Artigos e Materiais de Revistas Científicas - LIM/18
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- 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)(2023) HALPERN, Bruno; MANCINI, Marcio C.; SANDE-LEE, Simone van de; MIRANDA, Paulo Augusto CarvalhoObesity 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.
- Down the rabbit hole: reviewing the evidence for primary prevention of cardiovascular disease in people with obesity(2023) STUMPF, Matheo A. M.; CERCATO, Cintia; MELO, Maria E. de; SANTOS, Raul D.; MANCINI, Marcio C.Obesity is a prevalent chronic disorder and a well-known risk factor for cardiovascular disease. However, the evidence of treating obesity for primary prevention of major cardiovascular events is still scarce and controversial. In this review, we provided a comprehensive description of the current evidence in treating obesity regarding cardiovascular protection. Bariatric surgery appears to be the most robust method to reduce events in people without established cardiovascular disease. High compliance to lifestyle interventions can further reduce cardiovascular risk. Concerning pharmacological therapies, a post hoc analysis from SUSTAIN-6 and a meta-analysis from STEP trials suggest that semaglutide, a GLP-1 receptor agonist, could reduce cardiovascular events in people without established cardiovascular disease. The first study addressed specifically a high-risk population with diabetes and, the second, low- or intermediary-risk individuals without diabetes. Tirzepatide, a novel dual GIP/GLP-1 agonist, although not yet tested in specific cardiovascular outcomes trials, could be an alternative since it induces loss in weight similar to the achieved by bariatric surgery. Therefore, extrapolated data in distinct baseline cardiovascular risk populations suggest that these two drugs could be used in primary prevention with the aim of preventing cardiovascular events, but the grade of this evidence is still low. Specifically designed studies are needed to address this specific topic.
- The impact of obesity in hospitalized patients with COVID-19: a retrospective cohort study(2024) CARRA, Fabio Alfano; MELO, Maria Edna de; STUMPF, Matheo A. M.; CERCATO, Cintia; FERNANDES, Ariana E.; MANCINI, Marcio C.; HIROTA, Adriana; KANASIRO, Alberto Kendy; CRESCENZI, Alessandra; FERNANDES, Amanda Coelho; MIETHKE-MORAIS, Anna; BELLINTANI, Arthur Petrillo; CANASIRO, Artur Ribeiro; CARNEIRO, Barbara Vieira; ZANBON, Beatriz Keiko; PINHEIRO, Bernardo; BATISTA, Senna Nogueira; NICOLAO, Bianca Ruiz; BESEN, Bruno Adler Maccagnan Pinheiro; BISELLI, Bruno; MACEDO, Bruno Rocha De; TOLEDO, Caio Machado Gomes De; CARVALHO, Carlos Roberto Ribeiro De; MOL, Caroline Gomes; STIPANICH, Cassio; BUENO, Caue Gasparotto; GARZILLO, Cibele; TANAKA, Clarice; FORTE, Daniel Neves; JOELSONS, Daniel; ROBIRA, Daniele; COSTA, Eduardo Leite Vieira; SILVA JUNIOR, Elson Mendes Da; REGALIO, Fabiane Aliotti; SEGURA, Gabriela Cardoso; LOURO, Giulia Sefrin; MARCELINO, Gustavo Brasil; HO, Yeh-Li; FERREIRA, Isabela Argollo; GOIS, Jeison Oliveira; SILVA-JR, Joao Manoel Da; JUNIOR, Jose Otto Reusing; RIBEIRO, Julia Fray; FERREIRA, Juliana Carvalho; GALLETI, Karine Vusberg; SILVA, Katia Regina; ISENSEE, Larissa Padrao; OLIVEIRA, Larissa Santos; TANIGUCHI, Leandro Utino; LETAIF, Leila Suemi; LIMA, Ligia Trombetta; PARK, Lucas Yongsoo; NETTO, Lucas Chaves; NOBREGA, Luciana Cassimiro; HADDAD, Luciana Bertocco Paiva; HAJJAR, Ludhmila Abrahao; MALBOUISSON, Luiz Marcelo Sa; PANDOLFI, Manuela Cristina Adsuara; PARK, Marcelo; CARMONA, Maria Jose Carvalho; ANDRADE, Maria Castilho Prandini H.; SANTOS, Mariana Moreira; BATELOCHE, Matheus Pereira; SUIAMA, Mayra Akimi; OLIVEIRA, Mayron Faria de; SOUSA, Mayson Laercio; GARCIA, Michelle Louvaes; HUEMER, Natassja; MENDES, Pedro Vitale; LINS, Paulo Ricardo Gessolo; SANTOS, Pedro Gaspar Dos; MOREIRA, Pedro Ferreira Paiva; GUAZZELLI, Renata Mello; REIS, Renato Batista Dos; DALTRO-OLIVEIRA, Renato; ROEPKE, Roberta Muriel Longo; PEDRO, Rodolpho Augusto Moura; KONDO, Rodrigo; RACHED, Samia Zahi; FONSECA, Sergio Roberto Silveira Da; BORGES, Thais Sousa; FERREIRA, Thalissa; JUNIOR, Vilson Cobello; SALES, Vivian Vieira Tenorio; FERREIRA, Willaby Serafim CassaBackground 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 Cl & iacute;nicas 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/m(2). 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.
- Mindful eating for weight loss in women with obesity: a randomised controlled trial(2023) PEPE, Renata Bressan; COELHO, Graziele Souza de Menezes Amorim; MIGUEL, Flavia da Silva; GUALASSI, Ana Carolina; SARVAS, Marcela Mosconi; CERCATO, Cintia; MANCINI, Marcio C. C.; MELO, Maria Edna deMindful 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.
- Treatment with Antiobesity Drugs in Weight Regain After Bariatric Surgery: a Retrospective Cohort Study(2023) BOGER, Bibiana S.; QUEIROZ, Nara L.; NORIEGA, Paulo E. P.; CANUTO, Maicon C.; STUMPF, Matheo A. M.; CERCATO, Cintia; MANCINI, Marcio C.; MELO, Maria E. deBackground Bariatric surgery is the most efficient treatment for obesity. However, in some cases, weight regain can occur. Currently, it is unknown the best antiobesity medication (AOM) for such clinical situation. This study aims to evaluate the effect of AOM in patients with weight regain after bariatric surgery. Methods A retrospective cohort study from December 2010 to July 2019 with patients submitted to bariatric surgery that had weight regain and received AOM for at least 2 years. Results Of 96 patients that had weight regain in the analyzed period and received AOM, 16 were excluded from the analysis due to non-compliance (n = 7), treatment failure (n = 5), intolerable side effects with all available AOM (n = 2), or interaction with other medications (n = 2). Eighty patients were included in the analysis. The mean age was 59.0 +/- 10.1 years, 88.8% were female, 91.2% white, and most of them were submitted to gastric bypass (87.6%). The mean preoperative and nadir weight after surgery were 127.9 +/- 25.5 kg and 84.7 +/- 22.8 kg, respectively. At the initiation of AOM, the mean baseline weight was 99.4 +/- 23.1 kg. After 2 years of follow-up, there was significant weight loss in the groups treated with topiramate-alone (- 3.2 kg), topiramate plus sibutramine (- 6.1kg), and orlistat-alone or in combination (- 3.9kg). No statistical difference was observed in the sibutramine- alone group. Conclusion Topiramate (alone or associated with sibutramine) and orlistat (alone or in combination) promoted significant weight loss after 2 years of use in patients submitted to bariatric surgery with weight regain.
- Fecal microbiota transplantation in patients with metabolic syndrome and obesity: A randomized controlled trial(2023) PONTE NETO, Alberto Machado da; CLEMENTE, Aniele Cristine Ott; ROSA, Paula Waki; RIBEIRO, Igor Braga; FUNARI, Mateus Pereira; NUNES, Gabriel Cairo; MOREIRA, Luana; SPARVOLI, Luiz Gustavo; CORTEZ, Ramon; TADDEI, Carla Romano; MANCINI, Marcio C.; MOURA, Eduardo Guimaraes Hourneaux deBACKGROUNDMetabolic syndrome is a multifactorial disease, and the gut microbiota may play a role in its pathogenesis. Obesity, especially abdominal obesity, is associated with insulin resistance, often increasing the risk of type two diabetes mellitus, vascular endothelial dysfunction, an abnormal lipid profile, hypertension, and vascular inflammation, all of which promote the development of atherosclerotic cardiovascular disease.AIMTo evaluate the outcomes of fecal microbiota transplantation (FMT) in patients with metabolic syndrome.METHODSThis was a randomized, single-blind placebo-controlled trial comparing FMT and a sham procedure in patients with metabolic syndrome. We selected 32 female patients, who were divided into eight groups of four patients each. All of the patients were submitted to upper gastrointestinal endoscopy. In each group, two patients were randomly allocated to undergo FMT, and the other two patients received saline infusion. The patients were followed for one year after the procedures, during which time anthropometric, bioimpedance, and biochemical data were collected. The patients also had periodic consultations with a nutritionist and an endocrinologist. The primary end point was a change in the gut microbiota.RESULTSThere was evidence of a postprocedural change in microbiota composition in the patients who underwent FMT in relation to that observed in those who underwent the sham procedure. However, we found no difference between the two groups in terms of the clinical parameters evaluated.CONCLUSIONThere were no significant differences in biochemical or anthropometric parameters, between the two groups evaluated. Nevertheless, there were significant postprocedural differences in the microbiota composition between the placebo group. To date, clinical outcomes related to FMT remain uncertain.
- Rare variants in the MECP2 gene in girls with central precocious puberty: a translational cohort study(2023) CANTON, Ana P. M.; TINANO, Flavia R.; GUASTI, Leonardo; MONTENEGRO, Luciana R.; RYAN, Fiona; SHEARS, Deborah; MELO, Maria Edna de; GOMES, Larissa G.; PIANA, Mariana P.; BRAUNER, Raja; ESPINO-AGUILAR, Rafael; ESCRIBANO-MUNOZ, Arancha; PAGANONI, Alyssa; READ, Jordan E.; KORBONITS, Marta; SERAPHIM, Carlos E.; COSTA, Silvia S.; KREPISCHI, Ana Cristina; JORGE, Alexander A. L.; DAVID, Alessia; KAISINGER, Lena R.; ONG, Ken K.; PERRY, John R. B.; ABREU, Ana Paula; KAISER, Ursula B.; ARGENTE, Jesus; MENDONCA, Berenice B.; BRITO, Vinicius N.; HOWARD, Sasha R.; LATRONICO, Ana ClaudiaBackground 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 & PRIME;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.
- Increased Expression of miR-223-3p and miR-375-3p and Anti-Inflammatory Activity in HDL of Newly Diagnosed Women in Advanced Stages of Breast Cancer(2023) SANTANA, Monique de Fatima Mello; SAWADA, Maria Isabela Bloise Alves Caldas; SANTOS, Aritania Sousa; REIS, Mozania; XAVIER, Jacira; CORREA-GIANNELLA, Maria Lucia; HIRATA, Andrea Harumy de Lima; GEBRIM, Luiz Henrique; SORIANO, Francisco Garcia; CAMACHO, Cleber Pinto; PASSARELLI, MarisaThe expression of inflammation-related miRs bound to high-density lipoproteins (HDLs), the anti-inflammatory activity of HDLs isolated from individuals with breast cancer, and controls were determined. Forty newly diagnosed women with breast cancer naive of treatment and 10 control participants were included. Cholesterol-loaded bone-marrow-derived macrophages were incubated with HDL from both groups and challenged with lipopolysaccharide (LPS). Interleukin 6 (IL6) and tumor necrosis factor (TNF) in the medium were quantified. The miRs in HDLs were determined by RT-qPCR. Age, body mass index, menopausal status, plasma lipids, and HDL composition were similar between groups. The ability of HDL to inhibit IL6 and TNF production was higher in breast cancer compared to controls, especially in advanced stages of the disease. The miR-223-3p and 375-3p were higher in the HDLs of breast cancer independent of the histological type of the tumor and had a high discriminatory power between breast cancer and controls. The miR-375-3p was greater in the advanced stages of the disease and was inversely correlated with the secretion of inflammatory cytokines. Inflammation-related miRs and the anti-inflammatory role of HDLs may have a significant impact on breast cancer pathophysiology.
- Position statement on nutrition therapy for overweight and obesity: nutrition department of the Brazilian association for the study of obesity and metabolic syndrome (ABESO-2022)(2023) PEPE, Renata Bressan; LOTTENBERG, Ana Maria; FUJIWARA, Clarissa Tamie Hiwatashi; BEYRUTI, Monica; CINTRA, Dennys Esper; MACHADO, Roberta Marcondes; RODRIGUES, Alessandra; JENSEN, Natalia Sanchez Oliveira; CALDAS, Ana Paula Silva; FERNANDES, Ariana Ester; ROSSONI, Carina; MATTOS, Fernanda; MOTARELLI, Joao Henrique Fabiano; BRESSAN, Josefina; SALDANHA, Juliana; BEDA, Lis Mie Masuzawa; LAVRADOR, Maria Silvia Ferrari; BOSCO, Mariana Del; CRUZ, Patricia; CORREIA, Poliana Espindola; MAXIMINO, Priscila; PEREIRA, Silvia; FARIA, Silvia Leite; PIOVACARI, Silvia Maria FragaObesity is a chronic disease resulting from multifactorial causes mainly related to lifestyle (sedentary lifestyle, inadequate eating habits) and to other conditions such as genetic, hereditary, psychological, cultural, and ethnic factors. The weight loss process is slow and complex, and involves lifestyle changes with an emphasis on nutritional therapy, physical activity practice, psychological interventions, and pharmacological or surgical treatment. Because the management of obesity is a long-term process, it is essential that the nutritional treatment contributes to the maintenance of the individual's global health. The main diet-related causes associated with excess weight are the high consumption of ultraprocessed foods, which are high in fats, sugars, and have high energy density; increased portion sizes; and low intake of fruits, vegetables, and grains. In addition, some situations negatively interfere with the weight loss process, such as fad diets that involve the belief in superfoods, the use of teas and phytotherapics, or even the avoidance of certain food groups, as has currently been the case for foods that are sources of carbohydrates. Individuals with obesity are often exposed to fad diets and, on a recurring basis, adhere to proposals with promises of quick solutions, which are not supported by the scientific literature. The adoption of a dietary pattern combining foods such as grains, lean meats, low-fat dairy, fruits, and vegetables, associated with an energy deficit, is the nutritional treatment recommended by the main international guidelines. Moreover, an emphasis on behavioral aspects including motivational interviewing and the encouragement for the individual to develop skills will contribute to achieve and maintain a healthy weight. Therefore, this Position Statement was prepared based on the analysis of the main randomized controlled studies and meta-analyses that tested different nutrition interventions for weight loss. Topics in the frontier of knowledge such as gut microbiota, inflammation, and nutritional genomics, as well as the processes involved in weight regain, were included in this document. This Position Statement was prepared by the Nutrition Department of the Brazilian Association for the Study of Obesity and Metabolic Syndrome (ABESO), with the collaboration of dietitians from research and clinical fields with an emphasis on strategies for weight loss.
- Variant rs17619600 in the gene encoding serotonin receptor 2B (HTR2B) increases the risk of gestational diabetes mellitus: a case-control study(2023) PENNO, Juliana Regina Chamlian Zucare; SANTOS-BEZERRA, Daniele Pereira; CAVALEIRO, Ana Mercedes; SOUSA, Ana Maria da Silva; ZACCARA, Tatiana Assuncao; COSTA, Rafaela Alkmin da; FRANCISCO, Rossana Pulcineli Vieira; CORREA-GIANNELLA, Maria LuciaBackgroundDuring pregnancy, the increase in maternal insulin resistance is compensated by hyperplasia and increased function of maternal pancreatic beta cells; the failure of this compensatory mechanism is associated with gestational diabetes mellitus (GDM). Serotonin participates in beta cell adaptation, acting downstream of the prolactin pathway; the blocking of serotonin receptor B (HTR2B) signaling in pregnant mice impaired beta cell expansion and caused glucose intolerance. Thus, given the importance of the serotoninergic system for the adaptation of beta cells to the increased insulin demand during pregnancy, we hypothesized that genetic variants (single nucleotide polymorphisms [SNPs]) in the gene encoding HTR2B could influence the risk of developing GDM.MethodsThis was a case-control study. Five SNPs (rs4973377, rs765458, rs10187149, rs10194776, and s17619600) in HTR2B were genotyped by real-time polymerase chain reaction in 453 women with GDM and in 443 pregnant women without GDM.ResultsOnly the minor allele C of SNP rs17619600 conferred an increased risk for GDM in the codominant model (odds ratio [OR] 2.15; 95% confidence interval [CI] 1.53-3.09; P < 0.0001) and in the rare dominant model (OR 2.32; CI 1.61-3.37; P < 0.0001). No associations were found between the SNPs and insulin use, maternal weight gain, newborn weight, or the result of postpartum oral glucose tolerance test (OGTT). In the overall population, carriers of the XC genotype (rare dominant model) presented a higher area under the curve (AUC) of plasma glucose during the OGTT, performed for diagnostic purposes, compared with carriers of the TT genotype of rs17619600.ConclusionsSNP rs17619600 in the HTR2B gene influences glucose homeostasis, probably affecting insulin release, and the presence of the minor allele C was associated with a higher risk of GDM.
- Differences in the gut microbiota of women according to ultra- processed food consumption(2023) FERNANDES, Ariana E.; ROSA, Paula W. L.; MELO, Maria E.; MARTINS, Roberta C. R.; SANTIN, Fernanda G. O.; MOURA, Aline M. S. H.; COELHO, Graziele S. M. A.; SABINO, Ester C.; CERCATO, Cintia; MANCINI, Marcio C.Background and aims: High consumption of ultra-processed food (UPF) has been associated with increased risk of obesity and other metabolic diseases, and this dietary pattern seems to be responsible for chronic changes in the gut microbiota. The aim of this study was to assess the associations of UPF with the gut microbiota and obesity-associated biometrics in women. Methods and results: This cross-sectional study examined 59 women. The following parameters were evaluated: food consumption using NOVA classification, anthropometric and metabolic parameters, and gut microbiome by next-generation sequencing. The mean age was 28.0 & PLUSMN; 6.6 years. The mean caloric intake was 1624 & PLUSMN; 531 kcal, of which unprocessed or minimally processed food (G1) accounted for 52.4 & PLUSMN; 13.5%, and UPF accounted for 31.4 & PLUSMN; 13.6%. Leptin levels adjusted for fat mass were negatively associated with G1 and positively associated with UPF. We found 15 species in the gut microbiota that correlated with G1 (3 positively and 12 negatively) and 9 species associated with UPF (5 positively and 4 negatively). Conclusion: Higher consumption of UPF was directly associated with leptin resistance, and this study suggests that the consumption of UPF or G1 may affect the composition of the gut micro biota. & COPY; 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University.
- MiRNA-30d and miR-770-5p as potential clinical risk predictors of Vasoplegic Syndrome in Patients undergoing on-pump coronary artery bypass grafting(2023) MEJIA, Omar Asdrubal Vilca; SOUZA, Renato Cesar de; SANTOS, Aritania S.; MENEGHINI, Bianca; SILVA, Ana Carolina Carvalho; BRASIL, Guilherme Visconde; RIGAUD, Vagner Oliveira Carvalho; DALLAN, Luis Roberto Palma; MOREIRA, Luiz Felipe Pinho; LISBOA, Luiz Augusto Ferreira; DALLAN, Luis Alberto Oliveira; KALIL, Jorge; CUNHA-NETO, Edecio; FERREIRA, Ludmila Rodrigues Pinto; JATENE, Fabio BiscegliThe aims of this study were to perform pre-surgery miRNA profiling of patients who develop Vasoplegic syndrome (VS) after coronary artery bypass grafting (CABG) and identify those miRNAs that could be used as VS prognostic tools and biomarkers. The levels of 754 microRNAs (miRNAs) were measured in whole blood samples from a cohort of patients collected right before the coronary artery bypass grafting (CABG) surgery. We compared the miRNA levels of those who developed VS (VASO group) with those who did not (NONVASO group) after surgery. Six miRNAs (hsa-miR-548c-3p, -199b-5p, -383-5p -571 -183-3p, -30d-5p) were increased and two (hsa-1236-3p, and hsa-miR770-5p) were decreased in blood of VASO compared to NONVASO groups. Receiver Operating Characteristic (ROC) curve analysis revealed that a combination of the miRNAs, hsa-miR-30d-5p and hsa-miR-770-5p can be used as VS predictors (AUC = 0.9615, p < 0.0001). The computational and functional analyses were performed to gain insights into the potential role of these dysregulated miRNAs in VS and have identified the ""Apelin Liver Signaling Pathway"" as the canonical pathway containing the most target genes regulated by these miRNAs. The expression of the combined miRNAs hsa-miR-30d and hsa-miR-770-5p allowed the ability to distinguish between patients who could and could not develop VS, representing a potential predictive biomarker of VS.
- Islet transplantation: overcoming the organ shortage(2023) MANTOVANI, Marluce da Cunha; GABANYI, Ilana; PANTANALI, Carlos Andres; SANTOS, Vinicius Rocha; CORREA-GIANNELLA, Maria Lucia Cardillo; SOGAYAR, Mari CleideBackground Type 1 diabetes mellitus (T1D) is a condition resulting from autoimmune destruction of pancreatic beta cells, leading patients to require lifelong insulin therapy, which, most often, does not avoid the most common complications of this disease. Transplantation of isolated pancreatic islets from heart-beating organ donors is a promising alternative treatment for T1D, however, this approach is severely limited by the shortage of pancreata maintained under adequate conditions. Methods In order to analyze whether and how this problem could be overcome, we undertook a retrospective study from January 2007 to January 2010, evaluating the profile of brain-dead human pancreas donors offered to our Cell and Molecular Therapy NUCEL Center (www.usp.br/nucel) and the basis for organ refusal. Results During this time period, 558 pancreata were offered by the Sao Paulo State Transplantation Central, 512 of which were refused and 46 were accepted for islet isolation and transplantation. Due to the elevated number of refused organs, we decided to analyze the main reasons for refusal in order to evaluate the possibility of improving the organ acceptance rate. The data indicate that hyperglycemia, technical issues, age, positive serology and hyperamylasemia are the top five main causes for declination of a pancreas offer. Conclusions This study underlines the main reasons to decline a pancreas offer in Sao Paulo-Brazil and provides some guidance to ameliorate the rate of eligible pancreas donors, aiming at improving the islet isolation and transplantation outcome.
- Increased plasma lipids in triple-negative breast cancer and impairment in HDL functionality in advanced stages of tumors(2023) SAWADA, Maria Isabela Bloise Alves Caldas; SANTANA, Monique de Fatima Mello; REIS, Mozania; ASSIS, Sayonara Ivana Santos de; PEREIRA, Lucas Alves; SANTOS, Danielle Ribeiro; NUNES, Valeria Sutti; CORREA-GIANNELLA, Maria Lucia Cardillo; GEBRIM, Luiz Henrique; PASSARELLI, MarisaThe association between plasma lipids and breast cancer (BC) has been extensively explored although results are still conflicting especially regarding the relationship with high-density lipoprotein cholesterol (HDLc) levels. HDL mediates cholesterol and oxysterol removal from cells limiting sterols necessary for tumor growth, inflammation, and metastasis and this may not be reflected by measuring HDLc. We addressed recently diagnosed, treatment-naive BC women (n = 163), classified according to molecular types of tumors and clinical stages of the disease, in comparison to control women (CTR; n = 150) regarding plasma lipids and lipoproteins, HDL functionality and composition in lipids, oxysterols, and apo A-I. HDL was isolated by plasma discontinuous density gradient ultracentrifugation. Lipids (total cholesterol, TC; triglycerides, TG; and phospholipids, PL) were determined by enzymatic assays, apo A-I by immunoturbidimetry, and oxysterols (27, 25, and 24-hydroxycholesterol), by gas chromatography coupled with mass spectrometry. HDL-mediated cell cholesterol removal was determined in macrophages previously overloaded with cholesterol and C-14-cholesterol. Lipid profile was similar between CTR and BC groups after adjustment per age. In the BC group, lower concentrations of TC (84%), TG (93%), PL (89%), and 27-hydroxicholesterol (61%) were observed in HDL, although the lipoprotein ability in removing cell cholesterol was similar to HDL from CRT. Triple-negative (TN) BC cases presented higher levels of TC, TG, apoB, and non-HDLc when compared to other molecular types. Impaired HDL functionality was observed in more advanced BC cases (stages III and IV), as cholesterol efflux was around 28% lower as compared to stages I and II. The altered lipid profile in TN cases may contribute to channeling lipids to tumor development in a hystotype with a more aggressive clinical history. Moreover, findings reinforce the dissociation between plasma levels of HDLc and HDL functionality in determining BC outcomes.
- Postmortem Brains from Subjects with Diabetes Mellitus Display Reduced GLUT4 Expression and Soma Area in Hippocampal Neurons: Potential Involvement of Inflammation(2023) YONAMINE, Caio Yogi; PASSARELLI, Marisa; SUEMOTO, Claudia Kimie; PASQUALUCCI, Carlos Augusto; JACOB-FILHO, Wilson; ALVES, Venancio Avancini Ferreira; MARIE, Suely Kazue Nagahashi; CORREA-GIANNELLA, Maria Lucia; BRITTO, Luiz Roberto; MACHADO, Ubiratan FabresDiabetes mellitus (DM) is an important risk factor for dementia, which is a common neurodegenerative disorder. DM is known to activate inflammation, oxidative stress, and advanced glycation end products (AGEs) generation, all capable of inducing neuronal dysfunctions, thus participating in the neurodegeneration progress. In that process, disturbed neuronal glucose supply plays a key role, which in hippocampal neurons is controlled by the insulin-sensitive glucose transporter type 4 (GLUT4). We investigated the expression of GLUT4, nuclear factor NF-kappa B subunit p65 [NFKB (p65)], carboxymethyllysine and synapsin1 (immunohistochemistry), and soma area in human postmortem hippocampal samples from control, obese, and obese+DM subjects (41 subjects). Moreover, in human SH-SY5Y neurons, tumor necrosis factor (TNF) and glycated albumin (GA) effects were investigated in GLUT4, synapsin-1 (SYN1), tyrosine hydroxylase (TH), synaptophysin (SYP) proteins, and respective genes; NFKB binding activity in the SLC2A4 promoter; effects of increased histone acetylation grade by histone deacetylase 3 (HDAC3) inhibition. Hippocampal neurons (CA4 area) of obese+DM subjects displayed reduced GLUT4 expression and neuronal soma area, associated with increased expression of NFKB (p65). Challenges with TNF and GA decreased the SLC2A4/GLUT4 expression in SH-SY5Y neurons. TNF decreased SYN1, TH, and SYP mRNAs and respective proteins, and increased NFKB binding activity in the SLC2A4 promoter. Inhibition of HDAC3 increased the SLC2A4 expression and the total neuronal content of CRE-binding proteins (CREB/ICER), and also counterbalanced the repressor effect of TNF upon these parameters. This study revealed reduced postmortem human hippocampal GLUT4 content and neuronal soma area accompanied by increased proinflammatory activity in the brains of DM subjects. In isolated human neurons, inflammatory activation by TNF reduced not only the SLC2A4/GLUT4 expression but also the expression of some genes related to neuronal function (SYN1, TH, SYP). These effects may be related to epigenetic regulations (H3Kac and H4Kac status) since they can be counterbalanced by inhibiting HDAC3. These results uncover the improvement in GLUT4 expression and/or the inhibition of HDAC3 as promising therapeutic targets to fight DM-related neurodegeneration.
- Proteomics of high-density lipoprotein subfractions and subclinical atherosclerosis in type 1 diabetes mellitus: a case-control study(2023) TOYOSHIMA, Marcos Tadashi K.; SANTANA, Monique F. M.; SILVA, Amanda R. M.; MELLO, Gabriela B. B.; SANTOS-BEZERRA, Daniele P. P.; GOES, Marisa F. S.; BOSCO, Adriana A. A.; CARAMELLI, Bruno; RONSEIN, Graziella E. E.; CORREA-GIANNELLA, Maria Lucia; PASSARELLI, MarisaBackgroundSubclinical atherosclerosis is frequently observed in type 1 diabetes (T1D) although the mechanisms and markers involved in the evolution to established cardiovascular disease are not well known. High-density lipoprotein cholesterol in T1D is normal or even high, and changes in its functionality and proteomics are considered. Our aim was to evaluate the proteomics of HDL subfractions in T1D and control subjects and its association with clinical variables, subclinical atherosclerosis markers and HDL functionality.MethodsA total of 50 individuals with T1D and 30 matched controls were included. Carotid-femoral pulse wave velocity (PWV), flow-mediated vasodilation (FMD), cardiovascular autonomic neuropathy (CAN), and ten-year cardiovascular risk (ASCVDR) were determined. Proteomics (parallel reaction monitoring) was determined in isolated HDL2 and HDL3 that were also utilized to measure cholesterol efflux from macrophages.ResultsAmong 45 quantified proteins, 13 in HDL2 and 33 in HDL3 were differentially expressed in T1D and control subjects. Six proteins related to lipid metabolism, one to inflammatory acute phase, one to complement system and one to antioxidant response were more abundant in HDL2, while 14 lipid metabolism, three acute-phase, three antioxidants and one transport in HDL3 of T1D subjects. Three proteins (lipid metabolism, transport, and unknown function) were more abundant in HDL2; and ten (lipid metabolism, transport, protease inhibition), more abundant in HDL3 of controls. Individuals with T1D had higher PWV and ten-year ASCVDR, and lower FMD, Cholesterol efflux from macrophages was similar between T1D and controls. Proteins in HDL2 and HDL3, especially related to lipid metabolism, correlated with PWV, CAN, cholesterol efflux, HDLc, hypertension, glycemic control, ten-year ASCVDR, and statins use.ConclusionHDL proteomics can be predictive of subclinical atherosclerosis in type 1 diabetes. Proteins that are not involved in reverse cholesterol transport may be associated with the protective role of HDL.
- A Case Series of Follow-ups in COVID-Related Diabetes: Could the Damage in Beta Cells be Recovered?(2022) STUMPF, Matheo Augusto Morandi; LINS, Lais Pinheiro; CUKIER, Priscilla; NERY, Marcia; GIANNELLA, Maria Lucia Cardillo Correa; SILVA, Maria Elizabeth Rossi daSARS-CoV-2 infection may be related to new-onset diabetes and diabetic ketoacidosis (DKA). We describe a long-term follow-up of 3 cases presented in the Emergency Department with DKA and COVID-19. In 2 of them, the clinical course permitted withdrawal of insulin therapy during follow-up. The third case, a more serious one with pulmonary thromboembolism, continued to require bedtime insulin during the follow-up period. Such cases demonstrate that insulin treatment can control glucotoxicity and help beta cells recover after an acute insult such as COVID-19.
- The new obesity classification based on weight history is not proposed as a guideline(2022) HALPERN, Bruno; MANCINI, Marcio C.; MELO, Maria Edna de; LAMOUNIER, Rodrigo N.; MOREIRA, Rodrigo O.; CARRA, Mario K.; CERCATO, Cintia; BOGUSZEWSKI, Cesar Luiz
- Epidemiology and risk factors of hypoglycemia in subjects with type 1 diabetes in Brazil: a cross-sectional, multicenter study(2022) SOUZA, Alexandre Barbosa Camara de; CORREA-GIANNELLA, Maria Lucia Cardillo; GOMES, Marilia Brito; NEGRATO, Carlos Antonio; NERY, MarciaObjective: The aim of this study was to investigate the factors associated with hypoglycemia and severe hypoglycemia (SH) in individuals with type 1 diabetes mellitus (T1D) in Brazil. Materials and methods: This multicenter, cross-sectional study was conducted between August 2011 and August 2014 across 10 Brazilian cities. The data were obtained from 1,760 individuals with T1D. Sociodemographic and clinical characteristics related to hypoglycemic events in the previous 4 weeks were evaluated. Results: Of 1,760 individuals evaluated, 1,319 (74.9%) reported at least one episode of hypoglycemia in the previous 4 weeks. The main factors associated with hypoglycemia were lower hemoglobin A1c (HbA1c) level, better adherence to self-monitoring of blood glucose (SMBG), and higher education level. Episodes of SH were reported by 251 (19%) individuals who, compared with subjects with nonsevere hypoglycemia, received lower doses of prandial insulin and higher doses of basal insulin, in addition to reporting less frequent use of long-acting basal insulin analogs. The percentage of SH episodes was evenly distributed across all ranges of HbA1c levels, and there were no correlations between the mean number of nonsevere or severe hypoglycemic events and HbA1c values. Higher alcohol consumption and more frequent hospitalizations were independently associated with SH. Conclusion: Although individuals presenting with hypoglycemia had lower HbA1c values than those not presenting hypoglycemia, there were no correlations between the number of nonsevere hypoglycemia or SH and HbA1c values. Also, the frequency of SH was evenly distributed across all ranges of HbA1c values. Better adherence to SMBG and higher education level were associated with hypoglycemia, while alcohol consumption, higher doses of basal insulin, and more frequent hospitalizations in the previous year were associated with SH. Arch Endocrinol Metab. 2022;66(6):784-91
- Identification of two patterns of mitochondrial DNA-copy number variation in postcentral gyrus during aging, influenced by body mass index and type 2 diabetes(2022) SEKIYA, Felipe Seiti; SILVA, Clarisse Pereira Nunes da; OBA-SHINJO, Sueli Mieko; SANTOS-BEZERRA, Daniele Pereira; RAVAGNANI, Felipe Gustavo; PASQUALUCCI, Carlos Augusto; GIL, Saulo; GUALANO, Bruno; BAPTISTA, Mauricio da Silva; CORREA-GIANNELLA, Maria Lucia; MARIE, Suely Kazue NagahashiAimsMitochondrial (mt) DNA replication is strongly associated with oxidative stress, a condition triggered by aging and hyperglycemia, both of which contribute to mitophagy disruption and inflammation. This observational exploratory study evaluated mtDNA-copy number (mtDNA-CN) and expression of genes involved in mitochondriogenesis (PPARGC1A, TFAM, TFB1M, TFB2M), mitophagy (PINK1, PRKN), and inflammatory pathways triggered by hyperglycemia (TXNIP, NLRP3, NFKB1), in the postcentral gyrus of adults and older individuals with and without type 2 diabetes mellitus (T2D).Main methodsQuantitative real-time PCR was employed to evaluate mtDNA-CN and gene expression; tissue autofluorescence, a marker of aging and of cells with damaged organelles, was also quantified.Key findingsNo correlation was found between age and mtDNA-CN, but a direct correlation was observed for cases with mtDNA-CN >1000 (r = 0.41). The mtDNA-CN >1000 group had greater tissue autofluorescence and higher body mass index compared to the mtDNA-CN <1000 group (BMI; 25.7 vs 22.0 kg/m(2), respectively). mtDNA-CN correlated with tissue autofluorescence in the overall sample (r = 0.55) and in the T2D group (r = 0.64). PINK and PRKN expressions were inversely correlated with age. Mitochondriogenesis genes and TXNIP expressions were higher in the T2D group, and correlations among the mitochondriogenesis genes were also stronger in this group, relative to the subgroup with mtDNA-CN >1000.