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ABSTRACT Objective: 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.

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ABSTRACT Objectives: The objective of the present study was to evaluate a possible association between personality factors (PF) and the health-related quality of life (HRQoL) of type 1 diabetes (T1D) patients. This allows for the investigation of obstacles related to treatment type and the presence of complications in HRQoL. Materials and methods: This cross-sectional study enrolled 78 patients aged 13-67 years from two diabetes clinics. PF was evaluated using the validated questionnaire Inventory of the Five Great Personality Factors. HRQoL was determined using the Brazilian Problem Areas in Diabetes Scale (B-PAID) questionnaire. The chi-square test, Fisher's exact test, and Welch's modified two-sample t-test were used to establish relationships. Results: In this sample of 46 women and 32 men with T1D and mean A1C of 8%-9%, we observed great suffering in 58.97% and that HRQoL was worse in women. “Openness” was the most prevalent PF and “extroversion” the least prevalent. “Neuroticism” facilitated a tendency to tolerate suffering. Conclusion: T1D patients’ personalities influence their treatment. The PF “neuroticism” is potentially related to better HRQoL. Brazilian T1D patients indicated great suffering in their HRQoL, which may be characteristic across the country. Women experienced worse HRQoL, which is in line with world literature. However, the limited sample size in this study warrant further research to test the hypotheses.

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ABSTRACT Objective: To evaluate the effect of curcumin supplementation on the body compositions and biochemical parameters of Brazilian women with high waist circumferences. Materials and methods: This is a blind, randomized, placebo-controlled clinical trial conducted in 2016 with 35 Brazilian women with high waist circumference (WC). In total, 80 participants were randomized [38 in the placebo group (PG) and 42 in the supplemented group (SG)], but at the end of the protocol, 20 individuals in the PG and 15 in the SG were evaluated. The sample consumed one capsule of curcumin (500 mg/day) (Curcumin C3 Complex®) or a placebo for 90 days. Body weight, height, body mass index, WC, body fat, fat free mass, fasting glucose (FG), lipid profile [triglycerides (TGs), total cholesterol (TC), HDL-c and LDL-c], physical activity level and food intake (energy, carbohydrate, total fat and protein) data were evaluated before and after the intervention. Results: Curcumin supplementation reduced body mass (p < 0.040) but did not alter other anthropometric parameters or body composition (p ≥ 0.050). In relation to the biochemical profile, the SG saw reductions in FG (p < 0.001), TGs (p < 0.001) and TC (p = 0.001) compared with the PG. At the baseline and during the intervention, the practice of physical activity and food intake did not differ between the SG and PG (p ≥ 0.050). Conclusion: Curcumin supplementation improved the blood glucose and lipid profile of Brazilian women with high WC, without altering body composition. New studies with larger sample sizes and longer durations are important for identifying more robust data regarding the proposal of this work.

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ABSTRACT Objective: The aim of this study was to assess the effect of hyperthyroidism and its treatment on body weight and composition, insulin resistance, and mediators of appetite and energy homeostasis, namely ghrelin, leptin, adiponectin, and fibroblast growth factor 21 (FGF21). Subjects and methods: Thirty-five adult patients (27 female and 8 male, aged 39.63 ± 9.70 years) with overt hyperthyroidism were evaluated for leptin, ghrelin, adiponectin, and FGF21 levels; insulin resistance; and body composition using DEXA both at baseline and a minimum of two months following normalization of serum thyroxin on carbimazole treatment. Comparison of means between the baseline and post treatment values was performed by the paired t test for normally distributed parameters and by the Wilcoxon signed-rank test for non-normally distributed data. Results: Hyperthyroidism correction resulted in an increase in weight from 51.15 ± 8.50 kg to 55.74 ± 8.74 kg (P < 0.001), paradoxically accompanied by a decrease in insulin resistance as measured by HOMA-IR from 1.35 (1.02-1.72) to 0.73 (0.52-0.93) ( P < 0.001). Correction of hyperthyroidism was also associated with a decrease in FGF21 from 58 (55-64) to 52 (47-58) pg/mL ( P < 0.001) and in leptin levels from 17 (7-36) to 11 (4.6-28) ng/mL ( P = 0.03). Conclusion: Despite lower body weight, thyrotoxicosis is associated with insulin resistance. High levels of thermogenic hormones, leptin, and FGF21 were observed in thyrotoxicosis and may be partly responsible for the excessive heat production typical of this condition.

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ABSTRACT Objective: The objective of this study was to evaluate the impact of probiotic supplementation therapy on anthropometric values and body composition of children and adolescent with obesity. Subjects and methods: This is a nonrandomized controlled, prospective, double-blind interventional clinical trial with primary data analysis. The sample comprised 44 pubertal children and adolescent (8-17 years old) with obesity. The patients were allocated to probiotic (Lactobacillus rhamnosus) or placebo group, with matching of gender and chronological age. Both groups received nutritional guidance, and were followed for six months. In all patients the anthropometric assessment was carried out by a nutritionist and data on weight, height and waist circumference (WC) were collected. Body composition was assessed using dual emission X-ray absorptiometry (DXA). Results: After six months, both groups had increased weight, height but reduced body index mass (BMI) standard deviation score, with no differences between groups. After the intervention, both groups showed a reduction in the percentage of total body fat and an increase in lean mass, but only the placebo group showed a reduction in the percentage of trunk fat. However, the variation in these parameters did not differ between groups. Conclusions: The probiotic group does not seem to have benefited from supplementation. However, we suggest that this reduction in BMI SDS in both groups may have occurred due to improvements in diet because of the nutritional advice given throughout the therapy. We concluded that supplementation with this strain of probiotic was not effective in promoting weight loss or improving the body composition of this population.

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ABSTRACT Objective: Describe the clinical profile of patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) and analyze the risk predictors of hepatic fibrosis in outpatient follow-up at a university hospital. Subjects and methods: Demographic, clinical and laboratory data of a cohort of 143 patients with biopsy-proven NAFLD were retrospectively analysed under univariate analyses. Diagnostic accuracy, determined by AUROC, was evaluated for variables that showed a significant difference in univariate comparison analysis and diagnostic performances were determined by sensitivity and specificity. Results: The mean age of studied patients were 48 years, 66.4% of them were women. Age, presence of diabetes mellitus, hypertension, metabolic syndrome and laboratory variables such as AST/ALT ratio, GGT, platelet count and fasting glucose were significantly associated with advanced fibrosis. FIB-4 and NAFLD fibrosis score (AUROC 0.82 and 0.89, respectively) outperformed APRI (AUROC 0.73) for advanced liver fibrosis and cirrhosis (P of 0.04). Conclusion: In our study, metabolic syndrome, diabetes, hypertension, AST/ALT ratio, GGT, platelet count and fasting glucose were associated with hepatic fibrosis in patients with NAFLD. The non-invasive tests FIB-4 and NAFLD fibrosis score showed the best accuracy to stratify disease severity.

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ABSTRACT Objective: Test if the MRI FAST1.2 protocol can detect extra-pituitary midline structural brain abnormalities in patients with ectopic posterior pituitary (EPP), and highlighting their radiological-laboratory correlations. Subjects and methods: Cross-sectional study of patients with EPP and control group. All individuals were submitted to FAST1.2, which combines the FAST1 protocol developed by our group with 3D T2DRIVE imaging. Results: We evaluated 36 individuals with EPP and 78 as control group. Pituitary stalk (PS) was identified in 7/36 patients in EPP group by FAST1, and in 24/36 patients in FAST1.2 (p < 0.001). FAST1 failed to detect PS in one individual in the control group, while the FAST1.2 defined the PS in all individuals. In EPP group, eleven had interhypothalamic adhesion (IHA), three septo-optic dysplasia, and one cerebellar malformation. We didn’t observe higher frequency of panhypopituitarism or developmental delay in patients with IHA. In control group, three had pars intermedia cysts, one hydrocephalus, and one hypothalamic hamartoma. Conclusions: FAST1.2 allows confident recognition of midline structural abnormalities, including the pituitary stalk and IHA, thereby making MRI acquisition faster and with no need for contrast administration. IHA could be associated with defects in neuronal migration, as occur in patients with EPP, with no clinical significance.

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ABSTRACT Objective: We investigated the effects of aerobic training on adipokine concentrations in women with polycystic ovary syndrome (PCOS). Subjects and methods: 120 women, including 60 with PCOS and 60 without PCOS, were divided into six groups (n = 20) based on body fat percentages of 22%-27%, 28%-32%, and 33%-37%. All groups were submitted the same evaluations before and after 16 weeks of aerobic training. These included anthropometric and hemodynamic analyses, cardiopulmonary tests, and laboratory tests. Two-way analysis of variance was performed to evaluate the differences between women with and without PCOS, effect of the body fat percentage, and effect of aerobic training. Results: Body fat and PCOS were associated with high values of blood glucose, insulin, and testosterone. Body fat also reduced adiponectin levels and increased leptin, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). In contrast, the PCOS increased only TNF-α and IL-6 levels. In the PCOS group, aerobic training reduced insulin, triglycerides, leptin, and IL-6 levels. It also promoted an increase in adiponectin and high-density lipoprotein levels. However, aerobic training did not alter TNF-α concentrations. Conclusion: The body fat potentiates metabolic impairments that may be harmful to women with PCOS. Aerobic training appears to promote an important beneficial effect on the metabolic regulation of adipokines, except TNF-α.

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ABSTRACT Objective: The aim of this study was to estimate the prevalence of insulin resistance (IR) in a rural population in Brazil, to verify its association with sociodemographic, labor, lifestyle, and health factors. Subjects and methods: This is a cross-sectional study with 790 farmers in the state of Espírito Santo/Brazil. Triglyceride-glucose (TyG) was calculated and a cut-off point of Ln 4.52 was used. A hierarchical logistic regression for the association of insulin resistance with sociodemographic, labor, lifestyle and health variables of farmers living in Espírito Santo was performed. Results: The prevalence of insulin resistance was 33.7% (n = 266), and the association with insulin resistance was found in the age group 31 to 40 years of age (OR = 1.85; 95% CI 1.19-2.87); in smokers or former smokers (OR = 1.63; 95% CI 1.08-2.48) and overweight (OR = 3.06; 95% CI 2.22-4.23). Conclusion: The prevalence of insulin resistance was high in a rural population of Brazil, and was mainly associated with age, smoking and obesity. The use of TyG as an instrument for assessing the health of individuals living in areas where access to health services is difficult, such as rural areas, can represent an important advance in terms of health promotion, protection and recovery. In addition, by identifying the risk factors associated with IR, as well as their consequences, a more adequate scheme for the prevention and treatment of these comorbidities can be defined.

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ABSTRACT Objective: We aimed to investigate the association between glucose coefficient of variation (CV) and mortality and disease severity in hospitalized patients with coronavirus disease-19 (COVID-19). Subjects and methods: Retrospective cohort study in a tertiary center of patients with COVID-19 admitted to designated departments between March 11th, 2020, and November 2nd, 2020. We divided patients based on quartiles of glucose CV after stratification to those with and without diabetes mellitus (DM). Main outcomes were length of stay and in-hospital mortality. Results: The cohort included 565 patients with a mean age of 67.71 ± 15.45 years, and 62.3% were male. Of the entire cohort, 44.4% had DM. The median glucose CV was 32.8% and 20.5% in patients with and without DM, respectively. In patients with DM, higher glucose CV was associated with a longer hospitalization in the unadjusted model (OR = 2.7, 95% CI [1.3,5.6] for Q4), and when adjusted for age, sex, comorbidities, and laboratory markers, this association was no longer statistically significant (OR = 1.3, 95% CI [0.4,4.5] for Q4). In patients with and without DM, higher glucose CV was associated with higher rates of in-hospital mortality in the unadjusted model, but adjustment for comorbidities and laboratory markers eliminated the association (OR = 0.5, 95% CI [0.1,3.4] for Q4 in patients with DM). Conclusion: Higher glucose CV was associated with increased in-hospital mortality and length of stay, but this association disappeared when the adjustment included laboratory result data. Glucose CV can serve as a simple and cheap marker for mortality and severity of disease in patients with COVID-19.

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ABSTRACT Objective: The COVID-19 pandemic has profoundly disrupted health care worldwide. We aimed to evaluate the impact of the first COVID-19 wave on the treatment of our patients with acromegaly. Subjects and methods: A standard questionnaire was systematically applied to all patients and included questions on general health status, whether all laboratory workup had been done, common signs and symptoms of acromegaly, treatment adherence, and previous COVID-19 symptoms and diagnosis. Results: We attempted to contact 136 patients with acromegaly at regular follow-up at our institution and contacted 101 of them successfully. In all, 37% of the patients reported symptoms of acromegaly, which was more common among women. A total of 27 patients were lost to follow-up (including 19 who interrupted treatment during the pandemic) mainly for fear of becoming infected by the SARS-CoV-2. Of these, 24 resumed follow-up after our contact. Conclusions: The current COVID-19 pandemic has strongly impacted the follow-up of patients with acromegaly. Telemedicine can be an important tool to maintain regular treatment in the current or future pandemics.

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“What's in a name? That which we call a rose / By any other name would smell as sweet” (Juliet, from Romeo and Juliet by William Shakespeare). Shakespeare's implication is that a name is nothing but a word and it therefore represents a convention with no intrinsic meaning. Whilst this may be relevant to romantic literature, disease names do have real meanings, and consequences, in medicine. Hence, there must be a very good rational for changing the name of a disease that has a centuries-old historical context. A working group of representatives from national and international endocrinology and endocrine pediatric societies now proposes changing the name of “diabetes insipidus” to “Arginine Vasopressin Deficiency (AVP-D)” for central etiologies, and “Arginine Vasopressin Resistance (AVP-R)” for nephrogenic etiologies This editorial provides both the historical context and the rational for this proposed name change.

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ABSTRACT Primary hypothyroidism is a common disorder in clinical practice. The management of most cases of hypothyroidism is usually straightforward, but the best approach in some special situations may raise questions among physicians. This position statement was prepared by experts from the Brazilian Society of Endocrinology and Metabolism to guide the management of three special situations, namely, hypothyroidism in the elderly, subclinical hypothyroidism in patients with heart disease, and difficult-to-control hypothyroidism. The authors prepared the present statement after conducting a search on the databases MEDLINE/PubMed, LILACS, and SciELO and selecting articles with the best evidence quality addressing the selected situations. The statement presents information about the current approach to patients in these special situations.

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

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ABSTRACT High blood pressure (BP) is not restricted to adults; children and adolescents may also be affected, albeit less frequently. Aside from unfavorable environmental factors, such as obesity and sedentary life leading to early-onset essential hypertension (HT), several secondary causes must be investigated in the occasional hypertensive child/adolescent. Endocrine causes are relevant and multiple, related to the pituitary, thyroid, parathyroid, gonads, insulin, and others, but generally are associated with adrenal disease. This common scenario has several vital components, such as aldosterone, deoxycorticosterone (DOC), cortisol, or catecholamines, but there are also monogenic disorders involving the kidney tubule that cause inappropriate salt retention and HT that simulate adrenal disease. Finally, a blood vessel disease was recently described that may also participate in this vast spectrum of pediatric hypertensive disease. This review will shed some light on the diagnosis and management of conditions, focusing on the most prevalent adrenal (or adrenal-like) disturbances causing HT.

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ABSTRACT Congenital malformations are more frequently found among children born to mothers with diabetes than in the background population. There are several complex mechanisms involved in the development of congenital malformations in the offspring of mothers with hyperglycemia, such as the overexpression of glucose transporters (GLUTs) 1 and 2, the increased activity of the hexosamine biosynthetic pathway and the reduced expression of the PAX3 gene with a consequent increase in p53 protein expression. These alterations can lead to increased glucose and free radical concentrations in the embryo, thus promoting the process of apoptosis and causing malformation. The most frequent malformations found in the offspring of mothers with diabetes are heart and neural tube defects, urinary tract and kidney malformations, and cleft lip with or without cleft palate. Strict glycemic control should be obtained before and during pregnancy, aiming to avoid or minimize the risk of congenital malformations in the offspring. Beyond hyperglycemia, several factors may also be associated with increased risks of malformations in the offspring of these women, such as obesity, multiple pregnancies, advanced maternal age, folic acid deficiency, use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, assisted reproduction techniques, and exposure to different types of environmental pollutants.

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ABSTRACT In the late 19th century, José Dantas de Souza Leite, a physician born in Sergipe, published the first detailed clinical description of acromegaly under the guidance of the French neurologist Pierre Marie. In 2014, the Brazilian Society of Endocrinology and Metabolism created the “José Dantas de Souza Leite Award”, which is granted every two years to a Brazilian researcher who has contributed to the development of endocrinology. In 2022, the award was given to another physician from Sergipe, Manuel Hermínio de Aguiar Oliveira, from the Federal University of Sergipe for the description of “Itabaianinha syndrome” in a cohort of individuals with isolated GH deficiency due to a homozygous inactivating mutation in the GH-releasing hormone receptor gene. This research, which was carried out over almost 30 years, was performed in partnership with Roberto Salvatori from Johns Hopkins University and in collaboration with other researchers around the world. This review article tells the story of Souza Leite, some milestones in the history of GH, and summarizes the description of Itabaianinha syndrome.