Actigraphy-based sleep behavior and rest-activity circadian rhythm in metabolic syndrome

The rest-activity circadian rhythm (RAR) is a key marker of the circadian timing system and has been increasingly recognized as an important factor in metabolic and cardiovascular regulation. Alterations in RAR, as well as impaired sleep and reduced daily activity levels, have been associated with an increased risk of metabolic syndrome (MS), a condition characterized by a cluster of cardiometabolic risk factors. In this context, the objective assessment of RAR through actigraphy and the identification of targeted therapeutic strategies are essential to improve the clinical management of MS. In the first study, a cross-sectional analysis, investigated RAR characteristics in individuals with MS (n= 97) using both parametric and non-parametric approaches, with a particular focus on sex differences and their association with MS parameters. Actigraphic data revealed significant differences between males and females. Female participants exhibited significantly higher values of MESOR (243.3 ± 20.0 vs 197.6 ± 17.9 activity counts, p= 0.001), amplitude (184.5 ± 18.5 vs 144.2 ±17.2 activity counts, p= 0.002), and the most active 10-hour period (M10: 379.08 ± 16.43 vs 295.13 ± 12.88 activity counts, p= 0.001), all indicating a higher overall level of daily activity. Additionally, women showed significantly lower intradaily variability (IV: 0.75 ± 0.03 vs 0.85 ± 0.03 activity counts, p= 0.026), suggesting a more stable and less fragmented circadian rhythm compared to men. These findings provide preliminary experimental evidence of sex-related differences in RAR parameters among individuals with MS (1). In the second study, a randomized placebo-controlled trial, evaluated the effects of metformin (1.700 mg/day) on sleep and daily activity in individuals with MS (n= 133), assessed through 7-day actigraphic monitoring at baseline and after one year of intervention. A total of 105 participants were included in the final analysis. The metformin group showed significant improvements in anthropometric and metabolic parameters compared with placebo, including reductions in body weight (p= 0.01), body mass index (p= 0.01), waist circumference (p= 0.03), and glucose levels (p< 0.001). Regarding sleep outcomes, metformin treatment was associated with a significant increase in actual sleep time (p= 0.01) and sleep efficiency (p= 0.04). However, no significant changes were observed in RAR parameters (2). Overall, these findings highlight the central role of circadian rhythm and sleep in the pathophysiology of metabolic syndrome. The observed sex differences in RAR suggest the importance of personalized approaches to daily activity and circadian regulation while the beneficial effects of metformin on sleep indicate its potential as an adjuvant therapeutic strategy. Further research is needed to better understand the interactions between pharmacological interventions, circadian rhythms, and metabolic regulation. References 1. Mulè A, Bruno E, Pasanisi P, Galasso L, Castelli L, Caumo A, Esposito F, Roveda E and Montaruli A (2021). Sex Differences in Rest-Activity Circadian Rhythm in Patients With Metabolic Syndrome. Front. Physiol. 12:641461. doi: 10.3389/fphys.2021.641461 2. Bruno E, Mulè A, Galasso L, Castelli L, Baldassari I, Oliverio A, Venturelli E, Berrino F, Montaruli A, Roveda E and Pasanisi P (2023). Sleep behavior and daily activity levels in people with metabolic syndrome: effect of 1 year of metformin treatment. Front. Nutr. 10:1240762. doi: 10.3389/fnut.2023.1240762