Evaluation of plasma homocysteine level according to the C677T and A1298C polymorphism of the enzyme MTHRF in type 2 diabetic adults

Objective: To determine plasma homocysteine levels during fasting and after methionine overload, and to correlate homocysteinemia according to methylenetetrahydrofolate reductase (MTHFR) polymorphism in type 2 diabetic adults. Subjects and methods: The study included 50 type 2 diabetic adults (DM group) and 52 healthy subjects (Control group). Anthropometric data, and information on food intake, serum levels of vitamin B 12, folic acid and plasma homocysteine were obtained. The identification of C677T and A1298C polymorphisms was carried out in the MTHFR gene. Results: There was no significant difference in homocysteinemia between the two groups, and hyperhomocysteinemia during fasting occurred in 40% of the diabetic patients and in 23% of the controls. For the same polymorphism, there was not any significant difference in homocysteine between the groups. In the Control group, homocysteinemia was greater in those subjects with C677T and A1298C polymorphisms. Among diabetic subjects, those with the A1298C polymorphism had lower levels of homocysteine compared with individuals with C677T polymorphism. Conclusion: The MTHFR polymorphism (C677T and A1298C) resulted in different outcomes regarding homocysteinemia among individuals of each group (diabetic and control). These data suggest that metabolic factors inherent to diabetes influence homocysteine metabolism. Arq Bras Endocrinol Metab. 2012;56(7):429-34

Incidental mild hyperglycemia in children: two MODY 2 families identified in Brazilian subjects

Maturity-onset diabetes of the young (MODY) is characterized by an autosomal dominant mode of inheritance, early onset of hyperglycemia, and defects of insulin secretion. MODY subtypes described present genetic, metabolic, and clinical differences. MODY 2 is characterized by mild asymptomatic fasting hyperglycemia, and rarely requires pharmacological treatment. Hence, precise diagnosis of MODY is important for determining management and prognosis. We report two heterozygous GCK mutations identified during the investigation of short stature. Case 1: a prepubertal 14-year-old boy was evaluated for constitutional delay of growth and puberty. During follow-up, he showed abnormal fasting glucose (113 mg/dL), increased level of HbA1c (6.6%), and negative beta-cell antibodies. His father and two siblings also had slightly elevated blood glucose levels. The mother had normal glycemia. A GCK heterozygous missense mutation, p.Arg191Trp, was identified in the proband. Eighteen family members were screened for this mutation, and 11 had the mutation in heterozygous state. Case 2: a 4-year-old boy investigated for short stature revealed no other laboratorial alterations than elevated glycemia (118 mg/dL); beta-cell antibodies were negative. His father, a paternal aunt, and the paternal grandmother also had slightly elevated glycemia, whereas his mother had normal glycemia. A GCK heterozygous missense mutation, p.Glu221Lys, was identified in the index patient and in four family members. All affected patients had mild elevated glycemia. Individuals with normal glycemia did not harbor mutations. GCK mutation screening should be considered in patients with chronic mild early-onset hyperglycemia, family history of impaired glycemia, and negative beta-cell antibodies. Arq Bras Endocrinol Metab. 2012;56(8):519-24

Comparison of venous plasma glycemia and capillary glycemia for the screening of type 2 diabetes mellitus in the Japanese-Brazilian community of Mombuca (Guatapará-SP)

Abstract Background To identify the most appropriate cut-off points of fasting glycemia for the screening of diabetes mellitus type 2 (DM2) with the comparison of the properties of capillary glycemia (CG) and venous blood plasma glycemia (PG) in a population of Japanese origin from the community of Mombuca, Guatapará - SP, Brazil. Methods This was a population-based descriptive cross-sectional study conducted on a sample of 131 individuals of both genders aged 20 years or more (66.8% of the target population). CG was measured with a glucometer in a blood sample obtained from the fingertip and PG was determined by an enzymatic method (hexokinase) in venous blood plasma, after a 10-14 hour fast in both cases. Data were analyzed by the receiver operating characteristic (ROC) curve in order to identify the best cut-off point for fasting glycemia (CG and PG) for the diagnosis of DM, using the 2-hour plasma glycemia > 200 mg/dl as gold - standard. Results The ROC curve revealed that the best cut-off point for the screening of DM was 110 mg/dl for CG and 105 mg/dl for PG, values that would optimize the relation between individuals with positive and false-positive results. The area under the ROC curve was 0.814 for CG (p < 0.01) and 0.836 for PG (p < 0.01). Conclusions The cut-off points of 105 mg/dl(5.8 mmol/l) for PG and of 110 mg/dl(6.1 mmol/l) for CG appear to be the most appropriate for the screening of DM2 in the population under study, with emphasis on the fact that the value recommended for CG is 5 mg/dl higher than that for PG, in contrast to WHO recommendations.

Insulin analogues in the treatment of diabetes in pregnancy

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.

Causas referidas para o desenvolvimento de úlceras em pés de pessoas com diabetes mellitus

OBJETIVO: Analisar as causas referidas na etiologia das úlceras em pés de pessoas com Diabetes mellitus (DM). MÉTODOS: Estudo seccional, quantitativo, realizado no Ambulatório de Diabetes de um Hospital Universitário em Ribeirão Preto - SP. Os dados foram coletados com instrumento estruturado e exame físico dos pés de amostra de 30 pacientes diabéticos. RESULTADOS: Amostra com idade média de 57,5 anos, predominância do sexo masculino e baixa escolaridade; 90% possuíam DM tipo 2, de longa duração e mal controlado; obesidade/sobrepeso em 77% e insensibilidade plantar em 93,3%. A região metatarsiana foi o local de úlcera referido com maior frequência, e a causa foi a calosidade. CONCLUSÃO: as causas referidas envolvidas na etiologia das úlceras correspondem, de forma direta ou indireta, a fatores extrínsecos que podem ser prevenidos com cuidados básicos e de baixo custo. A insensibilidade plantar, fator fundamental desencadeador das úlceras, no entanto não foi reconhecida pelas pessoas.

Identifying common and specific microRNAs expressed in peripheral blood mononuclear cell of type 1, type 2, and gestational diabetes mellitus patients

Abstract Background Regardless the regulatory function of microRNAs (miRNA), their differential expression pattern has been used to define miRNA signatures and to disclose disease biomarkers. To address the question of whether patients presenting the different types of diabetes mellitus could be distinguished on the basis of their miRNA and mRNA expression profiling, we obtained peripheral blood mononuclear cell (PBMC) RNAs from 7 type 1 (T1D), 7 type 2 (T2D), and 6 gestational diabetes (GDM) patients, which were hybridized to Agilent miRNA and mRNA microarrays. Data quantification and quality control were obtained using the Feature Extraction software, and data distribution was normalized using quantile function implemented in the Aroma light package. Differentially expressed miRNAs/mRNAs were identified using Rank products, comparing T1DxGDM, T2DxGDM and T1DxT2D. Hierarchical clustering was performed using the average linkage criterion with Pearson uncentered distance as metrics. Results The use of the same microarrays platform permitted the identification of sets of shared or specific miRNAs/mRNA interaction for each type of diabetes. Nine miRNAs (hsa-miR-126, hsa-miR-1307, hsa-miR-142-3p, hsa-miR-142-5p, hsa-miR-144, hsa-miR-199a-5p, hsa-miR-27a, hsa-miR-29b, and hsa-miR-342-3p) were shared among T1D, T2D and GDM, and additional specific miRNAs were identified for T1D (20 miRNAs), T2D (14) and GDM (19) patients. ROC curves allowed the identification of specific and relevant (greater AUC values) miRNAs for each type of diabetes, including: i) hsa-miR-1274a, hsa-miR-1274b and hsa-let-7f for T1D; ii) hsa-miR-222, hsa-miR-30e and hsa-miR-140-3p for T2D, and iii) hsa-miR-181a and hsa-miR-1268 for GDM. Many of these miRNAs targeted mRNAs associated with diabetes pathogenesis. Conclusions These results indicate that PBMC can be used as reporter cells to characterize the miRNA expression profiling disclosed by the different diabetes mellitus manifestations. Shared miRNAs may characterize diabetes as a metabolic and inflammatory disorder, whereas specific miRNAs may represent biological markers for each type of diabetes, deserving further attention.

Potent Antiretroviral Therapy for Human Immunodeficiency Virus Infection Increases Aortic Stiffness

Background: Highly active antiretroviral therapy for AIDS is known to increase cardiovascular risk, but the effects of potent antiretroviral agents according to gender are unknown. Objective: The present study evaluated the impact of HIV infection treatment on aortic stiffness according to gender. Methods: From university-affiliated hospitals, we recruited 28 AIDS patients undergoing highly active antiretroviral treatment (HAART), 28 treatment-naive HIV-infected patients, 44 patients with type 2 diabetes, and 30 controls. Aortic stiffness was determined by measuring pulse wave velocity (PWV) using a validated and non-invasive automatic device. Results: The crude mean PWV values and 95% confidence intervals (95% CI) for HAART, diabetics, and controls were 9.77 m/s (95% CI 9.17-10.36),, 9.00 m/s (95% CI 8.37-9.63), 9.90 m/s (95% CI 9.32-10.49), and 9.28 m/s (95% CI 8.61-9.95), respectively, for men (P-value for trend = 0.14), and 9.61 m/s (95% CI 8.56-10.66), 8.45 m/s (95% CI 7.51-9.39), 9.83 (95% CI 9.21-10.44), and 7.79 m/s (95% CI 6.99-8.58), respectively, for women (P-value for trend <0.001). Post-hoc analysis revealed a significant difference between the mean PWV values in the HAART group and controls in women (P-value <0.01). After adjusting for other potential covariates, including systolic blood pressure and diabetes, these results did not change. The findings indicate that the impact of HAART treatment on aortic stiffness was amplified in women with hypertension, dyslipidemia, and metabolic syndrome. Conclusion: Potent anti-retroviral agents used in the treatment of HIV infection increases aortic stiffness, mainly among women with higher cardiovascular risk. (Arq Bras Cardiol 2012;99(6):1100-1107)

Advanced QSAR Studies on PPAR delta Ligands Related to Metabolic Diseases

PPAR delta is a nuclear receptor that, when activated, regulates the metabolism of carbohydrates and lipids and is related to metabolic syndrome and type 2 diabetes. To understand the main interactions between ligands and PPAR delta, we have constructed 2D and 3D QSAR models and compared them with HOMO, LUMO and electrostatic potential maps of the compounds studied, as well as docking results. All QSAR models showed good statistical parameters and prediction outcomes. The QSAR models were used to predict the biological activity of an external test set, and the predicted values are in good agreement with the experimental results. Furthermore, we employed all maps to evaluate the possible interactions between the ligands and PPAR delta. These predictive QSAR models, along with the HOMO, LUMO and MEP maps, can provide insights into the structural and chemical properties that are needed in the design of new PPAR delta ligands that have improved biological activity and can be employed to treat metabolic diseases.

Molecular confirmation of ovine herpesvirus 2-induced malignant catarrhal fever lesions in cattle from Rio Grande do Norte, Brazil

Molecular findings that confirmed the participation of ovine herpesvirus 2 (OVH-2) in the lesions that were consistent with those observed in malignant catarrhal fever of cattle are described. Three mixed-breed cattle from Rio Grande do Norte state demonstrated clinical manifestations that included mucopurulent nasal discharge, corneal opacity and motor incoordination. Routine necropsy examination demonstrated ulcerations and hemorrhage of the oral cavity, corneal opacity, and lymph node enlargement. Significant histopathological findings included widespread necrotizing vasculitis, non-suppurative meningoencephalitis, lymphocytic interstitial nephritis and hepatitis, and thrombosis. PCR assay performed on DNA extracted from kidney and mesenteric lymph node of one animal amplified a product of 423 base pairs corresponding to a target sequence within the ovine herpesvirus 2 (OVH-2) tegument protein gene. Direct sequencing of the PCR products, from extracted DNA of the kidney and mesenteric lymph node of one cow, amplified the partial nucleotide sequences (423 base pairs) of OVH-2 tegument protein gene. Blast analysis confirmed that these sequences have 98-100% identity with similar OVH-2 sequences deposited in GenBank. Phylogenetic analyses, based on the deduced amino acid sequences, demonstrated that the strain of OVH-2 circulating in ruminants from the Brazilian states of Rio Grande do Norte and Minas Gerais are similar to that identified in other geographical locations. These findings confirmed the active participation of OVH-2 in the classical manifestations of sheep associated malignant catarrhal fever.

Periodontal disease and diabetes mellitus

Periodontal disease (PD) is one of the most commonly known human chronic disorders. The relationship between PD and several systemic diseases such as diabetes mellitus (DM) has been increasingly recognized over the past decades. Objective The purpose of this review is to provide the reader with knowledge concerning the relationship between PD and DM. Many articles have been published in the English and Portuguese literature over the last 50 years examining the relationship between these two chronic diseases. Data interpretation is often confounded by varying definitions of DM, PD and different clinical criteria were applied to determine the prevalence, extent and severity of PD, levels of glycemic control and diabetes-related complications. Methods This paper provides a broad overview of the predominant findings from research conducted using the BBO (Bibliografia Brasileira de Odontologia), MEDLINE, LILACS and PubMed for Controlled Trials databases, in English and Portuguese languages published from 1960 to October 2012. Primary research reports on investigations of relationships between DM/DM control, PD/periodontal treatment and PD/DM/diabetes-related complications identified relevant papers and meta-analyses published in this period. Results 7This paper describes the relationship between PD and DM and answers the following questions: 1- The effect of DM on PD, 2- The effects of glycemic control on PD and 3- The effects of PD on glycemic control and on diabetes-related complications. Conclusions The scientific evidence reviewed supports diabetes having an adverse effect on periodontal health and PD having an adverse effect on glycemic control and on diabetes-related complications. Further research is needed to clarify these relationships and larger, prospective, controlled trials with ethnically diverse populations are warranted to establish that treating PD can positively influence glycemic control and possibly reduce the burden of diabetes-related complications.

Terapia antirretroviral altamente eficaz para infecção pelo vírus da imunodeficiência humana aumenta a rigidez aórtica

FUNDAMENTO: Sabe-se que a terapia antirretroviral altamente potente para Aids reconhecida aumenta o risco cardiovascular, mas os efeitos dos agentes antirretrovirais de acordo com o gênero ainda são desconhecidos. OBJETIVO: O presente estudo avaliou o impacto do tratamento para o vírus da imunodeficiência humana (HIV) na rigidez aórtica de acordo com o gênero. MÉTODOS: Foram recrutados 28 pacientes com Aids submetidos à terapia antirretroviral altamente potente (HAART), 28 pacientes infectados pelo HIV virgens de tratamento, 44 pacientes com diabetes tipo 2, e 30 controles. A rigidez aórtica foi determinada pela medição da Velocidade da Onda de Pulso (VOP), utilizando um equipamento automático validado e não invasivo. RESULTADOS: Os resultados médios brutos da VOP (e intervalo de confiança de 95%) para participantes nos grupos terapia antirretroviral potente, HIV virgem de tratamento, diabéticos, e controles foram 9,77 m/s (9,17-10,36), 9,00 m/s (8,37-9,63), 9,90 m/s (9,32-10,49) e 9,28 m/s (8,61-9,95), respectivamente, para os homens (p de tendência = 0,14) e 9,61 m/s (8,56-10,66), 8,45 m/s (7,51-9,39), 9,83 (9,21-10,44) e 7,79 m/s (6,99-8,58), respectivamente, para as mulheres (p valor de tendência < 0,001). Análises post-hoc revelaram uma diferença significativa entre os valores médios de VOP no grupo com HAART e controles em mulheres (p < 0,01). Ajustes para as demais covariáveis potenciais, incluindo pressão arterial sistólica e diabetes, não alteraram esses resultados. Os achados indicam que o impacto do tratamento com HAART na rigidez aórtica foi amplificado nas mulheres com hipertensão, dislipidemia e síndrome metabólica. CONCLUSÃO: Agentes antirretrovirais potentes utilizados no tratamento da infecção pelo HIV aumentam a rigidez da aorta, especialmente em mulheres com maior risco cardiovascular.

Children with Type 1 Diabetes Mellitus and their friends: the influence of this interaction in the management of the disease

Friends' support is a key element in the management of Type 1 Diabetes Mellitus. This study describes the influence of friends on the lives of children with Diabetes Mellitus and its implications for managing the disease. Empirical data were collected through semi-structured interviews, supported with the use of puppets, with 19 children aged between seven and 12 years old. The qualitative analysis of the testimonies allowed understanding the phenomenon from two perspectives: the attitude of friends towards the child, positively or negatively affecting the disease's management, and the attitude of the child toward friends. The knowledge of those involved and the interaction between the children with DM1 and their friends impacts the management of the disease. Understanding the implications of these interactions contributes to the delivery of qualified nursing care to this population.

Potencial envolvimento da adiponectina e seus receptores na modulação da esteroidogênese em corpo lúteo de cadelas ao longo do diestro

No ciclo estral de cadelas a fase luteínica, denominada diestro, compreende um período que varia de 60 a 100 dias em animais não-prenhes, caracterizado pela elevação plasmática de progesterona nos primeiros 20 dias pós ovulação (p.o). A adiponectina é a mais abundante proteína secretada pelo tecido adiposo, porém sua concentração plasmática diminui significativamente em alterações metabólicas como resistência insulínica e Diabetes mellitus tipo2, alterações descritas como relacionadas em algumas cadelas com o período de diestro. O objetivo do estudo foi determinar a expressão e imunolocalização do sistema adiponectina (adiponectina e seus receptores, adipoR1 e adipoR2) no corpo lúteo de cadelas ao longo do diestro, correlacionando-o ao perfil hormonal de 17β-estradiol e progesterona, assim como à expressão de um dos genes alvo do sistema, o PPAR-γ. Para realização do estudo foram coletados corpos lúteos de 28 cadelas durante ovariosalpingohisterectomia de eleição nos dias 10, 20, 30, 40, 50, 60 e 70 pós ovulação (o dia zero da ovulação foi considerado aquele no qual a concentração plasmática de progesterona atingiu 5ng/mL). Os corpos lúteos foram avaliados por imunohistoquímica para adiponectina e seus receptores e a expressão do RNAm do PPAR-γ por PCR em tempo real. A análise estatística da avaliação gênica foi realizada com o teste ANOVA, seguido por comparação múltipla Newman-Keuls. O sinal da adiponectina apresentou-se mais intenso até os primeiros 20 dias p.o, momento de regência da progesterona; houve queda gradativa após este período, coincidindo com a ascensão do 17β-estradiol, cujo pico foi notado próximo do dia 40 p.o. A queda marcante da adiponectina ocorreu após 50 dias p.o. O sinal do adipoR1 mostrou-se bem evidente até os 40 dias p.o e o do adipoR2 até os 50 dias p. o, decaindo posteriormente. Foi observada maior expressão do gene PPAR-γ aos 10, 30 e 70 dias p.o. Estes resultados mostram que a expressão protéica da adiponectina e de seus receptores se altera ao longo do diestro e que estas alterações podem estar relacionados às alterações hormonais e expressão do PPAR- γ, participando do mecanismo fisiológico de desenvolvimento, manutenção, atividade e regressão luteínica em cadelas.

Resistance to octreotide LAR in acromegalic patients with high SSTR2 expression: analysis of AIP expression

We present here the clinical and molecular data of two patients with acromegaly treated with octreotide LAR after non-curative surgery, and who presented different responses to therapy. Somatostatin receptor type 2 and 5 (SSTR2 and SSTR5), and aryl hydrocarbon receptor-interacting protein (AIP) expression levels were analyzed by qPCR. In both cases, high SSTR2 and low SSTR5 expression levels were detected; however, only one of the patients achieved disease control after octreotide LAR therapy. When we analyzed AIP expression levels of both cases, the patient whose disease was controlled after therapy exhibited AIP expression levels that were two times higher than the patient whose disease was still active. These two cases illustrate that, although the currently available somatostatin analogs bind preferentially to SSTR2, some patients are not responsive to therapy despite high expression of this receptor. This difference could be explained by differences in post-receptor signaling pathways, including the recently described involvement of AIP. Arq Bras Endocrinol Metab. 2012;56(8):501-6