Dipeptidyl Peptidase 4: A New Link between Diabetes Mellitus and Atherosclerosis?

Type 2 diabetes mellitus (T2DM) has become one of the most prevalent noncommunicable diseases in the past years. It is undoubtedly associated with atherosclerosis and increased risk for cardiovascular diseases. Incretins, which are intestinal peptides secreted during digestion, are able to increase insulin secretion and its impaired function and/or secretion is involved in the pathophysiology of T2DM. Dipeptidyl peptidase 4 (DPP4) is an ubiquitous enzyme that regulates incretins and consequently is related to the pathophysiology of T2DM. DPP4 is mainly secreted by endothelial cells and acts as a regulatory protease for cytokines, chemokines, and neuropeptides involved in inflammation, immunity, and vascular function. In T2DM, the activity of DPP4 seems to be increased and there are a growing number of in vitro and in vivo studies suggesting that this enzyme could be a new link between T2DM and atherosclerosis. Gliptins are a new class of pharmaceutical agents that acts by inhibiting DPP4. Thus, it is expected that gliptin represents a new pharmacological approach not only for reducing glycemic levels in T2DM, but also for the prevention and treatment of atherosclerotic cardiovascular disease in diabetic subjects. We aimed to review the evidences that reinforce the associations between DPP4, atherosclerosis, and T2DM.

[Biochemical, hormonal and genetic evaluation of the families of two Brazilian patients with type 2 familial partial lipodystrophy]. / Avaliação bioquímica, hormonal e genética das famílias de duas pacientes brasileiras portadoras de lipodistrofia parcial familiar tipo 2.

OBJECTIVE: To evaluate clinical, biochemical, hormonal and genetic characteristics of relatives of two patients with familial partial lipodystrophy (FPLD) type 2. MATERIALS AND METHODS: Fifty subjects, members of two non-related Brazilian families from two different probands with FPLD phenotype, were evaluated. A mutation in exon 8 of LMNA gene was confirmed in 18 of them, and a heterozygous substitution at codon 482 was identified, predicting a p.R482W mutation. Based on the presence or absence of the mutation, subjects were classified in affected and unaffected, and compared in terms of clinical, biochemical and hormonal parameters. RESULTS: Affected subjects were 2.8 times more likely to manifest diabetes and PCOS, higher HOMA-IR, insulin and triglyceride levels, and lower levels of leptin. These changes preceded the onset of diabetes, because they were observed in diabetic and non-diabetic affected patients. A phenotypic heterogeneity was found among mutation carriers. CONCLUSION: A mutation in the LMNA gene is a determinant of clinical, biochemical and hormonal changes that imply in metabolic deterioration in mutation carriers.

Avaliação bioquímica, hormonal e genética das famílias de duas pacientes brasileiras portadoras de lipodistrofia parcial familiar tipo 2 / Biochemical, hormonal and genetic evaluation of the families of two Brazilian patients with type 2 familial partial lipodystrophy

OBJETIVO: Avaliar características clínicas, bioquímicas, hormonais e genéticas de familiares de duas pacientes portadoras de lipodistrofia parcial familiar (FPLD) tipo 2. MATERIAIS E MÉTODOS: Foram avaliados 50 indivíduos de duas famílias brasileiras não relacionadas a partir de dois propósitos com fenótipo de FPLD. Foi confirmada a mutação no éxon 8 do gene LMNA em 18 destes e identificada a substituição em heterozigose no códon 482, resultando na mutação p.R482W. Com base na presença ou não da mutação, os indivíduos foram separados em afetados e não afetados, e comparados quanto a parâmetros clínicos, bioquímicos e hormonais. RESULTADOS: Indivíduos afetados tiveram 2,8 vezes mais chance de manifestar diabetes e síndrome dos ovários policísticos (SOP), maiores índices HOMA-IR, níveis de insulina e de triglicérides e menores níveis de leptina. Essas alterações precedem o início do diabetes, pois foram evidenciadas nos afetados diabéticos e não diabéticos. Foi constatada heterogeneidade fenotípica entre os portadores da mutação. CONCLUSÃO: A mutação no gene da LMNA é determinante de alterações clínicas, bioquímicas e hormonais que implicam deterioração metabólica nos portadores da mutação.

OBJECTIVE: To evaluate clinical, biochemical, hormonal and genetic characteristics of relatives of two patients with familial partial lipodystrophy (FPLD) type 2. MATERIALS AND METHODS: Fifty subjects, members of two non-related Brazilian families from two different probands with FPLD phenotype, were evaluated. A mutation in exon 8 of LMNA gene was confirmed in 18 of them, and a heterozygous substitution at codon 482 was identified, predicting a p.R482W mutation. Based on the presence or absence of the mutation, subjects were classified in affected and unaffected, and compared in terms of clinical, biochemical and hormonal parameters. RESULTS: Affected subjects were 2.8 times more likely to manifest diabetes and PCOS, higher HOMA-IR, insulin and triglyceride levels, and lower levels of leptin. These changes preceded the onset of diabetes, because they were observed in diabetic and non-diabetic affected patients. A phenotypic heterogeneity was found among mutation carriers. CONCLUSION: A mutation in the LMNA gene is a determinant of clinical, biochemical and hormonal changes that imply in metabolic deterioration in mutation carriers.

Effects of weight loss induced by bariatric surgery on the prevalence of metabolic syndrome.

BACKGROUND: Metabolic Syndrome (MS) is often linked to overweight/obesity and can improve after weight loss, such improvement is expected to be proportional to the intensity of weight loss. OBJECTIVE: The aim of this study was to evaluate the impact of weight loss induced by bariatric surgery (BS) on the prevalence of MS in a middle-term period. METHODS: Thirty-five (35) patients who underwent surgical Roux's Y gastrojejunal by-pass from October 2001 until October 2005 in our University Hospital were evaluated. 88.5% were female, with a mean age at the time of surgery of 37.8+/-11.1 years and a mean BMI of 45.0+/-6.2 Kg/m(2). During the first stage of our study demographic and clinical-anthropomorphic data were collected prior to the BC procedure, including those criteria needed for the diagnosis of MS, according to the guidelines of the US NCEP. The second stage consisted of reevaluation of those patients in the post-surgical period in order to determine the prevalence of MS in an outpatient setting. RESULTS: Prior to surgery, MS was diagnosed in 27 patients (77.1%). When those patients were reevaluated 34.4+/-15 months after surgery, a reduction of mean BMI to 28.3+/-5.0 Kg/m(2) and MS was identified in only two patients (5.7%) (p<0.001). Prevalence of individual criteria such as abdominal circumference, fasting glucose levels, arterial blood pressure, HDL-cholesterol and triglycerides had a reduction of 45.8%, 83%, 87.5%, 57.13% and 94% respectively. CONCLUSION: MS is a rather common feature in obese patients enrolled for BS and this procedure has been proved to be extremely efficient reversing the metabolic syndrome, with an expressive reduction of prevalence of each and all of the NCEP criteria.

Efeito da perda ponderal induzida pela cirurgia bariátrica sobre a prevalência de síndrome metabólica / Efecto de la pérdida ponderal inducida por la cirugía bariátrica sobre la prevalencia de síndrome metabólico / Effects of weight loss induced by bariatric surgery on the prevalence of metabolic syndrome

FUNDAMENTO: A síndrome metabólica (SM) está frequentemente ligada ao excesso de peso e melhora com a perda ponderal, sendo esperado que essa melhora seja proporcional à intensidade dessa perda. OBJETIVO: Avaliar o impacto da perda ponderal induzida pela cirurgia bariátrica (CB) sobre a prevalência da SM, em médio prazo. MÉTODOS: Foram analisados 35 pacientes submetidos à cirurgia de by-pass gastrojejunal em Y de Roux, no período de outubro de 2001 a outubro de 2005, em nosso HU, sendo 88,5 por cento do sexo feminino, com uma média de idade de 37,8±11,1 anos e um IMC médio de 45,0±6,2 kg/m². Na primeira etapa da pesquisa, foram obtidos dados demográficos e clínico-antropométricos antes da realização da CB, incluindo os critérios para o diagnóstico da SM, de acordo com as diretrizes do NCEP dos Estados Unidos. Na segunda etapa, os pacientes operados foram reavaliados ambulatorialmente quanto à prevalência da SM. RESULTADOS:Antes da cirurgia, a SM foi diagnosticada em 27 pacientes (77,1 por cento). Em reavaliação 34,4±15 meses após a cirurgia, observou-se uma queda do IMC médio para 28,3±5,0 kg/m² e a SM foi detectada em apenas dois pacientes (5,7 por cento) (p<0,001). A prevalência dos critérios cintura abdominal, glicemia, pressão arterial, HDL-colesterol e triglicerídeos foi reduzida em, respectivamente, 45,8 por cento, 83 por cento, 87,5 por cento, 57,13 por cento e 94 por cento. CONCLUSÃO: A SM é ocorrência comum em obesos candidatos à CB e esse procedimento se mostrou extremamente eficaz na indução da regressão da síndrome, verificando-se redução expressiva da prevalência de todos os critérios do NCEP.

BACKGROUND: Metabolic Syndrome (MS) is often linked to overweight/obesity and can improve after weight loss, such improvement is expected to be proportional to the intensity of weight loss. OBJECTIVE: The aim of this study was to evaluate the impact of weight loss induced by bariatric surgery (BS) on the prevalence of MS in a middle-term period. METHODS: Thirty-five (35) patients who underwent surgical Roux's Y gastrojejunal by-pass from October 2001 until October 2005 in our University Hospital were evaluated. 88.5 percent were female, with a mean age at the time of surgery of 37.8±11.1 years and a mean BMI of 45.0±6.2 Kg/m². During the first stage of our study demographic and clinical-anthropomorphic data were collected prior to the BC procedure, including those criteria needed for the diagnosis of MS, according to the guidelines of the US NCEP. The second stage consisted of reevaluation of those patients in the post-surgical period in order to determine the prevalence of MS in an outpatient setting. RESULTS: Prior to surgery, MS was diagnosed in 27 patients (77.1 percent). When those patients were reevaluated 34.4±15 months after surgery, a reduction of mean BMI to 28.3±5.0 Kg/m² and MS was identified in only two patients (5.7 percent) (p<0.001). Prevalence of individual criteria such as abdominal circumference, fasting glucose levels, arterial blood pressure, HDL-cholesterol and triglycerides had a reduction of 45.8 percent, 83 percent, 87.5 percent, 57.13 percent and 94 percent respectively. CONCLUSION: MS is a rather common feature in obese patients enrolled for BS and this procedure has been proved to be extremely efficient reversing the metabolic syndrome, with an expressive reduction of prevalence of each and all of the NCEP criteria.

FUNDAMENTO: El síndrome metabólico (SM) frecuentemente está vinculado al exceso de peso y mejora con la pérdida ponderal, esperándose que esta mejora sea proporcional a la intensidad de esa pérdida. OBJETIVO: Evaluar el impacto de la pérdida ponderal inducida por la cirugía bariátrica (CB) sobre la prevalencia de la SM, a medio plazo. MÉTODOS: Se estudiaron 35 pacientes sometidos a cirugía de bypass gastroyeyunal en Y de Roux, en el período de octubre de 2001 a octubre de 2005, en nuestro HU, siendo el 88,5 por ciento del sexo femenino, con un promedio de edades de 37,8±11,1 años y un IMC promedio de 45,0±6,2 Kg/m². En la primera etapa de la investigación, se obtuvieron datos demográficos y clínico antropométricos antes de la realización de la CB, incluyendo los criterios para el diagnóstico de la SM, de acuerdo con las directrices del NCEP de los Estados Unidos. En la segunda etapa, los pacientes operados se reevaluaron ambulatoriamente con relación a la prevalencia de la SM. RESULTADOS: Antes de la cirugía, fue diagnostica la SM en 27 pacientes (77,1 por ciento). En la reevaluación 34,4±15 meses después de la cirugía, se observó una disminución del IMC promedio para 28,3±5,0 Kg/m² y se detecto la SM sólo en dos pacientes (5,7 por ciento) (p<0,001). La prevalencia de los criterios cintura abdominal, glicemia, presión arterial, HDL-colesterol y triglicéridos, se redujeron respectivamente en: 45,8 por ciento, 83 por ciento, 87,5 por ciento, 57,13 por ciento y 94 por ciento. CONCLUSIÓN: La SM es común en obsesos candidatos a CB y este procedimiento se mostró extremadamente eficaz en la inducción de la regresión del síndrome, verificándose una reducción expresiva de la prevalencia de todos los criterios del NCEP.

Prevalence of true hypertensive crises and appropriateness of the medical management in patients with high blood pressure seen in a general emergency room.

BACKGROUND: High blood pressure is a common reason for patients to seek an emergency room, and many of them may possibly be wrongly diagnosed with hypertensive crisis and, consequently, be inappropriately treated. OBJECTIVE: To analyze the cases of patients seen in a general emergency room because of high blood pressure as for meeting the criteria for the diagnosis of hypertensive crisis and the appropriateness of medical management. METHODS: Of the 1012 patients consecutively seen in a private referral general emergency room in the city of São Luís, State of Maranhão, between August and November 2003, 198 (19.56%) had a main diagnosis of high blood pressure in that visit. Of these, proper information could only be obtained from the patient charts of 169 patients; 54.4% of them were females with a mean age of 53.3 +/- 15.2 years. Data regarding patients and the attendant physicians were collected, and each case was classified as an urgency, emergency or pseudohypertensive crisis; the medical management was classified as appropriate or inappropriate. We also sought to identify the factors associated with the medical management and with the use of antihypertensive medication. RESULTS: Criteria for the characterization of a hypertensive crisis were present in only 27 patients (16%), and all were classified as urgencies. Medical management was considered appropriate in 72 cases (42.6%), and was neither influenced by specialty (p=0.5) nor by the physician's experience (p=0.9). Blood pressure levels, but not the presence or absence of symptoms, were predictive of the use of antihypertensive medication (p<0.001). CONCLUSION: In the population analyzed, less than one fifth of the patients seen in an emergency room with a presumed hypertensive crisis met defined criteria for this diagnosis. Medical management was considered appropriate in less than half of the occurrences.

Prevalência de verdadeiras crises hipertensivas e adequação da conduta médica em pacientes atendidos em um pronto-socorro geral com pressão arterial elevada / Prevalence of true hypertensive crises and appropriateness of the medical management in patients with high blood pressure seen in a general emergency room

FUNDAMENTO: Pressão arterial elevada é motivo freqüente de procura por pronto-socorro, sendo possível que muitos pacientes recebam erroneamente um diagnóstico de crise hipertensiva e, conseqüentemente, um tratamento inapropriado. OBJETIVO: Analisar os casos de pacientes com pressão arterial elevada atendidos em um pronto-socorro geral, quanto ao preenchimento de critérios para o diagnóstico de crise hipertensiva e a adequação da conduta médica. MÉTODOS: Dos 1.012 pacientes atendidos consecutivamente em um pronto-socorro geral privado de referência, em São Luís, Maranhão, entre agosto e novembro de 2003, 198 (19,56 por cento) tiveram como diagnóstico principal do atendimento pressão arterial elevada. Destes, de apenas 169 pacientes foi possível obter informação adequada nos boletins de atendimento, sendo 54,4 por cento do sexo feminino, com média de idade de 53,3 ± 15,2 anos. Coletaram-se dados referentes aos pacientes e aos médicos atendentes, a fim de classificar cada caso como urgência, emergência ou pseudocrise hipertensiva, e a conduta médica como adequada ou inadequada. Procurou-se ainda identificar os fatores associados à conduta e ao uso de medicação anti-hipertensiva. RESULTADOS: Em apenas 27 pacientes (16 por cento) houve critérios para caracterização de uma crise hipertensiva, sendo todos estes classificados como urgências. A conduta médica foi considerada adequada em 72 casos (42,6 por cento), não sofrendo influência da especialidade (p = 0,5) nem da experiência do médico (p = 0,9). Níveis tensionais, e não a presença ou ausência de sintomas, foram preditivos do uso de medicação anti-hipertensiva (p < 0,001). CONCLUSÃO: Na população analisada, menos de 1/5 dos pacientes atendidos em um pronto-socorro com suposta crise hipertensiva apresentou critérios definidos para tal diagnóstico. A conduta médica foi considerada adequada em menos da metade dos atendimentos.

BACKGROUND: High blood pressure is a common reason for patients to seek an emergency room, and many of them may possibly be wrongly diagnosed with hypertensive crisis and, consequently, be inappropriately treated. OBJECTIVE: To analyze the cases of patients seen in a general emergency room because of high blood pressure as for meeting the criteria for the diagnosis of hypertensive crisis and the appropriateness of medical management. METHODS: Of the 1012 patients consecutively seen in a private referral general emergency room in the city of São Luís, State of Maranhão, between August and November 2003, 198 (19.56 percent) had a main diagnosis of high blood pressure in that visit. Of these, proper information could only be obtained from the patient charts of 169 patients; 54.4 percent of them were females with a mean age of 53.3 ± 15.2 years. Data regarding patients and the attendant physicians were collected, and each case was classified as an urgency, emergency or pseudohypertensive crisis; the medical management was classified as appropriate or inappropriate. We also sought to identify the factors associated with the medical management and with the use of antihypertensive medication. RESULTS: Criteria for the characterization of a hypertensive crisis were present in only 27 patients (16 percent), and all were classified as urgencies. Medical management was considered appropriate in 72 cases (42.6 percent), and was neither influenced by specialty (p=0.5) nor by the physician's experience (p=0.9). Blood pressure levels, but not the presence or absence of symptoms, were predictive of the use of antihypertensive medication (p<0.001). CONCLUSION: In the population analyzed, less than one fifth of the patients seen in an emergency room with a presumed hypertensive crisis met defined criteria for this diagnosis. Medical management was considered appropriate in less than half of the occurrences.

Prevalência e fatores associados à presença de disfunção erétil em portadores de hipertensão arterial / Prevalence and factors associated to the presence of erectile dysfunction in hypertensive patients

Objetivos: Determinar a prevalência de disfunção erétil(DE) em uma amostra de hipertensos ambulatoriais e pesquisar as variáveis associadas à sua ocorrência. Métodos: Foram analisados 102 pacientes do sexo masculino atendidos consecutivamente no ambulatório de cardiologiado Hospital Universitário Presidente Dutra, em São Luís, Maranhão. Aplicou-se o questionário Índice Internacional da Função Erétil–5 (IIFE-5), que contempla a função erétil masculina. DE foi definida por somatório menor ou igual a 21 pontos no IIFE-5. Os dados foram analisados utilizando-se o programa Stata 6.0, considerando-se significativo um p menor que 0,05. Resultados: A média de idade dos pacientes foi de 60,1 mais ou menos 14,3 anos, sendo 74,3 por cento em estágios 2 e 3 de hipertensão arterial sistêmica (HAS). A prevalência de DE foi de 73,5 por cento. Na análise univariada estiveram associados à presença de DE as seguintes variáveis: idade maior que 50 anos (p = 0,001), estado civil solteiro ou viúvo (p= 0,046), aposentadoria (p = 0,002), baixo nível de escolaridade (até 1º grau) (p = 0,034), baixa renda (menor que 1 salário-mínimo) (p = 0,01), lesão cardíaca (p=0,014) e estar sob tratamento farmacológico (p=0,049). Após análise multivariada, apenas as seguintes variáveis permaneceram associadas à presença de DE: aposentadoria (p=0,002; OR=8,29 e IC=2,23-30,8) e lesão cardíaca (p=0,015; OR=3,47 e IC= 1,26-9,49). Conclusão: Nesta amostra de hipertensos ambulatoriais, a prevalência de DE foi elevada e, apesar de sua associação com muitas variáveis tradicionais, talvez pelo pequeno tamanho da amostra, apenas aposentadoria e a presença de lesão cardíaca se mostraram significativamente associadas à DE, após a análise multivariada