poorer glycemic control. In conclusion, the study highlighted the significance of fostering consistent sleep habits, including maintaining regular sleep timing, to potentially improve metabolic and cardiovascular health among individuals with T1DM [52]. Sleep and diabetes are not only T1DM but also T2DM. It is therefore important to consider both the predisposing exposures to T2DM by sleep and the impact that diabetes has on sleep. Disturbances such as peripheral neuropathy or nocturia due to poor glycemic control might cause the patient pain at night, and diabetes may predispose to sleep disturbances. Patients with diabetes complain of more frequent periodic breathing disorders during sleep and restless legs syndrome that can cause sleep disruption [53]. One of the main relationships between sleep and T2DM is mediated by the effects of sleep on insulin sensitivity. Insulin is also secreted by the pancreas and is involved in the uptake of glucose into cells and the regulation of blood sugar levels. Prolonged sleep loss causes insulin resistance, which in turn raises blood glucose levels and the symptoms of T2DM. Moreover, sleep-wake cycle disruption and shift work could affect circadian rhythms, which may lead to glucose metabolism disorders and insulin resistance [52]. The relation of sleep to diabetes risk is also explained by the effects of sleep on hormones such as cortisol, growth hormone, and other factors affecting glucose homeostasis [52]. Therefore, the length and quality of sleep have emerged as one of the critical predictors of health in patients with T2DM. Both short sleep, durations and long sleep durations have been associated with T2DM. Lack of sleep, which can be defined as getting less than 6 hours of sleep, is associated with an unhealthy diet, low physical activity, and insulin resistance. However, sleeping for more than 9 hours every night is less frequently associated with the increased risk but may indicate a poor quality of sleep or health complications. Last but not least, there is a complex interaction between sleep and diabetes. Sleep disturbances have an impact on insulin sensitivity, glucose metabolism, and the risk of T2DM. However, diabetes may also cause sleep disturbances, so one can speak about the vicious cycle here as well. That sleep duration and sleep quality are both involved in metabolism indicates that sleep health and sleep disorders should be an integral part of overall health. Combined, these factors can assist in the prevention of T2DM and better health [52].

Jet lag

Social jet lag is a chronic but substantial disruption of CRs and refers to the difference between the body’s circadian rhythm and sleep-wake cycles that are influenced by work schedules and social commitments [54]. Defined as the difference in the timing of sleep between workdays and free days when people often have late nights and long mornings, social jet lag is measured by the shift in the mean sleep midpoint between weekdays and weekends. It is highly common, occurring in more than half of the population, and is considered a potent circadian rhythm disruptor [55].

The review study exploring the interrelations between social jet lag and multiple aspects of metabolic syndrome and T2DM revealed interesting evidence. Social jet lag was found to have a positive correlation with higher HbA1c, higher body mass index, bigger waist circumference, and higher probability of obesity [56]. Interestingly, its consequences are not limited to patients with T1D, where social jet lag negatively affects glycemic control, HbA1c levels, and insulin dosing [57,58]. Although the literature on social jet lag in adults with T2DM is still scarce, available data suggest that it has a negative influence on glycemic control. Research suggests that sleep disturbances and social jet lag are detrimental for people with T2DM, and lead to poor glycemic regulation [59–61]. For instance, Kelly et al. [60] found a strong correlation between social jet lag and increased HbA1c values in a group of 252 participants with T2DM. Nevertheless, it is crucial to recognize the limitations of the previous research, which include cross-sectional studies, small samples, and insufficient control for confounding variables, such as age, gender, education, employment status, and complications associated with diabetes [59–62]. Age, a potential source of confounding of the prevalence of social jet lag, has been associated with metabolic and glycemic variables. This underlines the importance of proper change in the analyses to address its effects [63]. Furthermore, social jet lag disrupts circadian rhythm, leading to disruption of the hypothalamic-pituitary-adrenal axis and promoting metabolic and glycemic shifts [56]. These associated factors form a complex interlinked system of sleep architecture changes, mood swings, impact on incretin hormones, and changes in the distribution of visceral fat [35,54]. Further, stress or job strain might explain the associations with blood pressure [64]. In addition to these factors, the timing of administration of the drugs also forms part of the considerations. Research has shown that medication for blood pressure has improved results when taken in the evening and regularly. This has practical significance for T2DM patients who take blood pressure medication daily [65]. Social jet lag and other variations in sleep timing may interfere with medication efficacy, which provides a strong line of inquiry. In future studies, further investigations of the exact effects of social jet lag on glycemic and metabolic control should focus on particular working populations with a higher level of exposure to social jet lag. Moreover, research with multiple time points, assessing social jet lag, provides information about the chronic effects on metabolic health. Understanding these complex relationships could open up the possibility for specific approaches that may help to prevent metabolic diseases.

Shared mechanisms and metabolic effects

Although these three disrupting factors arise at different times, they share important mechanisms of action that disrupt circadian alignment, and they also together increase risks to metabolic health, particularly in individuals with diabetes or at risk of diabetes. These mechanisms of action are:

Circadian misalignment

All three of these disruptors will mismatch the coordination between the peripheral (metabolic) clocks found in metabolic organs (liver, pancreas, and adipose) and the central clock (suprachiasmatic nucleus). This circadian misalignment will downregulate control of glucose metabolism, hormone release (e.g., glucagon, insulin), and insulin sensitivity [15,32, 42–45,55].

Melatonin suppression and light exposure

Exposure to light at night further reduces melatonin, which regulates glucose and has a protective role for pancreatic β-cells, as seen in case of shift and irregular sleepers. No matter if the source of melatonin suppression was a light exposure and/or misalignment of its circadian period, studies have shown that melatonin suppression has a greater potential of predisposing to oxidative stress and greater insulin resistance [41].

Hormones

Irregular sleep and disrupted timing of activities contribute to misaligned secretion of important metabolic hormones, including insulin, cortisol, leptin, ghrelin, and adiponectin [52]. Thus, these misalignments will disrupt the regulation of appetite and glucose metabolism.

Impaired β-cell function

Disruption of circadian clock function impairs rhythmicity and function of β-cells, and the β-cells are less able to respond postprandially (after eating) to glucose spikes. Chronodisruption can lead to β-cell fatigue or exhaustion, which is an important part of type 2 diabetes etiology.

Increased inflammatory and oxidative stress

Circadian misalignment or disruption has been associated with systemic inflammation and increased oxidative stress, both of which can contribute to insulin resistance and endothelial dysfunction [32].

Altered feeding and activity rhythms

Increased variability in meal timing and less physical activity during the biological inactive phase has been shown to enhance metabolic dysregulation, which adds to poor glycemic control [37,66].

In summary, these overlapping lifestyle related pathways collectively demonstrate circadian disruptors reducing glucose tolerance and insulin sensitivity, leading to further loss of metabolic homeostasis and contributing to onset and progression of diabetes (Table 1).

Treatment and management strategies for chronobiological disruptions

Chronobiological interventions for persons with diabetes focus on altering the external factors that disrupt the circadian rhythms, as well as procedures that ensure internal biological rhythms are in harmony with external rhythms. Here are some key strategies.

Light therapy

Light therapy entails the use of certain wavelengths of light in controlling CRs. Circadian rhythm disruption is a common problem for shift workers or people with irregular sleep schedules; the timed exposure to bright light at certain times of the day will help to regulate the clock and improve the quality of night’s sleep. In patients with diabetes, light therapy can decrease the disturbances of circadian rhythms and enhance metabolic outcomes [67].

Sleep hygiene education

It is suggested that people with diabetes must be encouraged to follow proper sleeping and wake-up timings as well as follow the basic regimen related to sleep for the enhancement in the quality as well as synchronization in the CRs. This includes the setting of a time for going to bed and time to wake up, the setting of a conducive sleeping environment and elimination of stimulants such as caffeine, and the use of artificial light such as electronic devices close to bedtime [68].

Meal timing

The results of the present study also show that the coordination of the timing of meals along the given CRs can improve metabolic status in diabetes patients. According to the latest research, it has been suggested that people should take their meals in the morning rather than late at night, as this will help to manage the glycemic index and insulin levels in the body. Meal timing has been shown to have a positive impact on glucose metabolism and CRs in diabetic clients, after a review of the meal timing [66].

Chronotherapy

Chronotherapy is a process of administering medications and other therapeutic procedures at a time when the body clock is sensitive to them. Diabetes patients should take insulin injections, oral hypoglycemic agents, and other therapies in relation to peak insulin sensitivity and glucose tolerance to enhance the treatment results and minimize side effects. According to Barandas et al. [69], chronotherapy is helpful in improving glycemic control and decreasing the complications in diabetes.

Physical activity

In regard to people with diabetes, CRs and metabolic health have been shown to be influenced by physical activity. Physical activity during the day ensures the sleep-wake cycle is maintained and also enhances the body’s sensitivity to insulin. Physical activity can therefore be prescribed as part of diabetes management to enhance circadian rhythm and quality of life [70].

Stress management

It also becomes apparent that these CRs can be disrupted by chronic stress and actually lead to further deterioration of metabolic derangements in diabetic individuals. Some stress management strategies include mindfulness meditation, relaxation techniques, and cognitive-behavioral stress reduction, which can reduce the amount of stress experienced and benefit circadian health. Practical stress control measures should also fit into diabetes care plans since they help enhance glycemic control besides the metabolic processes [71].

Pharmacological interventions

SDF in patients with diabetes can be severe and may necessitate pharmacological management. For instance, melatonin has been found to improve sleep-wake cycles and other aspects of circadian rhythm disorders such as shift work sleep disorder and jet lag. However, the use of one or another pharmacological drug can be promising for the treatment of circadian disorders in diabetes, including drugs that act on specific circadian pathways, for example, melatonin receptor agonists or clock gene modulators [72].

Such treatment and management strategies can help healthcare professionals in supporting patients with diabetes to achieve the best possible timing of circadian rhythms and metabolic health. In order to maintain long-term, sustainable, and effective management of circadian disruptions in diabetes a more individualized approach to the management strategies is required.

CONCLUSION

Circadian rhythm plays a crucial role in glucose metabolism, insulin sensitivity, and overall diabetes management. Disruptions to the body’s internal clock—such as those caused by shift work, irregular sleep patterns, or mistimed eating—can contribute to insulin resistance and poor glycemic control. Understanding the interplay between circadian biology and metabolic regulation offers valuable insights for optimizing diabetes treatment strategies. Aligning meal timing, medication administration, and lifestyle interventions with the body’s natural rhythms may enhance glycemic control and reduce diabetes-related complications. Future research should focus on personalized chronotherapy approaches to improve outcomes for individuals with diabetes.

NOTES

Conflicts of Interest

The authors have no potential conflicts of interest to disclose.

Availability of Data and Material

Data sharing not applicable to this article as no datasets were generated or analyzed during the study.

Author Contributions

Conceptualization: Saurabh Srivastava, Varun Chauhan. Data curation: Varun Chauhan, Deepak Sharma. Formal analysis: Varun Chauhan. Investigation: Saurabh Srivastava, Varun Chauhan. Methodology: all authors. Project administration: Saurabh Srivastava. Resources: all authors. Software: Varun Chauhan. Supervision: Saurabh Srivastava. Validation: Varun Chauhan. Visualization: all authors. Writing—original draft: Varun Chauhan, Deepak Sharma. Writing—review & editing: Saurabh Srivastava.

Funding Statement

None

Acknowledgments

We thank Multi-Disiplinary Research Unit (MRU) of ICMR-DHR for providing support in writing down the present review.

Figure 1

Flowchart depicting the overall points discussed in the review.

Figure 2

Diurnal variations in glucose tolerance and insulin sensitivity. Based on data from [24].

Figure 3

Causes of circadian rhythm disruption and their relationship with cardiometabolic risk factors.

Table 1

Impact of circadian misalignment on metabolic parameters, summarizing how lifestyle-related circadian disruptors affect metabolic health in the context of diabetes

Circadian disruptor	Affected metabolic parameter	Mechanism of disruption	Resulting impact
Shift work	Insulin Sensitivity, glucose tolerance, Î²-cell function	Melatonin suppression, meal timing misalignment, light exposure at night	Reduced insulin action, impaired glucose clearance, risk of T2DM
Irregular sleep patterns	Insulin resistance, glycaemic control, hormonal balance	Sleep fragmentation, altered hormone secretion (cortisol, insulin)	Increased insulin resistance, poor glycaemic control, metabolic dysfunction
Social jet lag	HbA1c levels, body mass index, Î²-cell rhythmicity	Desynchronization of sleep-wake cycles, weekend-weekday variability	Higher HbA1c, increased adiposity, impaired glycemic regulation

T2DM, type 2 diabetes mellitus.

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