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. 2025 Apr 22;110(5):e1351-e1357.
doi: 10.1210/clinem/dgae580.

Circadian Alignment, Cardiometabolic Disease, and Sex-Specific Differences in Adults With Overweight/Obesity

Affiliations

Circadian Alignment, Cardiometabolic Disease, and Sex-Specific Differences in Adults With Overweight/Obesity

Brooke M Shafer et al. J Clin Endocrinol Metab. .

Abstract

Context: Circadian disruption promotes weight gain and poor health. The extent to which sex plays a role in the relationship between the circadian timing of behaviors and health outcomes in individuals with overweight/obesity is unclear.

Objective: We investigated the sex-specific associations between circadian alignment and cardiometabolic health markers in females and males with overweight/obesity.

Methods: Thirty volunteers with overweight/obesity (15 female; body mass index ≥25.1 kg/m2) underwent an evening in-laboratory assessment for dim-light melatonin onset (DLMO), body composition via dual energy x-ray absorptiometry, and a fasted blood sample. Circadian alignment was determined as the time difference between DLMO and average sleep onset over 7 days (phase angle), with participants categorized into narrow/wide phase angle groups based on median phase angle split. Due to known differences in metabolic markers between sexes, participants were subdivided based on sex into narrow and wide phase angle groups.

Results: Males in the narrow phase angle group had higher android/gynoid body fat distribution, triglycerides, and metabolic syndrome risk scores, while females had higher overall body fat percentage, glucose, and resting heart rates (all P < .04). Furthermore, a narrower phase angle in males was negatively associated with android/gynoid body fat (r = -0.53, P = .04) and negatively associated with body fat (r = -0.62, P = .01) and heart rate (r = -0.73, P < .01) in females.

Conclusion: Circadian disruption may not only promote a trajectory of weight gain but could also contribute to negative health consequences in a sex-dependent manner in those already with overweight/obesity. These data may have implications for clinical utility in sex-specific sleep and circadian interventions for adults with overweight/obesity.

Keywords: cardiometabolic health; circadian disruption; circadian misalignment; obesity; sex differences.

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Figures

Figure 1.
Figure 1.
Cardiometabolic health metrics in females and males with narrow and wide phase angles. Box and whisker plots for BMI (A), body fat percentage (B), android/gynoid percentage (C), glucose (D), triglycerides (E), and metabolic syndrome risk score (F) in females and males with narrow vs wide phase angles, where the median (dark grey line), the first and the third quartile (lower and upper limits of the boxplots, respectively), and the minimum and the maximum value no more than 1.5× the interquartile range (lower and upper limits of the whiskers, respectively) are plotted. Data beyond the end of the whiskers are outlying points. n = 30 (15 F). Values are presented as mean ± SD. *Statistically significant difference between groups (P < .05) from independent t-test comparisons. Abbreviation: BMI, body mass index.
Figure 2.
Figure 2.
Correlation matrices of sleep, circadian, and cardiometabolic health markers in males and females with overweight/obesity. The correlation matrix displays Pearson correlation results between each labeled variable at the end of the row/column. *Denotes correlations reaching statistical significance (dark gray boxes) (P < .05). Indicates nonsignificant trending correlations (light gray boxes) (P < .1).
Figure 3.
Figure 3.
Associations between sleep, circadian, and cardiometabolic health markers in males and females with overweight/obesity. The solid lines represent the Pearson correlation regression lines and the shaded region represents 95% confidence intervals.

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