Efficacy of the hybrid closedloop insulin delivery system in children and adolescents with type 1 diabetes: a meta-analysis with trial sequential analysis.

The aim of this study was to assess the efficacy and safety of hybrid closed-loop (HCL) systems for insulin delivery in children and adolescents with type 1 diabetes (T1D). We searched Embase, PubMed, and Cochrane Library for randomized controlled trials (RCTs) published until March 2023 comparing the HCL therapy with control therapies for children and adolescents with T1D. We computed weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) with 95% confidence intervals (CIs) for binary endpoints. Four RCTs and 501 patients were included, of whom 323 were randomized to HCL therapy. Compared with control therapies, HCL significantly improved the period during which glucose level was 70-180 mg/dL (WMD 10.89%, 95% CI 8.22-13.56%) and the number of participants with glycated hemoglobin (HbA1c) level < 7% (RR 2.61, 95% CI 1.29-5.28). Also, HCL significantly reduced the time during which glucoselevel was > 180 mg/dL (WMD-10.46%, 95% CI-13.99 to-6.93%) and the mean levels of glucose (WMD-16.67 mg/dL, 95% CI-22.25 to-11.09 mg/dL) and HbA1c (WMD-0.50%, 95% CI-0.68 to-0.31). There were no significant differences between therapies regarding time during which glucose level was < 70 mg/dL or <54 mg/dL or number of episodes of ketoacidosis, hyperglycemia, and hypoglycemia. In this meta-analysis, HCL compared with control therapies was associated with improved time in range and HbA1c control in children and adolescents with T1D and a similar profile of side effects. These findings support the efficacy of HCL in the treatment of T1D in this population.

Continuous Glucose Monitoring Systems in Noninsulin-Treated People with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Introduction: Continuous glucose monitoring (CGM) has shown favorable outcomes in patients with type 2 diabetes (T2D) who are on insulin therapy. However, the efficacy of CGM in managing glucose levels in noninsulin-treated people with T2D remains controversial. Methods: PubMed, Cochrane, and Embase were searched for randomized controlled trials (RCTs) comparing CGM to self-monitoring of blood glucose (SMBG) in people with T2D not using insulin. We computed weighted mean differences (WMDs) and standard mean differences (SMD) for continuous outcomes, with 95% confidence intervals (CIs). Heterogeneity was assessed using I2 statistics. Statistical analyses were performed using R version 4.2.3. Results: We included six RCTs comprising 407 noninsulin-treated people with T2D of whom 228 were randomized to CGM. Diabetes duration ranged from 5.4 to 13.9 years. The mean age was 57.9 years and the mean body mass index was 30.8 kg/m2. Four trials used real-time CGM (rt-CGM) and two intermittent scanning CGM (is-CGM). Compared with SMBG, CGM significantly reduced the glycated hemoglobin level (WMD -0.31%; 95% CI -0.42 to -0.21; I2 = 0%), glucose level (WMD -11.16 mg/dL; 95% CI -19.94 to -2.39; I2 = 0%), time in hypoglycemia level 2 (WMD -0.28%; 95% CI -0.52 to -0.03; I2 = 91%), glucose time >180 mg/dL (WMD -7.75%; 95% CI -12.04 to -3.45; I2 = 0%), and the standard deviation of glucose variation (WMD -4.00 mg/dL; 95% CI -6.86 to -1.14; I2 = 0%). CGM also increased time in range (WMD 8.63%; 95% CI 4.54-12.71; I2 = 0%) and treatment satisfaction (SMD 0.79; 95% CI 0.54-1.05; I2 = 0%). Conclusion: In this meta-analysis, rt-CGM and is-CGM were associated with improvement in glycemic control in people with T2D not using insulin when compared to SMBG.

"Anti-obesity medications" or "medications to treat obesity" instead of "weight loss drugs" - why language matters - an official statement of the Brazilian Association for the Study of Obesity and Metabolic Syndrome (ABESO) and the Brazilian Society of Endocrinology and Metabolism (SBEM).

Obesity is largely undertreated, in part because of the stigma surrounding the disease and its treatment. The use of the term "weight loss drugs" to refer to medications for the treatment of obesity may contribute to this stigma, leading to the idea that anyone who wants to lose weight could use them and that short-term use, only in the active weight loss phase would be enough. On the contrary, the use of terms such as "medications to treat obesity" or "anti-obesity medications" conveys the idea that the treatment is directed at the disease rather than the symptom. This joint statement by the Brazilian Association for the Study of Obesity and Metabolic Syndrome (ABESO) and the Brazilian Society of Endocrinology and Metabolism (SBEM) intends to alert the press, healthcare professionals and scientific community about the importance of the appropriate use of language, with the aim of improving obesity care.

Efficacy and safety of bexagliflozin in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

AIM: To assess the efficacy of bexagliflozin in reducing glycated haemoglobin (HbA1c) and the occurrence of side effects in patients with type 2 diabetes (T2DM). METHODS: We searched the PubMed, Embase, Cochrane and ClinicalTrials.gov databases for placebo-controlled, randomized clinical trials published up until 15 February 2023. The primary outcome was change in HbA1c. We computed weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). RESULTS: A total of six studies and 3111 patients were included, of whom 1951 were prescribed bexagliflozin. Compared with placebo, bexagliflozin significantly reduced HbA1c levels (WMD -0.53%; 95% CI -0.75, -0.31), fasting plasma glucose levels (WMD -1.45 mmol/L; 95% CI -2.32, -0.57), systolic blood pressure (WMD -4.66 mmHg; 95% CI -6.41, -2.92), diastolic blood pressure (WMD -2.12 mmHg; 95% CI -3.94, -0.30), body weight overall (WMD -1.61 kg; 95% CI -2.14, -1.07), and body weight in patients with a body mass index >25 kg/m2 (WMD -2.05 kg; 95% CI -2.78, -1.31). The proportion of patients who achieved HbA1c < 7% was higher in patients who received bexagliflozin as compared with placebo (OR 1.94; 95% CI 1.36-2.78). There were no significant differences between groups regarding side effects such as hypoglycaemia, genital mycotic infection, urinary tract infection, diarrhoea, headache, nausea, polyuria, diabetic ketoacidosis, or all-cause mortality. CONCLUSIONS: In this meta-analysis, the use of bexagliflozin was associated with improved clinical and laboratory measures in patients with T2DM compared with placebo, with a similar profile of side effects. These findings support the efficacy of bexagliflozin in the treatment of T2DM.

Flash glucose monitoring system in special situations.

The management of diabetes mellitus (DM) requires maintaining glycemic control, and patients must keep their blood glucose levels close to the normal range to reduce the risk of microvascular complications and cardiovascular events. While glycated hemoglobin (A1C) is currently the primary measure for glucose management and a key marker for long-term complications, it does not provide information on acute glycemic excursions and overall glycemic variability. These limitations may even be higher in some special situations, thereby compromising A1C accuracy, especially when wider glycemic variability is expected and/or when the glycemic goal is more stringent. To attain adequate glycemic control, continuous glucose monitoring (CGM) is more useful than self-monitoring of blood glucose (SMBG), as it is more convenient and provides a greater amount of data. Flash Glucose Monitoring (isCGM /FGM) is a widely accepted option of CGM for measuring interstitial glucose levels in individuals with DM. However, its application under special conditions, such as pregnancy, patients on hemodialysis, patients with cirrhosis, during hospitalization in the intensive care unit and during physical exercise has not yet been fully validated. This review addresses some of these specific situations in which hypoglycemia should be avoided, or in pregnancy, where strict glycemic control is essential, and the application of isCGM/FGM could alleviate the shortcomings associated with poor glucose control or high glycemic variability, thereby contributing to high-quality care.

Bariatric surgery-induced weight loss in patients with and without type 2 diabetes mellitus.

Surgical treatment of obesity leads to weight loss and metabolic improvement, but it is unclear if the response differs between patients with and without type 2 diabetes. Retrospective cohort study comparing weight loss and metabolic outcomes between patients with and without type 2 diabetes, matched for body mass index (BMI), gender and age, 12 months after Roux-en-Y gastric bypass. Forty-eight patients with type 2 diabetes (D) and 48 without type 2 diabetes (ND) were evaluated, 87.5% female, mean age 42.2 ± 0.9 years. The mean baseline weight and BMI of the D and ND groups were, respectively, 120.3 ± 21.6 vs 123.7 ± 20.8 kg (P = .45) and 47.2 ± 7.5 vs 47.2 ± 6.9 kg/m2 (P = .70). After 12 months, there was no significant difference in weight (40.4 ± 16.9 vs 44.1 ± 12.2 kg, P = .28) and BMI (15.8 ± 6.5 vs 16.9 ± 4.5 kg/m2 , P = .26) variation between groups. The parameters that presented significant variation were (D vs ND): fasting blood glucose (41.6 ± 43.0 vs 12.7 ± 17.2 mg/dL, P < .01), HbA1c (1.8 ± 1.6 vs 0.6 ± 0.7%; P < .01), triglycerides (91.1 ± 100.4 vs 54.2 ± 43.8 mg/dL; P = .04), low-density lipoprotein (27.2 ± 41.5 vs 37.5 ± 24.2 mg/dL; P < .01) and gamma glutamyl transferase (46.5 ± 55.3 vs 17.7 ± 11.9 UI/L; P = .04). Weight loss 12 months after a gastric bypass was similar in patients with and without type 2 diabetes, the greater metabolic benefits appearing in patients with type 2 diabetes as they had more pronounced changes at baseline.

Radiologic evidence that hypothalamic gliosis is improved after bariatric surgery in obese women with type 2 diabetes.

BACKGROUND/OBJECTIVES: Hypothalamic neurons play a major role in the control of body mass. Obese subjects present radiologic signs of gliosis in the hypothalamus, which may reflect the damage or loss of neurons involved in whole-body energy homeostasis. It is currently unknown if hypothalamic gliosis (1) differs between obese nondiabetic (ND) and obese diabetic subjects (T2D) or (2) is modified by extensive body mass reduction via Roux-n-Y gastric bypass (RYGB). SUBJECTS/METHODS: Fifty-five subjects (all female) including lean controls (CT; n = 13), ND (n = 28), and T2D (n = 14) completed at least one study visit. Subjects underwent anthropometrics and a multi-echo MRI sequence to measure mean bilateral T2 relaxation time in the mediobasal hypothalamus (MBH) and two reference regions (amygdala and putamen). The obese groups underwent RYGB and were re-evaluated 9 months later. Analyses were by linear mixed models. RESULTS: Analyses of T2 relaxation time at baseline showed a group by region interaction only in the MBH (P < 0.0001). T2D had longer T2 relaxation times compared to either CT or ND groups. To examine the effects of RYGB on hypothalamic gliosis a three-way (group by region by time) mixed effects model adjusted for age was executed. Group by region (P < 0.0001) and region by time (P = 0.0005) interactions were significant. There was a reduction in MBH relaxation time by RYGB, and, although the T2D group still had higher T2 relaxation time overall compared to the ND group, the T2D group had significantly lower T2 relaxation time after surgery and the ND group showed a trend. The degree of reduction in MBH T2 relaxation time by RYGB was unrelated to clinical outcomes. CONCLUSION: T2 relaxation times, a marker of hypothalamic gliosis, are higher in obese women with T2D and are reduced by RYGB-induced weight loss.

Effect of pioglitazone treatment on brown adipose tissue volume and activity and hypothalamic gliosis in patients with type 2 diabetes mellitus: a proof-of-concept study.

AIMS: This study aimed to evaluate the effect of pioglitazone on brown adipose tissue function and hypothalamic gliosis in humans. Brown adipose tissue and the hypothalamus are regarded as important potential pharmacological targets to metabolic diseases, and defining the impact of current therapies on their structure and/or function could provide therapeutic advance in this field. METHODS: Six patients with type 2 diabetes were treated for 24 weeks with pioglitazone 30 mg/day as an add-on therapy. Brown adipose tissue glucose uptake and volume were determined using 18F-FDG PET/CT scans; hypothalamic gliosis was determined using MRI scans; blood was collected for hormone and biochemistry measurements. All tests were performed at inclusion and six months after pioglitazone introduction. RESULTS: Pioglitazone treatment led to a significant 3% body mass increase. There were neither changes in cold-induced brown adipose tissue glucose uptake and volume nor changes in hypothalamic gliosis. CONCLUSIONS: This is a proof-of-concept study that provides clinical evidence for a lack of action of a thiazolidinedione, pioglitazone, to promote homogeneous and measurable changes in brown adipose tissue volume and also in hypothalamic gliosis after 6 months of treatment.

Effects of Bariatric Surgery in Male Obesity-Associated Hypogonadism.

INTRODUCTION: The prevalence of obesity has grown exponentially over the last several decades. Research has linked male obesity to changes in the gonadal axis, which can induce functional hypogonadism. Bariatric surgery provides sustained weight loss and metabolic improvement. This was a retrospective cohort study to evaluate the male gonadal axis and metabolic profiles of obese individuals during the bariatric pre- and post-operative periods while comparing them to a normal body mass index (BMI) group. METHODS: Twenty-nine obese men, who underwent bariatric surgery between 2012 and 2016 at the Federal University of Santa Catarina Hospital and a control group (CG) of 29 age-matched men with normal BMI, were analyzed. Bariatric pre- and 6-month post-operative data were compared with the CG. RESULTS: The study group (G1) presented an average age, weight, and BMI of 42.8 ± 9.5 years, 155.2 ± 25.8 kg, and 50.6 ± 7.1 kg/m2, respectively. The pre-operative total testosterone (TT) G1 values were different from the CG (229.5 ± 96.4 versus 461.5 ± 170.8 ng/dL, p < 0.01). Bariatric surgery promoted a statistically significant improvement in weight, TT, and metabolic profiles in surgical patients. CONCLUSION: Functional hypogonadism is prevalent in obese men, and we must be aware of this diagnosis. Although studies defining the best diagnostic parameters and indication of adequate hormone replacement therapy are lacking, an increase in TT levels during the first 6 months after bariatric surgery was identified in our study. Previous studies have shown that gonadal function can normalize after metabolic improvement.

Níveis séricos de 25(OH)-vitamina D em pacientes com obesidade grau 2 e 3 / Serum 25(OH)-vitamin D levels in patients with grade 2 and 3 obesity

Introdução: Deficiência de vitamina D é reconhecida hoje como pandemia e fator de impacto no desenvolvimento de várias doenças, sendo recentemente relacionada à fisiopatologia da obesidade e da síndrome metabólica. Objetivos: Analisar os níveis séricos de vitamina D em pacientes obesos em avaliação pré-operatória para cirurgia bariátrica correlacionando-os com variáveis clínicas, laboratoriais e epidemiológicas. Métodos: Estudo observacional transversal, com 170 pacientes obesos grau 2 e 3 avaliados no ambulatório de cirurgia bariátrica do HU-UFSC em 2013. Foram coletados dados clínicos, epidemiológicos, antropométricos e laboratoriais. Resultados: A média de idade foi de 40 ± 10 anos, sendo a maioria do sexo feminino, caucasiana e habitante do litoral. O peso e o IMC médios foram 126,0 ± 24,2 kg e 48,0 ± 7,1 kg/m² respectivamente. As comorbidades mais prevalentes foram diabetes mellitus tipo 2 (24,7%) e hipertensão arterial sistêmica (55,3%). A média dos níveis de 25(OH)-vitamina D foi de 26,3 ± 8,4 ng/mL. Deficiência e insuficiência de vitamina D foram encontrados em 23,5 e 45,3% dos pacientes, respectivamente. Não houve correlação significativa entre os níveis de vitamina D e as demais variáveis estudadas, exceto o cálcio corrigido para a albumina. Conclusão: Os pacientes obesos em avaliação para cirurgia bariátrica neste serviço apresentam alta prevalência de deficiência/insuficiência de vitamina D. Estes níveis apresentaram correlação negativa estatisticamente significativa com o cálcio sérico corrigido, mas não com as demais variáveis estudadas.

Background: Vitamin D deficiency nowadays is recognized as a pandemic and important factor for development of a variety of diseases. It has been recently related to the physiopathology of obesity and metabolic syndrome. Objectives: To analyze serum levels of vitamin D in obese patients on preoperative evaluation for bariatric surgery and correlate them to clinical, laboratory and epidemiological variables. Methods: Cross-sectional observational study, including 170 patients with grade 2 and 3 obesity evaluated at the obesity outpatient clinic of the University Hospital (HU-UFSC) in 2013. Clinical, epidemiological, anthropometric and laboratory data were collected. Results: Mean age was 40 ± 10 years, the majority was females, Caucasian and living on the coast. Average weight and BMI were 126.0 ± 24.2 kg e 48.0 ± 7.1 kg/m² respectively. The most prevalent comorbidities were type 2 diabetes mellitus (24.7%) and hypertension (55.3%). Mean serum level of 25(OH)-vitamin D was 26.3 ± 8.4 ng/mL. Vitamin D deficiency and insufficiency were found in 23.5 and 45.3% of patients, respectively. There was no significant correlation between serum vitamin D levels and variables analyzed in this study, except albumin-corrected serum calcium. Conclusion: Obese patients evaluated for bariatric surgery in this service present a high prevalence of vitamin D deficiency/insufficiency. These levels were significantly negatively correlated with albumin-corrected serum calcium, but not with the other studied variables.

Escores de neuropatia periférica em diabéticos / Peripheral neuropathy scores in diabetic

OBJETIVO: Diabetes mellitus é uma doença crônica prevalente, associada a inúmeras complicações. A neuropatia periférica diabética é a mais comum, acometendo 50% dos diabéticos, mas muitas vezes não é diagnosticada. Por cursar com insensibilidade distal e alterações arquiteturais dos pés, predispõe a úlceras, podendo culminar no pé diabético com risco de amputação. O diabetes mellitus é responsável por 70% das amputações de membros, que poderiam ser prevenidas com o diagnóstico precoce da neuropatia periférica diabética. Sugere-se avaliar o grau de neuropatia em diabéticos por meio de escores, visando homogeneizar o diagnóstico, quantificar a prevalência e promover medidas preventivas. MÉTODOS: Realizou-se entrevista, exame físico e coleta de dados de diabéticos atendidos ambulatorialmente, para pontuação e qualificação no Escore de Sintomas Neuropáticos e no Escore de Comprometimento Neuropático, validados na língua portuguesa para avaliar neuropatia periférica diabética, além de análise das características clínicas e epidemiológicas associadas. RESULTADOS: Foram incluídos 116 pacientes, constatando-se neuropatia periférica diabética em 31,9%. Houve correlação significativa de neuropatia periférica diabética coma idade dos pacientes, mas não com as demais variáveis clínicas e laboratoriais. Os pacientes avaliados apresentaram médias de idade de 55±15 anos e tempo de diabetes de 14,8±10,9 anos, sendo predominantemente caucasianos, mulheres e portadores de diabetes mellitus tipo 2. Eram hipertensos 67,2% e 42,2%, obesos. CONCLUSÃO: A prevalência encontrada corrobora a literatura, embora poucos estudos tenham utilizado critérios similares para diagnosticar neuropatia periférica diabética. Empregando os escores padronizados, de baixo custo e fácil aplicação possibilitamos o diagnóstico precoce e embasado dessa entidade, sendo possível, com isso, reduzir a prevalência de graves complicações do pé diabético e disseminar informações a respeito.

OBJECTIVE: Diabetes mellitus is a prevalent chronic disease, associated with numerous complications. Diabetic peripheral neuropathy is the most common, affecting 50% of diabetics, although is often not diagnosed. Presenting with distal numbness and architectural alterations of the feet, it predisposes ulcers and may culminate in diabetic foot at risk for amputation. Diabetes mellitus is responsible for 70% of limb amputations, which could be prevented with early diagnosis of diabetic peripheral neuropathy. This study aims to evaluate the degree of neuropathy in diabetics through validated scores, in order to standardize the diagnosis, quantify the prevalence and promote preventive actions. METHODS: We performed an interview, physical examination and data collection of diabetic outpatients, for rating in the Neuropathy Symptom Score and the Neuropathy Disability Score, validated in Portuguese, to assess diabetic peripheral neuropathy, in addition to analysis of clinical and epidemiological associated characteristics. RESULTS: We included 116 patients and diabetic peripheral neuropathy was found in 31.9%. There was significant correlation diabetic peripheral neuropathy with age, but not with other clinical and laboratory variables. The mean age was 55±15 years, diabetes duration was 14.8±10.9 years and patients were predominantly Caucasian, women and had type 2 diabetes mellitus. Of the patients, 67.2 % were hypertensive and 42.2% obese. CONCLUSION: The prevalence found is supported by previous data, although few studies have used similar criteria to diagnose diabetic peripheral neuropathy. Employing the standard scores, of low cost and easy implementation, we enable early and accurate diagnosis of this condition, allowing to reduce the prevalence of severe diabetic foot complications and spread information about it.

[Hypothalamic dysfunction in obesity]. / Disfunção hipotalâmica na obesidade.

Obesity, defined as abnormal or excessive fat accumulation that may impair life quality, is one of the major public health problems worldwide. It results from an imbalance between food intake and energy expenditure. The control of energy balance in animals and humans is performed by the central nervous system (CNS) by means of neuroendocrine connections, in which circulating peripheral hormones, such as leptin and insulin, provide signals to specialized neurons of the hypothalamus reflecting body fat stores, and induce appropriate responses to maintain the stability of these stores. The majority of obesity cases are associated with central resistance to both leptin and insulin actions. In experimental animals, high-fat diets can induce an inflammatory process in the hypothalamus, which impairs leptin and insulin intracellular signaling pathways, and results in hyperphagia, decreased energy expenditure and, ultimately, obesity. Recent evidence obtained from neuroimaging studies and assessment of inflammatory markers in the cerebrospinal fluid of obese subjects suggests that similar alterations may be also present in humans. In this review, we briefly present the mechanisms involved with the loss of homeostatic control of energy balance in animal models of obesity, and the current evidence of hypothalamic dysfunction in obese humans.

Disfunção hipotalâmica na obesidade / Hypothalamic dysfunction in obesity

A obesidade, definida como o acúmulo excessivo ou anormal de gordura que pode causar dano à saúde do indivíduo, é considerada atualmente um dos principais problemas de saúde pública. Resulta de um desequilíbrio entre a ingestão alimentar e o gasto corporal de energia. O controle do balanço energético de animais e seres humanos é realizado pelo sistema nervoso central (SNC) por meio de conexões neuroendócrinas, em que hormônios periféricos circulantes, como a leptina e a insulina, sinalizam neurônios especializados do hipotálamo sobre os estoques de gordura do organismo e induzem respostas apropriadas para a manutenção da estabilidade desses estoques. A maioria dos casos de obesidade se associa a um quadro de resistência central à ação da leptina e da insulina. Em animais de experimentação, a dieta hiperlipídica é capaz de induzir um processo inflamatório no hipotálamo, que interfere com as vias intracelulares de sinalização por esses hormônios, resultando em hiperfagia, diminuição do gasto de energia e, por fim, obesidade. Evidências recentes obtidas por intermédio de estudos de neuroimagem e avaliação de marcadores inflamatórios no líquido cefalorraquidiano de indivíduos obesos sugerem que alterações semelhantes podem estar presentes também em seres humanos. Nesta revisão, apresentamos sumariamente os mecanismos envolvidos com a perda do controle homeostático do balanço energético em modelos animais de obesidade e as evidências atuais de disfunção hipotalâmica em humanos obesos.

Obesity, defined as abnormal or excessive fat accumulation that may impair life quality, is one of the major public health problems worldwide. It results from an imbalance between food intake and energy expenditure. The control of energy balance in animals and humans is performed by the central nervous system (CNS) by means of neuroendocrine connections, in which circulating peripheral hormones, such as leptin and insulin, provide signals to specialized neurons of the hypothalamus reflecting body fat stores, and induce appropriate responses to maintain the stability of these stores. The majority of obesity cases are associated with central resistance to both leptin and insulin actions. In experimental animals, high-fat diets can induce an inflammatory process in the hypothalamus, which impairs leptin and insulin intracellular signaling pathways, and results in hyperphagia, decreased energy expenditure and, ultimately, obesity. Recent evidence obtained from neuroimaging studies and assessment of inflammatory markers in the cerebrospinal fluid of obese subjects suggests that similar alterations may be also present in humans. In this review, we briefly present the mechanisms involved with the loss of homeostatic control of energy balance in animal models of obesity, and the current evidence of hypothalamic dysfunction in obese humans.

Partial reversibility of hypothalamic dysfunction and changes in brain activity after body mass reduction in obese subjects.

OBJECTIVE: Inflammation and dysfunction of the hypothalamus are common features of experimental obesity. However, it is unknown whether obesity and massive loss of body mass can modify the immunologic status or the functional activity of the human brain. Therefore, the aim of this study was to determine the effect of body mass reduction on brain functionality. RESEARCH DESIGN AND METHODS: In humans, changes in hypothalamic activity after a meal or glucose intake can be detected by functional magnetic resonance imaging (fMRI). Distinct fMRI analytic methods have been developed to explore changes in the brain's activity in several physiologic and pathologic conditions. We used two analytic methods of fMRI to explore the changes in the brain activity after body mass reduction. RESULTS: Obese patients present distinct functional activity patterns in selected brain regions compared with lean subjects. On massive loss of body mass, after bariatric surgery, increases in the cerebrospinal fluid (CSF) concentrations of interleukin (IL)-10 and IL-6 are accompanied by changes in fMRI patterns, particularly in the hypothalamus. CONCLUSIONS: Massive reduction of body mass promotes a partial reversal of hypothalamic dysfunction and increases anti-inflammatory activity in the CSF.