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Studies of subcutaneous and visceral abdominal fat thickness evaluated by ultrasound as a predictor of gestational diabetes mellitus (GDM) have been published, but the best technique and standardization are unknown. To identify, critically evaluate, and analyze studies using subcutaneous and visceral abdominal fat as a model for predicting GDM in the first and second trimesters of pregnancy and evaluate their methodological quality.PubMed, Scopus, and Web of Science databases were searched from May to July 2019. We included studies of any sample size performed for any duration and in any configuration. Model development and validation studies were eligible for inclusion. Two authors independently performed the eligibility assessment of the studies by reviewing the titles and abstracts. Data on study design, gestational age, diagnostic criteria for GDM, device, ultrasound fat measurement technique, and cutoff point for GDM prediction were extracted.The electronic search resulted in 1331 articles, of which 14 were eligible for systematic review. Different criteria for diagnosing GDM and fat measurement techniques were used. The cutoff point for subcutaneous, visceral, and total abdominal fat for predicting GDM in the first and second trimesters varied between the studies.No study validated the model for predicting GDM using subcutaneous and visceral abdominal fat measurements. External validation studies are recommended to improve the generalization of this GDM predictor in clinical practice.

Interleukin-18 (IL-18), a proinflammatory and proatherogenic cytokine, has been associated with type 2 diabetes, metabolic syndrome, stroke and coronary artery disease. Some studies have indicated that the IL-18 promoter -137 G/C polymorphism seems to be associated with changes in the IL-18 expression and may contribute to the development of cardiovascular disease (CVD). The aim of this study was to evaluate the association between -137 G/C polymorphism and the levels of IL-18, biochemical markers for cardiovascular disorders, anthropometric profile and cardiovascular disease in Brazilian patients with type 2 diabetes (T2DM).Study subjects comprised 125 T2DM patients undergoing follow-up at a reference endocrinology service in northeastern Brazil. The -137G/C polymorphism in the IL-18 gene and serum IL-18 levels were determined by using allele-specific polymerase chain reaction (PCR) and enzyme-linked immune assay (ELISA), respectively. The anthropometric parameters were assessed using a Body Composition Monitor with Scale, and the laboratory data were measured using an automatic analyzer as well as spectrophotometric analysis.The genotype distribution of IL-18 -137 G/C genetic polymorphism was significantly different among T2DM patients with and without CVD. The results show an association between the CC genotype of -137G/C polymorphism and CVD in T2DM patients (p 0.001). Serum levels of IL-18 were significantly higher in CC carriers (843.1 pg/mL) compared with GG or GC carriers (303.6 pg/mL and 292.0 pg/mL, respectively). In addition, the present study showed that carriers of the CC genotype also had significantly higher concentrations of creatinine and albuminuria than carriers of the GG or GC genotypes (p 0.05 in both).These results suggest that Brazilian T2DM patients with the CC genotype seem to show a predisposition to CVD, as well as an elevation in markers of renal function.

A literature review on the clinical, laboratory, and treatment features of type B insulin resistance syndrome (TBIRS). Data from PubMed, the Virtual Health Library and Cochrane database were selected and analyzed using the REDCap application and R statistical program. From 182 papers, 65 were selected, which assessed 119 clinical cases, 76.5% in females and 42.9% in African-Americans, with an average age of 44 years. A common feature of TBIRS is co-occurrence of autoimmune diseases, such as systemic lupus erythematosus (most frequently reported). Hyperglycemia of difficult control was the mostly reported condition. Tests for anti-insulin receptor antibodies were positive in 44.2% of the cases. Disease management comprised fractional diet, insulin therapy (maximum dose given was 57 600 IU/day), plasmapheresis and immunosuppression with several classes of drugs, mainly glucocorticoids. Remission occurred in 69.7% of cases, in 30.3% of these spontaneously. The mortality rate was 15.38%. There was an inverse relationship between anti-insulin antibodies and remission (p = 0.033); and a positive correlation between combined immunosuppressive therapy and remission (p = 0.002). Relapse occurred in 7.6% of the cases. This rare syndrome has difficult-to-control diabetes, even with high doses of insulin, and it is usually associated with autoimmune diseases. Therapeutic advances using immunomodulatory therapy have led to significant improvements in the rate of remission.

Background A new strain of human coronavirus (HCoV) spread rapidly around the world. Diabetes and obesity are associated with a worse prognosis in these patients. Congenital Generalized Lipodystrophy (CGL) patients generally have poorly controlled diabetes and require extremely high doses of insulin. There is no documentation in the literature of cases of COVID in CGL patients. Thus, we aimed to evaluate the prevalence of SARS-CoV-2 infection in CGL patients, and the association of their clinical and metabolic characteristics and outcomes. Methods This is a cross-sectional study carried out between July and October 2020. Clinical data collected were respiratory or other flu-like symptoms, need of hospitalization in the last three months, CGL comorbidities, and medications in use. Cholesterol, triglycerides, glycohemoglobin A1c levels, anti-SARS-CoV-2 antibodies and nasopharyngeal swab for RT-qPCR were also obtained in all CGL patients. Mann-Whitney U test was used to analyze the characteristics of the participants, verifying the non-adherence of the data to the Gaussian distribution. In investigating the association between categorical variables, we used Pearson's chi-square test and Fisher's exact test. A significance level of 5% was adopted. Results Twenty-two CGL patients were assessed. Eight subjects (36.4%) had reactive anti-SARS-CoV-2 antibodies. Only one of these, also presented detectable RT-qPCR. Five individuals (62.5%) were women, median age of 13.5 years (1 to 37). Symptoms like fever, malaise, nausea, diarrhea and chest pain were present, and all asymptomatic patients were children. All subjects had inadequate metabolic control, with no difference between groups. Among positive individuals there was no difference between those with AGPAT2 (75%) and BSCL2 gene mutations (25%) (p > 0.05). No patient needed hospitalization or died. Conclusions We described a high prevalence of SARS-CoV-2 infection in CGL patients with a good outcome in all of them. These findings suggest that at least young CGL patients infected by SARS-COV-2 are not at higher risk of poor outcome, despite known severe metabolic comorbidities.

Background Congenital generalized lipodystrophy (CGL) is a rare disorder characterized by the absence of subcutaneous adipose tissue, severe insulin resistance, diabetes mellitus, and cardiovascular complications, including cardiac autonomic neuropathy (CAN), left ventricular hypertrophy (LVH), and atherosclerosis. The present study aimed to access the association between CAN parameters and cardiovascular abnormalities in CGL patients. Methods A cross-sectional study was conducted with 10 CGL patients and 20 healthy controls matched for age, sex, BMI, and pubertal stage. We evaluated clinical, laboratory, and cardiovascular parameters—left ventricular mass index (LVMI), interventricular septum thickness (IVS), systolic and diastolic function determined by two-dimensional transthoracic echocardiography; carotid intimal media thickness (cIMT); and cQT interval. Heart rate variability (HRV) was evaluated by spectral analysis components—high frequency (HF), low frequency (LF), very low frequency (VLF), LF/HF ratio, and total amplitude spectrum (TAS)—and cardiovascular reflexes tests (postural hypotension test, respiratory, orthostatic and Valsalva coefficients). Results In CGL group, four patients (40%) had LVH and diastolic dysfunction. HF component (parasympathetic control) was lower in LVH patients. CGL patients presented higher values of cIMT and cQT interval than heathy subjects. Inverse association between LVMI and LF (p = 0.011), IVS and LF (p = 0.007), and cIMT and leptin (p

Background New-onset diabetes after transplant is a severe complication that can present in liver transplant recipients, negatively impacting quality of life and graft survival. It also contributes to increased risk of infection, cardiovascular disease, and rejection, which are the main causes of death among liver transplant recipients. The aim of the present study was to assess the risk factors associated with new-onset diabetes after transplant. Method This was a case control study based on the data from 146 liver transplant patients at a reference hospital. The data from the charts were collected using a 2-part form: Part I (sociodemographic variables) and Part II (clinical variables). Results Multiple analysis showed that pre-existing systemic arterial hypertension (odds ratio [OR], 2.65; 95% CI, 1.12–6.28) and the use of sodium mycophenolate associated with tacrolimus (OR, 2.68; 95% CI, 1.02–7.06) increased the risk of new-onset diabetes after transplant. On comparing the anthropometric variables, lipid panel, and blood glucose levels of liver transplant patients with and without diabetes, higher glycemic levels were found in the group with diabetes (P Conclusion Pre-existing systemic arterial hypertension and the associated use of sodium mycophenolate and tacrolimus increased the risk of new-onset diabetes after transplant.

Introduction: the standard hypoparathyroidism treatment consists of replacing calcium and active vitamin D (calcitriol), but it does not correct the underlying abnormality, parathyroid hormone (PTH) deficiency. Both the disease and its treatment are responsible for many morbidities that affect multiple organs and systems. Therefore, parathyroid allotransplantation has been described as an alternative treatment option, especially in refractory cases. Objectives: to verify if parathyroid allotransplantation is effective as a treatment for permanent hypoparathyroidism. Methodology: fresh parathyroid tissue was obtained from a 36-year- old male with a past medical history of hyperparathyroidism secondary to end-stage renal disease and immediately implanted in the recipient’s non-dominant forearm, a 57-year-old female with refractory hypoparathyroidism, despite high doses of calcium and calcitriol replacement. Corticosteroid immunosuppression was performed for 10 days. Results: the allograft showed no evidence of functionality eleven months after transplant. The procedure was considered safe. Conclusion: more studies are required to validate this technique and improve its results Introdução: o tratamento padrão do hipoparatireoidismo consiste na reposição de cálcio e vitamina D ativa (calcitriol), mas não corrige a anormalidade de base: a deficiência de paratormônio (PTH). Tanto a doença quanto o seu tratamento são responsáveis por diversas morbidades que afetam múltiplos órgãos e sistemas. O alotransplante de paratireóide tem sido descrito como uma alternativa de tratamento, especialmente em casos refratários. Objetivo: verificar se o alotransplante de paratireoide é efetivo como tratamento do hipoparatireoidismo permamente. Metodologia: tecido paratireoideano fresco foi obtido de um doador de 36 anos do sexo masculino, portador de hiperparatireoidismo secundário a insuficiência renal crônica terminal e imediatamente implantado no antebraço não dominante da receptora, uma mulher de 57 anos com controle inadequado da doença, apesar de reposição de altas doses de cálcio e de calcitriol. Imunossupressão com corticosteroides foi realizada por 10 dias. Resultado: o aloenxerto não mostrou evidência de funcionalidade onze meses após o transplante. O procedimento foi considerado bastante seguro. Conclusão: mais estudos são necessários para validar esta técnica e melhorar seus resultados.

Adequate management of diabetes requires professional improvement programs. This study aimed to analyze the effect of a simulation activity on the acquisition of knowledge about blood glucose monitoring and hypoglycemia management. The study employed a pre-post intervention approach and was carried out in a university hospital located in Brazil. The participants were 82 graduating nursing students and nursing professionals studying/working at the university hospital. The intervention consisted of theoretical sessions, a practical simulation about glycemic monitoring and hypoglycemia management, and the pre- and post-tests. The simulation consisted of a rubber hand mannequin that allows simulating the glucose testing. There was a significant increase in knowledge after intervention with the total number of correct answers increasing from 186 in the pre-test to 326 in the post-test (+140, p < .001). The intervention was effective in increasing the participants' knowledge about glycemic monitoring and hypoglycemia management, favoring a better nursing care for people with diabetes. El manejo adecuado de la diabetes requiere programas de desarrollo profesional. Este estudio tuvo como objetivo analizar el efecto de una actividad de simulación en la adquisición de conocimientos sobre el control glucémico y el manejo de la hipoglucemia. El estudio utilizó un enfoque pre y post intervención y se llevó a cabo en un hospital universitario de Brasil. Los participantes fueron 82 estudiantes de enfermería y profesionales de enfermería que estudian o trabajan en un hospital universitario. La intervención consistió en sesiones teóricas, simulación práctica de monitorización glucémica y manejo de hipoglucemias, pre y post test. La simulación se realizó mediante un maniquí que permite simular la prueba de glucosa. Hubo un aumento significativo en el conocimiento después de la intervención y el número total de respuestas correctas aumentó de 186 en la prueba previa a 326 en la prueba posterior (+140, p

Type 1 diabetes mellitus (T1DM) results from the immune cell-mediated destruction of functional pancreatic β-cells. In the presymptomatic period, T1DM is characterized by the presence of two or more autoantibodies against the islet cells in patients without glycemic decompensation. Therapeutic strategies that can modify the autoimmune process could slow the progression of T1DM. Dipeptidyl peptidase-4 (DPP-4) or CD26, a multifunctional serine protease with a dual function (regulatory protease and binding protein), can modulate inflammation and immune cell-mediated β-cell destruction. CD26 is involved in T-cell co-stimulation, migration, memory development, thymic maturation, and emigration patterns. DPP-4 degrades the peptide hormones GLP-1 and GIP. In addition to regulating glucose metabolism, DPP-4 exerts anti-apoptotic, regenerative, and proliferative effects to promote β-cell mass expansion. GLP-1 receptor signaling may regulate murine lymphocyte proliferation and maintenance of peripheral regulatory T-cells. In patients with T1DM, the serum DPP-4 activity is upregulated. Several studies have suggested that the upregulated DPP-4 activity is correlated with T1DM pathophysiology. DPP-4, which is preferentially expressed on the Th1 surface, can promote the polarization of Th1 immunity, a prerequisite for T1DM development. CD26 inhibition can suppress T-cell proliferation and Th1 cytokine production and stimulate tumor growth factor beta-1 (TGF-β1) secretion, which plays an important role in the regulation of autoimmunity in T1DM. Studies on humans or animal models of T1DM have suggested that DPP-4 inhibitors can improve β-cell function and attenuate autoimmunity in addition to decreasing insulin dependence. This review summarizes the emerging roles of DPP-4 inhibitors in potentially delaying the progression of T1DM.

Objective This study aimed to determine the thyroid-stimulating hormone (TSH) reference interval (RI) and to assess the influence of the use of thyroid ultrasonography (TUS) on reference individual selection from a healthy adult population in Fortaleza, Brazil. Subjects and methods This cross-sectional study recruited patients (N = 272; age = 18-50 years) with normal thyroid function (NTF) and placed them in three groups according to their test results: NTF (n = 272; all participants), TUS (n = 170; participants who underwent thyroid US), RI (n = 124; reference individuals with normal TSH levels). TSH, FT4, TT3, TgAb, and TPOAb concentrations were determined by electrochemiluminescence assay. TUS was performed using a 7-12 MHz multifrequency linear transducer by two radiologists. The 2.5th and 97.5th percentiles of the distribution curve corresponded to lower and upper TSH RI levels, respectively. Results The mean TSH level was 1.74 ± 0.96 mIU/L, and TSH range was 0.56-4.45 mIU/L. There was no difference in the TSH concentrations between men and women nor between the groups. TUS did not appear to be an essential tool for the reference group selection. Conclusion The upper limit of TSH was comparable to the reference interval provided by the assay manufacturer (4.45 vs. 4.20 mIU/L) but the lower limit was not (0.56 vs. 0.27 mIU/L). This finding may have a clinical impact since these values may lead to the misdiagnosis of euthyroid patients with subclinical hyperthyroidism.

Background Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by the near-total loss of subcutaneous adipose tissue soon after birth, resulting in ectopic fat deposition and severe metabolic disturbances. Most cases are caused by AGPAT2 or BSCL2 gene mutations. We aimed to report two unrelated CGL patients with a novel frameshift mutation in AGPAT2 (p.Leu124Serfs*26). Methods Clinical features and laboratory were obtained by medical interview and medical records review. DNA was extracted, amplified and sequenced. Mutation Taster was used to estimate the potential biological impact of the AGPAT2 mutations on the protein function. Results Patient 1: a 30-year-old woman with lipodystrophy phenotype at birth and diagnosis of diabetes at age 13 presented with severe hypertriglyceridemia and pancreatitis at age 17, hypertension and albuminuria at age 18, proliferative diabetic retinopathy with visual loss at age 25, and an acute myocardial infarction due to multivessel coronary disease during a hospitalization for forefoot amputation at age 29. At this time, she required hemodialysis due to end-stage renal disease. Patient 2: a 12-year-old girl with lipodystrophy phenotype and hypertriglyceridemia detected in the first year of life and abnormalities in the global longitudinal strain, evaluated by speckle-tracking echocardiography last year. Molecular analysis identified a c.369_372delGCTC (p.Leu124Serfs*26) AGPAT2 mutation in both unrelated patients, a compound heterozygous mutation in Patient 1, and homozygous mutation in Patient 2. Conclusion We describe two unrelated patients with type 1 CGL due to Leu124Serfs*26, a novel AGPAT2 frameshift mutation, presenting as early cardiovascular disease. These findings suggest an association between Leu124Serfs*26 and a more aggressive phenotype.

Christiane Bezerra Rocha Liberato, 1, 2 Natália Bitar da Cunha Olegario, 1, 2 Virginia Oliveira Fernandes, 1–3 Ana Paula Dias Rangel Montenegro, 2 Grayce Ellen da Cruz Paiva Lima, 1, 2 Lívia Aline de Araújo Batista, 1, 2 Lívia Vasconcelos Martins, 1, 2 Jaquellyne Gurgel Penaforte-Saboia, 1, 2 Ivan Lucas Rocha Liberato, 2 Larissa Ferreira Lopes, 2 Catarina Brasil d’Alva, 1, 2 Frederico Luís Braz Furtado, 1, 2 Ricardo Luiz De Medeiros Lima, 4 Lucia Helena Coelho Nóbrega, 4 Josivan Gomes Lima, 4 Renan Magalhães Montenegro Junior 1–3 Brazilian Group for the Study of Inherited and Acquired Lipodystrophies (BRAZLIPO) 1Department of Clinical Medicine, Federal University of Ceará, Fortaleza, Brazil; 2Clinical Research Unit, Walter Cantidio University Hospital, Federal University of Ceará, Fortaleza, Brazil; 3Department of Community Health, Federal University of Ceará, Fortaleza, Brazil; 4Department of Clinical Medicine, Onofre Lopes University Hospital, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, BrazilCorrespondence: Renan Magalhães Montenegro Junior Rua Professor Costa Mendes, 1608, Fortaleza, Ceará 60416-200, BrazilTel +55 85 3366-8600Fax +55 85 3366-8619Email renanmmjr@gmail.comPurpose: Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by the absence of functional adipocytes resulting in ectopic lipid storage, metabolic disorders and early cardiovascular disease. Two-dimensional speckle-tracking (2D-STE) allows the detection of early abnormalities in myocardial function. We aimed to evaluate myocardial deformation in a large sample of CGL patients using 2D-STE.Patients and Methods: A cross-sectional study of 22 patients with CGL and 22 healthy subjects, matched for sex and age, was conducted from 2013 to 2018. All participants had undergone standard conventional echocardiography (ECHO) and 2D-STE. Determination of blood glucose, lipids, insulin, and leptin were performed in all CGL patients.Results: In the CGL group the mean age was 14.6± 10.7 years where 68.2% (n=15) were younger than 18 years old. All the patients had hypoleptinemia, 95.4% (21/22) low HDL-c, 86.4% (19/22) hypertriglyceridemia, 68.2% (15/22) diabetes, 50% (11/22) hepatic steatosis, 41% (9/22) insulin resistance, 41% (9/22) hypercholesterolemia, and 18.2% (4/22) hypertension. ECHO showed that 36.6% (8/22) of CGL patients presented diastolic dysfunction, 31.8% (7/22) left ventricular hypertrophy (LVH), 27.3% (6/22) increased left atrial volume index (LAVI), and 18.2% (4/22) increased left ventricular systolic diameter (LVDS) but normal ejection fraction (EF), whether using 2D-STE, 68.2% (15/22) of CGL patients showed abnormal global longitudinal strain (GLS) (p< 0.01), and in almost LV segments. Positive association between abnormal GLS and A1c (r=0.57, p=0.005), glucose (r=0.5, p=0.018) and basal insulin (r= 0.69, p= 0.024), and negative association with leptin (r = − 0.51, p = 0.005) were found in these patients.Conclusion: The 2D-STE revealed precocious left ventricular systolic dysfunction in a young CGL population with normal systolic function by ECHO. Early exposure to common metabolic abnormalities as insulin resistance, hyperglycemia, and hypoleptinemia must be involved in myocardial damage in these patients.Keywords: Berardinelli-Seip congenital lipodystrophy, global longitudinal strain, cardiac function, early detection

Background and aims Metabolic Syndrome (MS) is increasing in developing countries. Different definitions of MS lead to discrepancies in prevalence estimates and applicability. We assessed the prevalence of MS as defined by the International Diabetes Federation (IDF), modified National Cholesterol Education Program Adult Treatment Plan III (Modified NCEP) and Joint Interim Statement (JIS); compared the diagnostic performance and association of these definitions of MS with pre-diabetes, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) risk. Methods A total of 714 randomly selected subjects from Northeastern Brazil were investigated in a cross-sectional study. Sociodemographic, anthropometric, and clinical data were recorded. Diagnostic test performance measures assessed the ability of the different MS definitions to identify those with pre-diabetes, T2DM and increased CVD risk. Results The adjusted prevalence of MS was 36.1% applying the JIS criteria, 35.1% the IDF and 29.5% Modified NCEP. Women were more affected by MS according to all definitions. MS was significantly associated with pre-diabetes, T2DM and CVD risk following the three definitions. However, the JIS and IDF definitions showed higher sensitivity than the Modified NCEP to identify pre-diabetes, T2DM and CVD risk. The odds ratios for those conditions were not significantly different when comparing the definitions. Conclusions MS is highly prevalent in Brazil, particularly among those with pre-diabetes, T2DM, and high CVD risk. The IDF and JIS criteria may be better suited in the Brazilian population to identify pre-diabetes, T2DM and CVD risk. This may also signify the importance of the assessment of MS in clinical practice.

Background A premature myocardial infarction (PMI) is usually associated with a familial component. This study evaluated cardiovascular risk factors in first-degree relatives (FDR) of patients with PMI not presenting the familial hypercholesterolemia phenotype. Methods A cross-sectional study comprising FDR of non-familial hypercholesterolemia patients who suffered a myocardial infarction

Congenital Generalized Lipodystrophy (CGL) is a rare syndrome characterized by the almost total absence of subcutaneous adipose tissue due to the inability of storing lipid in adipocytes. Patients present generalized lack of subcutaneous fat and normal to low weight. They evolve with severe metabolic disorders, non-alcoholic fatty liver disease, early cardiac abnormalities, and infectious complications. Although low body weight is a known risk factor for osteoporosis, it has been reported that type 1 and 2 CGL have a tendency of high bone mineral density (BMD). In this review, we discuss the role of bone marrow tissue, adipokines, and insulin resistance in the setting of the normal to high BMD of CGL patients. Data bases from Pubmed and LILACS were searched, and 113 articles published until 10 April 2021 were obtained. Of these, 76 were excluded for not covering the review topic. A manual search for additional literature was performed using the bibliographies of the studies located. The elucidation of the mechanisms responsible for the increase in BMD in this unique model of insulin resistance may contribute to the understanding of the interrelationships between bone, muscle, and adipose tissue in a pathophysiological and therapeutic perspective.

Valzimeire do Nascimento de Oliveira,1,2 Abelardo Barbosa Moreira Lima-Neto,1 Maurício Fraga van Tilburg,2 Ana Cristina de Oliveira Monteiro-Moreira,3 Marina Duarte Pinto Lobo,3 Davide Rondina,4 Virgínia Oliveira Fernandes,5 Ana Paula Dias Rangel Montenegro,5 Renan Magalhães Montenegro Júnior,5 Maria Izabel Florindo Guedes1,2 1Collegiate Nutrition Science, Laboratory of Biotechnology and Molecular Biology, Ceará State University, Fortaleza, Ceará, Brazil; 2Collegiate Biotechnology, Northeast Network of Biotechnology, Laboratory of Biotechnology and Molecular Biology, Ceará State University, Fortaleza, Ceará, Brazil; 3Center of Experimental Biology, University of Fortaleza, Fortaleza, Ceará, Brazil; 4School of Veterinary Science, Ceará State of University, Fortaleza, Ceará, Brazil; 5Faculty of Medicine, Federal University of Ceará and University Hospitals, Fortaleza, Ceará, Brazil Purpose: Type 1 diabetes mellitus (DM1) is one of the most common chronic diseases observed during childhood. The incidence of DM1 is increasing worldwide, and there is currently no way to prevent or delay the onset or to cure the disease. Most diseases, including diabetes, stem from abnormalities in the functioning of proteins, and some studies have reported the expression of protein variation to be involved in the development of DM1. Thus, the aim of this study was to investigate the differential expression of serum proteins in patients with DM1. Materials and methods: Serum of patients with DM1 (n=30) and healthy controls (n=30) was collected. A proteomic approach was used with depletion of albumin and immunoglobulin G chromatography on serum samples followed by data-independent, label-free mass spectrometric analysis. Results: A total of eight serum proteins were identified as being differentially expressed and involved in the immune system, lipid metabolism, and pathways of coagulation. DM1 was associated with the upregulation of six proteins: alpha-2-macroglobulin, apolipoprotein A-II, β2 glycoprotein I, Ig alpha-2 chain C region, alpha-1-microglobulin, and prothrombin. A total of two proteins were downregulated, including pregnancy zone protein and complement C4. Conclusion: To the best of our knowledge, these findings show differential expression of proteins revealing new proteins that may be involved in the development and progression of diabetes. Keywords: proteome, mass spectrometry, precision medicine, diagnosis

Background Metabolic abnormalities in congenital generalized lipodystrophy (CGL) are associated with microvascular complications. However, the evaluation of different types of neuropathy in these patients, including the commitment of cardiovascular autonomic modulation, is scarce. The objective of the present study was to determine the prevalence of cardiovascular autonomic neuropathy (CAN) in patients with CGL compared with individuals with type 1 diabetes and healthy subjects. Methods Ten patients with CGL, 20 patients with type 1 diabetes and 20 healthy subjects were included in the study. Controls were paired 1:2 for age, gender, BMI and pubertal stage. Heart rate variability (HRV) was analyzed using cardiovascular autonomic reflex tests, including postural hypotension test, Valsalva (VAL), respiratory (E/I) and orthostatic (30/15) coefficients, and spectral analysis of the HRV, determining very low (VLF), low (LF) and high (HF) frequencies components. The diagnosis of CAN was defined as the presence of at least two altered tests. Results CAN was detected in 40% of the CGL patients, 5% in type 1 diabetes patients and was absent in healthy individuals (p

Vitamin B12 is a water-soluble essential micronutrient, required by all the body cells. Its deficiency has been implicated not only in hematological and neurological disorders, but also in many metabolic processes, such as insulin resistance and body composition changes, which have aroused particular interest in recent years. This study reviews the physiology of vitamin B12 from its digestion and absorption to its distribution in tissues, metabolic effects and controversies regarding the diagnosis of deficiency, and to dietary and pharmacological treatments.

This study aimed to verify the impact of levothyroxine replacement on health-related quality of life (HRQoL) in a Brazilian sample of primary hypothyroidism patients. A cross-sectional study was performed with 2,057 consecutive primary hypothyroidism patients on levothyroxine (LT4) replacement at four referral centers in Brazil (median age = 53; 25th percentile = 43; 75th percentile = 61 years). Patient biochemical data were acquired from medical records, and patients completed a questionnaire on socioeconomic issues and clinical signs and symptoms of hypothyroidism. HRQoL was assessed using the SF-36v2. Patients were divided into three groups according to TSH levels: overtreated (OvT; TSH0.4 mU/L), appropriately treated (AT; TSH between 0.4 and 4.0 mU/L), and undertreated (UnT; TSH4.0 mU/L). Patients were also analyzed by TSH and FT4 serum levels: overt hyperthyroidism (OHyper; TSH0.4 mU/L and FT41.9 ng/dL), subclinical hyperthyroidism (SHyper; TSH0.4 mU/L and FT4 0.8-1.9 ng/dL), subclinical hypothyroidism (SHypo; TSH4.0 mU/L and FT4 0.8-1.9 ng/dL), and overt hypothyroidism (OHypo; TSH4.0 mU/L and FT40.8 ng/dL). A total of 14.4 % of patients were OvT, with 13.0 % SHyper and 1.4 % OHyper. The prevalence of UnT was 25.9 %, with 21.5 % SHypo and 4.4 % OHypo. Overtreatment was not associated with HRQoL impairment. UnT patients had worse HRQoL than AT patients, especially for physical and emotional aspects, independent of SHypo or OHypo status. Hypothyroidism undertreatment is associated with poor patient HRQoL. Therefore, adequate LT4 therapy should be given to maintain serum TSH within the reference range.

Acromegalia é uma doença endócrina rara. Poucos estudos avaliaram sua associação com deficiência auditiva (DA) e os resultados são conflitantes. OBJETIVOS: Avaliar a prevalência e características da DA em um grupo de pacientes com acromegalia em tratamento. Analisar a transmissão auditiva central e periférica. MATERIAL E MÉTODOS: Estudo transversal. Um grupo de 34 pacientes com acromegalia submeteu-se à avaliação metabólica, audiometria tonal e potenciais evocados auditivos de tronco encefálico (PEATE). Considerou-se DA quando a média dos tons puros foi > 25 DBNA para baixas frequências (250, 500, 1000 e 2000 Hz) ou altas frequências (3000, 4000, 6000 e 8000 Hz). Os pacientes foram divididos em grupo A (com DA) e B (sem DA). RESULTADOS: Doze pacientes (35,3%) mostraram DA sensorioneural (grupo A), sendo oito bilateral e quatro unilateral. Nenhum apresentou DA mista ou condutiva. A prevalência de diabetes/intolerância à glicose de jejum foi similar entre os grupos. As frequências de 3000, 4000, 6000 e 8000 Hz foram as mais afetadas e com padrão similar em ambos os lados. CONCLUSÃO: DA sensorioneural esteve presente em 35,3% dos casos. Não foram notadas diferenças clínicas ou metabólicas significativas entre os grupos, bem como na transmissão neural auditiva periférica e central. Acromegaly is a rare endocrine disease. Few studies have evaluated its association with hearing loss (HL) and the results are conflicting. AIM: To evaluate the prevalence and features of HL in a group of patients being treated for acromegaly. To analyze peripheral and central auditory transmission. METHODS: Cross-sectional study. A group of 34 patients with acromegaly were submitted to metabolic evaluation, tonal audiometry and brainstem auditory evoked potentials. HL was considered when pure tone average was > 25 DBHL for low frequencies (250, 500, 1000 and 2000 Hz) or high frequencies (3000, 4000, 6000 and 8000 Hz). The patients were divided in group A (with HL) and B (without HL). RESULTS: Twelve patients (35.3%) had sensorineural HL (Group A), being 8 bilateral and 4 unilateral. No one had mixed or conductive HL. The prevalence of diabetes/impaired glucose tolerance was similar between the groups. The frequencies 3000, 4000, 6000 and 8000 Hz were the most affected and with a similar pattern in both ears. CONCLUSION: sensorineural HL was found in 38.9% of cases. Neither clinical nor metabolic differences were noted between the groups, as well as in regards to peripheral and central auditory transmission.

Objective To determine the prevalence of patients with type 1 diabetes mellitus who meet the glycemic and cardiovascular (CV) risk factors goals and the frequency of screening for diabetic complications in Brazil according to the American Diabetes Association guidelines. Research design and methods This was a cross-sectional, multicenter study conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 1774 adult patients (56.8% females, 57.2% Caucasians) aged 30.3 ± 9.8 years with diabetes duration of 14.3 ± 8.8 years. Results Systolic blood pressure was at goal in 40.3% and diastolic blood pressure was at goal in 26.6% of hypertensive patients. LDL cholesterol and HbA1c were at the goal in 45.2% and 13.2% of the patients, respectively. Overweight was presented in 25.6% and obesity in 6.9%. Among those with more than 5 years of disease, screening for retinopathy was performed in the preceding year in 70.1%. Nephropathy and feet complications were screened in 63.1% and 65.1%, respectively. Conclusions The majority of patients did not meet metabolic control goals and a substantial proportion was not screened for diabetic complications. These issues may increase the risk of chronic complications and negatively impact public health.

As reformas curriculares e a mudança do perfil na formação de profissionais da saúde apresentam muitos desafios. O objetivo deste estudo foi caracterizar as necessidades educacionais em saúde percebidas e representadas pelos profissionais de nível superior que atuam na Estratégia Saúde da Família (ESF) do município de Fortaleza/CE, recém-aprovados em concurso de âmbito municipal. Trata-se de um estudo descritivo com duas etapas. Um estudo transversal em 2006 com aplicação de inquérito para aferição das necessidades de Educação em Saúde, e a segunda etapa em 2011 com a análise documental sobre as ações realizadas para educação permanente dos profissionais da rede municipal de saúde pela Secretaria Municipal de Saúde de Fortaleza. O instrumento utilizado para coleta dos dados foi um questionário semiestruturado, aplicado a profissionais médicos, enfermeiros e odontólogos. Do universo de 900 profissionais recém-concursados, nossa amostra de conveniência contou com 375 respondentes. Observou-se, no estudo, que, quanto ao desejo de realização de pós-graduação, o mestrado profissional, a residência em medicina de família e comunidade, a residência multiprofissional em saúde da família, que são modalidades de pós-graduação que ocorrem em serviço, são necessidades manifestadas por significativa parte dos profissionais. Por outro lado, profissionais também assinalaram a necessidade de cursos de 40 horas de forma pontual. A educação permanente é apontada pela literatura e pelo atual estudo como um caminho para melhoria na qualidade da ESF, por centrar nos processos de trabalho a construção do processo educativo. Para a educação em Saúde gerar efetivos processos de reflexão-ação-reflexão no cotidiano de trabalho, deve-se promover a ligação política com a mudança da formação de perfil profissional e, para isso, colocar em evidência as necessidades educacionais dos profissionais é fundamental. Curricular reforms and the change in the training profile of health professionals face many challenges. The aim of this study was to characterize the educational needs in health perceived and represented by higher education professionals, who were recently approved in the municipal contest, practicing in the Family Health Strategy (FHS) in Fortaleza, State of Ceara. It is a two-phase descriptive study: a cross-sectional study, with the application of a survey to assess the needs of health education, carried out in 2006; and a documental analysis of the actions taken for the continuing education of professionals from the municipal health system performed by the Municipal Health Secretary of Fortaleza in 2011. Data was collected through a semi-structured questionnaire applied to physicians, nurses and dentists. From the universe of 900 newly gazetted professionals, our convenience sample counted on 375 respondents. Regarding the desire to carry out graduate studies, it was possible to observe that the master’s degree training, residency in family and community medicine, and multi-professional residency in family health were significant needs expressed by the professionals in this study. Moreover, practitioners also noted the need to punctual 40-hour courses. Continuing education is cited in the literature and in the current study as a way to improve the quality of the FHS, once it focuses on work processes to build the educational process. To generate effective health education processes of reflection-action-reflection in the daily working, a political connection with the change in the training profile of health professionals must be promoted and, to this end, highlighting the educational needs of professionals is essential. Las reformas curriculares y el cambio en el perfil de la formación del profesional de la Salud presentan muchos desafíos. El objetivo de este estudio fue caracterizar las necesidades educativas en Salud percibidas y representadas por los profesionales de nivel educativo superior que trabajan en la Estrategia de Salud Familiar (ESF), en Fortaleza / CE, Brasil, recientemente aprobados en concurso público municipal. Este estudio descriptivo tuvo dos fases: la primera fue un estudio transversal en 2006 con la aplicación de una encuesta para evaluar las necesidades de Educación para la Salud; la segunda fue en 2011 con el análisis de los documentos sobre las medidas adoptadas para la educación contínua de los profesionales de la red municipal de salud de la Secretaria Municipal de Salud de Fortaleza. Los datos se recolectaron con un cuestionario semi-estructurado, aplicado a los profesionales médicos, enfermeros y dentistas. Del universo de 900 profesionales recién contratados, nuestra muestra incluyó 375 encuestados Con relación al deseo de concretar una formación de postgrado: la maestría, la residencia en medicina familiar y comunitaria, y la residencia multiprofesional en salud de la familia (formas de posgrado que pueden cursarse durante el servicio) fueron necesidades manifestadas por una parcela significativa de los profesionales. Por otra parte, los trabajadores también señalaron la necesidad de tener cursos de 40 horas. La educación es citada permanentemente tanto en la literatura como en este estudio como una forma de mejorar la calidad de la ESF, para centrar en los procesos de trabajo la construcción del proceso educativo. Para que la Educación para la Salud genere procesos efectivos de reflexión-acción-reflexión en el trabajo diario, se debe promover la conexión política con el cambio en la formación del perfil profesional y, para ello, es fundamental poner en evidencia las necesidades educativas de los profesionales.

Objective: to evaluate the occurrence of polypharmacy and its association with the adherence to the pharmacological treatment in patients with diabetes mellitus type 2. Methods: cross-sectional study conducted with 235 patients with diabetes mellitus type 2 through interview about the demographic and clinical data, drug therapy prescribed and adherence to treatment. To analyze the data, we used Student t-tests and Chi-square, with significance level p

Resumen pt: Objetivo: Avaliar a audicao de criancas com hipotireoidismo congenito (HC). Metodos: E um estudo descritivo e transversal, de abordagem quantitativa, rea...

O diabetes mellitus (DM), uma doenca endocrino-metabolica de alta e crescente prevalencia, e citada como responsavel pela ocorrencia das candidiases orais. A candidiase constitui um espectro de infeccoes causadas por fungos do genero Candida, sendo o seu agente mais comum a Candida albicans, embora outras especies tenham sido identificadas (Candida tropicalis, Candida guillermondii, Candida glabrata, Candida krusei). O objetivo deste trabalho foi avaliar a frequencia e a atividade enzimatica de Candida spp. na cavidade oral de pacientes diabeticos atendidos no Servico de Endocrinologia do Hospital Universitario Walter Cantidio da Universidade Federal do Ceara (HUWC/UFC). Foram coletadas amostras de 48 pacientes diabeticos, de ambos os sexos, com situacoes variaveis de controle glicemico. Os materiais clinicos foram colhidos com ajuda de swabs e semeados em placas de Petri contendo agar-Sabouraud dextrose com cloranfenicol e incubado a 37°C. Os crescimentos foram identificados pelas provas classicas usadas em micologia. Depois, essas cepas de Candida foram submetidas a provas de deteccao de enzimas fosfolipase e proteinase. Destas, 15 amostras (31,25%) apresentaram cultura positiva para o genero Candida. A especie mais frequente foi a C. albicans, com 80%, seguida de C. tropicalis (13,3%) e C. guillermondii (6,7%). Quanto a pesquisa da atividade enzimatica de Candida spp., foi observado que 86,6% delas apresentaram atividade de proteinase e 80%, de fosfolipase. Conclui-se com tais resultados que a C. albicans e a mais frequente e que as especies de Candida isoladas possuem fortes atividades enzimaticas.

Background: In type 1 diabetes mellitus (T1DM) management, enhancing health-related quality of life (HRQoL) is as important as good metabolic control and prevention of secondary complications. This study aims to evaluate possible regional differences in HRQoL, demographic features and clinical characteristics of patients with T1DM in Brazil, a country of continental proportions, as well as investigate which variables could influence the HRQoL of these individuals and contribute to these regional disparities. Methods: This was a retrospective, cross-sectional, multicenter study performed by the Brazilian Type 1 Diabetes Study Group (BrazDiab1SG), by analyzing EuroQol scores from 3005 participants with T1DM, in 28 public clinics, among all geographical regions of Brazil. Data on demography, economic status, chronic complications, glycemic control and lipid profile were also collected. Results: We have found that the North-Northeast region presents a higher index in the assessment of the overall health status (EQ-VAS) compared to the Southeast (74.6 ± 30 and 70.4 ± 19, respectively; p < 0.05). In addition, North- Northeast presented a lower frequency of self-reported anxiety-depression compared to all regions of the country (North-Northeast: 1.53 ± 0.6; Southeast: 1.65 ± 0.7; South: 1.72 ± 0.7; Midwest: 1.67 ± 0.7; p < 0.05). These findings could not be entirely explained by the HbA1c levels or the other variables examined. Conclusions: Our study points to the existence of additional factors not yet evaluated that could be determinant in the HRQoL of people with T1DM and contribute to these regional disparities.

Objective: To evaluate the effect of sitagliptin on somatosensory-evoked potentials (SEPs) and metabolic control in patients with type 2 diabetes mellitus without clinical diabetic neuropathy. Materials and methods: Interventional, prospective, and open study. Patients with less than six months from the diagnosis were included. Examinations of SEPs and laboratory tests at fasting and after food stimulation were performed before and after three months of treatment with sitagliptin (100 mg/day). Results: There was a reduction in the mean levels of HbA1c (P < 0.0001), fasting glucose (P = 0.001), total cholesterol (P = 0.019), and ALT (P = 0.022). An increase in active GLP-1 was found at the end of the study (P = 0.0025). Several SEPs showed statistically significant differences when analyzed before and after treatment with sitagliptin. Conclusion: The results give a glimpse of the possible use of sitagliptin in the treatment of some neurodegenerative conditions of the peripheral nervous system, in addition to its already established role in glycemic control. Objetivo: Avaliar o efeito da sitagliptina nos potenciais evocados somatossensoriais (PESS) e controle metabólico de pacientes com diabetes melito tipo 2, sem neuropatia diabética. Materiais e métodos: Estudo de intervenção, prospectivo e aberto. Os pacientes com menos de seis meses de diagnóstico foram incluídos. Exames dos PESS e testes laboratoriais em jejum e após a estimulação com alimentos foram realizados antes e depois de três meses de tratamento com sitagliptina (100 mg/dia). Resultados: Houve redução nos níveis médios de HbA1c (P < 0,0001), glicemia de jejum (P = 0,001), colesterol total (P = 0,019) e ALT (P = 0,022). Verificou-se aumento de GLP-1 ativo (P = 0,0025). Vários PESS mostraram diferenças estatisticamente significativas quando os valores foram analisados antes e após o tratamento com sitagliptina. Conclusão: Os resultados vislumbram a possível utilização de sitagliptina no tratamento de algumas condições neurodegenerativas do sistema nervoso periférico, em adição ao seu papel no controle glicêmico.

Background: To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D). Methods: This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups. Results: We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). The majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001). Conclusions: Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits.

OBJECTIVE: To evaluate the frequency of diabetes mellitus and glucose intolerance in patients with cystic fibrosis treated at the Pediatric Gastroenterology Service of HC-FMRP-USP. METHODS: A cross-sectional analytical study was conducted on a group of 25 patients with mucoviscidosis who were followed up at HC-FMRP-USP. Oral glucose tolerance tests (OGTT) were performed, with simultaneous determination of glycemia and insulinemia. Areas under the curve were obtained for glycemia (G) and insulinemia (I) and the I/G ratio was calculated and correlated with the duration of clinical manifestation and pancreatic exocrine function. RESULTS: Five patients presented alterations: one was diabetic and four had glucose intolerance and/or hyperinsulinemia. There was a direct correlation between the area under the curve for insulinemia and the duration of mucoviscidosis. A significant inverse correlation was also observed between the area under the curve for insulinemia and I/G ratio, and number of enzyme capsules/kg/day. CONCLUSIONS: The frequency of alterations in glucose homeostasis observed in patients with mucoviscidosis was higher than in the population at large (20% of the total sample and 33% of the group of patients with glycemia and insulinemia on OGTT). Therefore, it is important that glucose tolerance tests be performed systematically in patients with mucoviscidosis so that metabolic abnormalities can be early detected, and proper treatment can be initiated.

Os autores apresentam a abordagem da paciente gestante, para rastreamento e diagnóstico do Diabetes mellitus Gestacional (DMG) e tratamento do Diabetes mellitus durante a gravidez, estabelecida como procedimento rotineiro pelo Setor de Gestação de Alto Risco do Departamento de Ginecologia e Obstetrícia e Divisão de Endocrinologia e Metabologia do Departamento de Clínica Médica da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo e adotado na avaliação pré-natal da Secretaria Municipal de Saúde de Ribeirão Preto para rastreamento e diagnóstico do DMG. Este protocolo foi baseado nas recomendações da Organização Mundial da Saúde e American Diabetes Association.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T19:04:05Z No. of bitstreams: 1 S0004-27302013000300003.pdf: 174729 bytes, checksum: 7306ee4425bad456035431ee48e4d3ae (MD5) Made available in DSpace on 2013-08-22T19:04:05Z (GMT). No. of bitstreams: 1 S0004-27302013000300003.pdf: 174729 bytes, checksum: 7306ee4425bad456035431ee48e4d3ae (MD5) Previous issue date: 2013-04-01 Made available in DSpace on 2013-09-30T20:06:41Z (GMT). No. of bitstreams: 2 S0004-27302013000300003.pdf: 174729 bytes, checksum: 7306ee4425bad456035431ee48e4d3ae (MD5) S0004-27302013000300003.pdf.txt: 89847 bytes, checksum: ba81a61af2dcb02cd4b1c4ea24bd4fc5 (MD5) Previous issue date: 2013-04-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:17:02Z No. of bitstreams: 2 S0004-27302013000300003.pdf: 174729 bytes, checksum: 7306ee4425bad456035431ee48e4d3ae (MD5) S0004-27302013000300003.pdf.txt: 89847 bytes, checksum: ba81a61af2dcb02cd4b1c4ea24bd4fc5 (MD5) Made available in DSpace on 2014-05-20T15:17:02Z (GMT). No. of bitstreams: 2 S0004-27302013000300003.pdf: 174729 bytes, checksum: 7306ee4425bad456035431ee48e4d3ae (MD5) S0004-27302013000300003.pdf.txt: 89847 bytes, checksum: ba81a61af2dcb02cd4b1c4ea24bd4fc5 (MD5) Previous issue date: 2013-04-01 INTRODUÇÃO: O hipotireoidismo subclínico (HSC), definido por concentrações elevadas do TSH em face de níveis normais dos hormônios tireoidianos, tem elevada prevalência no Brasil, particularmente entre mulheres e idosos. Embora um número crescente de estudos venha associando o HSC com maior risco de doença arterial coronariana e de mortalidade, não há ensaio clínico randomizado sobre o benefício do tratamento com levotiroxina na redução dos riscos e o tratamento permanece controverso. OBJETIVO: Este consenso, patrocinado pelo Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia e desenvolvido por especialistas brasileiros com vasta experiência clínica em tireoide, apresenta recomendações baseadas em evidências para uma abordagem clínica do paciente com HSC no Brasil. MATERIAIS E MÉTODOS: Após estruturação das questões clínicas, a busca das evidências disponíveis na literatura foi realizada inicialmente na base de dados do MedLine-PubMed e posteriormente nas bases Embase e SciELO - Lilacs. A força da evidência, avaliada pelo sistema de classificação de Oxford, foi estabelecida a partir do desenho de estudo utilizado, considerando-se a melhor evidência disponível para cada questão e a experiência brasileira. RESULTADOS: Os temas abordados foram definição e diagnóstico, história natural, significado clínico, tratamento e gestação, que resultaram em 29 recomendações para a abordagem clínica do paciente adulto com HSC. CONCLUSÃO: O tratamento com levotiroxina foi recomendado para todos os pacientes com HSC persistente com níveis séricos do TSH > 10 mU/L e para alguns subgrupos especiais de pacientes. INTRODUCTION: Subclinical hypothyroidism (SCH), defined as elevated concentrations of thyroid stimulating hormone (TSH) despite normal levels of thyroid hormones, is highly prevalent in Brazil, especially among women and the elderly. Although an increasing number of studies have related SCH to an increased risk of coronary artery disease and mortality, there have been no randomized clinical trials verifying the benefit of levothyroxine treatment in reducing these risks, and the treatment remains controversial. OBJECTIVE: This consensus, sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism and developed by Brazilian experts with extensive clinical experience with thyroid diseases, presents these recommendations based on evidence for the clinical management of SCH patients in Brazil. MATERIALS and METHODS: After structuring the clinical questions, the search for evidence in the literature was initially performed in the MedLine-PubMed database and later in the Embase and SciELO - Lilacs databases. The strength of evidence was evaluated according to the Oxford classification system and established based on the experimental design used, considering the best available evidence for each question and the Brazilian experience. RESULTS: The topics covered included SCH definition and diagnosis, natural history, clinical significance, treatment and pregnancy, and the consensus issued 29 recommendations for the clinical management of adult patients with SCH. CONCLUSION: Treatment with levothyroxine was recommended for all patients with persistent SCH with serum TSH values > 10 mU/L and for certain patient subgroups. Faculdade de Medicina de Marília Universidade Federal do Rio de Janeiro (UFRJ) Departamento de Clínica Médica Serviço de Endocrinologia Universidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de Clínica Médica Universidade Estadual Paulista Faculdade de Medicina de Botucatu Departamento de Clínica Médica Universidade Federal do Ceará (UFC) Universidade Estadual de Campinas Faculdade de Ciências Médicas Laboratório de Genética Molecular do Câncer Universidade Estadual Paulista Faculdade de Medicina de Botucatu Departamento de Clínica Médica

Pregnancy affects both maternal and fetal metabolism, and even in non-diabetic women, it exerts a diabetogenic effect. Among pregnant women, 2% to 14% develop gestational diabetes. Pregnancy can also occur in women with preexisting diabetes, which may predispose the fetus to many alterations in organogenesis, restrict growth, and the mother, to some diabetes-related complications, such as retinopathy and nephropathy, or to acceleration of the course of these complications, if they are already present. Women with gestational diabetes generally start their treatment with diet and lifestyle changes; when these changes are not enough for optimal glycemic control, insulin therapy must then be considered. Women with type 2 diabetes using oral hypoglycemic agents are advised to change to insulin therapy. Those with preexisting type 1 diabetes should start intensive glycemic control. As basal insulin analogues have frequently been used off-label in pregnant women, there is a need to evaluate their safety and efficacy. The aim of this review is to report the use of both short- and long-acting insulin analogues during pregnancy and to enable clinicians, obstetricians, and endocrinologists to choose the best insulin treatment for their patients. A gravidez afeta tanto o metabolismo materno quanto o fetal e, mesmo em mulheres não diabéticas, apresenta um efeito diabetogênico. Entre as mulheres grávidas, 2% a 14% desenvolvem o diabetes gestacional. A gravidez pode ocorrer também em mulheres já diabéticas, o que pode predispor o feto a muitas alterações na organogênese, restrição de crescimento e a mãe a algumas complicações relacionadas ao diabetes, tais como retinopatia e nefropatia, ou acelerar o curso dessas complicações se já estiverem presentes. Pacientes com diabetes gestacional geralmente iniciam seu tratamento com dieta e mudanças no estilo de vida; porém, quando essas medidas falham em atingir um controle glicêmico adequado, a insulinoterapia deve ser considerada. Pacientes com diabetes tipo 2 em uso de hipoglicemiantes orais são aconselhadas a iniciar o uso de insulina. Pacientes com diabetes tipo 1 preexistente devem iniciar um controle glicêmico estrito. Em função do fato de os análogos basais de insulina estarem sendo utilizados muito frequentemente off-label em pacientes grávidas, faz-se necessário avaliar sua segurança e eficácia nessa condição. O objetivo desta revisão é avaliar o uso de tais análogos, tanto de ação curta como prolongada, durante a gravidez, para possibilitar médicos clínicos, obstetras e endocrinologistas escolher o melhor regime terapêutico para suas pacientes.

Renal complications in acromegaly include glomerular hyperfiltration, insulin resistance, hypercalciuria and urolithiasis. The aim of this study was to investigate whether urinary calcium (U(Ca)) excretion is a direct consequence of growth hormone secretion or secondary to hyperfiltration and/or insulin resistance.We performed a cross-sectional study of 58 patients diagnosed with acromegaly. Demographic data were obtained, serum analysis was performed, including insulin-like growth factor (IGF)-1, and 24-h urine collection, to measure urinary protein excretion, U(Ca) and phosphate excretion, as well as fractional excretion of sodium and potassium. We also calculated the homeostasis model assessment of insulin resistance (HOMA-IR).Patients were predominantly male (60.3%), and their mean age was 45.9 ± 14 years. Hypercalciuria was present in 24% of patients. Patients with higher HOMA-IR had higher IGF-1 levels, a trend toward higher body mass index and higher U(Ca) excretion. In univariate analysis, U(Ca) excretion was associated with HOMA-IR (r = 0.472, P = 0.001), phosphaturia (r = 0.457, P = 0.001), IGF-1 (r = 0.398, P = 0.002) and creatinine clearance (r = 0.394, P = 0.001). HOMA-IR and phosphaturia were independently associated with U(Ca) excretion. No independent associations were found between phosphaturia and HOMA-IR or IGF-1.The present study revealed an association between hypercalciuria and insulin resistance in patients with acromegaly. Further studies are required to fully understand the pathogenesis of these abnormalities in patients with acromegaly.

Arterial hypertension is one of the main risk factors for the development of cardiovascular diseases and affects a substantial part of the Brazilian population. The objective of this study was to compare the level of knowledge between Physical Education Professionals who worked with hypertensive students in gyms and those who did not. A total of 400 professionals working in gyms in the Municipality of Fortaleza-CE participated in the study. A questionnaire containing the following information was used: knowledge about criteria for hypertension, types of laboratory tests, types of hypertension in the students, general care during physical activity, and recommendations for a better control of hypertension. Among the 400 professionals, 302 (75.5%) worked with hypertensive students. Of these, 236 (59%) based their diagnosis of hypertension solely on the report of the students. Regarding the situations in which the professionals contraindicated physical activity for the hypertensive students, 43.1% reported high blood pressure, 15.5% reported no situation, and 21.5% had no information. With respect o blood pressure measurement before and after physical activity, most of the professionals (62.3%) working with hypertensive students did not measure the student’s blood pressure. The knowledge of the professionals about hypertension in gyms was insufficient. More specific studies are necessary to obtain data that will contribute to the development of programs designed for Physical Education Professionals that establish the needs of hypertensive students in gyms.

A substituição gradual e progressiva das doenças infecciosas e parasitárias pelas doenças crônico-degenerativas como causas de morbidade e mortalidade, caracterizando o processo de transição epidemiológica, não tem sido observada em várias populações, em especial em países subdesenvolvidos ou em desenvolvimento, verificando-se, na realidade, uma sobre-posição desses perfis (transição incompleta). Além do aumento da prevalência de distúrbios metabólicos, várias doenças infecciosas permanecem endêmicas em diversas regiões, como é o caso da hanseníase, da tuberculose, da leishmaniose, das hepatites virais, entre outras, assim como condições emergentes nas últimas décadas, como a infecção pelo HIV/Aids. Nesse contexto, nos últimos anos tem sido dada uma maior atenção para a ocorrência de distúrbios metabólicos, principalmente a partir da observação de elevada incidência dessas anormalidades associadas à infecção pelo HIV/Aids e à sua terapia com as drogas antirretrovirais. Nesta revisão são abordados aspectos clínico-epidemiológicos dos distúrbios metabólicos reportados em algumas enfermidades infectoparasitárias de relevância mundial e local (no Brasil), assim como possíveis mecanismos e fatores envolvidos nessas associações.

OBJETIVO: verificar, com o emprego da ultra-sonografia pelvica, a existencia de mudancas na genitalia interna de meninas com puberdade precoce central submetidas a tratamento com analogo do hormonio liberador de gonadotrofinas (GnRH). METODOS: a ultra-sonografia pelvica foi realizada em 18 meninas com diagnostico de puberdade precoce central idiopatica, antes e tres meses apos o inicio do tratamento com analogo de GnRH, para avaliar o impacto da terapia na genitalia interna feminina. Foram avaliados os volumes uterino e ovariano, o diâmetro longitudinal do utero, a relacao entre os diâmetros longitudinais do corpo e colo uterinos, a relacao entre os diâmetros ântero-posteriores do corpo e colo uterinos e o eco endometrial. Para a analise estatistica foi aplicado o teste de Shapiro-Willks para verificacao da normalidade dos dados. Para os dados em que a normalidade foi satisfeita, foi aplicado o teste t de Student. Para os dados cuja distribuicao nao foi normal aplicou-se o teste nao parametrico (teste do sinal). RESULTADOS: apos o tratamento houve reducao estatisticamente significante da media dos volumes uterino (de 5,4 para 3,0 cm3, p

SUMMARY Thyroid carcinoma (TC) is rare in children, particularly in those aged < 10 years. Several studies have demonstrated a correlation between neoplasms and hyperinsulinemia and insulin resistance, which are often associated with a higher risk for and/or aggressiveness of the neoplasm. Congenital generalized lipodystrophy (CGL) with autosomal recessive inheritance is a rare disease and is characterized by the lack of adipose tissue, severe insulin resistance, and early metabolic disturbances. Here, we reported a rare case of a type 2 CGL in a girl who presented with a papillary TC (PTC) at the age of 7 years. She had no family history of TC or previous exposure to ionizing radiation. She had a generalized lack of subcutaneous fat, including the palmar and plantar regions, muscle hypertrophy, intense acanthosis nigricans, hepatomegaly, hypertriglyceridemia, severe insulin resistance, and hypoleptinemia. A genetic analysis revealed a mutation in the BSCL2 gene (p.Thr109Asnfs* 5). Ultrasound revealed a hypoechoic solid nodule measuring 1.8 × 1.0 × 1.0 cm, and fine needle aspiration biopsy suggested malignancy. Total thyroidectomy was performed, and a histopathological examination confirmed PTC with vascular invasion and parathyroid lymph node metastasis (pT3N1Mx stage). This is the first report to describe a case of differentiated TC in a child with CGL. Severe insulin resistance that is generally observed in patients with CGL early in life, especially in those with type 2 CGL, may be associated with this uncommon presentation of aggressive PTC during childhood.

article i nfo Objective: The objective of this study is to investigate the influence of the day-to-day variability of the measures of heart rate variability (HRV) on the sample size calculation for the study of cardiac autonomic neuropathy. Material and methods: We analyzed HRV in the frequency domain (very low (VLF), low (LF), and high frequency (HF) bands) and in the time domain (the root mean squared of successive RR intervals differences (RMSSD); the mean RR intervals (RRNN); the standard deviation of RR intervals (SDNN) and the coefficient of variation (CV)) during a 5-min electrocardiogram record. We also analyzed the heart rate response to deep breathing (expiration:inspiration ratio), to the Valsalva maneuver and to standing (maximum:minimum ratio) and the blood pressure response to standing. The day-to-day variability was assessed by calculating the within-subject standard deviations (WSSD), limits of agreement, typical errors and the ratio of the WSSD to the mean values obtained on days 1 and 2 (WSSD/GM). Results: Sixty-seven healthy subjects (45 females), aged 27 (19-39) years, were recruited. The RMSSD, CV, VLF, LF, HF and blood pressure response to standing showed marked variability (WSDD/GM (%) = 237.7, 455.1, 69.9, 126.5, 81.3 and 380.5, respectively), while the RRNN, SDNN, Valsalva, expiration:inspiration and maximum:minimum ratio showed less variability (WSSD/GM (%) = 6.4, 24.5, 18.6, 11.0 and 14.1, respectively). The minimum differ- ences expected to be statistically significant for the autonomic measurements were calculated. Conclusion: Some tests that assess HRV showed adequate reproducibility. This study allows the determination of a sample size calculation for longitudinal or drug-testing studies.

OBJECTIVE: The objectives of this study are to estimate the prevalence of arterial hypertension (AH) in an adult population with a predominance of families with low education and income levels, in the hinterlands of Pernambuco, Brazil, and to analyze its association with other factors related to cardiovascular diseases (CVD). METHODS: A cross-sectional study in 2008/2009 was conducted with a sample of 198 subjects stratified by age, and representative of the urban adult population of the Canaã district of city of Triunfo, in the hinterlands of Pernambuco, Brazil. RESULTS: One hundred ninety eight individuals with average age of 57.7 years old (31 to 90 years-old), mainly women (65.6%), and with low income and education levels (81.3% with a monthly income of less than one minimum wage) were evaluated. Among these, 127 (64.1%) were identified as having AH, 54 (42.5%) of whom had no prior diagnosis. From those who were previously diagnosed, only 31.3% had good blood pressure control. Higher prevalence was observed in those individuals with lower incomes, higher body mass indexes (BMI), and those with metabolic syndrome (MS). CONCLUSION: These data demonstrated that there was a high prevalence of AH in the urban, low education and income levels adult population of Triunfo, strongly associated with lower income levels, elevated BMI, and the presence of MS; and a high prevalence of bad blood pressure control among the previously diagnosed cases. These results indicate that more effective interventions for early detection and adequate control of this disease and its comorbidities are necessary.

SUMMARY Insulin autoimmune syndrome (IAS, Hirata's disease) is a rare hypoglycemic disorder characterized by spontaneous hypoglycemia associated with extremely high circulating insulin levels and positive anti-insulin antibody results. Thus far, most cases have been reported in Asian countries, notably Japan, with few cases reported in western countries. As a possible cause, it is associated with the use of drugs containing sulfhydryl radicals, such as captopril. This report refers to a 63-year-old female Brazilian patient with a history of postprandial hypoglycemia. After extensive investigation and exclusion of other causes, her hyperinsulinemic hypoglycemia was considered to have likely been induced by captopril. Most cases of IAS are self-limiting. However, dietary management, corticosteroids, plasmapheresis, and rituximab have already been used to treat patients with IAS. In our case, after discontinuation of captopril, an initial decrease in insulin autoantibody levels was observed followed by improvement in episodes of hypoglycemia. Although it is a rare disease, IAS should be considered in the differential diagnosis of endogenous hyperinsulinemic hypoglycemia. Patients with suspected IAS must be screened for autoimmunity-related drugs for insulin. Initial clinical suspicion of IAS can avoid unnecessary costs associated with imaging examinations and/or invasive surgical procedures.

OBJECTIVE: To examine excessive daytime sleepiness (EDS) in type 2 diabetes. SUBJECTS AND METHODS: Patients (N = 110) were evaluated regarding Epworth Sleepiness Scale (EDS), sleep quality (Pittsburgh Sleep Quality Index), depressive symptoms (Beck Depression Inventory), Restless Legs Syndrome (RLS), risk of obstructive sleep apnea (OSA) (Berlin questionnaire), and comorbidity severity (Charlson Comorbidity Index). Patients were compared with indivi-duals with arterial hypertension and without diabetes. RESULTS: Diabetic patients had more EDS, depressive symptoms, and higher comorbidity severity than hypertensive patients (p < 0.005). In diabetic patients, poor quality sleep (53.3%), and high risk of OSA (40.9%) and RLS (14.5%) were found; EDS (55.5%) was associated with depressive symptoms present in 44.5% indivi-duals (OR = 1.08; 95% CI: 1.01-1.15), and remained so after data were controlled for age, gender, body mass index, and glycated hemoglobin (OR = 2.27; 95% CI 1.03-5.03). CONCLUSIONS: Sleep abnormalities are frequent. EDS affects most of the patients and is independently associated with depressive symptoms. Adequate antidepressant therapy should be tested for the effects on EDS. OBJETIVO: Em pacientes com diabetes tipo 2, avaliar a sonolência excessiva diurna (SED). SUJEITOS E MÉTODOS: Pacientes (N = 110) foram investigados com relação a Escala de Sonolência de Epworth (SED), qualidade do sono (Índice de Qualidade de Sono Pittsburgh), sintomas depressivos (Inventário de Depressão de Beck), Síndrome das Pernas Inquietas (SPI), risco de apneia obstrutiva do sono (AOS) (Questionário de Berlim) e comorbidades (Índice de Comorbidade de Charlson), e foram comparados com indivíduos com hipertensão arterial sem diabetes. RESULTADOS: Pacientes diabéticos apresentavam mais SED, sintomas depressivos e comorbidades que os hipertensos (p < 0,005). Em pacientes diabéticos, má qualidade do sono (53,3%), risco de AOS (40,9%) e SPI (14,5%) foram encontrados. SED (55,5%) associou-se com os sintomas depressivos em 44,5% (OR = 1,08; 95% IC 1,01-1,15) e permaneceu após controle para idade, sexo, índice de massa corporal e hemoglobina glicosilada (OR = 2,27 95% IC 1,03-5,03). CONCLUSÕES: Anormalidades do sono são frequentes. SED afeta a maioria dos pacientes e associa-se de forma independente com os sintomas depressivos. Terapia antidepressiva pode melhorar a SED.