Does metformin reduce the risk of cancer in obesity and diabetes? A systematic review and meta-analysis.

AIM: To evaluate the effect of metformin on cancer incidence in subjects with overweight/obesity and/or prediabetes/diabetes. MATERIALS AND METHODS: We searched MEDLINE, Embase and CENTRAL for randomized controlled trials (RCTs) in adults with overweight/obesity and/or prediabetes/diabetes that compared metformin to other interventions for ≥24 weeks. Independent reviewers selected and extracted data including population and intervention characteristics and new diagnoses of cancer. We used the RoB 2.0 risk-of-bias tool and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework to assess risk of bias and certainty of evidence. RESULTS: From 14 895 records after removal of duplicates, 27 trials were included, providing a total of 10 717 subjects in the metformin group and 10 003 in the control group, with 170 and 208 new cases of cancer, respectively. Using a random-effects model, the relative risk was 1.07 (95% confidence interval 0.87-1.31), with similar results in subgroup analyses by study duration or effect of control intervention on weight. Risk of bias in most studies was low, and no evidence of publication bias was found. Trial sequential analysis provided evidence that the cumulative sample size was large enough to exclude a significant effect of metformin on cancer incidence. CONCLUSIONS: Metformin did not reduce cancer incidence in RCTs involving subjects with overweight/obesity and/or prediabetes/diabetes.

Acute Liver Failure Induces Glial Reactivity, Oxidative Stress and Impairs Brain Energy Metabolism in Rats.

Acute liver failure (ALF) implies a severe and rapid liver dysfunction that leads to impaired liver metabolism and hepatic encephalopathy (HE). Recent studies have suggested that several brain alterations such as astrocytic dysfunction and energy metabolism impairment may synergistically interact, playing a role in the development of HE. The purpose of the present study is to investigate early alterations in redox status, energy metabolism and astrocytic reactivity of rats submitted to ALF. Adult male Wistar rats were submitted either to subtotal hepatectomy (92% of liver mass) or sham operation to induce ALF. Twenty-four hours after the surgery, animals with ALF presented higher plasmatic levels of ammonia, lactate, ALT and AST and lower levels of glucose than the animals in the sham group. Animals with ALF presented several astrocytic morphological alterations indicating astrocytic reactivity. The ALF group also presented higher mitochondrial oxygen consumption, higher enzymatic activity and higher ATP levels in the brain (frontoparietal cortex). Moreover, ALF induced an increase in glutamate oxidation concomitant with a decrease in glucose and lactate oxidation. The increase in brain energy metabolism caused by astrocytic reactivity resulted in augmented levels of reactive oxygen species (ROS) and Poly [ADP-ribose] polymerase 1 (PARP1) and a decreased activity of the enzymes superoxide dismutase and glutathione peroxidase (GSH-Px). These findings suggest that in the early stages of ALF the brain presents a hypermetabolic state, oxidative stress and astrocytic reactivity, which could be in part sustained by an increase in mitochondrial oxidation of glutamate.

Effect of transcranial direct current stimulation associated with hypocaloric diet on weight loss and metabolic profile in overweight or obesity: study protocol for a double-blind, randomized controlled clinical trial.

BACKGROUND: Dietary interventions have limited success in promoting sustainable weight loss; new treatments allowing better compliance with hypocaloric diets should be developed. The aim of this trial is to describe the effects of a protocol combining repetitive active transcranial direct current stimulation (tDCS) with a hypocaloric diet on weight loss and food consumption in overweight or obese adults. METHODS/DESIGN: Overweight or obese adults between 20 and 50 years of age with stable weight over the last 4 months will be selected for a 4-week randomized clinical trial of fixed-dose tDCS (20 sessions; 5 consecutive weekdays/wk, 2 mA, 20 minutes) over the right dorsolateral prefrontal cortex associated with a weight loss diet. The subjects will be randomly assigned in a 1:1 ratio and stratified by sex to active tDCS + diet or sham tDCS + diet. The study will be conducted at the Endocrine and Metabolism Unit of the Hospital de Clínicas de Porto Alegre, Brazil. The primary outcome is weight loss. Energy and macronutrient consumption, as well as adherence to the diet, will be assessed using 3-day weighed dietary records. Changes in blood glucose and plasma insulin will be assessed, and participants will complete self-report questionnaires to assess changes in mood and food behavior. All analyses will be done on a per-protocol and intention-to-treat basis. DISCUSSION: This study explores the potential role of tDCS as an adjunctive treatment with a hypocaloric diet for obesity management. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02683902 . Registered on 11 January 2016.