Impact of exenatide on weight loss and eating behavior in adults with craniopharyngioma-related obesity: the CRANIOEXE randomized placebo-controlled trial.

IMPORTANCE: A major issue in the management of craniopharyngioma-related obesity (CRO) is the ineffectiveness of the current therapeutic approaches. OBJECTIVE: To study the efficacy of glucagon-like peptide-1 analogs compared with placebo in adults with obesity CRO. DESIGN: A double-blind multicenter superiority randomized clinical in trial in two parallel arms. SETTING: Eleven French University Hospital Centers. PARTICIPANTS: Adults with CRO (body mass index > 30 kg/m²) without the sign of recurrence of craniopharyngioma in the past year. INTERVENTIONS: Exenatide or placebo injected subcutaneously twice a day during 26 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the mean change in body weight at week 26 in the intention-to-treat population. Secondary outcomes were eating behavior, calories intake, energy expenditure, cardiovascular, metabolic risk factor, quality of life, and the tolerance profile. RESULTS: At week 26, weight decreased from baseline by a mean of -3.8 (SD 4.3) kg for exenatide and -1.6 (3.8) kg for placebo. The adjusted mean treatment difference was -3.1 kg (95% confidence interval [CI] -7.0 to 0.7, P = 0.11). Results were compatible with a higher reduction of hunger score with exenatide compared with placebo (estimated treatment difference in change from baseline to week 26: -2.3, 95% CI -4.5 to -0.2), while all other outcomes did not significantly differ between groups. Adverse events were more common with exenatide versus placebo, and occurred in, respectively, 19 (95%) participants (108 events) and 14 (70%) participants (54 events). CONCLUSIONS AND RELEVANCE: Combined with intensive lifestyle interventions, a 26-week treatment with exenatide was not demonstrated superior to placebo to treat craniopharyngioma-related obesity.

Quantitative MRI Biomarkers Measure Changes in Targeted Brain Areas in Patients With Obesity.

CONTEXT: Obesity is accompanied by damages to several tissues, including the brain. Pathological data and animal models have demonstrated an increased inflammatory reaction in hypothalamus and hippocampus. OBJECTIVE: We tested whether we could observe such pathological modifications in vivo through quantitative magnetic resonance imaging (MRI) metrics. METHODS: This prospective study was conducted between May 2019 and November 2022. The study was conducted in the Specialized Center for the Care of Obesity in a French University Hospital. Twenty-seven patients with obesity and 23 age and gender-paired normal-weight controls were prospectively recruited. All participants were examined using brain MRI. Anthropometric and biological data, eating behavior, anxiety, depression, and memory performance were assessed in both groups. The main outcome measure was brain MRI with the following parametric maps: quantitative susceptibility mapping (QSM), mean diffusivity (MD), fractional anisotropy (FA), magnetization transfer ratio map, and T2 relaxivity map. RESULTS: In the hypothalamus, patients with obesity had higher FA and lower QSM than normal-weight controls. In the hippocampus, patients with obesity had higher FA and lower MD. There was no correlation between imaging biomarkers and eating behavior or anxiety. CONCLUSION: Our findings are consistent with the presence of neuroinflammation in brain regions involved in food intake. In vivo brain biomarkers from quantitative MRI appear to provide an incremental information for the assessment of brain damages in patients with obesity.

High Risk of Acute Kidney Failure in Kidney Transplant Recipients Early after Bariatric Surgery.

Bariatric surgery is routinely proposed to patients suffering from obesity including kidney transplant recipients. In this specific population, bariatric surgery has a positive impact in long-term outcomes in terms of patient and graft survival. We report here the cases of 4 patients with five post-kidney transplantation bariatric surgeries who experimented acute renal injury early after surgery. Creatinine rising occurred between day 14 and day 20 after surgery. In all cases, it was due to dehydration leading to a pre-renal acute renal failure. The specific care of kidney transplanted patients is discussed: single kidney associated with pre-existing altered kidney function associated with concomitant use of nephrotoxic drugs. Specific education intervention before surgery associated with careful early management of hydration after surgery is mandatory for these patients.

A novel pathogenic variant in MRAP2 in an obese patient with successful outcome of bariatric surgery.

Mutations in genes encoding proteins located in the leptin/melanocortin pathway have been identified in the rare cases of genetic obesities. Heterozygous variants of MRAP2, encoding a G coupled-protein receptor accessory protein implicated in energy control notably via the melanocortin-4 receptor, have been recently identified. A 24-year-old patient with early-onset severe obesity (body mass index [BMI]: 64 kg/m2) associated with hypertension, respiratory complications, nonalcoholic fatty liver disease, and type 2 diabetes was referred to our department. Sleeve gastrectomy was successful. A new heterozygous variant in MRAP2 (NM_138409.4: c.154G>C/p.G52R) variant was identified in the patient DNA. Functional assessment confirmed that this new variant was pathogenic. We report a new pathogenic loss-of-function mutation in MRAP2 in a patient suffering from a severe multicomplicated obesity. This confirms the metabolic phenotype in patients with this monogenic form of obesity. Longer follow-up will be necessary. Our finding will allow a personalized medicine.

Out-of-Pocket Expenses in Households of People Living with Obesity in France.

BACKGROUND/OBJECTIVES: Overweight and obesity result in a substantial economic burden in both low- and high-income countries. Moreover, this burden is often underestimated because it only partially accounts for unreimbursed out-of-pocket expenses (OOPE) related to obesity. The objective of our study was not only to evaluate OOPE incurred by people with obesity in relation to their disease with respect to direct medical expenditures and direct non-medical expenditures but also the proportion of people living with obesity who have forgone obesity-related healthcare due to the costs of such care. METHODS: An observational descriptive survey was conducted among people with class II/III obesity attending six obesity treatment centers in France. Volunteer adult participants completed a written/phone questionnaire on their related expenditures over the last 6 months for current expenditures and over the last 5 years for occasional ones. The costs were expressed in 2022 EUR. RESULTS: 299 people participated (age: 46 years [SD: 13.9], women: 72%, BMI ≥40 kg/m2: 62% and 48% with comorbidities). 65% had a professional activity. 83% declared that they had OOPE related to obesity representing annually EUR 2027/individual on average (5% of the household revenue), including weight loss and nutritional products, vitamins, meal programs, gym memberships, psychologists, but mainly adapted clothing, additional travel costs, and others. 15% of the respondents had to modify their professional activity due to obesity and 15% forwent some medical care in the last 12 months. CONCLUSIONS: OOPE is a significant part of the economic burden of obesity. Despite some limitations due to the specificities of the participants and because some costs may be more related to social activities affected by obesity than to healthcare, it seems important to consider these expenditures in cost estimates for obesity.

Does food use disorder exist? Item response theory analyses of a food use disorder adapted from the DSM-5 substance use disorder criteria in a treatment seeking clinical sample.

BACKGROUND: Increased consumption of food that are high in energy and sugar have been pointed as a major factor in the obesity epidemic. Impaired control of food intake and the concept of food addiction has been developed as a potential contributor. Our objective was to evaluate the dimensionality and psychometric validity of diagnostic criteria for food addiction adapted from the 11 DSM-5 substance use disorder (SUD) criteria (i.e.: Food Use Disorder (FUD) criteria), and to evaluate the influence of age, gender, and body mass index (BMI). METHODS: Cross-sectional observational study including 508 participants (56.1% male; mean age 42.2) from outpatient treatment clinics for obesity or addiction disorders at time of admission. FUD diagnostic criteria were analyzed using confirmatory factor and 2-parameter item response theory analyses. Differential Item and Test Functioning analyses were performed across age, gender, and BMI. RESULTS: We demonstrated the one-factor dimensionality of the criteria set. The criterion "craving" presented the strongest factor loading and discrimination parameter and the second-lowest difficulty. We found some significant uniform differential item functioning for body mass index. We found some differential test functioning for gender and BMI. CONCLUSIONS: This study reports, for the first time, the validity of a potential Food Use Disorder (derived from the 11 DSM-5 SUD criteria adapted to food) in a sample of treatment seeking adults. This has great implications both at the clinical level and in terms of public health policy in the context of the global obesity epidemic.

Long-Term Results After Bariatric Surgery in Super-Super-Obese Patients.

Introduction: Despite addressing to high risk population, we can propose laparoscopic bariatric surgery to super-super-obese (SSO) patients (body mass index [BMI] ≥60 kg/m2). The aim of this study was to report our experience in terms of weight loss and improvement of medical comorbidities after a follow-up of 5 years in the SSO population who underwent different bariatric procedures. Methods: This retrospective study includes all SSO patients who underwent bariatric surgery (sleeve gastrectomy [SG] and/or gastric bypass) between 2006 and 2017. The population was divided in three groups (SG alone; Roux-en-Y gastric bypass [RYGB] alone and SG+RYGB). The rate of complication and the weight-loss results were analyzed. Results: Among 43 patients who underwent surgery, the mean age was 42[31-54]. There were more women (72%) with the mean preoperative BMI of 64.9 kg/m2 [59.6-70.1]. There were 9 SGs, 26 RYGB, and 8 SG revised to gastric bypass (SG+RYGB) after a median delay of 23.5 months [16.5-32]. The perioperative complication rate was 25%, and there was 1 postoperative death. The median follow-up was 69 months [1-128]. The mean percentage of excess weight loss (%EWL) was 39.2% [18.2-60.3] after 5 years. For the SG group, the %EWL was inferior -27.1 [-3.6 to 57.8], but with no significant difference. An improvement of comorbidities' rate was recorded in all groups of patients. Conclusion: Bariatric surgery in SSO patients leads to an improvement of comorbidities even if the weight-loss results, especially in the SG group, are less favorable. The two steps approach should be re-evaluated by shortening the interval between. Other surgical strategies than RYGB are needed to be evaluated to improve long-term weight loss.

Heterozygous pathogenic variants in POMC are not responsible for monogenic obesity: Implication for MC4R agonist use.

PURPOSE: Recessive deficiency of proopiomelanocortin (POMC) causes childhood-onset severe obesity. Cases can now benefit from the melanocortin 4 receptor agonist setmelanotide. Furthermore, a phase 3 clinical trial is evaluating setmelanotide in heterozygotes for POMC. We performed a large-scale genetic analysis to assess the effect of heterozygous, pathogenic POMC variants on obesity. METHODS: A genetic analysis was performed in a family including 2 cousins with childhood-onset obesity. We analyzed the obesity status of heterozygotes for pathogenic POMC variants in the Human Gene Mutation Database. The association between heterozygous pathogenic POMC variants and obesity risk was assessed using 190,000 exome samples from UK Biobank. RESULTS: The 2 cousins carried a compound heterozygous pathogenic variant in POMC. Six siblings were heterozygotes; only 1 of them had obesity. In Human Gene Mutation Database, we identified 60 heterozygotes for pathogenic POMC variants, of whom 14 had obesity. In UK Biobank, heterozygous pathogenic POMC variants were not associated with obesity risk, but they modestly increased body mass index levels. CONCLUSION: Heterozygous pathogenic POMC variants do not contribute to monogenic obesity, but they slightly increase body mass index. Setmelanotide use in patients with obesity, which would only be based on the presence of a heterozygous POMC variant, can be questioned.

Long-term changes in body image after bariatric surgery: An observational cohort study.

BACKGROUND: While body image improves in the first few months after surgery, data on long-term changes in body image after bariatric surgery are scarce and contradictory. METHODS: We assessed body image through the Stunkard Figure Rating Scale and the Multidimensional Body-Self Relations Questionnaire-Appearance Scale, which measures appearance evaluation and orientation, overweight preoccupation, and self-classified weight. Surveys were conducted before surgery and at regular intervals until 5 years after bariatric surgery. RESULTS: 61 patients were included in the study. No patients were lost to follow-up until 18 months after bariatric surgery. At 5 years, there were 21 patients (34%) lost to follow-up. We detected an overall improvement in body image until 12-18 months post-surgery. Scores declined after 5 years post-surgery but were still higher than preoperative evaluations. Overweight preoccupation did not change throughout the follow-up period. There was a positive correlation between body weight lost and appearance evaluation. There was also a positive correlation between weight loss and the Body Areas Satisfaction Scale. There was a negative correlation between weight loss and overweight preoccupation. Appearance orientation and self-classified weight were not correlated with weight loss. CONCLUSIONS: Body image improved after bariatric surgery but was not maintained for all 5 years after surgery.

The Challenging Management of Craniopharyngiomas in Adults: Time for a Reappraisal?

Craniopharyngiomas (CPs) are rare tumors of the skull base, developing near the pituitary gland and hypothalamus and responsible for severe hormonal deficiencies and an overall increase in mortality rate. While surgery and radiotherapy represent the recommended first-line therapies for CPs, a new paradigm for treatment is currently emerging, as a consequence of accumulated knowledge concerning the molecular mechanisms involved in tumor growth, paving the way for anticipated use of targeted therapies. Significant clinical and basic research conducted in the field of CPs will undoubtedly constitute a real step forward for a better understanding of the behavior of these tumors and prevent associated complications. In this review, our aim is to summarize the multiple steps in the management of CPs in adults and emphasize the most recent studies that will contribute to advancing the diagnostic and therapeutic algorithms.

Analysis of Microvascular Abnormalities in Obesity: A Comparative Study with Healthy Subjects Using Swept Source Optical Coherence Tomography Angiography and Adaptive Optics.

PURPOSE: The aim of this study was to analyze retinal microvasculature in obese subjects as compared to a normal-weight population. METHODS: In this case-control observational study, swept-source optical coherence tomography angiography (SS-OCTA) and adaptive optics (AO) were performed in eyes of nondiabetic, nonhypertensive, obese patients and in healthy controls. AO was used to calculate the wall-to-lumen ratio (WLR). The foveal avascular zone (FAZ), the macular vessel density, and the macular perfusion density of the superficial and deep capillary plexuses were analyzed in 6 × 6 mm macular OCTA cubes. SS-OCTA was also used to measure the choroidal thickness, the retinal nerve fiber layer (RNFL), and the vascular density of the retinal peripapillary capillary plexus. RESULTS: The obese group included 45 eyes (24 patients), and the control group included 46 eyes (23 subjects). The central macular density and perfusion density were significantly lower in obese patients compared to controls, in the deep retinal layer (0.28 [0.01-0.69] vs. 1.24 [0.82-1.66], p = 0.006 and 0.006 [0.001-0.015] vs. 0.025 [0.016-0.034], p = 0.01), respectively, after adjustment for systolic blood pressure. No differences were found in macular vascular density in other areas, FAZ (circularity, area, perimeter), choroidal thickness, RNFL. WLR was increased in obese patients (0.252 [0.246-0.259] vs. 0.239 [0.231-0.245] in controls, p = 0.016). CONCLUSION: Obesity was associated with retinal microvascular changes regardless of the presence of diabetes and hypertension. Our findings suggest the presence of infraclinical microvascular changes directly associated with obesity, which can be identified noninvasively through retinal imaging.

Five-Year Changes in Weight and Diabetes Status After Bariatric Surgery for Craniopharyngioma-Related Hypothalamic Obesity: a Case-Control Study.

PURPOSE: Craniopharyngiomas are tumors located in the hypothalamic region which leads to obesity in about 50% of cases. Long-term efficacy and safety of bariatric surgery are lacking in this peculiar population. The aim of this study is to determine the 5-year weight loss and resolution of type 2 diabetes (T2D) after bariatric surgery in patients operated on craniopharyngioma who had developed hypothalamic obesity. MATERIALS AND METHODS: This is a multicenter french retrospective case-control study. Subjects with craniopharyngioma (n = 23) who underwent sleeve gastrectomy (SG) (n = 9) or Roux-en-Y gastric bypass (RYGB) (n = 14) (median age 35 years [25;43] and BMI 44.2 kg/m2 [40.7; 51.0]; 8/23 with T2D) were individually matched to 2 subjects with common obesity for age, gender, preoperative body mass index, T2D, and type of surgery. RESULTS: TWL% after 1 and 5 years was lower in the craniopharyngioma group than in the control group: 23.1 [15.4; 31.1] (23/23) vs 31.4 [23.9; 35.3] at 1 year (p = 0.008) (46/46) and 17.8 [7.1; 21.9] (23/23) vs 26.2 [18.9; 33.9] at 5 years (p = 0.003) (46/46). After RYGB, TWL% was lower in the craniopharyngioma group compared to the control group (p < 0.001) and comparable after SG both at 1 and 5 years. No difference between the two groups was observed in T2D remission rate and in early and late adverse events. No hormonal deficiency-related acute disease was reported. CONCLUSIONS: Bariatric surgery induced a significant weight loss in the craniopharyngioma group at 1 and 5 years, but less than in common obesity. SG may be more effective than RYGB but this remains to be demonstrated in a larger cohort.

[Place of biomarkers in the renutrition of patients with serious Covid-19 infection: discussion around a clinical case]. / Place des biomarqueurs dans la renutrition des patients ayant une infection grave à Covid-19 : discussion autour d'un cas clinique.

Covid-19 infection is a potentially serious disease. Overweight, obesity, and diabetes are comorbidities frequently found in the severe form of the disease. Appropriate nutritional management of the patient is an integral part of care. We will discuss the renutrition of a 76-year-old, obese (BMI = 35kg/m2), malnourished patient, according to the 2021 Haute Autorité de santé criteria, with Covid-19 infection, admitted to the intensive care unit at the Bordeaux University Hospital for an acute respiratory distress syndrome. Adaptation of nutritional intakes was achieved by clinical and biological monitoring. A refeeding syndrome was treated on the first day of hospitalization in the intensive care unit. After thiamine supplementation and when kalemia and phosphatemia have been normalized, renutrition was started. Parenteral nutrition as a complement to oral nutrition was used. Parenteral nutrition was well tolerated; recommended caloric and protein intakes were achieved by the fourth day of hospitalization. The clinical evolution was favorable. In conclusion, patients with Covid-19 infection should be considered malnourished when admitted to the intensive care unit. Macro and micronutrient intakes adapted to metabolically stressed patients are essential. Biological monitoring including monitoring of ionogram, phosphate, uremia, creatinine, liver function tests and blood glucose is essential in the nutritional management of patients with serious Covid-19 infection.

Guideline compliance in bariatric surgery: a French nationwide study.

BACKGROUND: Strict adherence to guidelines with a comprehensive preoperative assessment and rigorous follow-up are essential to improve postoperative and long-term outcomes of bariatric surgery (BS). OBJECTIVES: To investigate the trends in BS in France and to assess the compliance to guidelines in people with obesity before and after BS. SETTING: University Hospital of Bordeaux, France. METHODS: Data on patients who were admitted for a primary BS procedure in France between January 1 and April 1, 2014, were extracted from the French national health insurance system database. Data on patients' characteristics, preoperative assessment, hospitalization, and postoperative follow-up, including medical consultations, laboratory tests, and drug consumption, during the year preceding and the 2 years after BS were collected. RESULTS: Most of the 11,824 patients (60.4%) had sleeve gastrectomy. Rates of reimbursement for preoperative consultations with general practitioners, digestive surgeons, and endocrinologists or internists were 94.5%, 89.2%, and 63%, respectively. Laboratory tests for nutritional and obesity-related co-morbidity evaluations were performed in 94.3% and 91.4%, respectively. Rates of consultation with general practitioners, digestive surgeons, and endocrinologists or internists dropped from 93.1%, 91.2%, and 29.2%, respectively, the first year to 88.4%, 50.3%, and 20%, respectively, the second year after BS (P < .001). Reimbursements for vitamin, iron, and calcium supplementation dropped from 66.6%, 24.9%, and 21%, respectively, the first year to 52.1%, 19.3%, and 11.7%, respectively, the second year after BS (P < .001). CONCLUSION: Overall compliance with guidelines is improving. While preoperative medical assessment is nearly optimal, efforts still should be made in order to improve long-term follow-up in general and patient adherence to micronutrient supplementation in particular.

Exploring eating behavior and psychological mechanisms associated with obesity in patients with craniopharyngioma: a scoping review protocol.

OBJECTIVE: The objective of the review is to explore the evidence on the behavioral and psychological mechanisms underlying the development of obesity in patients with craniopharyngioma. The review will map the available evidence, identify gaps in the literature, and find avenues of future intervention. INTRODUCTION: Craniopharyngiomas are low-grade intracranial tumors of the supersellar region. Obesity is associated with the tumor or surgery or radiotherapy to treat the tumor; however, the behavioral and psychological processes contributing to that association are not clear. This review will provide a synthesized evidence base of the relevant research. INCLUSION CRITERIA: This review will consider published studies with all types of study designs, including patients with childhood- or adult-onset craniopharyngioma. Articles assessing factors that may impact eating behavior will be included based on the following categories: eating behavior, obesity, neuroimaging, endocrine response, energy expenditure, sleep, and neuropsychology. METHODS: MEDLINE, Embase, and PsycINFO will be searched, in addition to the Cochrane Library, Web of Science, Scopus, ClinicalTrials.gov, NICE evidence search, and International Standard Randomised Controlled Trial Number (ISRCTN). No limits will be placed on the scope of the search. The methodology will follow a three-stage process with two independent reviewers at each stage, including an initial database search, screening of titles and abstracts of retrieved studies, full-text assessment for inclusion criteria, and hand-searching of reference lists. Data will be extracted using a standardized charting form and summarized in tables. The data will be synthesized using a narrative summary and diagrammatic map and will be based on the evidence for each of the proposed research categories.

Gut Microbiota and Mycobiota Evolution Is Linked to Memory Improvement after Bariatric Surgery in Obese Patients: A Pilot Study.

Patients with obesity are known to exhibit gut microbiota dysbiosis and memory deficits. Bariatric surgery (BS) is currently the most efficient anti-obesity treatment and may improve both gut dysbiosis and cognition. However, no study has investigated association between changes of gut microbiota and cognitive function after BS. We prospectively evaluated 13 obese patients on anthropometric data, memory functions, and gut microbiota-mycobiota before and six months after BS. The Rey Auditory Verbal Learning Test (AVLT) and the symbol span (SS) of the Weschler Memory Scale were used to assess verbal and working memory, respectively. Fecal microbiota and mycobiota were longitudinally analyzed by 16S and ITS2 rRNA sequencing respectively. AVLT and SS scores were significantly improved after BS (AVLT scores: 9.7 ± 1.7 vs. 11.2 ± 1.9, p = 0.02, and SS scores: 9.7 ± 23.0 vs. 11.6 ± 2.9, p = 0.05). An increase in bacterial alpha-diversity, and Ruminococcaceae, Prevotella, Agaricus, Rhodotorula, Dipodascus, Malassezia, and Mucor were significantly associated with AVLT score improvement after BS, while an increase in Prevotella and a decrease in Clostridium, Akkermansia, Dipodascus and Candida were linked to SS scores improvement. We identified several changes in the microbial communities that differ according to the improvement of either the verbal or working memories, suggesting a complex gut-brain-axis that evolves after BS.

Reproducibility and associations with obesity and insulin resistance of circadian-rhythm parameters in free-living vs. controlled conditions during the PREVIEW lifestyle study.

BACKGROUND: Circadian rhythm is altered in individuals with obesity and insulin resistance, showing a smaller amplitude, less stability, and increased intradaily variation. OBJECTIVE: We compared reproducibility of circadian-rhythm parameters over time and under free-living vs. controlled conditions in participants with obesity and pre-diabetes after 2- and 3-year weight-loss maintenance during the 3-year PREVIEW (PREVention of diabetes through lifestyle intervention and population studies In Europe and around the World) study. Associations of obesity and insulin resistance with circadian-rhythm parameters were assessed. SUBJECTS AND METHODS: Circadian-rhythm parameters were determined using continuous wrist-temperature measurements in free-living environments at year 2 (n = 24; age 56.8 ± 10.3 y; body mass index (BMI) = 30 ± 3.9 kg/m2; homeostatic model assessment of insulin resistance (HOMA-IR) 2.4 ± 1.1), at year 3 (n = 97; age 61.7 ± 7.8; BMI = 29.7 ± 3.9; HOMA-IR 2.9 ± 2.1), and at year 3 in a controlled condition (n = 38; age 63.4 ± 6.7; BMI = 28.7 ± 3.9; HOMA-IR 3.8 ± 1.4). Reproducibility was assessed by analyzing repeatability coefficients (CR), differences, and associations, over time as well as between conditions. Associations of BMI and HOMA-IR with circadian-rhythm parameters were assessed at y-3 in both conditions using factor analysis, followed by Pearson's correlations. RESULTS: Reproducibility of circadian-rhythm parameters over time in the free-living environments was high (CR 0.002-5.26; no significant differences; associated amplitudes r = 0.57; p < 0.01). In contrast, reproducibility between different conditions was low (CR 0.02-11.36; significant differences between most parameters (p < 0.05); yet associated amplitudes r = 0.59; p < 0.01). In the controlled vs. free-living condition circadian-rhythm was more stable; BMI and HOMA-IR were associated with the physiological amplitude-related parameters (r = -0.45; p < 0.01; r = -0.33; p < 0.05). In the free-living environment, BMI and behavioral circadian-rhythm parameters indicating circadian alignment, contributed most to the explained variation (47.1%), and were inversely associated (r = -0.22; p < 0.05), while HOMA-IR was inversely associated with stability-related circadian-rhythm parameters (r = -0.21; p < 0.05). CONCLUSIONS: Circadian rhythm was highly reproducible over time in the free-living environments, yet different under different conditions, being more stable in the controlled condition. BMI may play a significant role in circadian alignment and vice versa in the free-living environment.