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PURPOSE: To evaluate glycemic variability (GV) using continuous glucose monitoring (CGM) in individuals with and without type 2 diabetes mellitus (T2DM) undergoing Roux-en-Y gastric bypass (RYGB). METHODS: This prospective cohort study compared the CGM data of fourteen patients with T2DM (n = 7) and without T2DM (n = 7) undergoing RYGB. After 6 months, these patients were compared to a non-operative control group (n = 7) matched by BMI, sex, and age to the T2DM group. RESULTS: Fourteen patients underwent RYGB, with a mean BMI of 46.9 ± 5.3 kg/m2 and an average age of 47.9 ± 8.9 years; 85% were female. After 6 months post-surgery, the total weight loss (TWL) was 27.1 ± 6.3%, with no significant differences between the groups. Patients without diabetes had lower mean interstitial glucose levels (81 vs. 94 and 98 mg/dl, p < 0.01) and lower glucose management indicator (GMI) (5.2 vs. 5.6 and 5.65%, p = 0.01) compared to the control and T2DM groups, respectively. The coefficient of variation (CV) significantly increased only in patients with diabetes (17% vs. 26.7%, p < 0.01). Both groups with (0% vs. 2%, p = 0.03) and without (3% vs. 22%, p = 0.03) T2DM experienced an increased time below range with low glucose (54-69 mg/dL). However, patients without T2DM had significantly less time in rage (70-180 mg/dL) (97% vs. 78%, p = 0.04). CONCLUSION: Significant differences in CGM metrics among RYGB patients suggest an increase in glycemic variability after surgery, with a longer duration of hypoglycemia, especially in patients without T2DM.

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BACKGROUND: Obesity is believed to be a risk factor for COVID-19 and unfavorable outcomes, although data on this remains to be better elucidated. OBJECTIVE: To evaluate the impact of obesity on the endpoints of patients hospitalized due to SARS-CoV-2. METHODS: This retrospective cohort study evaluated patients hospitalized at a tertiary hospital (Hospital das Clínicas da Faculdade de Medicina da USP) from March to December 2020. Only patients positive for COVID-19 (real-time PCR or serology) were included. Data were collected from medical records and included clinical and demographic information, weight and height, SAPS-3 score, comorbidities, and patient-centered outcomes (mortality, and need for mechanical ventilation, renal replacement therapy, or vasoactive drugs). Patients were divided into categories according to their BMI (underweight, eutrophic, overweight and obesity) for comparison porpoise. RESULTS: A total of 2547 patients were included. The mean age was 60.3 years, 56.2% were men, 65.2% were white and the mean BMI was 28.1 kg/m2. SAPS-3 score was a risk factor for all patient-centered outcomes (HR 1.032 for mortality, OR 1.03 for dialysis, OR 1.07 for vasoactive drug use, and OR 1.08 for intubation, p < 0.05). Male sex increased the risk of death (HR 1.175, p = 0.027) and dialysis (OR 1.64, p < 0.001), and underweight was protective for vasoactive drug use (OR 0.45, p = 0.027) and intubation (OR 0.31, p < 0.003). CONCLUSION: Obesity itself was not an independent factor for worse patient-centered outcomes. Critical clinical state (indirectly evaluated by SAPS-3) appears to be the most important variable related to hard outcomes in patients infected with COVID-19.

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BACKGROUND: Identification of genetic causes of central precocious puberty have revealed epigenetic mechanisms as regulators of human pubertal timing. MECP2, an X-linked gene, encodes a chromatin-associated protein with a role in gene transcription. MECP2 loss-of-function mutations usually cause Rett syndrome, a severe neurodevelopmental disorder. Early pubertal development has been shown in several patients with Rett syndrome. The aim of this study was to explore whether MECP2 variants are associated with an idiopathic central precocious puberty phenotype. METHODS: In this translational cohort study, participants were recruited from seven tertiary centres from five countries (Brazil, Spain, France, the USA, and the UK). Patients with idiopathic central precocious puberty were investigated for rare potentially damaging variants in the MECP2 gene, to assess whether MECP2 might contribute to the cause of central precocious puberty. Inclusion criteria were the development of progressive pubertal signs (Tanner stage 2) before the age of 8 years in girls and 9 years in boys and basal or GnRH-stimulated LH pubertal concentrations. Exclusion criteria were the diagnosis of peripheral precocious puberty and the presence of any recognised cause of central precocious puberty (CNS lesions, known monogenic causes, genetic syndromes, or early exposure to sex steroids). All patients included were followed up at the outpatient clinics of participating academic centres. We used high-throughput sequencing in 133 patients and Sanger sequencing of MECP2 in an additional 271 patients. Hypothalamic expression of Mecp2 and colocalisation with GnRH neurons were determined in mice to show expression of Mecp2 in key nuclei related to pubertal timing regulation. FINDINGS: Between Jun 15, 2020, and Jun 15, 2022, 404 patients with idiopathic central precocious puberty (383 [95%] girls and 21 [5%] boys; 261 [65%] sporadic cases and 143 [35%] familial cases from 134 unrelated families) were enrolled and assessed. We identified three rare heterozygous likely damaging coding variants in MECP2 in five girls: a de novo missense variant (Arg97Cys) in two monozygotic twin sisters with central precocious puberty and microcephaly; a de novo missense variant (Ser176Arg) in one girl with sporadic central precocious puberty, obesity, and autism; and an insertion (Ala6_Ala8dup) in two unrelated girls with sporadic central precocious puberty. Additionally, we identified one rare heterozygous 3'UTR MECP2 insertion (36_37insT) in two unrelated girls with sporadic central precocious puberty. None of them manifested Rett syndrome. Mecp2 protein colocalised with GnRH expression in hypothalamic nuclei responsible for GnRH regulation in mice. INTERPRETATION: We identified rare MECP2 variants in girls with central precocious puberty, with or without mild neurodevelopmental abnormalities. MECP2 might have a role in the hypothalamic control of human pubertal timing, adding to the evidence of involvement of epigenetic and genetic mechanisms in this crucial biological process. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and the Wellcome Trust.

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Mindful eating (ME) has been linked to improvement in binge eating disorder, but this approach in obesity management has shown conflicting results. Our aim was to assess the effect of ME associated with moderate energy restriction (MER) on weight loss in women with obesity. Metabolic parameters, dietary assessment, eating behaviour, depression, anxiety and stress were also evaluated. A total of 138 women with obesity were randomly assigned to three intervention groups: ME associated with MER (ME + MER), MER and ME, and they were followed up monthly for 6 months. ME + MER joined seven monthly mindfulness-based intervention group sessions each lasting 90 min and received an individualised food plan with MER (deficit of 2092 kJ/d - 500 kcal/d). MER received an individualised food plan with MER (deficit of 2092 kJ/d - 500 kcal/d), and ME joined seven monthly mindfulness-based intervention group sessions each lasting 90 min. Seventy patients completed the intervention. Weight loss was significant, but no statistically significant difference was found between the groups. There was a greater reduction in uncontrolled eating in the ME group than in the MER group and a greater reduction in emotional eating in the ME group than in both the MER and the ME + MER groups. No statistically significant differences were found in the other variables evaluated between groups. The association between ME with energy restriction did not promote greater weight loss than ME or MER.

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INTRODUCTION: Although hyperferritinemia may reflect the inflammatory status of patients with non-alcoholic fatty liver disease (NAFLD), approximately 33% of hyperferritinemia cases reflect real hepatic iron overload. AIM: To evaluate a non-invasive method for assessing mild iron overload in patients with NAFLD using 3T magnetic resonance imaging (MRI) relaxometry, serum hepcidin, and the expression of ferritin subunits. METHODS: This cross-sectional study assessed patients with biopsy-proven NAFLD. MRI relaxometry was performed using a 3T scanner in all patients, and the results were compared with iron content determined by liver biopsy. Ferritin, hepcidin, and ferritin subunits were assessed and classified according to ferritin levels and to siderosis identified by liver biopsy. RESULTS: A total of 67 patients with NAFLD were included in the study. MRI revealed mild iron overload in all patients (sensitivity, 73.5%; specificity, 70%). For mild (grade 1) siderosis, the transverse relaxation rate (R2*) threshold was 58.9 s-1 and the mean value was 72.5 s-1 (SD, 33.9), while for grades 2/3 it was 88.2 s-1 (SD, 31.9) (p < 0.001). The hepcidin threshold for siderosis was > 30.2 ng/mL (sensitivity, 87%; specificity, 82%). Ferritin H and ferritin L subunits were expressed similarly in patients with NAFLD, regardless of siderosis. There were no significant differences in laboratory test results between the groups, including glucose parameters and liver function tests. CONCLUSIONS: MRI relaxometry and serum hepcidin accurately assessed mild iron overload in patients with dysmetabolic iron overload syndrome.

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Obesity is a chronic disease associated with impaired physical and mental health. A widespread view in the treatment of obesity is that the goal is to normalize the individual's body mass index (BMI). However, a modest weight loss (usually above 5%) is already associated with clinical improvement, while weight losses of 10%-15% bring even further benefits, independent from the final BMI. The percentage of weight reduction is accepted as a treatment goal since a greater decrease in weight is frequently difficult to achieve due to metabolic adaptation along with environmental and lifestyle factors. In this document, the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO) propose a new obesity classification based on the maximum weight attained in life (MWAL). In this classification, individuals losing a specific proportion of weight are classified as having "reduced" or "controlled" obesity. This simple classification - which is not intended to replace others but to serve as an adjuvant tool - could help disseminate the concept of clinical benefits derived from modest weight loss, allowing individuals with obesity and their health care professionals to focus on strategies for weight maintenance instead of further weight reduction. In future studies, this proposed classification can also be an important tool to evaluate possible differences in therapeutic outcomes between individuals with similar BMIs but different weight trajectories.

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ABSTRACT Obesity is a chronic disease associated with impaired physical and mental health. A widespread view in the treatment of obesity is that the goal is to normalize the individual's body mass index (BMI). However, a modest weight loss (usually above 5%) is already associated with clinical improvement, while weight losses of 10%-15% bring even further benefits, independent from the final BMI. The percentage of weight reduction is accepted as a treatment goal since a greater decrease in weight is frequently difficult to achieve due to metabolic adaptation along with environmental and lifestyle factors. In this document, the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO) propose a new obesity classification based on the maximum weight attained in life (MWAL). In this classification, individuals losing a specific proportion of weight are classified as having "reduced" or "controlled" obesity. This simple classification - which is not intended to replace others but to serve as an adjuvant tool - could help disseminate the concept of clinical benefits derived from modest weight loss, allowing individuals with obesity and their health care professionals to focus on strategies for weight maintenance instead of further weight reduction. In future studies, this proposed classification can also be an important tool to evaluate possible differences in therapeutic outcomes between individuals with similar BMIs but different weight trajectories.

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BACKGROUND: Most patients undergoing Roux-en-Y gastric bypass (RYGB) are women in reproductive age. It is not known if bariatric surgery affects the pharmacokinetics of oral contraceptives. OBJECTIVES: The primary objective was to evaluate ethinylestradiol (EE) and levonorgestrel (LNG) absorption in women undergoing RYGB, compared with nonoperated controls matched by age and body mass index (BMI). A secondary objective was to assess whether the time since surgery and BMI in the postoperative period influenced the absorption parameters. SETTING: University hospital, Brazil. METHODS: This study was designed to compare the maximum plasma concentration (Cmax), the time to the peak plasma level (Tmax), the area under the curve (AUC0-8 and AUC0-∞) after a single dose of a combined oral contraceptive with 0.03 mg EE and 0.15 mg LNG among 20 women after RYGB and 20 controls. Blood samples were obtained for 8 hours. RESULTS: The mean LNG AUC0-8 and LNG AUC0-∞ were higher in RYGB group (P = .048 and P = .004, respectively). We found a positive correlation for LNG AUC0-8 (P = .045) and AUC0-∞ (P = .004) and the time since surgery, and we found a negative correlation for LNG Cmax (P = .018), AUC0-8 (P = .003), and AUC0-∞ (P = .001) and BMI. CONCLUSION: No significant differences were found in oral EE pharmacokinetics. The operated group showed higher mean LNG AUC0-8 and AUC0-∞ but it was not considered clinically significant. The present study suggests that RYGB may not affect EE and LNG absorption.

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Melatonin, a pineal hormone synthesized at night, is critical for the synchronization of circadian and seasonal rhythms, being a key regulator of energy metabolism in many animal species. Although studies in humans are lacking, several reports, mainly on hibernating animals, demonstrated that melatonin supplementation and a short photoperiod increase brown adipose tissue (BAT) mass. The present proof-of-concept study is the first, to our knowledge, to evaluate BAT in patients with melatonin deficiency (radiotherapy or surgical removal of pineal gland) before and after daily melatonin (3 mg) replacement for 3 months. All four studied patients presented increased BAT volume and activity measured by positron emission tomography-MRI. We also found an improvement in total cholesterol and triglyceride blood levels without significant effects on body weight, liver fat, and HDL and LDL levels. Albeit not statistically significant, fasting insulin levels and HOMA of insulin resistance decreased in all four patients. The present results show that oral melatonin replacement increases BAT volume and activity and improves blood lipid levels in patients with melatonin deficiency, suggesting that melatonin is a possible BAT activator. Future studies are warranted because hypomelatoninemia is usually present in aging and appears as a result of light-at-night exposure and/or the use of ß-blocker drugs.

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AIM: We aimed to assess the influence of fasting insulin resistance on metabolically healthy obesity (MHO) prevalence in adolescents and to identify associated factors. METHODS: This retrospective, registry-based, cross-sectional study included 418 (51.9% girls) 10- to 18-year-old adolescents with obesity from a tertiary outpatient clinic in Sao Paulo, Brazil, between 2009 and 2013. The prevalence of MHO was estimated according to two definitions: (i) no cardiometabolic risk factors (CMRF) by the International Diabetes Federation parameters and (ii) no CMRF and homeostatic model assessment for insulin resistance <3.16. Adjusted prevalence ratios and 95% confidence intervals (CI) evaluated the association of gender, age, pubertal stages, skin colour and degree of obesity with MHO. RESULTS: Metabolically healthy obesity prevalence was lower in definition II than definition I (12.7%; 95% CI 9.1-16.3% versus 43.1%; 95% CI 38.0-48.2%, respectively). Adjusted results showed negative association between severe obesity and MHO by both definitions (p ≤ 0.01). Male and later pubertal stages were also less likely to have MHO, but neither remained significant in definition II. CONCLUSION: Metabolically healthy obesity prevalence decreased when insulin resistance was part of the definition. Detecting pre-clinical insulin resistance may improve the management of treatment-seeking adolescents, especially when they present no CMRF.

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PURPOSE OF REVIEW: The purpose of this study is to present changes of policies and norms aimed to reduce obesity levels that have been adopted in some Latin American countries. RECENT FINDINGS: The global increase of the excess weight within the population has been demanding governmental actions aimed at preventing health impacts generated by obesity. Over recent years, many Latin American countries have established a number of regulations aimed at reducing weight in the population using interventions that could effectively prevent childhood obesity, including the taxation of sugar-sweetened beverages (SSBs), increasing physical activity in open spaces, and, especially, front-of-package labeling. Some strategies are part of the Action Plan for Prevention of Child and Adolescence Obesity signed by all countries in Latin America, which currently have among the highest prevalence of childhood obesity in the world. Among them are the implementation of fiscal policies on energy-dense and nutrient-poor foods and taxes on SSBs; improvements in nutrition labeling, highlighting the front-of-package (FOP) labeling to promote the choice of healthier products at the time of purchase; and promotion of an active lifestyle, such as encouraging the use of bicycle paths or physical activity programs at school. The real impact of these prevention strategies implemented in Latin America on the prevalence of obesity is still unknown.

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Childhood obesity is a major public health problem. It has a direct impact on the quality of life of children and adolescents, as well as on their future risk of developing chronic diseases. Dietary patterns rich in fats and sugars and lacking dietary fibers, vitamins, and minerals, as well as lack of physical exercise have been associated with the rise of obesity prevalence. However, factors that contribute to the preference for foods rich in these nutrients are not well established. Taste is recognized as an important predictor of food choices, and polymorphisms in taste-related genes may explain the variability of taste preference and food intake. The aim of this research is to evaluate the influence of polymorphisms of the sweet taste receptor gene TAS1R2 on diet and metabolic profile in obese children and adolescents. A cross-sectional study with 513 obese children and adolescents and 135 normal-weight children was carried out. A molecular study was performed for the single nucleotide polymorphisms (SNPs) rs9701796 and rs35874116 of TAS1R2, and dietary intake, anthropometric parameters (weight, height, waist circumference, waist-to-height ratio (WHtR)), and metabolic profile (including fasting glucose, insulin, triglyceride, high-density lipoprotein (HDL)-cholesterol, and leptin levels) were analyzed. The variant rs9701796 was associated with increased waist-height ratio, as well as with a higher chocolate powder intake in obese children. The variant rs35874116 was associated with a lower dietary fiber intake. In conclusion, there was no relationship between genotypes and risk of obesity. Obese adolescents carrying the serine allele of SNP rs9701796 in TAS1R2 showed higher waist-to-height ratio and chocolate powder intake, whereas those carrying the valine allele of SNP rs35874116 in TAS1R2 were characterized by lower dietary fiber intake.

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The prevalence of obesity increases worldwide. Treating obesity and its associated health problems has a significant economic impact on health care systems. The unsatisfactory long-term outcomes observed in the obesity treatment are due to its complex pathophysiology and the inherent difficulties associated with maintenance of lifestyle modifications. Determined by genetic and environmental factors, obesity has been officially recognized as a chronic disease, an action that allowed the recognition of anti-obesity drugs as legitimate therapeutic options to address the growing obesity endemic. Like other chronic diseases, obesity requires long-term treatment. Pharmacological interventions, when used as an adjunct to lifestyle changes, are useful to facilitate clinically meaningful weight loss, which may impact on obesity-associated comorbid conditions. In the past, medications for weight reduction were limited. However, the landscape has changed and new drugs provide additional options for weight management. Among the new drugs, liraglutide is the most studied, especially regarding its effects on the limbic system. As an adjunct to a reduced-calorie diet and increased physical activity, treatment with liraglutide 3.0 mg provides a statistically significant and clinically meaningful weight loss. Liraglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist that shares 97% homology to native GLP-1. Receptor agonists of GLP-1, including liraglutide, have emerged as effective therapies for type 2 diabetes and obesity. This review will address the major findings concerning the central regulation of appetite and the main studies that evaluated new drugs for obesity treatment, with a greater focus on liraglutide 3.0 mg.