SLEEP QUALITY AND REST-ACTIVITY CIRCADIAN RHYTHM IN PEOPLE WITH METABOLIC SYNDROME

Background. Alterations in sleep and Rest-Activity circadian Rhythm (RAR) increase the risk of developing many pathological conditions, including Metabolic Syndrome (MS). Moreover, people with MS have been shown to sleep poorly and exhibit impaired RAR. Recently, metformin, an insulin sensitizer drug widely used in various cardiometabolic diseases, was introduced as adjuvant agent for the management of sleep disorders. It is shown to have an opposite effect to sleep disorders on the same parameters. The aim of my PhD project was to assess whether changes in daily habits are able to modify sleep, daily activity levels, sedentary habits and MS parameters in healthy people with MS, and also to investigate whether metformin treatment can modify sleep and MS parameters. Methods. 133 subjects with MS were enrolled in the study. At baseline and after one year of intervention, all participants underwent a medical examination to evaluate anthropometric and MS parameters. Also, they carried out a continuous 7-day actigraphic monitoring to investigate the RAR and sleep. Participants received double randomization, based on drug (metformin or placebo) and dietary approach (cooking courses or general awareness). Randomization based on drug treatment, adjusted for dietary approach, age, gender and baseline values, was considered for the data analysis. Results. At baseline, most subjects showed poor sleep quality and quantity. The comparison between the two sexes showed no differences in sleep parameters, and no difference was present between people with different severity of MS. Regarding RAR, influences related to sex have been found. Females showed higher daily movement and a less fragmented RAR compared to males. After one year of intervention, an improvement of MS in 45.7% of the participants was found. In 37.5% of them it was no longer possible to diagnose the MS. Metformin and placebo groups showed an improvement of their syndrome condition, with higher effects in metformin-treated subjects. A statistically significant increase in actual sleep time was found in metformin group at follow-up compared to baseline. Moreover, metformin-treated subjects showed an improvement of actual sleep time and sleep efficiency, while people treated with placebo displayed no change in actual sleep time, and a worsening in sleep efficiency. Although not significant, metformin group also showed a good trend of improvement in almost all other sleep parameters, while opposite trends were found in people treated with placebo. Regarding the RAR, the intervention showed no effects. This result was rather predictable, as a change in daily activity levels is required to modify the RAR, for example by encouraging strategies to increase daily activity and decrease sedentary behaviors. Conclusions. The results of this PhD research project support the hypothesis that metformin may be a new valid approach, together with a healthy eating style, for the secondary prevention not only of the metabolic syndrome condition but also of any related sleep disorders.