High rate of abnormal glucose tolerance in Brazilian individuals undergoing coronary angiography.

INTRODUCTION: Undiagnosed hyperglycemia is common in high cardiovascular risk individuals, especially in those with coronary artery disease (CAD). There is no consensus about the optimal method for the screening of hyperglycemia in this population. SUBJECTS AND METHODS: Five hundred and fourteen Brazilian individuals undergoing coronary angiography, without previously known diabetes mellitus (DM), had their glycemic status evaluated by both fasting plasma glucose (FPG) and HbA1c, being classified in normal (N), prediabetes (PD), and DM according to American Diabetes Association criteria. Concordance between both methods was assessed by Cohen's κ. Accuracy of FPG and HbA1c to diagnose CAD was evaluated as proof-of-concept. RESULTS: Among individuals screened by FPG, 41.2% had PD and 6% had DM. Among those screened by HbA1c, 52.7% had PD and 12.7% had DM. Concordance for a positive screening of PD occurred in 125 individuals (κ = 0.084). Eighteen individuals had a concordant positive screening of DM (κ = 0.310). As a predictor of CAD, accuracy of FPG was 0.554 (p = 0.009) and of HbA1c 0.557 (p = 0.006). CONCLUSION: a high frequency of hyperglycemia, between 47 and 65%, was found in individuals submitted to coronary angiography without previously known glucose disturbances, using FPG and HbA1c as screening methods respectively.HbA1c detected significantly more individuals with both PD and DM than FPG. Concordance between both methods is low. The question of which is the gold-standard method to diagnose hyperglycemia in this population is still open.

Association of ADIPOQ variants, total and high molecular weight adiponectin levels with coronary artery disease in diabetic and non-diabetic Brazilian subjects.

OBJECTIVE: To investigate the association of ADIPOQ variants, total and high molecular weight adiponectin (HMW) adiponectin levels with the prevalence of diabetes mellitus and coronary artery disease (CAD) diagnosed by coronary angiography in Brazilian subjects with high cardiovascular risk. METHODS: 603 subjects undergoing coronary angiography were studied in regard to their glycemic status and presence of CAD (lesions >0%). We evaluated baseline concentrations of total and HMW adiponectin and three ADIPOQ variants: -11391G>A (rs17300539), +45T>G (rs2241766) and+276G>T (rs1501299). RESULTS: The G-allele of rs2241766 was associated with higher levels of total and HMW adiponectin, and the A-allele of rs17300539 was associated with higher levels of HMW adiponectin. Lower levels of total and HMW adiponectin were independently associated with CAD. The G-allele of rs2241766 (OR 2.45, 95% C.I. 1.05-6.04, p=0.04) and the G-allele of rs1501299 (OR 1.89, 95% C.I. 1.04-3.45, p=0.03) were associated with CAD, and these associations were independent of circulating levels of adiponectin. CONCLUSIONS: In Brazilian subjects with high cardiovascular risk, CAD was associated with lower total and HMW adiponectin levels. The rs2241766 and rs1501299 polymorphisms were associated with CAD. The rs2241766 variant was associated with total and HMW adiponectin levels, while rs17300539 was associated with HMW adiponectin levels.

ADIPOQ and adiponectin: the common ground of hyperglycemia and coronary artery disease?

Plasma adiponectin and the coding gene for adiponectin, ADIPOQ, are thought to explain part of the interaction between obesity, insulin resistance, type 2 diabetes (T2DM) and coronary artery disease (CAD). Here, we illustrate the role that adiponectin and ADIPOQ variants might play in the modulation of CAD, especially in the occurrence of hyperglycemia. Recent evidence suggests that total and high molecular weight (HMW) adiponectin levels are apparent markers of better cardiovascular prognosis in patients with low risk of CAD. However, in subjects with established or high risk of CAD, these levels are associated with poorer prognosis. We also provide recent evidences relating to the genetic control of total and HMW adiponectin levels, especially evidence regarding ADIPOQ. Accumulated data suggest that both adiponectin levels and polymorphisms in the ADIPOQ gene are linked to the risk of CAD in patients with hyperglycemia, and that these associations seem to be independent from each other, even if adiponectin levels are partly dependent on ADIPOQ.

ADIPOQ and adiponectin: the common ground of hyperglycemia and coronary artery disease? / ADIPOQ e adiponectina: base comum da hiperglicemia e doença arterial coronariana?

Plasma adiponectin and the coding gene for adiponectin, ADIPOQ, are thought to explain part of the interaction between obesity, insulin resistance, type 2 diabetes (T2DM) and coronary artery disease (CAD). Here, we illustrate the role that adiponectin and ADIPOQ variants might play in the modulation of CAD, especially in the occurrence of hyperglycemia. Recent evidence suggests that total and high molecular weight (HMW) adiponectin levels are apparent markers of better cardiovascular prognosis in patients with low risk of CAD. However, in subjects with established or high risk of CAD, these levels are associated with poorer prognosis. We also provide recent evidences relating to the genetic control of total and HMW adiponectin levels, especially evidence regarding ADIPOQ. Accumulated data suggest that both adiponectin levels and polymorphisms in the ADIPOQ gene are linked to the risk of CAD in patients with hyperglycemia, and that these associations seem to be independent from each other, even if adiponectin levels are partly dependent on ADIPOQ.

Os níveis plasmáticos de adiponectina e o gene codante desta proteína, ADIPOQ, parecem explicar parte da interação de doenças como obesidade, resistência à insulina, diabetes melito tipo 2 (DM2) e doença arterial coronariana (DAC). Apresentamos as evidências do papel tanto dos níveis de adiponectina quanto das variantes no ADIPOQ na modulação da DAC, sobretudo na presença de hiperglicemia. Estudos recentes sugerem que níveis de adiponectina total e de alto peso molecular (HMW) são marcadores de bom prognóstico DAC, sobretudo em pacientes de baixo risco cardiovascular, enquanto nos pacientes de alto risco ou com doença já estabelecida podem se associar com pior prognóstico. Apresentamos também as evidências em relação ao possível controle genético dos níveis circulantes de adiponectina, tanto total quanto da isoforma de alto peso molecular, sobretudo em relação ao ADIPOQ. A análise global dos dados sugere que tanto os níveis circulantes de adiponectina quanto polimorfismos no gene ADIPOQ estão implicados na evolução de DAC em pacientes com hiperglicemia e que essas associações podem existir de forma independente.

Visfatin, glucose metabolism and vascular disease: a review of evidence.

The adipose tissue is an endocrine organ producing substances called adipocytokines that have different effects on lipid metabolism, metabolic syndrome, and cardiovascular risk. Visfatin was recently described as an adipocytokine with potentially important effects on glucose metabolism and atherosclerosis. Visfatin has been linked to several inflammatory conditions, beta cell function, and cardiovascular disease. The growing number of publications on the subject shall bring further evidence about this adipocytokine. Its findings may contribute in the identification of higher risk individuals for diabetes and cardiovascular disease with a better comprehension about the complex intercorrelation between adiposity, glucose metabolism and vascular disease.

Low prevalence of MODY2 and MODY3 mutations in Brazilian individuals with clinical MODY phenotype.

Prevalence of MODY2 and MODY3 mutations has been assessed in 23 Brazilian families with MODY phenotype. Mutations in HNF-1alpha have been found in 3 families (13%) and 2 families (8.7%) had new glucokinase mutations. These genes do not explain the majority of MODY cases in Brazilian population.

[Cardiovascular assessment of diabetic patients]. / Avaliação cardiovascular de pacientes diabéticos em ambulatório universitário.

INTRODUCTION: Type 2 diabetes is a cardiovascular disease. The morbidity and mortality among these patients are primarily due to cardiovascular diseases. There are many guidelines regarding clinical evaluation of cardiovascular disease in those patients. Implementation of these guidelines has been an argued subject. Our objective in this paper is to describe what basal cardiovascular evaluation has been carried out at a specialized university Diabetes Center. SUBJECTS AND METHODS: Data were collected from February to October 2006 of 121 type 2 diabetes individuals who were enrolled at the Diabetes Center of Federal University of São Paulo. We analyzed the type of cardiovascular disease evaluation that they had been submitted in the year that preceded the consultation. RESULTS: We have observed a high prevalence of several other cardiovascular risk factors in this population. The cardiovascular evaluations during this period has shown 36% of the patients had not been submitted to any cardiovascular test, 17% had been submitted to resting electrocardiogram and 27% of the patients had been submitted to exercise test. Rest echocardiogram, pharmacologic stress echocardiogram, myocardial perfusion scintigraphy, and coronary angiography have been carried out in a much lesser ratio. CONCLUSION: Our data has shown the variability and limitations on boarding diagnosing of DAC in university environment patients and point us the necessity of constructing defined and directed directives for the peculiarities of the Brazilian population and health system.

Avaliação cardiovascular de pacientes diabéticos em ambulatório universitário / Cardiovascular assessment of diabetic patients

INTRODUÇÃO: Baseado no conhecimento atual sobre o diabetes tipo 2 (DM), considerado como um estado de doença cardiovascular, várias diretrizes surgem no intuito de sugerir uma avaliação cardiovascular rotineira nesses indivíduos, na tentativa de se detectar precocemente a doença arterial coronariana (DAC). Neste trabalho, objetivamos descrever qual avaliação cardiovascular basal fora realizada em um período de seguimento dos mesmos, dentro de um centro universitário especializado no tratamento de diabetes, adequado para a realidade brasileira. SUJEITOS E MÉTODOS: Anotamos dados clínicos do prontuário de 121 pacientes portadores de DM tipo 2 atendidos no Centro de Diabetes da Universidade Federal de São Paulo e confrontamos com o tipo de avaliação cardiovascular a que os mesmos haviam sido submetidos no ano que precedia a consulta. RESULTADOS: Observamos que na população estudada havia uma alta prevalência de outros fatores de risco cardiovasculares associados. Quanto às avaliações cardiovasculares realizadas no período, cerca de 36 por cento dos pacientes não realizaram nenhum teste cardiológico, 17 por cento foram submetidos ao eletrocardiograma de repouso e 27 por cento dos pacientes foram submetidos ao teste ergométrico. Exames como ecocardiograma em repouso ou sob stress farmacológico, cintilografia de perfusão do miocárdio e cinecoronariografia foram realizados em menor proporção. CONCLUSÃO: Nossos dados mostraram a variabilidade e limitações na forma de abordagem diagnóstica de DAC de pacientes acompanhados em ambiente universitário e nos apontam para a necessidade de construir diretrizes mais bem definidas e dirigidas para as peculiaridades da população e sistema de saúde brasileiros.

INTRODUCTION: Type 2 diabetes is a cardiovascular disease. The morbidity and mortality among these patients are primarily due to cardiovascular diseases. There are many guidelines regarding clinical evaluation of cardiovascular disease in those patients. Implementation of these guidelines has been an argued subject. Our objective in this paper is to describe what basal cardiovascular evaluation has been carried out at a specialized university Diabetes Center. SUBJECTS AND METHODS: Data were collected from February to October 2006 of 121 type 2 diabetes individuals who were enrolled at the Diabetes Center of Federal University of São Paulo. We analyzed the type of cardiovascular disease evaluation that they had been submitted in the year that preceded the consultation. RESULTS: We have observed a high prevalence of several other cardiovascular risk factors in this population. The cardiovascular evaluations during this period has shown 36 percent of the patients had not been submitted to any cardiovascular test, 17 percent had been submitted to resting electrocardiogram and 27 percent of the patients had been submitted to exercise test. Rest echocardiogram, pharmacologic stress echocardiogram, myocardial perfusion scintigraphy, and coronary angiography have been carried out in a much lesser ratio. CONCLUSION: Our data has shown the variability and limitations on boarding diagnosing of DAC in university environment patients and point us the necessity of constructing defined and directed directives for the peculiarities of the Brazilian population and health system.

Estimation of diabetes risk in Brazilian population by typing for polymorphisms in HLA-DR-DQ, INS and CTLA-4 genes.

The study aimed to further characterise HLA encoded risk factors of type 1 diabetes (T1D) in Brazilian population and test the capability of a low resolution full-house DR-DQ typing method to find subjects at diabetes risk. Insulin and CTLA-4 gene polymorphisms were also analysed. The method is based on an initial DQB1 typing supplemented by DQA1 and DR4 subtyping when informative. Increased frequencies of both (DR3)-DQA1*05-DQB1*02 and DRB1*04-DQA1*03-DQB1*0302 haplotypes were detected among patients. DRB1*0401, *0402, *0404 and *0405 alleles were all common in DQB1*0302 haplotypes and associated with T1D. (DRB1*11/12/1303)-DQA1*05-DQB1*0301, (DRB1*01/10)-DQB1*0501, (DRB1*15)-DQB1*0602 and (DRB1*1301)-*0603 haplotypes were significantly decreased among patients. Genotypes with two risk haplotypes or a combination of a susceptibility associated and a neutral haplotype were found in 78 of 126 (61.9%) T1D patients compared to 8 of 75 (10.7%) control subjects (P < 0.0001). Insulin gene -2221 C/T polymorphism was also associated with diabetes risk: CC genotype was found among 83.1% of patients compared to 69.3% of healthy controls (P=0.0369, OR 1.98) but CTLA-4 gene +49 A/G polymorphism did not significantly differ between patients and controls. Despite the diversity of the Brazilian population the screening sensitivity and specificity of the used method for T1D risk was similar to that obtained in Europe.

Diabetes mellitus do tipo MODY / Diabetes mellitus of the MODY type

Estima-se que perto de 5 por cento dos indivíduos classificados como portadores de diabetes mellitus (DM) tipo 2 e 10 por cento daqueles considerados como tipo 1 (anteriormente classificado como juvenil) sejam, na verdade, portadores de mutaçöes MODY. Nesta forma de DM ocorre uma co-segregaçäo evidente de algumas mutaçöes com a hiperglicemia, fato este reproduzido em inúmeras famílias estudadas em várias populaçöes do mundo. Caracteriza-se por ser uma das poucas causas de DM cujo modo de transmissäo da predisposiçäo genética ocorre de uma forma autossômica-dominante, compondo o grupo chamado de DM monogênicos, onde os outros representantes têm uma prevalência bastante rara. As mutaçöes nos genes MODY, mesmo no estado heterozigoto, apresentam um forte impacto no fenótipo (alta penetrância), sendo que 95 por cento dos indivíduos nascidos com alguma mutaçäo MODY seräo diabéticos ou apresentaräo alteraçöes no âmbito do metabolismo glícídico antes dos 55 anos de idade. Este trabalho objetiva a discussäo desta forma de DM, enfatizando suas características clinicas e genéticas mais relevantes. A pesquisa sistemática de mutaçöes MODY começa a ser feita de forma rotineira em vários países, havendo uma tendência de se colocar este recurso diagnóstico como um exame na prática da diabetologia.