The dawn phenomenon (DP), initially described in 1981 by Schmidt et al. [1], refers to elevated fasting blood glucose levels or spontaneous increases in early-morning insulin requirements. This condition is now recognized as highly prevalent among diabetic populations [2]. Using continuous glucose monitoring (CGM), DP can be assessed by measuring the difference between the nocturnal nadir and fasting glucose levels [2]. The impact of DP is approximately a 0.4% increase in glycated hemoglobin A1c (HbA1c) and a 12.4 mg/dL rise in average 24-hour mean glucose concentrations [3]. Although direct evidence is limited, DP appears to contribute to elevated blood glucose levels that extend into both preprandial and postprandial phases [4, 5]. Previous studies have shown that the highest peak glucose values in people with diabetes occur during the post-breakfast period [3, 6, 7]. In addition, post-breakfast hyperglycemia is a consistent finding in individuals with type 2 diabetes mellitus, regardless of HbA1c level, therapeutic interventions, or $\beta$-cell function status [6]. For these reasons, the post-breakfast glucose excursion in individuals with diabetes is regarded as a continuation of DP, also known as the “extended dawn phenomenon” [3, 5].

Compared to DP, the “extended dawn phenomenon” may play a more critical role in postprandial glucose regulation due to its prolonged hyperglycemic effects. However, research on the “extended dawn phenomenon” remains scarce, and its underlying mechanisms are poorly characterized. Notably, there is currently limited evidence directly linking DP and post-breakfast hyperglycemia. Addressing this gap, our study hypothesizes that DP is independently associated with post-breakfast hyperglycemia and aims to investigate its potential as a target for glycemic control.

Our findings supported the existence of the “extended dawn phenomenon”. First, even when fasting glucose was matched, participants with DP had higher peak post-breakfast glucose and greater $\delta$Exdawn levels compared to those without DP. Second, glucose increments attributed to DP persisted into the postprandial period (median $\mathrm{\Delta }$ = 0.7 mmol/L). Third, logistic regression analysis identified $\delta$Dawn as an independent predictor associated with increased post-breakfast glucose. These results indicate that the impact of DP on blood glucose extends beyond fasting and also affects post-breakfast glucose levels.

Emerging evidence suggests that the mechanisms underlying DP in diabetes are multifactorial, including: (1) progressive $\beta$-cell dysfunction [4]; (2) growth hormone-mediated insulin resistance [13]; (3) circadian-driven elevations in insulin-like growth factor binding protein-1 during early morning hours [14]; (4) dyssynchrony of Gamma-Aminobutyric Acid-ergic (GABAergic) neuronal nuclear receptor subfamily 1 group D member 1 (REV-ERB$\alpha$) oscillations, a core circadian regulator [15, 16]; and (5) sleep architecture disturbances compounded by circadian rhythm dysregulation [7]. The mechanism of the extended dawn phenomenon may be similar to DP. In our study, both HOMA-IR and HOMA-$\beta$ were significantly and independently correlated with increased post-breakfast glucose, which indicates that increased insulin resistance and the decreased $\beta$-cell function contribute substantially to post-breakfast hyperglycemia. Additionally, a previous study suggested that the administration of growth hormone in the early evening can reduce insulin sensitivity 16 hours later [13], implicating growth hormone in the rise of post-breakfast glucose.

Monnier et al. [3], quantified the contribution of DP to chronic hyperglycemia, reporting a 0.4% increase in HbA1c and a 12.4 mg/dL increase in 24-hour mean glucose. Our data corroborate this metabolic burden, showing higher HbA1c (6.6% vs 6.4%) and 24-hour mean glucose (7.4 vs 7.0 mmol/L) in the DP compared to the non-DP group (Table 1). CGM revealed a dual circadian effect: DP participants exhibited 1.1 mmol/L higher post-breakfast hyperglycemia (10.0 vs 8.9 mmol/L) and a 5.9% absolute reduction in TIR (94.1% vs 100.0%), equivalent to 89 fewer daily minutes within the target range (3.9–10.0 mmol/L). This aligns with Monnier’s hypothesis that morning glucose surges may persist beyond fasting phases; our use of CGM provides higher temporal resolution, directly linking nocturnal glucose increments to postprandial peaks. Notably, while Monnier’s cohort focused on HbA1c-driven glucose exposure, our data delineate a metabolic gradient: DP participants demonstrated 16.7% higher insulin resistance (HOMA-IR 3.5 vs 3.0) and 23.8% worse $\beta$-cell function (HOMA-$\beta$ 59.2 vs 77.7) compared to non-DP controls (Table 1). This dyad drives a cycle in which elevated nocturnal glucose increments ($\delta$Dawn 1.8 vs 0.5 mmol/L) impair morning insulin sensitivity, resulting in a 1.591-fold increased risk of post-breakfast hyperglycemia per 1 mmol/L rise in $\delta$Dawn (OR = 1.591, 95% CI: 1.283–1.993; Table 3). In fasting glucose-matched cohorts (Table 2), DP participants maintained significantly higher postprandial peaks (peak post-breakfast: 9.7 vs 8.9 mmol/L; peak post-lunch: 8.9 vs 8.2 mmol/L) despite comparable HbA1c (6.4% vs 6.4%). This dissociation suggests that dawn phenomenon-induced hyperglycemia operates through meal-responsive pathways rather than through chronic exposure. The difference in TIR was decreased and not statistically significant in this matched cohort (93.1% vs 89.6%), suggesting that normalization of fasting glucose may partially mask the circadian rhythm-driven worsening of TIR. Nevertheless, DP participants exhibited significantly lower TIR compared to non-DP controls (median 94.1% vs 100.0%), with $\delta$Dawn levels 1.3 mmol/L higher in the DP group (1.8 vs 0.5 mmol/L; Table 1). These findings indicate a potential dose-response relationship between nocturnal glucose increments and TIR deterioration. The observed 1.591-fold increased risk of post-breakfast hyperglycemia per 1 mmol/L $\delta$Dawn rise may mechanistically contribute to TIR deterioration, as elevated postprandial glucose directly reduces TIR. Elevated postprandial blood glucose (PPG) is strongly associated with the development and progression of diabetic complications. Extensive evidence demonstrated that poor PPG control constitutes a critical risk factor for both microvascular and macrovascular complications in diabetes [17, 18], including diabetic retinopathy, nephropathy, neuropathy, and cardiovascular disease. Similarly, suboptimal TIR control has been extensively documented as a significant contributor to these complications in clinical studies [19, 20, 21, 22, 23, 24]. These findings highlight the importance of stringent management of both PPG and TIR, particularly in addressing clinical challenges linked to DP.

Notably, our stratified analysis revealed sex-specific differences in glycemic regulation pathways. As demonstrated in Table 3, female participants exhibited a stronger correlation between HbA1c elevation and post-breakfast hyperglycemia (OR = 3.235 vs 1.825 in males), whereas male participants showed greater susceptibility to dawn phenomenon-mediated glucose increments ($\delta$Dawn OR = 1.681 vs 1.452 in females). This sexual dimorphism may be attributable to fundamental differences in endocrine physiology. Estrogen has been shown to enhance insulin sensitivity by modulating hepatic gluconeogenesis and peripheral glucose uptake [25]. Specifically, activation of the Estrogen Receptor alpha-Protein Kinase B-Forkhead box protein O1 (ER$\alpha$-Akt-Foxo1) signaling pathway is a key mechanism by which estrogen controls glucose homeostasis [26], potentially mitigating the impact of nocturnal glucose surges in premenopausal women. Conversely, the fat mass and obesity-associated gene (FTO) rs9939609 T/A polymorphism appears to interact synergistically with lifestyle factors, particularly high saturated fat consumption, to promote visceral adipose tissue (VAT) accumulation in adult males, as demonstrated in longitudinal cohort analyses [27]. Increased VAT exacerbates insulin resistance through multiple interrelated mechanisms, aggravating circadian dysregulation of hepatic gluconeogenesis and skeletal muscle glucose uptake. This metabolic derangement ultimately impairs glycemic stability in insulin-resistant individuals, increasing susceptibility to dawn phenomenon-associated postprandial glycemic excursions and reducing TIR. The observed sex disparity in baseline characteristics (Table 1) provides additional context, with the DP group displaying a higher proportion of males (62.2% vs 48.6% in the non-DP group). Emerging evidence also suggests that testosterone may augment growth hormone pulsatility [28], potentially mediating DP pathophysiology through this mechanism.

Postprandial hyperglycemia is a hallmark of diabetes in China, with nationwide data indicating that 46.6% of newly diagnosed T2DM patients exhibit isolated postprandial hyperglycemia (50.2% in females vs 44.1% in males) [29]. In our cohort of well-controlled patients (HbA1c 7.5%), post-breakfast glucose $>$10 mmol/L persisted in 37.4%, consistent with previous reports that post-meal variability constitutes the major component of glycemic burden despite controlled fasting levels [30]. DP has emerged as a promising therapeutic target for optimizing glycemic control, given the suboptimal efficacy demonstrated by current therapeutic modalities—including lifestyle interventions (e.g., caloric restriction therapy), conventional pharmacological agents (e.g., insulin sensitizers and secretagogues), and even intensive insulin regimens—across diverse treatment algorithms [3, 4, 31, 32, 33]. While basal insulin and pre-breakfast exercise may mitigate the effects of DP [5, 34, 35], their efficacy requires further validation. Our sex-stratified analyses revealed distinct patterns of glycemic regulation: females exhibited stronger associations between HbA1c and postprandial hyperglycemia (OR = 3.235 vs 1.825 in males), whereas males were more susceptible to dawn phenomenon-driven excursions ($\delta$Dawn OR = 1.681 vs 1.452 in females). These differences likely reflect underlying hormonal and body composition profiles (e.g., estrogen-mediated enhancement of insulin sensitivity in females vs androgen-driven visceral adiposity in males). Clinically, these findings suggest that prioritizing HbA1c control (6.5%) in females and implementing dawn phenomenon-targeted interventions (e.g., bedtime insulin or exercise) in males may optimize glycemic outcomes. While these findings highlight DP as a potential therapeutic target, the observational design of our study precludes causal inference. Future research should investigate the role of hormonal modulation (e.g., menopausal status, testosterone levels) in glycemic regulation and conduct interventional trials to determine whether mitigating nocturnal glucose surges can improve TIR and postprandial glycemic control.

This cross-sectional study demonstrates that DP significantly exacerbates post-breakfast hyperglycemia in individuals with type 2 diabetes mellitus, independent of fasting glucose levels. Key metabolic determinants (e.g., HbA1c, insulin resistance, $\beta$-cell dysfunction, $\delta$Dawn)—independently predicted heightened postprandial glycemic excursions. Notably, sex differences were observed: females exhibited a higher risk associated with elevated HbA1c, while males were more susceptible to $\delta$Dawn, suggesting divergent therapeutic priorities. Circadian dysregulation underlying the DP prolongs postprandial hyperglycemia and reduces TIR, underscoring the clinical relevance of targeting nocturnal glucose increments to optimize glycemic control.

$\bullet$ The dawn phenomenon (DP) significantly exacerbates post-breakfast hyperglycemia in type 2 diabetes mellitus, with affected patients exhibiting 1.1 mmol/L higher glucose peaks and a 5.9% reduction in TIR, independent of fasting glucose levels.

$\bullet$ The magnitude of DP ($\delta$Dawn; OR = 1.591 per 1 mmol/L), HbA1c, insulin resistance and $\beta$-cell dysfunction independently predict postprandial hyperglycemia, highlighting the synergistic roles of nocturnal glucose surges, insulin resistance, and $\beta$-cell failure.

$\bullet$ Females demonstrate a stronger association between HbA1c and postprandial hyperglycemia risk (OR = 3.235 vs 1.825 in males), whereas males exhibit greater susceptibility to DP-driven excursions ($\delta$Dawn OR = 1.681 vs 1.452 in females), supporting sex-tailored therapeutic approaches.

$\bullet$ Targeting DP with interventions such as bedtime insulin or exercise may optimize glycemic control by reducing postprandial hyperglycemia and improving TIR, thereby lowering the risk of diabetic complications.

$\bullet$ Longitudinal and interventional studies are needed to confirm a causal association between nocturnal glucose suppression and improved TIR, as well as to explore the role of hormonal modulation (e.g., estrogen/testosterone) for precision diabetes management.

All data included in this study are available from the corresponding authors upon reasonable request.

WT and YH designed the study. WT and JZ acquired the data. WT, CJ and XT interpreted the data. WT drafted the manuscript. All authors contributed to the critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

The investigation protocol received ethical approval from the Ethics Committee of Huadong Hospital, Fudan University (approval number: 2020K033). The study followed the ethical guidelines outlined in the Declaration of Helsinki and the principles of confidentiality. All participants provided written informed consent following comprehensive disclosure of the study protocol.

Not applicable.

This work was supported by Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0507203) and Emerging Talent Program of Huadong Hospital, Fudan University (XXRC2217).

The authors declare no conflict of interest.

Supplementary material associated with this article can be found, in the online version, at https://doi.org/10.31083/BJHM51727.