Chronotype, Sleep Disturbances & Obesity

The panel discussed the use of a questionnaire to assess chronotype, named “MORNINGNESS-EVENINGNESS QUESTIONNAIRE: Self-Assessment Version (MEQ-SA)”. Please download this to use in your own COMs activities: MEQ-SA-2019

Transcripts are auto generated, if you spot an error, please email enquiries@easo.org

So, hi everyone, welcome to the latest edition of the ASO Comms Network webinar series. So my name is Lisa and I would just like to welcome you on behalf of ASO to today's session which focuses on chronotype sleep disturbances and obesity. So just a quick note, remember that today's webinar is being recorded and the recording and any relevant links are going to be shared after the event.

I'll take the time now to say that your feedback and comments are really, really valued. So I'll be dropping an evaluation survey link into the chat. So if you do have comments or suggestions for future improvements, please do let us know.

So I am just going to mention that the ASO Comms webinars are held monthly, but our chairs will let you know a little bit more information about that. And please, please do share some of the information on the comms when you see it with your colleagues. The comms are free and open to your team in the comms and we just hope that we can share this information with as many participants as possible.

So before we kick off, I just want to briefly let you know the house rules of today's webinar. So this is an informal setting. You can ask questions by raising your virtual hand and using the microphone when the question and answer session starts in the final 15 minutes of the webinar.

Or you can post the questions in the chat throughout the presentations and they will be asked by one of the chairs in the Q&A sessions. So please do follow us on Twitter. I will give you the handle to follow and the hashtag ASO Comms if you are talking about it online.

And that is all for me for now. I'm going to leave most of the talking to the chairs and the speakers. But I am going to start the webinar with a quick pre-recorded message from Professor Anna Maria Collau, who is the head of endocrinology at the University of Naples Federico, where most of the research that we're going to be hearing about today is based.

I'm then going to hand you over to our chairs and chair in the session today is Professor Luca Becetto, who is the co-chair of the ASO obesity and management task force and Dr Giovanna Muscurie, who leads the research into chronotype sleep disturbances and cardiometabolic diseases, which we're going to hear about today. So thanks very much for joining. I hope you enjoy today's webinar and that's it for me.

I will quickly play the welcome message. Welcome to this webinar dedicated to chronotype sleep disturbances and obesity. It's a pleasure for me to introduce this webinar and to present to you the research group in my unit at the Federico II University of Naples in Italy.

Giovanna Muscurie is the leader researcher for this project and there is more than five years that we are just discussing the role of the phenotype in terms of chronology and circadian rhythm in obesity, metabolic disorders and the role of sleep disturbances in determining metabolic diseases. So it's a pleasure for me that the part important of this group will show you some of the background and the research that we have done in these five years. I'm sure that you will enjoy this webinar.

Thanks everyone and I'll hand over to Luca now. Hi, good morning to everybody. I am Luca Busetto, the co-chairman of the European Association for the Study of Obesity Task Force dedicated to obesity management in adults.

Today I will chair this meeting with Giovanna Muscurie. Giovanna is a very good friend of mine. She is a very young and promising researcher in Italy.

Giovanna has been recently awarded by several important awards, one for the Nutrition Society, the Kuhn-Berson Award, a very important one. And in May 2021, she was awarded by the IESO New Investigator Award for Clinical Research. And the award was given to Giovanna mostly for the initial part of their work on chronotype and chrononutrition and the aspect that we learned today from her group.

So I prefer not to use much more time for this introduction and I will pass the chair to Giovanna for introducing the webinar and presenting the young speakers that we have today. Thank you, Luca. Today I'm very delighted to open the door of my research team to IESO and to share with you our findings.

A few years ago we started to investigate a new research topic, which is the role of circadian rhythm and sleep in the pathogenesis and management of obesity and obesity-related complications. Each member of the team has produced a brick that has contributed to the construction of this new line of research and is happy to present its results. I will be delighted to reply to all your questions at the end of the webinar.

So let's start with the first speaker, that is Ludovita Verde. Ludovita graduated in human nutrition at the University Federico II of Naples in 2021. She's currently attending a PhD in public health at the University of Naples, focusing her research on defects and management of circadian rhythm misalignments in obesity.

She's a nutritionist at the Cibo.com center and a nutritional approachist focused on the Mediterranean diet and very low-caloric ketogenic diet. She authored or co-authored 35 peer-reviewed publications to date. She's an IASO national clinical fellow and an active member of the Italian Society of Obesity Clinics.

So the title of her speech is Chronotype, Body Composition and Nutritional Habits. So Ludovica, the floor is yours. Good morning, everyone.

Can you see the presentation? Can you hear me? Yes. Good morning to everybody. I want to thank you for the introduction.

My name is Ludovica Verde and today I'm going to give you a brief overview of the complicated relationship between chronotype, body composition and nutrition. To begin with, what is chronotype? Chronotype is the behavioral expression of biological rhythms related to the external life cycle. There are three main categories of chronotype, morning, evening and intermediate.

People with a morning chronotype tend to wake up early and prefer activities early in the day, while those with an evening chronotype generally wake up later and prefer activities in the late afternoon or evening. There is also an intermediate chronotype with mixed characteristics between the previous two. Obesity, as we all know, is an unresting, growing issue.

The numerous efforts to counteract it are not having the desired effect, suggesting that there are probably still unused factors of this chronic condition. Therefore, our question is, does the chronotype play any role in obesity? Recent studies show that obesity and eating habits seem to be influenced by chronotype. In fact, individuals with evening chronotype are more likely to suffer from overweight or obesity and have unhealthy eating habits.

For example, in this systematic review, it is shown that individuals with evening chronotype, compared to those with other chronotypes, have higher BMI and worse body composition, in particular higher waist circumference and fat mass. On the other hand, from a nutritional point of view, subjects with evening chronotype are more likely to have unhealthy eating habits, such as eating late at night, often skipping breakfast and consuming processed foods, while morning types are more likely to have healthy and protective habits, such as eating early and consuming mostly minimally processed fresh food. Thus, our research group aimed to investigate the association between chronotype categories and adherence to the, that we can say, the best diet, the Mediterranean diet, in a population of middle-aged Italian adults.

They found that individuals with evening chronotype showed the lowest adherence to the Mediterranean diet, compared to morning and intermediate chronotypes. In addition, positive correlations of the chronotype score with age and adherence to the Mediterranean diet score were found. And of note, it was found that the overall set of all foods in the Mediterranean diet, rather than the intake of an individual food, predicted the chronotype categories.

Building on this finding, our research team went further and wanted to suggest a specific cut-off of the adherence of the Mediterranean diet score, which could identify subjects with an evening chronotype. Based on our analysis, a score higher than 8 could serve as a tissue to identify subjects with a morning chronotype. Thus, this score could help identify subjects at high risk of evening chronotype, who are likely to require specific nutritional strategies to reduce obesity and desynchronise circadian rhythms.

The chronotype assessment can also be an effective tool to explore the dietary and lifestyle habits of women with PPOS. As you can see from this study, women with PCOS and evening chronotype had lower adherence to the Mediterranean diet, and consumed more calories, total and simple carbohydrates, total fat and saturated fat, and less fibre than those with other chronotypes. With this other study, we wanted to investigate the relationship between vitamin D levels and chronotype in subjects with obesity.

As we expected, we found that the prevalence of vitamin D deficiency was higher in subjects with evening chronotype than those with morning chronotype. However, regression analysis showed that BMI was strongly associated with vitamin D levels, followed by chronotype score, thus indicating that vitamin D levels and chronotype are both independently related to obesity. And then, since subjects with evening chronotype are more likely to have healthy eating habits, while subjects with morning chronotypes are more likely to have healthy and protective habits, we sought to further characterise the nutritional habits of subjects with overweight or obesity, belonging to the different chronotype categories.

We then investigated eating speed, a well-known risk factor for obesity and its complications, we found that subjects with morning chronotype take longer at lunch than subjects with evening chronotype, and more time at dinner than subjects with intermediate chronotype. Furthermore, the chronotype score correlated positively with the minutes spent at lunch and dinner, namely, as the score increases, indicating a trend towards a morning chronotype, the time spent at meals increases. And this increases the speed at meals of the evening chronotype, in addition to better characterising the eating habits of this chronotype category, could have identified increased risk of also developing obesity-related cardiometabolic disease.

Finally, we recently investigated whether different chronotype could also impact the efficacy of the very low-calorie ketogenic diet, a promising nutritional approach for obesity. The outcomes were weight loss changes in body composition. Our study found that women with evening chronotype experienced less weight loss improvements in body composition than women with morning chronotype.

In addition, a lower score indicating evening preference was related to less variation in the outcome considered. And furthermore, using a linear regression model, we found that chronotype score was the main predictor of weight loss after a very low-calorie ketogenic diet. In light of all these findings, our research team had developed this practical nutritional recommendation to help resynchronise circadian rhythms as a tool for weight control.

And these, you can see, are the points on which that nutritional approach is based, like do not skip breakfast, balanced meals composed of carbohydrates, fibre, proteins and the right amount of fat, to take an adequate protein intake, eat a good reach of tryptophan as meat, poultry, fish and meat to regulate sleep, and melatonin in particular fruits, nuts, seeds or cereal and other foods, to limit fat consumption, preventing a special kind of fat like omega 3, and avoid coffee, alcohol and high food intake, especially in the last part of the day. I really thank you for the attention and I'm open to any kind of question. So, thank you, thank you Ludovica.

And the next speaker is Anna Maria Docimo. Anna Maria Docimo graduated cum laude in medicine from the Università della Campania Luigi Vambitelli in 2020. She works at the SIBO or COM Centre as an endocrinology resident, taking care of subjects with obesity and obesity metabolic disease.

Her research topic is focused on the role of circadian disruption in obesity related metabolic disorders and obesity related cancer. So, the title of the speech of Anna Maria is Chronotype and Obesity Related Cardiometabolic Complications. So, Anna Maria, the floor is yours.

Thank you very much. So, can you see the presentation? Yes. Okay.

So, good morning, everybody. I am Anna Maria Docimo and today, as you can see, we're going to talk about the relation between chronotype and obesity related cardiometabolic complications. This is the first article that I would like to talk about.

Ludovica has already spoke about that, but I would like to focus on other aspects and results of this study. This is a cross-sectional study that was based on a project held in Naples in 2019, called the Opera Prevention Project. And we wanted to evaluate if there was an association between the chronotype categories and the presence of type 2 diabetes and cardiovascular disease.

When I speak about cardiovascular diseases, I mean basically myocardial infarction, stroke, and hypertension. The assessed parameters were anthropometric parameters, lifestyle habits, and adherence to the Mediterranean diet, sleep quality, chronotype, and of course, the presence of type 2 diabetes and cardiovascular disease. So, now let's see which were the statistically significant results.

Okay. So, as we have seen, even in chronotype, compared to the morning and the intermediate chronotype, showed an unhealthier lifestyle on average, expressed in terms of higher prevalence in smoking and sedentariness, and they showed a lower predomain score, meaning a lower adherence to the Mediterranean diet. So, after an adjustment for gender, BMI, sleep quality, and adherence to the Mediterranean diet, we have seen that even in chronotype subjects, at a higher risk of developing type 2 diabetes and cardiovascular diseases when compared to the morning chronotype subjects.

Here in this article, we wanted to investigate the prevalence of chronotype categories and how they determine hormonal and metabolic aspects of the polycystic ovary syndrome. We have analyzed anthropometric parameters and we have assessed the Ferrum and Galway score, and glycemic, inflammatory, and hormonal parameters. Okay.

So, as you have seen in the previous slide, it resulted that women with PCOS tend to have more prevalence of even in chronotype when compared to a controlled group of women. Then, in particular, women with even in chronotype had statistically significant higher levels of CRP, testosterone, and Ferrum and Galway score. Then, a lower chronotype, meaning a more even in chronotype, is mostly associated to higher testosterone levels and PCR and Ferrum and Galway, but after we made a regression and we have assessed that lower chronotype score is mostly associated with the testosterone levels, and then by BMI and higher OMI index, meaning higher insulin resistance.

In this first section of the study, the aim was to investigate the prevalence of chronotype categories in postmenopausal women affected by obesity and to see how they play a role in menopause-related cardiometabolic risk. We have enrolled pre- and postmenopausal women and we have assessed their anthropometric parameters, lifestyle habits, meaning dietary and sleep habits, and the presence of type 2 and cardiovascular disease. So, here, as you can see, we have demonstrated that even in chronotype had a significantly higher risk of developing type 2 diabetes, both in pre- and postmenopausal women.

In this study, we have enrolled patients affected by type 2 diabetes because we wanted to investigate if chronotype had some influence on glycemic control expressed in terms of fasting blood glucose and glycosylated hemoglobin, anti-diabetic treatment, and risk of diabetic complications. The data were collected thanks to the diabetologists who filled out an online questionnaire with the patient's clinical and biochemical parameters. Interestingly, we found an inverse correlation between chronotype score, glycosylated hemoglobin, and fasting blood glucose.

And this correlation remains significant also when correcting the analysis for BMI, age, and type 2 diabetes duration. And this means that subjects with a more imminent chronotype had the worst control of type 2 diabetes. Then, when we performed a linear regression, we have seen which were the most influencing variables on glycosylated hemoglobin and fasting blood glucose.

And it resulted that chronotype was the main factor influencing glycosylated hemoglobin, followed by BMI and age. And then, we have seen that chronotype was also the main factor influencing fasting blood glucose, followed by age. Here, we can see the prevalence of anti-diabetic treatment in the three chronotype categories.

There were no statistically significant differences except for the prevalence of treatment with the insulin. In fact, the three chronotype groups had different prevalence of treatment with both basal and rapid insulin. And then, both evening and intermediate chronotype had the higher prevalence in treatment with basal and rapid insulin compared to the morning chronotype.

So, concerning the cardiovascular disease, we have found that evening chronotype subjects had a higher prevalence of both arterial hypertension and coronary heart disease when compared to the morning chronotype. So, in conclusion, we can say that evening chronotype is associated with a higher prevalence of cardiovascular diseases and poor lysemic control. And this was independent on BMI and this inspiration in subjects affected by type 2 diabetes.

Now, let's move on to which are the physiopathological aspects that could explain the higher prevalence of cardiometabolic complications in evening chronotype subjects. First of all, it is known that on average, evening chronotype associates to an unhealthy lifestyle in terms of inactivity, smoking, poor dietary habits, and sleep disturbances. Then, as Ludovica said before, people affected by obesity have a higher prevalence of evening chronotype.

So, that's the reason that could explain the augmented risk of obesity-related cardiometabolic complications. And last but not least, we have an impairment of cortisol secretion, but we'll talk about that in a few moments. Now, we'll see more in detail the hormonal changes that happen in a person living with obesity.

We see an increase of many hormones, such as insulin, IGF-1, leptin, and ghrelin. So, we have an insulin resistance and we have that leptin is augmented to a state of leptin resistance, and this leads to an increased hunger. And then we have ghrelin, which increases the calorie intake, mostly from sweet foods.

Then we have an impairment of endocannabinoid system. In particular, we have 2-arachidonoyl glycerol, which is one of the most abundant ligands of endocannabinoid receptors. And in obesity, its rhythm is amplified and the peak is delayed and extended, increasing the hunger.

And finally, we have decreased levels of hormones like adiponectin, which normally increases the insulin sensibility, and it's an anti-inflammatory hormone. And then we have melatonin, which its reduction causes weight gain, chronic inflammation, and increased oxidative stress, and of course, sleep disturbances. Okay, so we know that cortisol is a circadian hormone because normally its levels are higher during waking time and lower at night.

But in evening chronotype subjects, there is a reduced peak upon waking time. There is also an augmented concentration, yes, an augmented concentration from later morning until lunchtime. So, this means that we have a delayed peak.

But it's not only that. In fact, we have, in general, the suppression is increased during the whole day. So, these are the effects of a condition of hypercortisolism.

And cortisol, it increases the visceral adipogenesis, and this worsens the state of insulin resistance. It is also true that visceral fat itself, it's associated to a higher production of cortisol. So, it's a vicious circle.

The cortisol then increases the glycemic levels, and so the insulin resistance, and it increases also overeating. So, we have almost arrived at the end of this presentation, and these are the take-home messages. So, let's see them together.

We have that evening chronotype is associated with a higher BMI and obesity in general, with impaired glucose and lipid homeostasis, higher blood pressure, inflammation, and a higher prevalence of cardiovascular disease. So, for this reason, a careful assessment of the chronotype could lead to a tailored treatment in subjects with cardiometabolical diseases, promoting an alignment of their daily activities according to their circadian rhythm. So, thank you very much for your attention, and I will be glad to answer to your question.

Thank you very much. So, thank you, Anna Maria. Now, the next speaker will be Claudia Vetrani.

Claudia Vetrani is currently a nutritionist at the Chibokon Center. She's also Associate Professor of Clinical Nutrition at the Telematico University, Pega, South Italy. Her research activity centers upon the role of circadian rhythm in the pathogenesis of obesity-related hepatic amputation.

She's a member of the Diabetes and Nutrition Study Group of the Italian Diabetes Society. She won the Young Researcher Award from the Italian Diabetes Society in 2020. So, Claudia, the floor is yours.

Thank you, Giovanna, for your presentation. And in this talk, I will show you the association between a chronotype and non-alcoholic fatty liver disease. So, let's start with a little background.

As you can see here, non-alcoholic fatty liver disease includes a spectrum of liver disorder. In particular, it's characterized by fat accumulation in the liver. And we have two main classes of disease.

And we have non-alcoholic fatty liver disease and non-alcoholic seattle hepatitis. The most important thing is that these disorders are very common in patients with obesity. And cross-sectional studies show a prevalence between 50 to 90 percent.

And of course, this prevalence increases with the obesity rate. And another important thing is that in AFLD, there is a progression to fibrosis, cirrhosis, and also hepatocellular carcinoma. Why we talk about AFLD and chronotype? Because we know that in obesity, there are several factors that can increase AFLD onset.

And as you know, AFLD can generate and induce several metabolic complications and also progress to type 2 diabetes, hypertension, and also cardiovascular diseases. And recent studies, particularly in animal models, show that also in liver there is a clock. And so also the liver function can be influenced by chronotype.

But we have very few studies in humans. And so we decided to perform a cross-sectional evaluation among our patients in the Saibot Center in Naples. So we screen all patients attending our center.

And both men and women aged more than 18 years with obesity. We collected demographic information, personal medical history, so the prevalence of diseases and also medication, lifestyle habits, like smoking, alcohol uses, and physical activity. Of course, we perform the questionnaire to detect the chronotype.

We collected the anthropometric measure, weight, height, waist, and hip circumference. And also, we calculated the BMI. And we perform a fasting-blown draw to collect the major biochemical parameters.

I don't want to go deep in the equation that we used to calculate these indices, but I want to show that these indices, so visceral adiposity index, that is cardiovascular, which has been associated with cardiovascular risk, like liver fat equation, hepatic steatosis index, and the index of NASH are very easy to calculate since in the equation, you have to put very easy parameters like with anthropometric measure, fasting parameters, gender. So it's very easy to calculate these indices. And here, you can see how our study flow.

We assessed 188 patients for eligibility in this study. And then we analyzed, according to our inclusion criteria, 87 patients. 27 were morning chronotype, 32 intermediate chronotype, and 28 evening chronotype.

And in this table, you can see the main parameters. And as you can see here, evening chronotype have a more higher BMI and waist circumference and high circumference, but no difference for obesity prevalence, the grade of obesity prevalence, as well as for the prevalence of other diseases like thyroid disease, type 2 diabetes, hypertension, dyslipidemia, and metabolic syndrome. And also for medication and the other parameters we have evaluated.

As for the indices we have calculated, you can see here that the visceral adiposity index was significantly higher in the evening chronotype than the morning chronotype that was the Howard control group. And if you can see the hepatic cytosis index and also the liver fat proportion, you can see that all patients with obesity independently from the chronotype has an increased liver fat because the cutoff value for the hepatic cytosis index is 36. And for the liver fat proportion is 5. So, as expected, in Howard population with patients with obesity have a high prevalence of liver fat accumulation.

And also, as expected, also the hepatic, all the indices were higher in the evening chronotype than in the morning chronotype. And also the index of NASH was higher in the evening chronotype than the morning, the other chronotype. And this will suggest a possible progression to a more dangerous stages of the NAFLD.

And because of the difference in the BMI we have observed between the group, we also perform a univariate analysis. And also after adjusting for the main confounders like age, gender, and body mass index, you can see that the difference between the chronotype was still significant. So, the accumulation of liver fat was independent on the body weight.

And we also think about the possible mechanism behind these results. And as my colleagues told you in their presentation, the evening chronotype is associated with an healthier lifestyle, like lower physical activity and also inadequate meal timing, worse healthy habits. So, this can favor the accumulation of liver fat in evening chronotype individuals.

Also, evening chronotype, as Giovanni will show you, may have more sleep disorders. And you know that sleep disorders are associated also with impaired hormone regulation and also inflammation. As Anna-Maria told you, also evening chronotype presents an arrangement of cortisol secretion and it can stimulate the visceral adipogenesis and also the hepatic triglyceride synthesis.

And a recent study has shown also that evening chronotype presents the light expression of genes that regulate the circadian clock. And so, very interestingly, these genes are being associated also with sleep disorder and NAPFLD. So, what we can conclude that evening chronotype is associated with a more severe NAPFLD independently of age, gender, and BMI in individuals with obesity.

And so, the assessment of chronotype should be considered as part of the management of NAPFLD in individuals with obesity. And here, to conclude, there is our publication in the International Journal of Obesity if you want to go to further details. Thank you.

Thank you, Claudia, for your brilliant presentation. And now, the next speaker is Giovanni Chirico. Giovanni Chirico received his degree in medicine in March 2021 from the University of Campania Luigi Vambidelli.

He works at the ChivoCom Center as an endocrinology resident taking care of people with obesity and obesity metabolic disease. He's currently carrying out studies on the involvement of the arrangements of sleep quality and the pathogenesis of obesity and obesity metabolic disease. And he's also investigating nutritional approaches that could play a role in improving the sleep quality in subjects with obesity.

So, Giovanni, the floor is yours. Good morning. Can you hear me? Yes, perfectly.

Good morning. My name is Giovanni Chirico and today I'm going to talk to you about the association between sleep disorder and obesity through this presentation entitled Sleep Quality and Obesity, the chicken or the egg. The prevalence of obesity has really increased worldwide in the last few years.

And with it, the obesity related disease, for example, neurological, cardiovascular, gastrointestinal and pulmonary disease. Obesity is a risk factor for sleep disturbance. A six-unit increase in BMI results in a four-time greater risk of obstructive sleep apnea.

To date, there is an association between obesity and sleep disorder. But who comes first? Davidson and Patel showed that waist circumference and waist-hip ratio were the main predictor of sleep disturbance. Waist circumference and waist-hip ratio are an indirect measure of visceral fat.

So, this means that visceral fat is a risk factor for obesity. Visceral fat is an endocrine organ called adipose organ. It produces a lot of flow inflammatory cytokine, such as interleukin-1, interleukin-6, TNF, that cause inflammation and oxidative stress.

Poor dietary quality is associated with sleep disorder. The people affected by obesity have worse quality and duration of sleep than people with normal weight. There is an association between sleep disorder and obesity and vice versa.

But what is the possible pathophysiological mechanism linking these two conditions? The people affected by obesity have worse quality and duration of sleep that cause weight gain that in turn cause worse quality and duration of sleep, starting a vicious cycle. Obesity is a risk factor for sleep disturbance. There are many disease obesity related, for example, gastrointestinal disease and pulmonary disease.

Among pulmonary disease, one of the most common is obstructive sleep apnea. Obstructive sleep apnea is characterized by upper airway closure, nocturnal awaking, snoring and desaturation. Nocturnal awaking causes sympathetic activation, endothelial dysfunction, hypercoagulability, inflammation and oxidative stress.

Obstructive sleep apnea is associated with higher risk of systemic hypertension, myocardial ischemia, stroke and heart failure. Obesity, the patient affected by obesity have higher level of glucose, leptin and higher lipid level. They have also mitochondrial and endothelial dysfunction that cause oxidative stress with higher risk of a lot of disease.

Late, we know an association between obesity and sleep disorder, but at the same time, sleep disturbance is a risk factor for obesity. In fact, in 2016 conducted a four-year prospective study of 40,000 young people with persistently poor sleep duration, demonstrating 1.45 times increased the risk of developing obesity compared to the population with normal sleep duration. The like prevalence of obesity in patients with sleep restriction could be explained through an effect on calorie intake.

In fact, those who go to bed late and sleep early have a higher consumption of high calorie and high fat foods. Modern lifestyle contribute to altering our chronological chronobiology. Workers tend to go to bed late and wake up early.

This condition known as a social jet lag is associated with an increased risk of developing obesity, characterized by an increased risk of metabolic syndrome. Prolonged sleep disruption, lasting less than six and a half hours, are associated with a worse dietary pattern characterized by increased consumption of food with high glycemic index. The preference for unhealthy foods can be attributed to increased brain activity in area of the brain, such as putamen, nucleoacobins, thalamus, insula, and prefrontal cortex, in response to stimuli from food.

Sleep deprivation not only affects food preference, but also food intake. Inside, we see the main hormonal change in people with sleep disturbance. The people with sleep disturbance have high cortisol level, high cortisol level cause overeating, impaired glucose, homeostasis, insulin resistance, and high visceral fat.

The people affected, the people with the sleep disorder, have higher granule level, higher granule level, increased calorie intake, mostly sweet foods. They have also higher leptin level. Sleep disturbance has been associated to leptin resistance and consequently increased leptin level, which resulted in increased hunger.

And hunger to arachidonoyl glycerol, that is one of the most abundant ligands of endocannabinoid receptor. It has a circadian rhythm, and in people with sleep disturbance, this rhythm is amplified and the peak is delayed and extended. So, they have also lower melatonin level and decreased level of melatonin cause weight gain and chronic inflammation with oxidative stress, those blunting glucose metabolism.

This study demonstrated the effect of quarantine during COVID-19 pandemic on sleep quality and body mass index. Through this questionnaire, and the sleep quality index, that is a questionnaire used to evaluate the quality and duration of sleep in the past month. About 50% of subjects were good sleepers at the baseline and significantly decreased after quarantine.

Quarantine was associated to a worsening of sleep quality, particularly in males doing smart working and to an increase in BMI value. Conclusion, today, there is no association between obesity and sleep disorder, but at the same time, the sleep disorder may be responsible for hormonal change that cause weight gain and boost obesity. So, take-home message, sleep type, sleep matters.

Thank you all and thank you to my research team. Thank you Giovanni. If you can stop your sharing mode, thank you.

And thank you to all the speakers for the very, very impressive presentations and work. We have a nice group of questions on the chat function and I will present the question and you will decide who would like to respond to this question in between. I can reply, otherwise I would be annoyed.

So, I just want to do something. Okay, so please start to work. Go on.

So, of course, we have a question about how to measure the chronotype because, for instance, there is a note about Avtarani working in the UK and they found a very low prevalence of the evening chronotype in their population. Of course, there could be some regional or national or geographical variation, but can you explain better maybe to the general audience what kind of score you use or do you use only one score or you test the population with multiple methods? Okay, so we use to measure chronotype or better to categorize the chronotype using the morningness, the eveningness questionnaire. So, if you wish, we can give you the questionnaire that we use to administer to our patients.

And do you are aware of regional or national differences in the prevalence of the evening chronotype? Yes, because the chronotype is a multifactorial threat. So, we can say that there is a genetic predisposition, but also lifestyle can impact on determining chronotype category. So, we expect that, of course, the prevalence of morning or intermediate or evening chronotype would be different, for example, in Mediterranean countries compared to countries of North Europe.

Okay, it's clear, but I suggest that maybe you can provide the score system to Lisa after the meeting. So, there is a possibility to share some resources for all the audience. So, it could be very useful for other clinicians that are interested in doing the same work in different parts of Europe.

And one another question was about the stability of the circadian rhythm. So, the rhythm could change during the life of or we are, yes, since our birth. Yeah.

So, we are sure that chronotype changes over the life stages. For example, we carried out a study in comparing a chronotype in premenopausal versus postmenopausal women. And we saw that postmenopausal women tended to become evening chronotype after menopause.

And we hypothesized that this was like a mechanism to compensate the postmenopausal increased cardiovascular risk. Because as we know, evening chronotype is like to be protected from cardiovascular disease. And we also know that in postmenopause, there is an increase of cardiovascular risk.

So, we believe that the switch from evening chronotype to morning chronotype. So, I say evening. I want to say that morning chronotype is protected from cardiovascular risk.

And we found that in postmenopausal women, they switch from evening to morning chronotype categories. And we believe that this was a mechanism of compensation to the increase, to postmenopausal increased cardiovascular risk. So, we believe that there is a sort of protective mechanism after menopause that make the women more prone to switch from evening to morning chronotype in order to counteract the increased cardiovascular risk.

And also, we know that there is a change of chronotype categories, for example, from all youth lives compared to elderly. And also to premenopausal women that are non-pregnant versus premenopausal women that are pregnant. So, there are a switch.

It could be a switch from one chronotype categories to another in order to make that subjects more able to to counteract any complication or all the difficulties for health related to that life stage. Yeah, this of course, this opens also the possibility to induce shift of circadian rhythm as a therapeutic intervention. Yes, because one of the comments, obviously, from Avtarani and also from myself is here we are working on cross-sectional observation.

So, what we see, we see association. And of course, we would like to have more proof that the causal relationship is in the right direction. And this could be done only by performing intervention study and looking at the outcome of the intervention study.

So, what happens if you change the chronotype to the situation? Because of course, this kind of research would strain the importance of the chronotype as a causative mechanism, not only an association. Yes, so Ludovica is carrying out a study investigating the effect of VLCKD on chronotype categories. So, we have preliminary data and we saw that subjects with the evening chronotype after VLCKD switch to morning chronotype.

And this data was confirmed after adjustment for weight loss. There are evidence in the literature that ketone bodies could act on clock genes. So, in some way, we hypothesized that ketone bodies could play a role in the realignment of subjects with evening chronotype.

And there are also a lot of questions about the relationship in between sleep disturbances, chronotype and cardiometabolic outcomes. One question is, the first question was about the shift workers. So, there is a relationship between shift working, chronotype, metabolic disturbances.

Did you control in your study for particular pattern of sleeping that we, as a doctor, we know very well? We excluded, of course, the shift workers from our study and we know that, of course, the shift workers could have a role in determining evening, in determining chronotype because we know that chronotype is also partially determined by lifestyle. Anyway, we know that subjects with evening chronotype experience a delay of the peak of the cortisol in the morning and also are more prone to develop sleep disturbances because they tend to wake later in the day and also to go to bed later in the day. And, of course, this could have a negative impact on sleep quality.

And we know that the sleep disturbances are associated with an increase of appetite. So, sleep disturbances in turn could determine an increased risk of developing obesity and, of course, obesity metabolic diseases. For this reason, since subjects with evening chronotype are more prone to develop sleep disturbances, are also more prone to develop obesity and obesity cardiometabolic diseases.

So, the sleep disturbances could be, in theory, one of the mediators of the relationship in between. Yes. Also, another mediator is the peak of the cortisol, the delay of the peak of the cortisol because, of course, having the peak of the cortisol in a determined moment of the day, in which usually there is not the peak of the cortisol, could determine a detrimental impact on metabolism.

Yeah, and I am particularly interested in the role of the sleep disturbances because we have an increasing amount of data showing that the prevalence of metabolic diseases, but also the prevalence of or the progression of NAFLD to fibrosis and also some of the health structural problems that we have in obesity are related to the episodes of hypoxia during the night. So, and, of course, you can find a clear differences in all these parameters in between people with sleep disorder and without this disorder, even after controlling for all the anthropometric factors. So, probably, one is a very important, this is a very important mechanism that could be a link in between the two disorders.

For instance, we recently published a small paper on the fibrosis index and we found that the number of desaturation during the night is correlated with the fibrosis, liver fibrosis index, independently from BMI, waste and whatever you want. So, this could be very relevant. So, I think that the quality of the sleep is a very important point.

I don't know if you agree. Yes, we also found, for example, that well CKD is involved in the improvement of sleep quality in subjects with obesity because there are some animal evidence that ketone bodies play also a role in sleep regulation. And as we know that sleep disturbance are present also in subjects with the first grade of obesity, so that, for example, have not OSA.

So, we believe that using some nutritional or pharmacological approaches that are also evidence for a role on sleep regulation could be very important in the management of subjects with obesity and sleep disturbances. Yes, this is a very complex picture. So, there are many, many, many mechanisms involved and probably many ways to intervene also.

I have a very short personal question about the VLCKD. So, despite what you are saying that probably ketone bodies could have positive effect, in your study you observe a reduced weight loss during VLCKD in people with the evening chronotype. It is only a matter of adherence? So, did you check the level of ketone body in the patients or it could be a more complex effect or link? So, first we adjusted the data for weight loss.

And second, we compared this data that we found in subjects undergoing to VLCKD to subjects undergoing to Mediterranean diet that lost the same percentage of weight. In this way, we demonstrated that losing weight with VLCKD, losing the same percentage of weight with VLCKD and losing the same percentage of weight with the Mediterranean diet could have a different impact on sleep and chronotype. So, this was the way, the tool that we used to be sure that our findings were mostly related to VLCKD effect and that was not related to weight loss.

Yeah, but how you explain the fact that people with the evening chronotype lose less weight during the VLCKD as compared with the morning chronotype? So, because they have an inappropriate cortisol secretion, because our nutritionist also check the weekly adherence to VLCKD, the patient also measures ketone bodies in order to be sure that they reach metabolic ketosis. And we believe that these subjects had a need in inadequate cortisol secretion and this could antagonize weight loss in some way. Thank you for the possible explanation.

Of course, it's always really easy to understand. Yeah, it's a hypothesis. Yeah, I could add one additional hypothesis, more linked to the story of their sleep, because we also know that people with sleep apnea syndrome tend to lose less weight during any type of intervention.

So, like people with type 2 diabetes, the people with the sleep disturbances are usually poor responders to weight loss, whatever you are using for inducing weight loss. Maybe you remember one of the study with the Liragutide that it was performing people with sleep apnea and the weight loss was less than expected or less than observed in the population of people with obesity without sleep apnea syndrome. So, again, the link between chronotype and sleep could be also one of the mechanisms explaining why it is more difficult to lose weight in this particular group of patients.

So, if I can add a thing about this topic, we also see in the literature that sleep disorders that are common in meningoclonal type are predisposed to reduce the lipolysis. So, this can be another factor to this resistance to weight loss. And also, we found in literature that some genetic variants predisposing to weight loss resistance are common in the meningoclonal type.

So, there are many factors that can contribute to this resistance to the weight loss from this kind of chronotype. Thank you, very interesting observation. Okay, I think that we respond to the majority of the questions in the chat.

We are receiving very positive inputs or very positive responses from the audience. So, I think that most of the people enjoyed the meeting and this is good, of course. So, Giovanna, I think that we can close here and to leave the final words to Lisa for the final housekeeping rules or comments.

Do you like to say something in closure, Giovanna? Okay, I want to thank first my research team because they did most of this work that we show you today. And I want to thank Luca, that is my president of Italian Obesity Association. And the last but not the least, I want to thank IAASO for this opportunity.

Okay, so many thanks from Giovanna. Lisa, do you want to say something in closure? So, I think that we are perfectly on time. Sure, it's perfect timing.

Thanks very much to the chairs and the speakers. And thank you to the audience for keeping the discussion alive and asking very interesting questions. I just wanted to say the recording will be shared as soon as possible and also any relevant resources that were mentioned throughout the question and answer session.

If you have any questions specifically to do with the webinars in general, please do email me. I'll drop my email into the chat. And otherwise, please do join us for the next webinar, which will be held on the 27th of April.

And we will be looking at lipoedema from a patient's perspective. And there will also be talks from the clinical diagnosis and treatments perspective. So, we'll also drop the link there in the chat.

But otherwise, I think everyone is free to go. So, thank you very much, Luca and Giovanna. And thank you very much to the speakers.