The relevance of the optional use of fasting in laboratory measurements that make up the lipid profile: A systematic literature review.

The objective of this study was to evaluate the impact of fasting easing on laboratory measurements of the lipid profile, in order to contribute to the fidelity of interpretation of laboratory results. Starting in October 2022, a Systematic Literature Review (SRL) was carried out, using articles indexed in the electronic databases PubMed/MEDLINE, EMBASE, Scopus, LILACS and Cochrane Library, following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes Group (PRISMA). This RSL was registered with PROSPERO, under registration number CRD42022370007. For inclusion, articles had to be original and developed in humans. After evaluating the methodological quality and analyzing the risk of bias, we obtained 16 articles published between 1994 and 2021, providing data on a total of 398,709 individuals, aged between 3 and 93 years. According to the selected studies, lipid profile measurements performed with flexible fasting, in addition to bringing benefits to patients and the pre-analytical system of the clinical laboratory, are more suitable for determining cardiovascular risk, mainly through the assessment of values obtained in the determination of triglycerides. It is therefore concluded that the optional use of fasting must be established through medical advice. In addition, laboratory methods and readings must be readjusted to this reality, informing through the report the parameters related to the lipid profile with and without the use of a 12-hour fast.

Effect of Hypoenergetic Diet Combined With Pumpkin Seed Flour Consumption on Obese Women

Abstract Background Dietary treatment containing fiber-rich foods may contribute to lowering weight in obese women. Objective To investigate the effect of a hypoenergetic diet combined with pumpkin seed flour (PSF) consumption on diet quality, anthropometric indices, and glucose and lipid metabolism in obese women. Methods We conducted a randomized, double-blind, placebo-controlled, 90-day clinical trial with obese women, distributed into the following two groups: hypoenergetic diet + placebo (PG) and hypoenergetic diet + pumpkin seed flour (PSFG). A total of 100 participants were included in the PSFG (n = 47) and PG (n = 53). We evaluated neck circumference (NC); waist to height ratio; conicity index; fat mass (FM); lipid profile; blood concentrations of glucose and insulin; homeostatic model assessment for insulin resistance (HOMA-IR); quantitative insulin sensitivity check index (QUICKI); and blood pressure at baseline, 30, 60, and 90 days. Dietary analysis was determined by differences between diet quality indices before and after prescribing the experimental diet. Chi-squared, Student's t-tests and analysis for repeated measures were used, and values were considered significant at p < 0.05. Results The dietary pattern improved after 90 days in both groups. The PSFG presented lower NC (p < 0.001), FM (p = 0.010), triglycerides (TG) (p = 0.025), insulin (p = 0.003), and HOMA-IR (p = 0.018). The PG presented a lower diastolic blood pressure (p = 0.004) and low-density lipoprotein cholesterol (LDL-c) (p = 0.056). Conclusion A hypoenergetic diet combined with PSF consumption contributes to lowering NC, FM, HOMA-IR, TG, and insulin concentrations.

SH2B1 variants as potential causes of non-syndromic monogenic obesity in a Brazilian cohort.

PURPOSE: SH2B1 gene encodes an important adaptor protein to receptor tyrosine kinases or cytokine receptors associated with Janus kinases. This gene has been associated with the structural and functional modulation of neurons and other cells, and impacts on energy and glucose homeostasis. Several studies suggested that alterations in this gene are strong candidates for the development of obesity. However, only a few studies have screened SH2B1 point variants in individuals with obesity. Therefore, the aim of this study was to investigate the prevalence of SH2B1 variants in a Brazilian cohort of patients with severe obesity and candidates to bariatric surgery. METHODS: The cohort comprised 122 individuals with severe obesity, who developed this phenotype during childhood. As controls, 100 normal-weight individuals were included. The coding region of SH2B1 gene was screened by Sanger sequencing. RESULTS: A total of eight variants were identified in SH2B1, of which p.(Val345Met) and p.(Arg630Gln) variants were rare and predicted as potentially pathogenic by the in the silico algorithms used in this study. The p.(Val345Met) was not found in either the control group or in publicly available databases. This variant was identified in a female patient with severe obesity, metabolic syndrome and hyperglycemia. The p.(Arg630Gln) was also absent in our control group, but it was reported in gnomAD with an extremely low frequency. This variant was observed in a female patient with morbid obesity, metabolic syndrome, hypertension and severe binge-eating disorder. CONCLUSION: Our study reported for the first time two rare and potentially pathogenic variants in Brazilian patients with severe obesity. Further functional studies will be necessary to confirm and elucidate the impact of these variants on SH2B1 protein function and stability, and their impact on energetic metabolism. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Effects of a high-fat meal on inflammatory and endothelial injury biomarkers in accordance with adiposity status: a cross-sectional study.

BACKGROUND: It is known that consuming a high-fat meal (HFM) induces microvascular dysfunction (MD) in eutrophic women and aggravates it in those with obesity. Our purpose was to investigate if the MD observed after a single HFM intake is caused by endothelial damage or increased inflammatory state, both determined by blood biomarkers. METHODS: Nineteen women with obesity (BMI 30-34.9 kg/m2) and 18 eutrophic ones (BMI 20.0-24.9 kg/m2) were enrolled into two groups: Obese (OBG) and Control (CG), respectively. Blood samples were collected at five-time points: before (fasting state) and 30, 60, 120, and 180 min after HFM intake to determine levels of adipokines (adiponectin, leptin), non-esterified fatty acid (NEFA), inflammatory [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)] and endothelium damage [soluble E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor-1 (PAI-1)] biomarkers. RESULTS: Levels of soluble E-selectin, leptin, and PAI-1 were higher in OBG at all-time points (P < 0.05) compared to CG. In the fasting state, OBG had higher levels of NEFA compared to CG (P < 0.05). In intra-group analysis, no significant change in the levels of circulating inflammatory and endothelial injury biomarkers was observed after HFM intake, independently of the group. CONCLUSION: Our findings suggest that women with obesity have an increased pro-inflammatory state and more significant endothelial injury compared to eutrophic ones. However, the consumption of a HFM was not sufficient to change circulating levels of inflammatory and endothelial injury biomarkers in either group. REGISTRATION NUMBER FOR CLINICAL TRIALS: NCT01692327.

A Rare Potential Pathogenic Variant in the BDNF Gene is Found in a Brazilian Patient with Severe Childhood-Onset Obesity.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a pro-survival factor in the brain that also regulates energy balance. BDNF loss-of-function point mutations are responsible for haploinsufficiency, causing severe early-onset obesity. Up to date, only a few studies have sequenced this gene to search for rare mutations related to obesity. In this study, we aimed to investigate the prevalence of BDNF variants in a cohort of adults with severe obesity from Brazil. MATERIAL AND METHODS: This study comprised 201 adults with severe obesity (BMI ≥ 35.0 kg/m2) with onset during childhood- or adolescence/youth. As controls, 73 subjects with normal weight (18.5 ≤ BMI ≤ 24.9 kg/m2) were selected. The exclusion criteria were pregnancy, lactation, the use of medication to lose or gain weight, and the presence of symptoms suggestive of syndromic obesity (only for the case group). The coding region of the BDNF gene was screened by Sanger sequencing. Demographic, anthropometric, and blood pressure parameters were obtained from the participants as well as serum hormone and cytokines concentrations and biochemical values. RESULTS: As a result, three missense variants [p.(Thr2Ile), p.(Val66Met), and p.(Arg209Gln)] and four synonymous variants (p.Leu107=, p.Thr149=, p.Ala150=, and p.Ser213=) were identified. The p.(Arg209Gln) was predicted as pathogenic by all in silico algorithms used and was not observed in the control group. The individuals carrying the p.(Val66Met) mutated allele had higher waist circumference, HDL-cholesterol and MCP1 levels, and reduced risk of developing metabolic syndrome. CONCLUSION: We observed that the common BDNF p.(Val66Met) variant has influenced waist circumference, HDL-cholesterol, and MCP1 levels. This polymorphism has also a protective effect on metabolic syndrome susceptibility. Additionally, we described for the first time a rare potentially pathogenic BDNF variant in a Brazilian patient with severe obesity and childhood-onset.

Dipeptidyl peptidase-4 activity, lipopolysaccharide, C-reactive protein, glucose metabolism, and gut peptides 3 months after bariatric surgery.

BACKGROUND: Bariatric surgery induces weight loss, but changes in glucose metabolism, gut peptides, and inflammatory biomarkers still have conflicting results. SETTINGS: University hospital. OBJECTIVES: We investigated glucose metabolism, gut hormones, and inflammatory profile after bariatric surgery and medical treatment. METHODS: Forty patients with obesity were recruited and were subjected to Roux-en-Y gastric bypass (n = 15; Bariatric Surgery Group - BSG) or received medical care (n = 20; MG). Sleeve gastrectomy was performed in five patients who were excluded from analysis. Glucose, insulin, homeostatic model for the assessment of insulin resistance (HOMA-IR), glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), glucagon, ghrelin, dipeptidyl peptidase-4 (DPP-4) activity, circulating lipopolysaccharide (LPS), LPS-binding protein (LPB) and high-sensitivity C-reactive protein (hs-CRP) were evaluated before and three months after each treatment. Except for HOMA-IR, hs-CRP, and LBP, all variables were assessed at fasting and 30- and 60-minutes after a standard meal. RESULTS: After 3 months, both groups lost weight. However, BSG had a more extensive reduction than MG (respectively, 17.6% vs. 4.25%; P < 0.01). Except for LPS levels, higher on BSG than MG (1.38 ± 0.96 vs. 0.83 ± 0.60 EU/ml, P < 0.01), groups were similar before treatment. In respect to metabolic/hormonal changes, the BSG showed higher glucose, insulin, GLP-1, and GIP levels at 30-min and also GLP-1 at 30- and 60-minutes. DPP-4 activity, HOMA-IR, and fasting LBP did not change. LPS levels at 60-minutes decreased after surgery in the BSG. hs-CRP decreased on BSG compared to MG. CONCLUSIONS: Bariatric surgery resulted in more extensive effects on glucose metabolism, gut hormones, and inflammation.

Study of LEP, MRAP2 and POMC genes as potential causes of severe obesity in Brazilian patients.

PURPOSE: Monogenic forms of obesity are caused by single-gene variants which affect the energy homeostasis by increasing food intake and decreasing energy expenditure. Most of these variants result from disruption of the leptin-melanocortin signaling, which can cause severe early-onset obesity and hyperphagia. These mutation have been identified in genes encoding essential proteins to this pathway, including leptin (LEP), melanocortin 2 receptor accessory proteins 2 (MRAP2) and proopiomelanocortin (POMC). We aimed to investigate the prevalence of LEP, MRAP2 and POMC rare variants in severely obese adults, who developed obesity during childhood. To the best of our knowledge, this is the first study screening rare variants of these genes in patients from Brazil. METHODS: A total of 122 Brazilian severely obese patients (BMI ≥ 35 kg/m2) were screened for the coding regions of LEP, MRAP2 and POMC by Sanger sequencing. All patients are candidates to the bariatric surgery. Clinical characteristics were described in patients with novel and/or potentially pathogenic variants. RESULTS: Sixteen different variants were identified in these genes, of which two were novel. Among them, one previous variant with potentially deleterious effect in MRAP2 (p.Arg125Cys) was found. In addition, two heterozygous mutations in POMC (p.Phe87Leu and p.Arg90Leu) were predicted to impair protein function. We also observed a POMC homozygous 9 bp insertion (p.Gly99_Ala100insSerSerGly) in three patients. No pathogenic variant was observed in LEP. CONCLUSION: Our study described for the first time the prevalence of rare potentially pathogenic MRAP2 and POMC variants in a cohort of Brazilian severely obese adults. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Prevalência de anemia e deficiência de vitamina A e consumo de ferro e de vitamina A entre crianças usuárias do Sistema Único de Saúde na cidade do Rio de Janeiro, Brasil / Prevalence of anemia and vitamin A deficiency and iron and vitamin A intake in children that use the Brazilian Unified National Health System in Rio de Janeiro, Brazil / Prevalencia de anemia, deficiencia de vitamina A, y consumo de hierro y de vitamina A entre niños pacientes del Sistema Único de Salud en la ciudad de Río de Janeiro, Brasil

Estratégias nacionais para o controle de anemia e deficiência de vitamina A em crianças estão baseadas em estimativas de suas prevalências produzidas em âmbito nacional em 2006 com métodos não validados para este grupo etário e com nível de desagregação para macrorregiões. Com o intuito de subsidiar a gestão local para o (re)direcionamento de medidas de controle desses agravos, o presente trabalho apresenta estimativas de sua prevalência e, também, de marcadores de consumo alimentar de fontes de micronutrientes e do uso de suplementos de vitaminas e minerais em amostra probabilística de crianças de 6 a 59 meses, usuárias da atenção básica de saúde do Município do Rio de Janeiro, Brasil (n = 536). Foram coletadas amostras de sangue venoso para análise de hemoglobina, ferritina e retinol sérico e dados sobre o consumo alimentar, o uso de suplementos de vitaminas e minerais e as características sociodemográficas. As prevalências de anemia, anemia ferropriva e deficiência de vitamina A foram de, respectivamente, 13,7%, 5,5% e 13%. Quase todas as crianças haviam consumido alimentos ricos em ferro no dia anterior à entrevista, sendo altas as prevalências de consumo de fontes de origem animal. Somente 49,4% haviam consumido alimentos ricos em vitamina A. As prevalências de uso de algum suplemento, de suplemento com ferro e com vitamina A foram de, respectivamente, 51%, 14,7% e 24,4%. Os resultados apontam a necessidade de redirecionamento das estratégias de prevenção e controle de anemia e deficiência de vitamina A. Estudos futuros são necessários para examinar a evolução desses indicadores, tendo em vista as políticas de austeridade que entraram em vigor nos últimos anos e a crise econômica decorrente da pandemia da COVID-19.

Brazilian national strategies for the control of anemia and vitamin A deficiency in children are based on estimates of their nationwide prevalence rates in 2006 with methods not validated for this age group and with disaggregation at the level of major geographic regions. To back local administrations in (re)directing control measures for these two disorders, the current study presents estimates of their prevalence and markers of dietary intake of sources of micronutrients and use of vitamin and mineral supplements in a probabilistic sample of children 6 to 59 months of age, users of primary healthcare in the city of Rio de Janeiro, Brazil (n = 536). Venous blood samples were drawn for analysis of hemoglobin, ferritin, and serum retinol, besides collection of data on food consumption, use of vitamin and mineral supplements, and sociodemographic characteristics. Prevalence rates for anemia, iron deficiency anemia, and vitamin A deficiency were 13.7%, 5.5%, and 13%, respectively. Nearly all the children had consumed iron-rich food the day before the interview, with high prevalence of animal sources. Only 49.4% had consumed foods high in vitamin A. The prevalence rates for use of any supplement, iron supplements, and vitamin A supplements were 51%, 14.7%, and 24.4%, respectively. The findings point to the need to redirect the strategies for prevention and control of anemia and vitamin A deficiency. Future studies are necessary to examine trends in these indicators, focusing on austerity policies implemented in recent years and the economic crisis resulting from the COVID-19 pandemic.

Las estrategias brasileñas para el control de anemia y deficiencia de vitamina A en niños están basadas en estimaciones de sus prevalencias, producidas en el ámbito nacional en 2006 con métodos no validados para este grupo etario, y con un nivel de desagregación en las macrorregiones. Con el fin de apoyar la gestión local para la (re)orientación de medidas de control de esos problemas de salud, este trabajo presenta estimaciones de su prevalencia y, también, de los marcadores de consumo alimentario de fuentes de micronutrientes y del uso de suplementos de vitaminas y minerales, en una muestra probabilística de niños de 6 a 59 meses, pacientes de atención básica de salud del Municipio de Río de Janeiro, Brasil (n = 536). Se recogieron muestras de sangre venosa para el análisis de hemoglobina, ferritina y retinol sérico, así como datos sobre el consumo alimentario, de suplementos de vitaminas y minerales, así como de características sociodemográficas. Las prevalencias de anemia, anemia ferropénica y deficiencia de vitamina A fueron de, respectivamente, 13,7%, 5,5% y 13%. Casi todos los niños habían consumido alimentos ricos en hierro el día anterior a la entrevista, siendo altas las prevalencias de consumo de fuentes de origen animal. Solamente un 49,4% habían consumido alimentos ricos en vitamina A. Las prevalencias de consumo de algún suplemento, de suplemento con hierro y de suplemento con vitamina A fueron de, respectivamente, 51%, 14,7% y 24,4%. Los resultados apuntan la necesidad de reorientar las estrategias de prevención y control de la anemia y deficiencia de vitamina A. Se necesitan estudios futuros para examinar la evolución de esos indicadores, teniendo en vista las políticas de austeridad que entraron en vigor en los últimos años y la crisis económica a consecuencia de la pandemia de COVID-19.

Effects of multiple doses of simvastatin and artesunate monotherapy on SCHISTOSOMA MANSONI adult worms during infection in hyperlidemic mice / Efectos de múltiples dosis de simvastatina y artesunato en monoterapia en gusanos adultos de SCHISTOSOMA MANSONI durante la infección en ratones hiperlidémicos / Efeitos de doses múltiplas de monoterapia com sinvastatina e artesunato em vermes adultos SCHISTOSOMA MANSONI durante a infecção em camundongos hiperlidêmicos

A single dose of simvastatin and of artesunate monotherapy cause damage to the reproductive system of schistosomes as well as severe tegumental damage in male worms recovered from mice fed high-fat chow. This study aims to investigate whether treatment with multipledose regimes may offer more antischistosomal activity advantages than single daily dosing in mice fed high-fat chow. For this purpose, nine weeks post-infection, Swiss Webster mice were gavaged with simvastatin (200 mg/kg) or artesunate (300 mg/kg) for five consecutive days and euthanized two weeks post-treatment. Adult worms were analyzed using brightfield microscopy, confocal microscopy and scanning electron microscopy, presenting damages caused by simvastatin and artesunate to the reproductive system of males and females as well as tegument alterations, including peeling, sloughing areas, loss of tubercles, tegumental bubbles and tegument rupture exposing subtegumental tissue. The overall findings in this study revealed the potential antischistosomal activity of simvastatin and artesunate against Schistosoma mansoni adult worms, in addition to showing that multiple doses of either monotherapy caused severe damage to the tegument.

Una sola dosis de simvastatina y de artesunato en monoterapia causa daño al sistema reproductivo de los esquistosomas, así como daño tegumental severo en gusanos machos recuperados de ratones alimentados con comida rica en grasas. Este estudio tiene como objetivo investigar si el tratamiento con regímenes de dosis múltiples puede ofrecer más ventajas de actividad antiesquistosomal que la dosis única diaria en ratones alimentados con comida rica en grasas. Para este propósito, nueve semanas después de la infección, los ratones Swiss Webster se alimentaron por sonda con simvastatina (200 mg / kg) o artesunato (300 mg / kg) durante cinco días consecutivos y se sacrificaron dos semanas después del tratamiento. Los gusanos adultos se analizaron utilizando campo claro microscopía, microscopía confocal y microscopía electrónica de barrido, presentando daños causados ​​por simvastatina y artesunato en el sistema reproductivo de machos y hembras, así como alteraciones del tegumento, incluyendo descamación, desprendimiento, pérdida de tubérculos, burbujas tegumentales y rotura del tegumento exponiendo tejido subtegumental. Los hallazgos generales de este estudio revelaron la posible actividad antiesquistosomal de la simvastatina y el artesunato contra los gusanos adultos de Schistosoma mansoni, además de mostrar que dosis múltiples de cualquiera de las dos monoterapia causaron daños graves al tegumento.

Uma única dose de sinvastatina e de monoterapia com artesunato causa danos ao sistema reprodutivo dos esquistossomos, bem como danos graves ao tegumento em vermes machos recuperados de camundongos alimentados com ração rica em gordura. Este estudo tem como objetivo investigar se o tratamento com regimes de múltiplas doses pode oferecer mais vantagens da atividade anti-esquistossomótica do que uma única dose diária em ratos alimentados com ração rica em gordura. Para tanto, nove semanas após a infecção, camundongos Swiss Webster foram inoculados com sinvastatina (200 mg / kg) ou artesunato (300 mg / kg) por cinco dias consecutivos e sacrificados duas semanas após o tratamento. Vermes adultos foram analisados ​​usando campo claro microscopia, microscopia confocal e microscopia eletrônica de varredura, apresentando danos causados ​​pela sinvastatina e artesunato ao sistema reprodutivo de homens e mulheres, bem como alterações do tegumento, incluindo descamação, áreas de descamação, perda de tubérculos, bolhas tegumentais e ruptura do tegumento com exposição de tecido subtegumentar. Os achados gerais deste estudo revelaram a potencial atividade anti-esquistossomótica da sinvastatina e do artesunato contra vermes adultos do Schistosoma mansoni, além de mostrar que doses múltiplas de ambas as monoterapias causaram danos graves ao tegumento.

Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity.

BACKGROUND: The melanocortinergic pathway orchestrates the energy homeostasis and impairments in this system often lead to an increase in body weight. Rare variants in the melanocortin 4 receptor (MC4R) gene resulting in partial or complete loss of function have been described with autosomal co-dominant inheritance. These mutations are the most common cause of non-syndromic monogenic obesity. In this context, this study aimed to sequence the MC4R gene in a Brazilian cohort of adults with severe obesity. METHODS: This study included 163 unrelated probands with Body Mass Index (BMI) ≥ 35 kg/m2, stratified into three groups, according to the period of obesity onset. From the total sample, 25 patients were enrolled in the childhood-onset group (0-11 years), 19 patients in the adolescence/youth-onset group (12-21 years), and 119 patients in the adult-onset group (>21 years). Blood pressure, anthropometric and biochemical characteristics were obtained, and the MC4R coding region of each subject's DNA was assessed using automated Sanger sequencing. RESULTS: Significant anthropometric differences between the groups were observed. Higher body weight and BMI medians were found in patients with childhood-onset or adolescence/youth-onset when compared to the adulthood-onset obesity group. A total of five mutations were identified, including four missense variants: p.Ser36Thr, p.Val103Ile, p.Ala175Thr, and p.Ile251Leu. Additionally, we observed one synonymous variant (p.Ile198=). The p.Ala175Thr variant was identified in a female case with severe obesity and adulthood-onset. This variant was previously described as a partial loss-of-function mutation, in which the minor allele poses dominant-negative effect, probably resulting in reduced cAMP activity. CONCLUSION: This study showed a prevalence of common and rare variants in a cohort of Brazilian adults with severe obesity and candidates to bariatric surgery. We have identified a rare potentially pathogenic MC4R variant in a Brazilian patient with severe and adulthood-onset obesity.

Acute Effects of Metformin and Vildagliptin after a Lipid-Rich Meal on Postprandial Microvascular Reactivity in Patients with Type 2 Diabetes and Obesity: A Randomized Trial.

BACKGROUND: Type 2 diabetes mellitus and obesity are both related to endothelial dysfunction. Postprandial lipemia is a cardiovascular risk. Notably, it is known that a high-fat diet may elicit microvascular dysfunction, even in healthy subjects. Since anti-diabetic drugs have different mechanisms of action and also distinct vascular benefits, we aimed to compare the results of two anti-diabetic drugs after the intake of a lipid-rich meal on microcirculation in patients with type 2 diabetes and obesity. In parallel, we also investigated the metabolic profile, oxidative stress, inflammation, plasma viscosity, and some gastrointestinal peptides. SUBJECTS/METHODS: We included 38 drug-naïve patients, all women aged between 19 and 50 years, with BMI ≥ 30 kg/m2. We performed endothelial measurements and collected samples before (fasting) and after the intake of a lipid-rich meal at 30, 60, 120, and 180 min. Patients were randomized to metformin or vildagliptin, given orally just before the meal. Endothelial function was assessed by videocapillaroscopy and laser-Doppler flowmetry to investigate microvascular reactivity. Besides, we also investigated plasma viscosity, inflammatory and oxidative stress biomarkers, gastrointestinal peptides, and metabolic profile in all time points. RESULTS: No differences at baseline were noted between groups. Vildagliptin increased glucagon-like peptide-1 compared to metformin. Paired comparisons showed that, during the postprandial period, vildagliptin significantly changed levels of insulin and glucagon-like peptide-1, and also the dipeptidyl peptidase-4 activity, while metformin had effects on plasma glucose solely. Metformin use during the test meal promoted an increase in functional capillary density, while vildagliptin kept non-nutritive microvascular blood flow and vasomotion unchanged. CONCLUSIONS: After the intake of a lipid-rich meal, the use of vildagliptin preserved postprandial non-nutritive microflow and vasomotion, while metformin increased capillary recruitment, suggesting protective and different mechanisms of action on microcirculation.

Comparison between Conventional Cytology and Liquid-Based Cytology in the Tertiary Brazilian Navy Hospital in Rio de Janeiro.

INTRODUCTION: Cervical cancer screening is an important tool in public health. Liquid-based cytology (LBC) has been performed at the studied hospital for 7 years. The present study compares the performance of 2 LBC techniques with conventional cytology. OBJECTIVE: Our objective is to verify the sensitivity for the detection of neoplastic and preneoplastic epithelial atypia, as well as the positive predictive value of the 3 methodologies. METHODS: We analyzed retrospectively 24,529 cases and evaluated the conventional cytology, ThinPrep®, and BD SurePath® performance categorizing the results according to the Bethesda system. We also compared the level of unsatisfactory samples, the presence of elements from the squamocolumnar junction, and the detection of pathogenic microorganisms. RESULTS: ThinPrep® (1.43%) showed superior sensitivity over BD SurePath® (0.91%) and conventional cytology (0.71%) in terms of the detection of high-grade lesions; however, in terms of squamous atypia as a whole (ASC-US+), BD SurePath® (6.44%) proved to be more sensitive than conventional cytology (5.28%) and ThinPrep® (3.73%). CONCLUSIONS: The results show the advantage of implementing LBC in routine screening for cervical lesions. In this study, BD SurePath® achieved the overall best performance considering the studied variables.

Genetic Variants in the Activation of the Brown-Like Adipocyte Pathway and the Risk for Severe Obesity.

BACKGROUND: Regular physical activity has an important role in energy expenditure and combats the development of obesity. During exercise, PPARGC1A is overexpressed, stimulating an increase of the expression of FNDC5. This protein is cleaved to release the hormone irisin, which activates a browning process in white adipose tissue through an increase in UCP1 expression. As a result, irisin leads to mitochondrial heat production and energy expenditure. OBJECTIVES: The aim of this study was to investigate whether genetic variants in genes related to browning are associated with severe obesity and obesity-related features. This case-control study comprised 210 individuals with severe obesity (median body mass index [BMI] 45.6 [range 40.5-52.2]) and 191 normal-weight subjects (BMI 22.8 [21.1-23.9]). METHODS: Genomic DNA was extracted from peripheral blood and the genotypes of the PPARGC1A(rs8192678, rs3736265, rs2970847, and rs3755863) and UCP1 (rs6536991 and rs12502572) genes were obtained using Taqman® assay. For the FNDC5 gene, screening of exons 3-5 as well as their intron-exon boundaries was performed using automatic sequencing. RESULTS: Our results demonstrated that PPARGC1Ars2970847 and UCP1rs12502572 are associated with severe obesity. Furthermore, these polymorphisms influence anthropometric traits, such as BMI, body weight, and body adiposity index. Our findings also showed a dose-effect relationship between PPARGC1A rs8192678 and fasting plasma glucose. Finally, 5 rare mutations were identified in FNDC5, and 1 of these is a novel missense mutation. CONCLUSION: This study shows that genetic variants in the activation of brown-like adipocyte pathway play an important role in the susceptibility to severe obesity.

Genetic variants in the fat mass and obesity-associated (FTO) gene confer risk for extreme obesity and modulate adiposity in a Brazilian population.

Obesity is a major public health problem worldwide. It has a complex etiology, influenced by environmental and genetic factors. FTO has been recognized as an important genetic factor for obesity development. This study evaluated the contribution of FTO polymorphisms (rs9939609 and rs17817449) for extreme obesity in terms of the period of obesity onset, anthropometric, and biochemical parameters. The haplotype and the combined effects of FTO risk alleles on obesity susceptibility were evaluated. We investigated 169 normal-weight subjects (body mass index, BMI: 22.8 [21.0; 24.0] kg/m2) and 123 extremely obese individuals (BMI: 47.6 [44.1; 53.1] kg/m2). Genotyping was performed by real time PCR. Our results showed a strong association between FTO variants and extreme obesity. Carriers of the AT haplotype had an increased risk for extreme obesity. Gene scores suggested that the risk of developing extreme obesity was increased 1.37-fold per risk allele added. Both polymorphisms also influenced BMI and body weight. Additionally, rs17817449 influenced triglyceride levels. No effect of FTO variants on the period of obesity onset was found. In conclusion, the FTO polymorphisms showed a strong association with development of extreme phenotype of obesity and adiposity modulation in a Brazilian population.

Reproducibility and validity of portable haemoglobinometer for the diagnosis of anaemia in children under the age of 5 years.

Portable haemoglobinometers have been used in order to estimate the prevalence of anaemia in diverse settings. However, few studies have been conducted to evaluate their performance in children of different age groups in distinct epidemiological contexts. To evaluate the reproducibility and reliability of a portable haemoglobinometer for the diagnosis of anaemia in children <5 years Hb was measured in the venous blood of 351 children <5 years by an automated system (standard method) and in three capillary blood samples, using a portable haemoglobinometer (HemoCue®; test method). The reproducibility of the device and of the test method was evaluated using the intraclass correlation coefficient (ICC) (Hb in its continuous form), κ and prevalence-adjusted bias-adjusted κ (PABAK) (categorised variable: anaemia: yes/no). For test method validation, Bland-Altman analyses were performed and sensitivity, specificity, accuracy rate, positive predictive value (PPV) and negative predictive values (NPV) were calculated. The haemoglobinometer presented good device reproducibility (ICC = 0·79) and reasonable method reproducibility (puncture, collection and reading) (ICC = 0·71). Superficial and fair agreement (κ) and good agreement (PABAK) were observed among the diagnoses obtained through the test method. The prevalence of anaemia was 19·1 and 19·7 % using the standard and the test method, respectively, with no statistically significant differences. The test method presented higher specificity (87·7 %) and NPV (88·3 %) than sensitivity (50·7 %) and PPV (49·3 %), and intermediary accuracy rate (57·8 %). HemoCue® showed good device reproducibility and reasonable method reproducibility, as well as good performance in estimating the prevalence of anaemia. Nevertheless, it showed a fair reliability and low individual diagnostic accuracy.

Effects of a hypoenergetic diet associated with açaí (Euterpe oleracea Mart.) pulp consumption on antioxidant status, oxidative stress and inflammatory biomarkers in overweight, dyslipidemic individuals.

OBJECTIVE: To evaluate the effects of a hypoenergetic diet (HD)associated with açaí pulp consumption on oxidative stress, antioxidant status and inflammatory biomarkers in overweight, dyslipidemic individuals. RESEARCH METHODS & PROCEDURES: A randomized, double-blind, placebo-controlled clinical trial was conducted for 90 days. The study began with a 30-day run-in period, during which the intervention was exclusively a HD. Following this period, volunteers were randomized into 2 groups, and 200 g of either açaí pulp or placebo were added to the HD for 60 days. Anthropometric measurements, arterial pressure, oxidative stress and antioxidant status biomarkers, inflammatory and biochemical biomarkers were evaluated. RESULTS: Sixty-nine volunteers completed the clinical trial, 30 of which were in the HD + açaí group and 39 in HD + placebo group. Plasma 8-isoprostane concentrations significantly reduced 60 days after the intervention in the açaí group (p = 0.000), and there was a significant difference between the groups (açaí versus placebo; p = 0.037). Regarding inflammatory status parameters, a significant reduction in IL-6 was observed in the HD + açaí group (p = 0.042), and IFN-γ decreased significantly in both groups, HD + açaí (p = 0.001) and HD + placebo (p = 0.008); there were, however, no differences between the groups. Lipid profile parameters and blood glucose levels did not show change, regardless of nutritional intervention. CONCLUSION: The addition of açaí to a HD, for 60 days, reduced oxidative stress and improved inflammation in overweight, dyslipidemic individuals.

30-days effects of vildagliptin on vascular function, plasma viscosity, inflammation, oxidative stress, and intestinal peptides on drug-naïve women with diabetes and obesity: a randomized head-to-head metformin-controlled study.

BACKGROUND: Obesity is the main risk factor for diabetes and excessive visceral fat triggers low-grade inflammatory process, mediated by activation and release of cytokines and high flow of free fatty acids that contribute to insulin resistance, increased oxidative stress, and impaired endothelial function. Metformin and vildagliptin have known vasculoprotective actions, but the value of these drugs on drug-naïve diabetic patients during 30 days use warrants investigation. Our purpose was to observe their effects on endothelial function, oxidative stress, inflammatory biomarkers, and plasma viscosity. METHODS: 38 women with obesity and type 2 diabetes drug-naïve, aged between 19 and 50 years, BMI ≥ 30 kg/m2, were recruited and subjected to measurements of endothelial function, nutritive skin microvascular reactivity, plasma viscosity, inflammatory and oxidative stress biomarkers at baseline and randomized 1:1 to ingest metformin (850 mg twice/day) or vildagliptin (50 mg twice/day) during 30 days, and then, re-evaluated. RESULTS: No differences between groups were noticed at baseline. After treatment, vildagliptin promoted an improvement on endothelial-dependent and -independent vasodilatations, at arteriole level, while metformin resulted in improved nutritive microvascular reactivity, at the capillary level. Intragroup analysis showed that vildagliptin reduced insulin, C-peptide and oxidized LDL, and increased adiponectin and glucagon-like peptide-1 while metformin reduced weight, plasma glucose, total cholesterol, HDL-c, LDL-c, and dipeptidyl peptidase-4 activity, with an unexpected increase on tumor necrosis factor-α. No significant difference in plasma viscosity was noted. CONCLUSIONS: In the vascular beds investigated, both drugs used for only 30 days improved endothelial function, through distinct, and possibly, complementary mechanisms on drug-naïve diabetic women.Trial Registration ClinicalTrials.gov: NCT01827280.

The association of the fat mass and obesity-associated gene (FTO) rs9939609 polymorphism and the severe obesity in a Brazilian population.

Background: Obesity occurs due to the interaction between the genetic background and environmental factors, including an increased food intake and a sedentary lifestyle. Nowadays, it is clear that there is a specific circuit, called leptin-melanocortin pathway, which stimulates and suppresses food intake and energy expenditure. Therefore, the aim of this study was to evaluate the influence of genetic variants related to appetite regulation and energy expenditure on severe obesity susceptibility and metabolic phenotypes in a Brazilian cohort. Material and methods: A total of 490 participants were selected (298 severely obese subjects and 192 normal-weight individuals). Genomic DNA was extracted and polymorphisms in protein related to agouti (AGRP; rs5030980), ghrelin (GHRL; rs696217), neuropeptide Y (NPY; rs535870237), melanocortin 4 receptor (MC4R; rs17782313), brain-derived neurotrophic factor (BDNF; rs4074134) and fat mass and obesity-associated (FTO; rs9939609) genes were genotyped using TaqMan® probes. Demographic, anthropometric, biochemical and blood pressure parameters were obtained from the participants. Results: Our results showed that FTO rs9939609 was associated with severe obesity susceptibility. This polymorphism was also related to body weight, body mass index (BMI), waist to weight ratio (WWR) and inverted BMI. Individuals carrying the mutant allele (A) showed higher levels of BMI as well as lower values of WWR and inverted BMI. Conclusion: This study showed that FTO rs9939609 polymorphism plays a significant role in predisposing severe obesity in a Brazilian population.

Dipeptidyl Peptidase 4 Activity Is Related to Body Composition, Measures of Adiposity, and Insulin Resistance in Subjects with Excessive Adiposity and Different Degrees of Glucose Tolerance.

BACKGROUND: The enzyme dipeptidyl peptidase 4 (DPP4) has been recently recognized as an adipo-myokine. However, studies that associate its constitutive activity with body composition, anthropometry, and insulin resistance (IR) are very scarce and included only healthy people. METHODS: First, we investigated the relationships of constitutive DPP4 activity, body composition (assessed by bioelectrical impedance analysis), and measures of adiposity and IR in fifty-two subjects of both sexes, 18-50 years, and BMI ≥25.0 kg/m2 who comprised three groups according to glucose tolerance. Additionally, we evaluated associations among DPP4 activity and adipokines, gut peptides, and biochemical variables at fasting and 30 and 60 min after a standardized meal intake. RESULTS: DPP4 activity was no different among the three groups. At fasting, pooled analysis showed it was positively correlated with measures of central adiposity, such as WC (P = 0.011) and WHR (P = 0.009), and with all measures of IR, but inversely related to indexes of general adiposity, such as fat mass percentage (P = 0.014) and BAI (P = 0.0003). DPP4 activity was also associated with lean mass (r = 0.57, P < 0.0001). After meal intake, DPP4 activity remained significantly associated with insulin, leptin, and resistin. In multiple regression analysis, BAI, WHR, percent lean mass, HOMA-IR, and leptin influenced DPP4 activity and explained approximately 26% of the variance on it. CONCLUSIONS: Constitutive DPP4 activity is positively associated with lean mass, central adiposity, and IR and negatively to general adiposity. Furthermore, it seems to be influenced by body composition and IR and could also be viewed as an adipo-myokine in subjects with excessive adiposity and different stages of glucose tolerance.

Identification of the MC4R start lost mutation in a morbidly obese Brazilian patient.

BACKGROUND: Melanocortin 4 receptor gene (MC4R) is an important regulator of food intake, body weight, and blood pressure. Mutations in MC4R are associated with the most common form of nonsyndromic monogenic obesity. MC4R variations have an autosomal co-/dominant model of inheritance. MC4R screening could reveal individuals previously unrecognized with Mendelian form of obesity for further clinical management and genetic counseling. However, there are limited data regarding MC4R variants in patients with obesity from Brazil. The aim of this study was to screen the coding region of the MC4R gene in a Brazilian cohort of severely obese adults and to investigate the phenotype-genotype correlation within MC4R variant carriers. METHODS: This study comprised 157 adult participants, stratified according to the period of obesity onset. The first group included 97 patients with childhood-onset obesity (0-11 years) and the second group comprised 60 subjects with adolescence/youth-onset obesity (12-21 years). The entire coding region of MC4R gene was screened by Sanger sequencing. RESULTS: As a result, five previously described variants (Met1?, Ser36Thr, Val103Ile, Ile98=, and Phe202Leu) were identified. Met1? is a start lost codon variant, which affects the translation of MC4R. It was found in a female patient with childhood-onset obesity. We also compared the anthropometric and metabolic parameters between patients with MC4R missense variants (Ser36Thr, Val103Ile, and Phe202Leu) and noncarriers. Patients carrying MC4R variants had higher median of waist-hip ratio when compared to noncarriers (P=0.048). These missense variants were also associated with hypertension (P=0.014). Additionally, Val103Ile carriers had lower diastolic blood pressure and lower systolic blood pressure compared to noncarriers (P=0.020 and P=0.065, respectively). Val103Ile was also associated with hypertension (P=0.003). CONCLUSION: This study showed the prevalence of MC4R variants in a cohort of Brazilian adults with severe obesity. We also identified significant phenotype differences between carriers and noncarriers of missense variants in our sample, suggesting an important role of MC4R on body fat distribution and blood pressure.