Effects of Coexistence Hypertension and Type II Diabetes on Heart Rate Variability and Cardiorespiratory Fitness / Efeitos da Coexistência de Diabetes Tipo 2 e Hipertensão sobre a Variabilidade da Frequência Cardíaca e Capacidade Cardiorrespiratória

Abstract Background: Type 2 diabetes Mellitus (T2DM) is associated with cardiac autonomic dysfunction, which is an independent predictor of mortality in chronic diseases. However, whether the coexistence of systemic arterial hypertension (HTN) with DMT2 alters cardiac autonomic modulation remains unknown. Objective: To evaluate the influence of HTN on cardiac autonomic modulation and cardiorespiratory fitness in subjects with DMT2. Methods: 60 patients of both genders were evaluated and allocated to two groups: DMT2 patients (n = 32; 51 ± 7.5 years old) and DMT2 + HTN patients (n = 28; 51 ± 6.9 years old). RR intervals were obtained during rest in supine position. Linear and nonlinear indices of heart rate variability (HRV) were computed using Kubios HRV software. Pulmonary gas exchange was measured breath-by-breath, using a portable telemetric system during maximal incremental exercise testing on a cycle ergometer. Statistical analysis included Shapiro-Wilk test followed by Student's t Test, Pearson correlation and linear regression. Results: We found that patients in the DMT2+HTN group showed lower values of mean RR intervals (801.1 vs 871.5 ms), Shannon entropy (3 vs 3.2) and fractal dimension SD 1 (9.5 vs 14.5), when contrasted with patients in the DMT2 group. Negative correlations were found between some HRV nonlinear indices and exercise capacity indices. Conclusion: HTN negatively affects the cardiac autonomic function in diabetic patients, who are already prone to develop autonomic dysfunction. Strategies are need to improve cardiac autonomic functionality in this population.

Resumo Fundamento: A diabetes mellitus tipo 2 (DM2) está associada com disfunção autonômica cardíaca, que é um preditor independente de mortalidade em doenças crônicas. No entanto, ainda não se sabe se a coexistência de hipertensão arterial sistêmica (HAS) e DM2 altera a modulação cardíaca autonômica. Objetivos: O objetivo deste estudo foi avaliar a influência de HAS sobre a modulação da função autonômica cardíaca e capacidade cardiopulmonar em indivíduos com DM2. Métodos: 60 pacientes de ambos os sexos foram avaliados e alocados em dois grupos; pacientes DM2 (n = 32; 51 ± 7,5 anos) e pacientes DM2 + HAS (n = 28; 51 ± 6,9 anos). Intervalos RR foram obtidos durante repouso e em posição supina. Índices lineares e não lineares da variabilidade da frequência cardíaca (VFC) foram registrados utilizando-se o programa Kubios HRV software. A troca gasosa pulmonar foi medida a cada inspiração, utilizando-se um sistema telemétrico portátil durante o teste incremental máximo de exercício em cicloergômetro. A análise estatística incluiu o teste Shapiro-Wilk seguido do teste t de Student, a correlação de Pearson e a regressão linear. Resultados: Encontramos que pacientes do grupo DM2+HAS apresentaram valores mais baixos de intervalos RR (801,1 vs 871,5 ms), entropia de Shannon (3,0 vs 3,2) e DP1 da dimensão fractal em comparação aos pacientes do grupo DM2. Foram encontradas correlações negativas entre alguns índices não lineares da VFC e índices da capacidade do exercício. Conclusão: A HAS afeta negativamente a função autonômica cardíaca em pacientes diabéticos, os quais já são propensos a desenvolverem disfunção autonômica. Estratégias são necessárias para melhorar a função autonômica cardíaca nessa população.

Riesgo vascular en personas con diabetes mellitus tipo 2 y dislipidemia / Vascular risk in people with type 2 diabetes mellitus and dyslipidemia

Introducción: la dislipidemia constituye un factor de riesgo vascular frecuente en la diabetes tipo 2. Objetivo: identificar la relación entre las alteraciones lipídicas y el riesgo vascular en la diabetes tipo 2. Métodos: estudio transversal y correlacional de 111 personas con diabetes tipo 2 y dislipidemia (41 con primaria y 70 con secundaria), atendidas en el Centro de Atención al Diabético del Instituto Nacional de Endocrinología, durante 2014-2015. Se analizaron las variables: edad, sexo, tabaquismo, índice de masa corporal, circunferencia de cintura, índices cintura-cadera y cintura-talla, presión arterial sistólica y de pulso, colesteroles total, lipoproteínas de baja densidad y las lipoproteínas de alta densidad, triglicéridos, apoproteínas A y B, hemoglobina glucosilada, complejo íntima-media carotídeo y riesgo cardiovascular por tablas de la OMS y Gaziano. Para comparar variables cualitativas (porcentaje), se utilizó prueba de Fisher y para cuantitativas ( ± DE), U de Mann-Whitney. Para todos los análisis, se asumió una p< 0,05. Resultados: la disminución de lipoproteínas de alta densidad-colesterol fue la alteración de fracción lipídica que más se relacionó con alteración de variables clínicas y bioquímicas, para ambas dislipidemias. La dislipidemia primaria se asoció con mayor riesgo cardiovascular según tablas de la OMS (p= 0,015). Conclusiones: la dislipidemia primaria y la disminución de lipoproteínas de alta densidad-colesterol se relacionaron con mayor riesgo vascular(AU)

Introduction: dyslipidemia is a frequent vascular risk factor in type 2 diabetes. Objective: to identify the relation between lipid alterations and vascular risk in type 2 diabetes. Methods: cross-sectional and correlational study of 111 people with type 2 diabetes and dyslipidemia (41 of them with primary and 70 with secondary) attended at the Diabetics Care Center of the National Institute of Endocrinology during 2014-2015. The variables analyzed were: age, sex, smoking habit, body mass index, waist circumference, waist-hip and waist-height indexes, systolic and pulse blood pressure, total cholesterol, low density lipoproteins and high density lipoproteins, triglycerides, apoproteins A and B, glycosylated hemoglobin, carotid intima-media complex; and cardiovascular risk by WHO and Gaziano tables. To compare qualitative variables (percentage), Fisher's test was used, and for quantitative ( ± DE), Mann-Whitney U. For all analyzes, a p< 0.05 was assumed. Results: the decrease of high density-cholesterol´s lipoproteins was the alteration of lipid fraction that was more related to the alteration of clinical and biochemical variables, for both dyslipidemias. Primary dyslipidemia was associated with a higher cardiovascular risk according to WHO tables (p= 0.015). Conclusions: primary dyslipidemia and the decrease of high density-cholesterol´s lipoproteins were associated with a higher vascular risk(AU)

Estado nutricional y factores de riesgo vascular en pacientes ingresados en el Centro de Atención al Diabético de La Habana / Nutritional state and vascular risk factors of patients admitted to the Center of Diabetic Care in Havana

Introducción: la obesidad y la diabetes constituyen una asociación frecuente y letal, que a su vez, también se relacionan con otros factores que incrementan el riesgo cardiovascular. Objetivo: caracterizar el estado nutricional e identificar factores de riesgo vascular en personas con diabetes ingresadas en el Centro de Atención al Diabético de La Habana. Métodos: estudio descriptivo transversal. Se revisaron 1 916 historias clínicas, y las variables estudiadas fueron: tipo de diabetes, índice de masa corporal, circunferencia de la cintura, hipertensión arterial, tabaquismo, hipercolesterolemia, control glucémico y excreción urinaria de albúmina. Resultados: el 88,2 por ciento de los pacientes tenían diabetes tipo 2; de ellos, 74,5 por ciento eran sobrepeso u obesos, 62,5 por ciento tenían circunferencia de cintura incrementada, hipertensión el 67,2 por ciento, descontrol glucémico el 55,2 por ciento, hipercolesterolemia el 50,6 pr ciento, tabaquismo el 44,4 pore ciento y excreción urinaria de albúmina el 27,6 por ciento. El 11,8 por ciento tenía diabetes tipo 1, de ellos 66,4 por ciento eran normopesos; con descontrol glucémico 57,5 por ciento, con sobrepeso u obesidad 33,7 por ciento, con excreción urinaria de albúmina el 31,4 por ciento, con hipercolesterolemia el 29,9 por ciento, con tabaquismo el 28,7 por ciento, con hipertensión el 23,9 por ciento y el 21,2 por ciento tenía incrementada la circunferencia de la cintura. Conclusiones: la mayoría de los pacientes tenían diabetes tipo 2 y sobrepeso, con predominio de la obesidad abdominal. La asociación de varios factores de riesgo fue muy frecuente, independientemente del tipo de diabetes. Se deben diseñar estrategias efectivas para el tratamiento integral de la diabetes y los factores de riesgo asociados(AU)

Introduction: obesity and diabetes is a frequent and lethal association that, in turn, is related to other factors increasing the cardiovascular risks. Objective: to characterize the nutritional state and to identify vascular risk factors in diabetic persons who were admitted to the Center of Diabetic Care in Havana. Methods: cross-sectional and descriptive study that reviewed 1 916 medical histories and the studied variables were type of diabetes, body mass index, waist circumference, blood hypertension, smoking, hypercholesterolemia, glycemic control and urinary excretion of albumin. Results: in the study group, 88.2 percent of patients suffered type 2 diabetes, 74.5 percent of them was overweighed or obese; 62.5 percent had increased waist circumference; 67.2 percent were hypertensive; 55.2 percent had no glycemic control; 50.6 percent had hypercholesterolemia; 44.4 percent were smokers and 27.6 percent had urinary excretion of albumin. Type 1 diabetes was present in 11.8 percent ; 66.4 percent of the latter were normoweighed; 57.5 percent had no glycemic; 33.7 percent were overweighed or obese; 31.4 percent showed urinary excretion of albumin; 29.9 percent hypercholesterolemia; 28.7 percent were smokers and 23.9 percent hypertensive whereas 21.2 percent had increased waist circumference. Conclusions: most of patients had type 2 diabetes and overweight, with abdominal obesity. The association of several risk factors was very common, regardless of the type of diabetes. Effective strategies must be designed to treat diabetes and the associated risk factors in a comprehensive way(AU)

Cirurgia bariátrica e metabólica e complicações microvasculares do diabetes mellitus tipo 2 (DM2) / Bariatric and metabolic surgery and microvascular complications of type 2 diabetes mellitus

ResumoIntrodução:O diabetes mellitus tipo 2 (DM2) é caracterizado por uma desregulação metabólica, originando complicações microvasculares, mais especificamente a retinopatia, nefropatia e a neuropatia. A prevenção e tratamento das complicações são alvo da farmacoterapia, porém, evidências demonstram que a cirurgia bariátrica/metabólica é superior ao melhor tratamento farmacológico, pois apresenta melhor controle da glicemia, hipertensão e dislipidemias.Métodos:Por meio de pesquisa no PubMed, são discutidas as recentes publicações que evidenciam o efeito positivo das intervenções cirúrgicas sobre as complicações microvasculares, como melhora da microalbuminúria e mesmo preservação de função renal.Discussão:Existem evidências de benefício das operações bariátricas/metabólicas sobre a nefropatia diabética. Os dados sobre retinopatia são ainda ambivalentes. Na literatura, há uma diferença significativa no benefício da cirurgia em neuropatia.Conclusão:Apesar de resultados surpreendentes e positivos, para que se estabeleça definitivamente o papel da cirurgia bariátrica/metabólica nas complicações micovasculares do DM2, há a necessidade de novos estudos randomizados controlados e prospectivos.

AbstractIntroduction:Metabolic dysregulation is the defining characteristic of type 2 diabetes mellitus (T2DM) and may lead to microvascular complications, specifically retinopathy, nephropathy and neuropathy. Medical treatment and lifestyle interventions targeting risk factors for microvascular complications can yield therapeutic gains, particularly retinopathy and nephropathy. Bariatric/metabolic surgery is superior to the best medical treatment in several randomized controlled trials. Consequently, evidence of the effect of bariatric/metabolic surgery on microvascular complications is now emerging in the literature.Methods:A search of the recent published evidence base on the effects of bariatric/metabolic surgery on microvascular complications reveals further evidence that supports the efficacy of surgery in preventing the incidence and progression of albuminuria and preserving renal functional decline.Discussion:Data on retinopathy are ambivalent representing the potential in some cases for an influence of reactive hypoglycaemia over the retina but the majority of data emphasize that the metabolic control can halt the progression of the eye disease. A significant gap in the literature remains in relation to the effects of surgery on diabetic neuropathy, although some information sheds a light on the benefits secondary to the surgical metabolic control.Conclusion:Overall, although data so far is exciting, there is a pressing need for prospective randomized controlled trials examining long-term microvascular outcomes following bariatric/metabolic surgery in patients with T2DM.

Importancia médica del glucocáliz endotelial: Parte 2: su papel en enfermedades vasculares y complicaciones de la diabetes mellitus / Medical significance of endothelial glycocalyx: Part 2: Its role in vascular diseases and in diabetic complications

El glucocáliz endotelial es una capa constituida por glucosaminoglicanos, proteoglicanos y glucoproteínas que cubre al endotelio en su cara luminal. La participación del deterioro del glucocáliz endotelial parece esencial en los pasos iniciales de la fisiopatología de la aterosclerosis, de las complicaciones microangiopáticas de la diabetes mellitus y de la enfermedad venosa crónica. Los factores de riesgo de la aterosclerosis como la hipercolesterolemia, la hiperglucemia, la inflamación, el exceso de sodio y las fuerzas de tensión alteradas causan deterioro del glucocáliz. Esto provoca disfunción endotelial y permite la filtración de lipoproteínas (LDL) y de leucocitos al espacio subendotelial, iniciando la formación de la placa de ateroma. En la diabetes el glucocáliz adelgazado, principalmente por estrés oxidativo, posibilita la filtración de proteínas (albuminuria) y el trastorno endotelial de la microangiopatía. La hipertensión venosa crónica altera las fuerzas de tensión y daña el glucocáliz, lo que permite la filtración de leucocitos a las partes más profundas de la pared venosa, iniciando la inflamación y el deterioro morfológico y funcional de las venas que lleva a la enfermedad venosa crónica. El tratamiento con glucosaminoglicanos (sulodexida) logra prevenir o revertir el daño al glucocáliz endotelial y algunas de sus consecuencias; es eficaz en la enfermedad venosa crónica, especialmente con úlceras venosas. También ha sido útil en aterosclerosis obliterante de miembros inferiores y en la nefropatía diabética con albuminuria.

Endothelial glycocalyx is a layer composed by glycosaminoglycans, proteoglycans and glycoproteins attached to the vascular endothelial luminal surface. Shredding of glycocalyx appears as an essential initial step in the pathophysiology of atherosclerosis and microangiopathic complications of diabetes mellitus, as well as in chronic venous disease. Atherosclerosis risk factors, as hypercholesterolemia (LDL), hyperglycemia, inflammation, salt excess and altered shear stress can damage glycocalyx. This lead to endothelial dysfunction and allows LDL and leukocytes to filtrate to the subendothelial space initiating atheroma plaque formation. Degradation of glycocalyx in diabetes mellitus is mainly due to oxidative stress and enables protein filtration (albuminuria) and endothelial disorder of microangiopathy. Chronic venous hypertension brings to altered shears stress which results in shredded glycocalyx, this allows leukocytes to migrate into venous wall and initiate inflammation leading to morphologic and functional venous changes of the chronic venous disease. Treatment with glycosaminoglycans (sulodexide) prevents or recovers the damaged glycocalyx and several of its consequences. This drug improves chronic venous disease and promotes healing of chronic venous ulcers. It has also been useful in peripheral arterial obstructive disease and in diabetic nephropathy with albuminuria.

Efecto del sulodexide sobre la capacidad de relajación y alteraciones estructurales de la arteria aorta en ratas diabéticas por estreptozotocina / Effect of sulodexide on aortic vasodilation capacity and associated morphological changes in rats with streptozotocin-induced diabetes

La disfunción endotelial (DE) se presenta en pacientes con hipercolesterolemia, hipertensión arterial, obesidad y diabetes mellitus. Evidencias sugieren un papel de los glicosaminoglicanos en la DE. Evaluamos el efecto del sulodexide (SLD), un glicosaminoglicano utilizado en el tratamiento de la albuminuria y la enfermedad isquémica en pacientes diabéticos, sobre la relajación arterial y los cambios morfológicos en un modelo experimental de diabetes tipo 1. La diabetes se indujo a ratas Sprague Dawley administrando estreptozotocina (STZ), 60 mg/kg, i.v. Los animales fueron distribuidos en los siguientes grupos: I= control, II= diabéticas, III: control + sulodexide, IV= diabéticas + sulodexide (15 mg/kg/día s.c). A los 3 meses fueron sacrificados, las aortas extraídas para evaluar la relajación vascular inducida por acetilcolina (Ach) y nitroprusiato de sodio en anillos precontraídos con fenilefrina. Fueron evaluadas histológicamente mediante microscopía de luz y coloraciones diversas. El SLD in vitro no modificó la tensión basal de los anillos arteriales en reposo o precontraídos con fenilefrina. La diabetes disminuyó la capacidad de relajación arterial en respuesta a la Ach en un 28,8-35,1% vs control, efecto que fue prevenido por SLD. No se observó diferencia significativa en la relajación inducida por nitroprusiato sódico entre los grupos. El estudio histológico en los animales diabéticos mostró alteraciones estructurales, particularmente en la íntima y la adventicia, cambios que fueron prevenidos por el tratamiento con SLD. Nuestros resultados apoyan la potencial utilidad terapéutica del SLD en el tratamiento de la disfunción endotelial.

Endothelial dysfunction (ED) is observed in patients with hypercholesterolemia, arterial hypertension, obesity and diabetes mellitus. Recent evidences suggest the involvement of glycosaminoglycans(GSG) in ED. We evaluated the effect of sulodexide (SLD), a natural GSG used in albuminuria and ischemic diabetes treatment, on arterial relaxation and vascular morphological changes in a diabetic type I model. Diabetes was induced, in Sprague-Dawley rats by streptozotocine (STZ) administration, 60 mg, iv. Rats were divided into four groups; I: control, II: diabetics, III: control + SLD, IV: diabetics treated with SLD (15 mg/day). After three months, phenylephrine precontracted aortic rings were used to evaluate acetylcholine (ACh) and sodium nitroprusside (NPS) relaxation capacities. Light microscopy of aorta was done with several staining procedures. In vitro, SLD did not change smooth muscle tone in resting or phenylephrine precontracted aortic rings. In diabetic rats, ACh relaxation was 28.8-35.1% lower than in control rats. Diabetic rats treated with SLD showed aortic ACh relaxation similar to control rats. No significative statistical difference was found in endothelium-independent NPS relaxation, between the different groups. Light microscopy histological studies revealed important morphological alterations, particularly in intima and adventitia layers of aortic artery; those changes were dramatically reversed in SLD treated rats. Our experiments support the conclusion that SLD is a potential drug for improving endothelial dysfunction in diabetes.

prevalence of macrovascular complications and risk factors among diabetic patients in Al-Gamhouria Teaching Hospital, Aden

Diabetes mellitus [DM] is a major public health problem in Yemen. The aim of this descriptive study is to determine the prevalence and risk factors of macrovascular complications among diabetic patients attending the medical ward at Al-Gamhouria Teaching Hospital during the period January 2005 to June 2006. Patients completed an interviewer-administered questionnaire, carried out by treating physicians, and underwent a complete medical assessment including measurement of height, weight, blood pressure and examination for evidence of macrovascular complications. A standard echocardiography was recorded and blood samples were taken to document fasting blood sugar, glycosylated hemoglobin [HbAic] and lipid profile. 198 of diabetic patients were studied, 108 [54.4%] of them were males and 90 [45.4%] were females, with a mean age of 57.63 years [SD +/- 12.86]. 65.6% of DM patients had evidence of macrovascular complications, 39.9% of patients had cardiovascular disease, 26.3% had cerebrovascular disease and 5.5% had peripheral vascular disease. About 57.7% of the study patients had hypertension. The study findings revealed that macrovascular complications in diabetic patients were more common among males, increased with age, with hypertension, and its prevalence increased steadily with duration of diabetes mellitus. Our data demonstrated that there is a significant association between hypertension and the presence of macrovascular complications among diabetic patients. However, a lack of correlation between macrovascular disease and glycemic control among diabetic patients was observed

Complicações macrovasculares do diabetes melito: peculiaridades clínicas, de diagnóstico e manejo / Macrovascular diabetic complications: clinical characteristics, diagnosis and management

O diabetes melito (DM) é um fator de risco independente para doença arterial coronariana, acidente vascular cerebral, doença vascular periférica e insuficiência cardíaca, que são as principais causas de morte nesses pacientes. Além disso, pacientes com DM e doença cardiovascular têm pior prognóstico, por apresentarem menor sobrevida, maior risco de recorrência da doença e pior resposta aos tratamentos propostos. Os avanços diagnósticos e terapêuticos das últimas décadas já mostram uma redução do risco de eventos cardiovasculares nesses pacientes, mas o risco absoluto desses é ainda duas vezes maior em relação ao dos pacientes não diabéticos. Portanto, é prioritária a adoção de um manejo intensivo, com controle rígido dos fatores de risco cardiovasculares. Esta revisão trata das principais características clínicas e apresenta uma abordagem prática do rastreamento, diagnóstico e tratamento da doença macrovascular nos pacientes com DM.

Diabetes mellitus (DM) is an independent risk factor for coronary heart disease, stroke, peripheral arterial disease and heart failure, which are the main causes of death in these patients. Moreover, patients with DM and cardiovascular disease have a worse prognosis than nondiabetics, present lower short-term survival, higher risk of recurrence of the disease and a worse response to the treatments proposed. In the last decades, diagnostic and therapeutic progress had already shown benefits concerning cardiovascular risk reduction in these patients, but their absolute mortality risk is still twice that of non-diabetic patients. Because of this, the adoption of intensive treatment, with strict cardiovascular risk factor control, is a priority. The present study presents the main clinical characteristics and also the practical approach for screening, diagnosis and treatment of patients with diabetic macrovascular disease.

Risk factors for micro and macrovascular disease in black and white patients with type 2 Diabetes mellitus / Comparação de fatores de risco para complicações micro e macrovasculares em pacientes com Diabetes mellitus tipo 2 negros e brancos

BACKGROUND: The prevalence of chronic complications in type 2 diabetes mellitus (DM) is higher in black patients. The reason for this finding is still unknown. The objective of this study was to analyze the micro and macrovascular risk factor profile of type 2 DM patients without advanced diabetic nephropathy according to ethnicity. METHODS: A cross-sectional multicentric regional study was conducted evaluating 780 patients. All patients were submitted to clinical and laboratory evaluation. Ethnicity was self-reported as white (n = 585) or black (n = 195). RESULTS: Black patients had lower triglycerides [115 (35-892) vs. 152 (34-1236) mg/dl; P <0.001] and higher HDL-cholesterol levels than whites (48.3 ± 13.5 vs. 44.8 ± 12.1 mg/dl; P = 0.002).White and black patients did not differ regarding fasting plasma glucose, A1c test, total and LDL cholesterol, blood pressure levels, insulin and HOMA-IR. There were no differences between groups regarding medication in use (statin: 18.5 vs. 19.3 percent, P = 1.000; fibrates: 1.5 vs. 0.7 percent, P = 0.680; angiotensin converting enzyme inhibitors: 39.5 vs. 43.8 percent, P = 0.375; acetylsalicylic acid: 29.9 vs. 27.7 percent, P = 0.673). CONCLUSIONS: There were no differences in the prevalence of the classic micro and macrovascular risk factors between ethnic groups. The study of non-conventional risk factors and genetic factors is essential to understand determinants of the worst outcomes presented by the African-Brazilian population.

OBJETIVO: A prevalência das complicações crônicas do Diabetes mellitus (DM) é maior nos negros. A razão para esse achado é desconhecida. O objetivo desse estudo é analisar os fatores de risco para doença micro e macrovascular em pacientes com DM tipo 2 de acordo com a etnia. MÉTODOS: Foi realizado estudo transversal avaliando 780 pacientes. Todos pacientes realizaram avaliação clinico/ laboratorial. A etnia foi autoreferida em branca (n = 585) ou negra (n = 195). RESULTADOS: Os pacientes negros apresentaram níveis menores de triglicerídeos [115 (35-892) vs. 152 (34-1236) mg/dl; P <0.001] e maiores de HDL colesterol que os brancos (48.3 ± 13.5 vs. 44.8 ± 12.1 mg/dl; P = 0.002). Não houve diferença entre os grupos quanto à glicemia de jejum, teste A1c, LDL e colesterol total, níveis pressóricos, insulina e Homa-ir. Não houve diferença no uso de medicações (estatinas: 18.5 vs. 19.3 por cento, P = 1.000; fibratos: 1.5 vs. 0.7 por cento, P = 0.680; inibidores da enzima conversora da angiotensina: 39.5 vs. 43.8 por cento, P = 0.375; acido acetilsaliscílico: 29.9 vs. 27.7 por cento, P = 0.673). CONCLUSÃO: Não houve diferença na prevalência dos fatores de risco convencionais para doença micro e macrovascular entre os grupos étnicos. O estudo de fatores não-convencionais e genéticos é essencial para a elucidação dos determinantes dos piores desfechos apresentados pela população diabética afrobrasileira.

O papel dos produtos finais da glicação avançada (AGEs) no desencadeamento das complicações vasculares do diabetes: [revisão] / The role of advanced glycation end-products (AGEs) in the development of vascular diabetic complications: [review]

Os produtos finais da glicação avançada (AGEs [do inglês, Advanced Glycation End-products]) constituem uma classe de moléculas heterogêneas formadas a partir de reações aminocarbonilo de natureza não-enzimática, que ocorrem aceleradamente no estado hiperglicêmico do diabetes. Considerados importantes mediadores patogênicos das complicações diabéticas, os AGEs são capazes de modificar, irreversivelmente, as propriedades químicas e funcionais das mais diversas estruturas biológicas. Na presente revisão, são apresentados os dados recentes da literatura que descrevem as vias de formação de AGEs, seu metabolismo, os principais mecanismos de ação dessas substâncias no desencadeamento dos processos patológicos, bem como os métodos de determinação de AGEs em amostras biológicas. Este artigo aponta, ainda, novas perspectivas de terapias anti-AGEs, a exemplo de estudos envolvendo a ação de compostos naturais dos alimentos, que podem oferecer potencial terapêutico para os portadores de diabetes ou de outras patologias associadas ao acúmulo degenerativo de AGEs.

The advanced glycation end-products (AGEs) constitute a class of heterogeneous molecules formed by amino-carbonyl reactions of a non-enzymatic nature, which occur at an accelerated rate in the hyperglycemic state of diabetes. Considered important pathogenic mediators of diabetic complications, AGEs are capable of irreversibly modifying the chemical properties and functions of diverse biological structures. In this review, recent data from literature is presented describing the pathways of AGEs formation, their metabolism, the main mechanisms of action of these substances in the triggering of pathological processes associated with diabetes, as well as methods of AGEs determination in biological samples. This text also points to new perspectives in anti-AGE therapies, an example of which is the studies involved with the action of natural compounds of food, which can represent a potential coadjuvant therapy for people with diabetes or other pathologies associated with the degenerative accumulation of AGEs.

E-selectina soluble en una población infanto-juvenil con diabetes tipo 1 / Soluble E- selectin in children and adolescents with type 1 diabetes

El estado de hiperglucemia crónica en los pacientes diabéticos produce una agresión al endotelio vascular, conduciendo al desarrollo prematuro de ateroesclerosis. El objetivo de este trabajo fue determinar niveles de E-selectina soluble (sE-S) en una población infanto-juvenil con diabetes tipo1 (DT1) y su relación con el control glucémico y el perfil lipídico. Se estudiaron 30 pacientes con DT1 (16 mujeres y 14 varones), de edades comprendidas entre 6 y 15 años, comparados con 20 sujetos controles. Se determinaron: sE-S, glucemia en ayunas, hemoglobina glicosilada (HbA1c), colesterol total (CT), HDL-C, LDL-C, no HDL-C y triglicéridos (TG). Los niveles de sE-S fueron 66% más altos en los diabéticos que en los sujetos controles (p = 0.0001). Los pacientes fueron agrupados en: diabéticos con buen control glucémico (DBCG, HbA1c < 8%) y diabéticos con pobre control glucémico (DPCG, HbA1c > 8%). La concentración de sE-S en DPCG y en DBCG fue: 111.3 ± 40.5 vs. 68.0 ± 11.3 ng/ml, respectivamente p = 0.02. En los diabéticos la incidencia de valores no deseables en el perfil lipídico fue: CT: 50%; HDL-C 14%; LDL-C 52%, no HDL-C 26.7% y TG 14%. La sE-S se correlacionó mejor con HbA1c (r = 0.53, p = 0.0001) que con la glucemia en ayunas (r = 0.36, p = 0.008) y CT (r = 0.36, p = 0.009). De los resultados obtenidos se sugiere que la sE-S es un marcador temprano de disfunción endotelial y de probable riesgo de aterosclerosis en pacientes infanto-juveniles con DT1.

The chronic hyperglycemic state in diabetic patients produces an aggression to the vascular endothelium leading to a premature development of atherosclerosis. The objective of this paper was to determine the soluble E-selectin (sE-S) levels in children with type 1 diabetes (DT1) and its relationship with glycemic control and lipid profile. Thirty patients with DT1, (16 girls and 14 boys), age between 6 and 15 years were studied, whose data were compared with 20 control subjects. In both groups sE-S was determined as well as fasting glycemia, glycosylated hemoglobin (HbA1c), total cholesterol (TC), HDL-C, LDL-C, non-HDL-C and triglycerides (TG). sE-S values were 66% higher in diabetics than in control subjects (p = 0.001). Patients were grouped in: good glycemic control diabetics (GGCD, HbA1c < 8%) and poor glycemic control diabetics (PGCD, HbA1c > 8%). sE-S concentratios were in PGCD an GGCD respectively. 111.3 ± 40.5 vs 68.0 ± 11.3 ng/ml, p = 0.02. In the diabetic group, the incidence of non desirable values in the lipid profile parameters were: TC 50%; HDL-C 14%; LDL-C 52%, non-HDL-C 26.7% and TG 14%. sE-S values were better correlated with HbA1c (r = 0.53, p = 0.0001) than fasting glycemia (r = 0.36, p = 0.008), and CT (r = 0.36, p = 0.009). These results suggest that sE-S is an early marker of endothelial dysfunction and a probable risk marker of atherosclerosis in children with DT1.

Evolução para hipertensão arterial em pacientes com diabetes tipo 1 / Type 1 diabetic patients evolution to hypertension

OBJETIVO: Determinar a evolução para hipertensão arterial (HA) e pré-hipertensão em pacientes diabéticos tipo 1 e os fatores preditores dos níveis pressóricos finais. MÉTODOS: Estudo observacional contendo 127 diabéticos tipo 1 avaliados clínica e laboratorialmente e seguidos por 5 (2,4-9,2) anos. RESULTADOS: Dos pacientes inicialmente normotensos, 21,7 por cento desenvolve-ram pré-hipertensão, 4,7 por cento HA e 73,6 por cento permaneceram normotensos. Dos pré-hipertensos, 35 por cento normalizaram níveis pressóricos, 50 por cento permanece-ram pré-hipertensos e 15 por cento desenvolveram HA. O risco relativo de desenvolver HA foi de 3,2 (0,8-12,3) no grupo pré-hipertenso comparado ao grupo normotenso. As prevalências de pré-hipertensão e hipertensão aumentaram de 15,7 por cento para 26 por cento e de 0,8 por cento para 7 por cento, respectivamente, durante o seguimento. Níveis iniciais de creatinina sérica foram preditores dos níveis finais de pressão arterial diastólica e sistólica. CONCLUSÃO: Destaca-se a necessidade de estabelecer vigilância quanto aos níveis pressóricos e de creatinina sérica, mesmo quando estes ainda se encontram dentro da faixa de normalidade no intuito de minimizar os efeitos deletérios da HA no desenvolvimento de nefropatia e doenças cardiovasculares.

PURPOSE: Check the evolution of type 1(T1) diabetic patients to hypertension and prehypertension and baseline factors related to final blood pressure levels (BP). METHODS: Observational study involving 127 T1 diabetic patients submitted to clinical and laboratorial evaluation and followed by for 5 (2.4-9.2) years. RESULTS: From the initially normotensive patients, 21.7 percent developed prehypertension, 4.7 percent developed hypertension and 73.6 percent remained with normal BP. From the prehypertensive patients, 35 percent returned to normal BP, 50 percent remained prehypertensive and 15 percent developed hypertension. The relative risk for hypertension development was 3.2 (0.8-12.3) in the prehypertensive compared to the normotensive group. The prevalence of prehypertension and hypertension increased from 15.7 percent to 26 percent and 0.8 percent to 7 percent respectively. Levels of serum creatinine predicted final levels of systolic and diastolic BP. CONCLUSION: It is emphasized the importance of renal function and BP evaluation even when they are in normal range to minimize the deleterious effects of hypertension in the development of nephropathy and cardiovascular disease.

Dislipidemias no diabetes melito tipo 1: abordagem atual / Dyslipidemias in type 1 diabetes: a current approach

Com a intensificação do controle glicêmico no tratamento do diabetes melito tipo 1 (DM1), houve uma mudança progressiva das causas de mortalidade com destaque para a DCV. A identificação de fatores de risco, como a dislipidemia, tornou-se de grande importância para minimizar o risco de complicações crônicas micro e macrovasculares. As diretrizes para prevenção de doença coronariana em diabetes, geralmente, fazem referência ao diabetes melito tipo 2 (DM2), com pouca recomendação específica para o DM1. Definir alvos terapêuticos ou indicação de intervenção farmacológica é mais controverso nesse tipo de diabetes, em virtude da faixa etária desses pacientes. O presente estudo busca destacar a importância de estabelecer o diagnósti-co da dislipidemia nesse grupo de pacientes e instituir terapêutica adequa- da e precoce, objetivando alcançar as metas estabelecidas para reduzir o perfil lipídico aterogênico desses pacientes.

With the intensive glycemic control in the therapy of type 1 diabetes mellitus (T1DM) patients, cardiovascular disease has been the main cause of mortality. Identification of risk factors, such as dyslipidemia is considered of great importance in terms of avoiding chronic micro and macro vascular complications. The statements for prevention of coronary artery disease in diabetes are generally are related do type 2 diabetes mellitus and little attention is paid to T1DM. Defining therapeutical targets and indications for treatment are more controversial in these patients due to their young ages. The present study aims to emphasize the importance of establishing the diagnosis of dyslipidemia in this group of patients as well as indicate the appropriate and early treatment, in order to reach the targets of treatment and reduce the atherogenic lipid profile.

Transplante de pâncreas e ilhotas em portadores de diabetes melito: [revisão] / Pancreas and islet transplantation in patients with diabetes mellitus: [review]

O transplante simultâneo de pâncreas/rim tem indicações específicas, riscos e benefícios. O procedimento, cada vez mais realizado, traz vantagens se comparado ao paciente em diálise, em relação à qualidade de vida, anos de vida ganhos e evolução das complicações crônicas. Se o paciente tiver a opção de realizar o transplante de rim com doador vivo, que apresenta sobrevida semelhante do enxerto e do paciente aos dez anos, o procedimento deverá ser considerado. O transplante de pâncreas após rim, quando efetivo, pode melhorar a evolução das complicações cardiovasculares, mas em contrapartida provoca maior mortalidade nos primeiros meses após a cirurgia. O transplante isolado de pâncreas também ocasiona a maior mortalidade pós-operatória, resultado da complexidade do procedimento e da imunossupressão. O transplante de ilhotas tem sua indicação para um seleto grupo de diabéticos com instabilidade glicêmica.

Pancreas and kidney transplants have specific indications, benefits and risks. The procedure has become more common and more often as long-term success has improved and risks have decreased. Compared with a patient being on dialysis, simultaneous pancreas-kidney transplant offers a distinct advantage when it comes to mortality, quality of life and diabetic complications. Since there can be a living-donor kidney transplant,, a possibly similar patient and graft survival by 10 years follow-up, this procedure should be considered. Pancreas after kidney transplants, when successful, can improve microvascular complications compared with kidney transplant alone, but immediate mortality may be higher. Solitary pancreas transplantation can improve the quality of life in selected patients, but it may also increase the immediate risk of mortality due to the complexity of the surgery and the risks of immunosupression. The results of Islet transplantation differ from the higher metabolic performance achieved by whole pancreas allotransplantation and its applicability is limited to selected adult diabetic patients.

Doença cardiovascular no diabetes melito tipo 1: [revisão] / Cardiovascular disease in type 1 diabetes mellitus: [review]

O risco de doença arterial coronariana (DAC) nos pacientes com diabetes melito tipo 1 (DM1) é conhecido desde o final dos anos 1970, sendo atualmente a principal causa de mortalidade na população adulta com diabetes tipo 1 de longa duração. A patogênese do processo aterosclerótico nesta doença ainda é obscura, acreditando-se que a hiperglicemia desenvolva aí um papel importante, entretanto vários estudos epidemiológicos mostraram que a associação entre doença coronariana e glicemia, em pacientes com DM1 seja fraca. Dados recentes do estudo DCCT/EDIC mostram que o grupo que recebeu tratamento insulínico intensificado durante o DCCT desenvolveu graus menores de aterosclerose, relacionado aos valores reduzidos de HbA1c durante a fase ativa do estudo, com melhor proteção nos pacientes mais jovens e com menor duração da doença. Há também evidências de que os benefícios são maiores nos pacientes sem nefropatia quando comparados aos com doença renal. Outros fatores de risco importante para o desenvolvimento de DAC em pacientes com DM1 são os mesmos descritos para DM2, incluindo os componentes da síndrome metabólica e marcadores de resistência insulínica. Sugere-se que pacientes com DM1 devam ter o melhor controle glicêmico possível, desde o início da sua doença acrescido de vigilância e tratamento rígido dos fatores de riscos clássicos para DAC, principalmente naqueles com história familiar de DM2.

The association between type 1 diabetes and coronary heart disease has become very clear since the late 1970. It has been demonstrated that there is an important increased risk in morbidity and mortality caused by coronary artery disease in young adults with type 1 diabetes compared with the non diabetic population. The underlying pathogeneses is still poorly understood. While the role of glycemic control in the development of microvascular disease complication is well established its role in CVD in patients with DM1 remains unclear with epidemiologic studies reporting conflicting data. Recent findings from the DCCT/EDIC showed that prior intensive diabetes treatment during the DCCT was associated with less atherosclerosis, largely because of reduced level of HbA1c during the DCCT. The improvement of glycemic control itself appeared to be particularly effective in younger patients with shorter duration of the disease. Other analyses suggested the glycemia may have a stronger effect on CAD in patients without than in those with albuminúria. Other major determinants of coronary artery disease are the components of metabolic syndrome and the surrogate measure of insulin resistence: eGDR. It is proposed that patients with DM1 should have aggressive medical therapy, risk factor modification and careful monitoring not only of his blood sugar but also of the other processes involved in the atherosclerotic process, mostly the ones with family history of type 2 diabetes.

Endothelial Dysfunction and Microvascular Complications in Type 1 Diabetes Mellitus

We examined whether alterations in vascular endothelial function and early structural changes in atherosclerosis are associated with microvascular complications in patients with type 1 diabetes mellitus (DM). Flow-mediated dilation (FMD) of the brachial artery and carotid intima-media thickness (IMT) measurement were performed in 70 young adults (aged 19 to 35 yr), 48 with type 1 DM, and 22 normal controls. Patients with diabetes had a lower peak FMD response (7.8+/-3.9 vs. 11.1 +/-1.9%, p<0.001) and increased IMT (0.51+/-0.10 vs. 0.42+/-0.07 mm, p<0.001) compared with controls. Twenty (41.7%) of the patients had microvascular complications including neuropathy, nephropathy, or retinopathy. In these complicated diabetic patients, we found a lower FMD response (6.1+/-2.5 vs. 9.9+/-3.5%, p=0.001) compared with diabetics without microvascular complications. The presence of microvascular complications was also associated with older age and longer duration of the disease. However, no differences were observed in IMT, body size, blood pressure, HbA1c, C-reactive protein, low-density lipoprotein or high-density lipoprotein cholesterol levels between complicated and non-complicated patients. Endothelial dysfunction and early structural atherosclerotic changes are common manifestations in type 1 DM, and endothelial dysfunction is thought to be an early event in the atherosclerotic process and important in the pathogenesis of microvascular complications.

Pathobiological role of advanced glycation endproducts via mitogen-activated protein kinase dependent pathway in the diabetic vasculopathy

Advanced glycation endproducts (AGEs) have been reported to play a role in neointimal formation and increase the rate of in-stent restenosis (ISR) in the diabetic coronary artery disease patients treated with stents, but the potential pathogenic mechanisms of AGEs in vascular smooth muscle cell proliferation remain unclear. We sought to determine the AGEs related pathobiological mechanism of diabetic vasculopathy. Rat aortic smooth muscle cell (RAoSMC) culture was done with different concentrations of AGEs and proliferation was assessed. Immunohistochemistry for receptor of AGEs (RAGE) was performed with human carotid atheroma. Western blotting was performed to assess the activation of MAP kinase system in the cultured RAoSMC. AGEs increased RAoSMC proliferation and were associated with increased phosphorylation of ERK and p38 kinase by time and dose dependent manner. The MAP kinase activity was decreased by RNA interference for RAGE. AGEs stimulation increased reactive oxygen species (ROS) generation in cultured RAoSMC. From this study it is concluded that AGEs played a key role in RAoSMC proliferation via MAP kinase dependent pathways. Activation of vascular smooth muscle cell (VSMC) proliferation by MAP kinase system and increased formation of ROS may be the possible mechanisms of AGEs induced diabetic vasculopathy.

A microcirculação no diabetes: implicações nas complicações crônicas e tratamento da doença / Microcirculation in diabetes: implications for chronic complications and treatment of the disease

A microangiopatia diabética ainda é responsável por importante taxa de morbidade e mortalidade relacionada à doença. O dano endotelial parece ser o fator desencadeante na patogênese das complicações microvasculares. O diabetes mellitus e outras doenças metabólicas estão associados à disfunção endotelial, que é o marcador mais precoce conhecido da aterosclerose. Alterações da reatividade microvascular estão presentes tanto em portadores de diabetes mellitus quanto em indivíduos com fatores de risco para essa doença. A avaliação das funções endotelial e microvascular é possível através de diferentes métodos invasivos ou não. O controle adequado do diabetes mellitus é capaz de retardar ou talvez mesmo prevenir a doença microvascular. A disfunção microvascular, quando expressa somente por alterações da reatividade microvascular, pode ser melhorada com a correção de fatores de risco ou uso de drogas.

Diabetic microangiopathy is responsible for an important rate of morbidity and mortality related to the disease. Endothelial damage seems to be the triggering factor in the pathogenesis of microvascular complications. Diabetes mellitus and other metabolic diseases are associated to endothelial dysfunction, the most precocious known marker of atherosclerosis. Changes on microvascular reactivity are present in patients with diabetes mellitus, as well as in individuals with risk factors for this disease. Evaluation of endothelial and microvascular functions is possible using different invasive or preferentially non-invasive methods. Adequate control of diabetes mellitus might postpone or perhaps even prevent the microvascular disease. Microvascular dysfunction, when seen only by changes on microvascular reactivity, could be ameliorated with correction of risk factors or drug treatment.

Postprandial glycemia and cardiovascular disease in diabetes mellitus

This article reviews the role of fasting and postprandial glycemia to the overall glycemic control of patients with type 2 diabetes and glucose intolerance, as well as their causal relationship upon micro and macrovascular complications. Recent studies have suggested that a third component of the glucose triad, the postprandial glucose excursions, might have a role in the overall glycemic load and might also reflect glycemic control. Epidemiological and intervention studies are presented in the article, supporting the conclusion that postprandial hyperglycemia in impaired glucose tolerance and diabetic subjects is a more powerful marker of cardiovascular disease risk than fasting hyperglycemia, then the treatment directed at specifically lowering postprandial glucose is crucial, as underlined by the American Diabetes Association.

O presente artigo revisa o papel da glicemia de jejum e pós-prandial em relação ao controle glicêmico de pacientes com diabetes do tipo 2 e com intolerância à glicose, assim como sua relação causal sobre as complicações micro e macrovasculares. Estudos recentes têm sugerido que um terceiro componente na tríade glicêmica, as excursões glicêmicas pós-prandiais, podem ter influência sobre a carga glicêmica total, e podem também refletir sobre o controle glicêmico. Estudos epidemiológicos e de intervenção são apresentados neste artigo, suportando a conclusão de que a hiperglicemia pós-prandial na intolerância à glicose e em pacientes com diabetes é um marcador mais potente de risco cardiovascular do que a hiperglicemia de jejum, portanto o tratamento dirigido especificamente para reduzir a glicemia pós-prandial é crucial, conforme sugerido pela American Diabetes Association.