OBJECTIVEInflammation 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 METHODSIn 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.RESULTSObese 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.CONCLUSIONSMassive reduction of body mass promotes a partial reversal of hypothalamic dysfunction and increases anti-inflammatory activity in the CSF.

In humans, the increase in brown/beige adipose tissue activity related to body mass reduction occurs independently of changes in hypothalamic activity as determined by functional magnetic resonance.

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 Licio A. Velloso,

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/m 2 (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.diabetes mellitus, type 2, glycated haemoglobin, sodium-glucose transporter 2 inhibitors | INTRODUCTIONGlycaemic control is a key aspect in the management of patients with type 2 diabetes (T2DM). This effort involves lifestyle changes, blood sugar monitoring, and use of pharmacotherapies. 1 One novel class of drugs for T2DM comprises the sodium-glucose cotransporter-2 (SGLT2) inhibitors, which act directly on the kidneys without requiring insulin secretion. SGLT2 is the primary glucose transporter located in

Body mass reduction has a more efficient effect to induce the activation of B/BAT in non-diabetic than in diabetic subjects. This effect is accompanied by more pronounced insulin sensitivity and serine 473 phosphorylation of Akt in B/BAT of non-diabetic than in diabetic subjects.