Diabetes subdiagnosticado e necrose miocárdica: preditores de hiperglicemia no infarto do miocárdio

FUNDAMENTO: Hiperglicemia na fase aguda do infarto do miocárdio é importante fator prognóstico. Entretanto, sua fisiopatologia não está completamente elucidada. OBJETIVO: Analisar simultaneamente correlação entre hiperglicemia e marcadores bioquímicos relacionados ao estresse,metabolismo glicídico e lipídico, coagulação, inflamação e necrose miocárdica. MÉTODOS: Oitenta pacientes com infarto agudo do miocárdio foram incluídos prospectivamente. Os parâmetros analisados foram: glicose, hormônios do estresse (cortisol e norepinefrina), fatores do metabolismo glicídico [hemoglobina glicada (HbA1c), insulina], lipoproteínas (colesterol total, LDL, HDL, LDL eletronegativa minimamente modificada e adiponectina), glicerídeos (triglicérides, VLDL e ácido graxo), fatores da coagulação (fator VII, fibrinogênio,inibidor do ativador do plasminogênio-1), inflamação (proteína C reativa ultrassensível) e necrose miocárdica (CK-MB e troponina). Variáveis contínuas foram convertidas em graus de pertinência por intermédio de lógica fuzzy. RESULTADOS: Houve correlação significativa entre hiperglicemia e metabolismo glicídico (p < 0,001), lipoproteínas (p = 0,03) e fatores de necrose (p = 0,03). Na análise multivariada, somente metabolismo glicídico (OR = 4,3; IC = 2,1-68,9 e p < 0,001) e necrose miocárdica (OR = 22,5; IC = 2-253 e p = 0,012) mantiveram correlação independente e significativa.Para análise da influência da história de diabetes mellitus , modelo de regressão, incluindo somente pacientes sem diabetes mellitus foi desenvolvido, e os resultados não alteraram. Finalmente, no modelo ajustado para idade, sexo e variáveis clínicas(história de diabetes mellitus, hipertensão arterial e dislipidemia), três variáveis mantiveram associação significativa e independente com hiperglicemia: metabolismo glicídico (OR = 24,1; IC = 4,8-122,1 e p < 0,001) necrose miocárdica (OR = 21,9; IC = 1,3-360,9 e p = 0,03) e história de DM (OR = 27, IC = 3,7-195,7 e p = 0,001). CONCLUSÃO: Marcadores do metabolismo glicídico e necrose miocárdica foram os melhores preditores de hiperglicemia em pacientes com infarto agudo do miocárdio.

Micronutrientes antioxidantes e risco cardiovascular em pacientes com diabetes: uma revisão sistemática

FUNDAMENTO: Associações inversas entre a ingestão de micronutrientes e desfechos cardiovasculares foram demonstradas previamente na população geral. OBJETIVO: Revisar sistematicamente o papel de micronutrientes no desenvolvimento/presença de desfechos cardiovasculares em pacientes com diabetes. MÉTODOS: Foi realizada uma busca nas bases de dados Medline, Embase e Scopus (Janeiro/1949-Março/2012) por estudos observacionais que avaliaram micronutrientes antioxidantes e desfechos cardiovasculares em pacientes com diabetes e, em seguida, os dados foram selecionados e extraídos (dois revisores independentes). RESULTADOS: Dos 15658 estudos identificados, cinco foram incluídos, sendo três de caso-controle e dois de coorte, com um acompanhamento de 7-15 anos. Uma metanálise não foi realizada devido aos diferentes micronutrientes antioxidantes (tipos e métodos de medição) e os desfechos avaliados. Os micronutrientes avaliados foram: vitamina C (dieta e/ou suplementação), cromo e selênio em amostras de unha, e α-tocoferol e zinco no soro. A ingestão de > 300 mg de vitamina C a partir de uplementos esteve associada a um risco aumentado de doença cardiovascular, doença arterial coronariana (DAC) e acidente vascular cerebral (RR 1,69-2,37). Altos níveis de α-tocoferol no soro foram associados a um risco 30% inferior de DAC em outro estudo (RR 0,71, IC 95% 0,53-0,94). Entre os minerais (zinco, selênio e cromo), foi observada uma associação inversa entre o zinco e a DAC: níveis inferiores a 14,1 μmol/L foram associados a um risco aumentado para DAC (RR 1,70, IC 95% 1,21-2,38). CONCLUSÃO: A informação disponível sobre essa questão é escassa. Estudos prospectivos adicionais são necessários para elucidar o papel desses nutrientes no risco cardiovascular de pacientes com diabetes.

Métodos não-lineares para avaliar mudanças na variabilidade da frequência cardíaca em pacientes com diabetes tipo 2

FUNDAMENTO: A variabilidade da frequência cardíaca (VFC) é um importante indicador da modulação autonômica da função cardiovascular. A diabetes pode alterar a modulação autonômica danificando as entradas aferentes, dessa forma aumentando o risco de doenças cardiovasculares. Foram aplicados métodos analíticos não lineares para identificar os parâmetros associados com VFC indicativos de alterações na modulação autonômica da função cardíaca em pacientes diabéticos. OBJETIVO: Analisamos as diferenças nos padrões da VFC entre pacientes diabéticos e controles saudáveis pareados por idade, utilizando métodos não-lineares. MÉTODOS: Plot de Poincaré Lagged, autocorrelação e análise de flutuação destendenciada foram aplicados para analisar a VFC em registros de eletrocardiograma (ECG). RESULTADOS: A análise do gráfico de Poincaré lagged revelou alterações significativas em alguns parâmetros, sugestivas de diminuição da modulação parassimpática. O expoente de flutuação destendencionada derivado de um ajuste em longo prazo foi maior que o expoente em curto prazo na população diabética, o que também foi consistente com a diminuição do input parassimpático. A função de autocorrelação do desvio dos intervalos inter-batimento exibiu um padrão altamente correlacionado no grupo de diabéticos em comparação com o grupo controle. CONCLUSÃO: O padrão de VFC difere significativamente entre pacientes diabéticos e indivíduos saudáveis. Os três métodos estatísticos utilizados no estudo podem ser úteis para detectar o início e a extensão da neuropatia autonômica em pacientes diabéticos.

Functional Vascular Study in Hypertensive Subjects with Type 2 Diabetes Using Losartan or Amlodipine

Background: Antihypertensive drugs are used to control blood pressure (BP) and reduce macro- and microvascular complications in hypertensive patients with diabetes. Objectives: The present study aimed to compare the functional vascular changes in hypertensive patients with type 2 diabetes mellitus after 6 weeks of treatment with amlodipine or losartan. Methods: Patients with a previous diagnosis of hypertension and type 2 diabetes mellitus were randomly divided into 2 groups and evaluated after 6 weeks of treatment with amlodipine (5 mg/day) or losartan (100 mg/day). Patient evaluation included BP measurement, ambulatory BP monitoring, and assessment of vascular parameters using applanation tonometry, pulse wave velocity (PWV), and flow-mediated dilation (FMD) of the brachial artery. Results: A total of 42 patients were evaluated (21 in each group), with a predominance of women (71%) in both groups. The mean age of the patients in both groups was similar (amlodipine group: 54.9 ± 4.5 years; losartan group: 54.0 ± 6.9 years), with no significant difference in the mean BP [amlodipine group: 145 ± 14 mmHg (systolic) and 84 ± 8 mmHg (diastolic); losartan group: 153 ± 19 mmHg (systolic) and 90 ± 9 mmHg (diastolic)]. The augmentation index (30% ± 9% and 36% ± 8%, p = 0.025) and augmentation pressure (16 ± 6 mmHg and 20 ± 8 mmHg, p = 0.045) were lower in the amlodipine group when compared with the losartan group. PWV and FMD were similar in both groups. Conclusions: Hypertensive patients with type 2 diabetes mellitus treated with amlodipine exhibited an improved pattern of pulse wave reflection in comparison with those treated with losartan. However, the use of losartan may be associated with independent vascular reactivity to the pressor effect.

Relevance of Target-Organ Lesions as Predictors of Mortality in Patients with Diabetes Mellitus

Background: Patients with diabetes are in extract higher risk for fatal cardiovascular events. Objective: To evaluate major predictors of mortality in subjects with type 2 diabetes. Methods: A cohort of 323 individuals with type 2 diabetes from several regions of Brazil was followed for a long period. Baseline electrocardiograms, clinical and laboratory data obtained were used to determine hazard ratios (HR) and confidence interval (CI) related to cardiovascular and total mortality. Results: After 9.2 years of follow-up (median), 33 subjects died (17 from cardiovascular causes). Cardiovascular mortality was associated with male gender; smoking; prior myocardial infarction; long QTc interval; left ventricular hypertrophy; and eGFR <60 mL/min. These factors, in addition to obesity, were predictors of total mortality. Cardiovascular mortality was adjusted for age and gender, but remained associated with: smoking (HR = 3.8; 95% CI 1.3-11.8; p = 0.019); prior myocardial infarction (HR = 8.5; 95% CI 1.8-39.9; p = 0.007); eGFR < 60 mL/min (HR = 9.5; 95% CI 2.7-33.7; p = 0.001); long QTc interval (HR = 5.1; 95% CI 1.7-15.2; p = 0.004); and left ventricular hypertrophy (HR = 3.5; 95% CI 1.3-9.7; p = 0.002). Total mortality was associated with obesity (HR = 2.3; 95% CI 1.1-5.1; p = 0.030); smoking (HR = 2.5; 95% CI 1.0-6.1; p = 0.046); prior myocardial infarction (HR = 3.1; 95% CI 1.4-6.1; p = 0.005), and long QTc interval (HR = 3.1; 95% CI 1.4-6.1; p = 0.017). Conclusions: Biomarkers of simple measurement, particularly those related to target-organ lesions, were predictors of mortality in subjects with type 2 diabetes.

Diabetes Mellitus and Glucose as Predictors of Mortality in Primary Coronary Percutaneous Intervention

Background: Diabetes mellitus and admission blood glucose are important risk factors for mortality in ST segment elevation myocardial infarction patients, but their relative and individual role remains on debate. Objective: To analyze the influence of diabetes mellitus and admission blood glucose on the mortality of ST segment elevation myocardial infarction patients submitted to primary coronary percutaneous intervention. Methods: Prospective cohort study including every ST segment elevation myocardial infarction patient submitted to primary coronary percutaneous intervention in a tertiary cardiology center from December 2010 to May 2012. We collected clinical, angiographic and laboratory data during hospital stay, and performed a clinical follow-up 30 days after the ST segment elevation myocardial infarction. We adjusted the multivariate analysis of the studied risk factors using the variables from the GRACE score. Results: Among the 740 patients included, reported diabetes mellitus prevalence was 18%. On the univariate analysis, both diabetes mellitus and admission blood glucose were predictors of death in 30 days. However, after adjusting for potential confounders in the multivariate analysis, the diabetes mellitus relative risk was no longer significant (relative risk: 2.41, 95% confidence interval: 0.76 - 7.59; p-value: 0.13), whereas admission blood glucose remained and independent predictor of death in 30 days (relative risk: 1.05, 95% confidence interval: 1.02 - 1.09; p-value ≤ 0.01). Conclusion: In ST segment elevation myocardial infarction patients submitted to primary coronary percutaneous intervention, the admission blood glucose was a more accurate and robust independent predictor of death than the previous diagnosis of diabetes. This reinforces the important role of inflammation on the outcomes of this group of patients.

Ernährungsmedizinische Kontrolle des Körpergewichts: Individuelle Einstellung zu verschiedenen Verfahren der Gewichtsreduktion bei Patienten mit Diabetes mellitus

Die ernährungsmedizinische Kontrolle des Körpergewichts bei Patienten mit Typ 1- und Typ 2-Diabetes stand im Vordergrund dieser Studie. Untersucht wurde dabei die individuelle Einstellung der beiden Typen zu verschiedenen Verfahren der Gewichtsreduktion. Es wurden Daten von je 60 Patienten mit Typ 1- und Typ 2-Diabetes für die Studie erhoben. Ausgeschlossen wurden Patienten mit schwerwiegenden Herzschwächen mit Luftnot bei geringen körperlichen Anstrengungen oder ausgeprägter Wassereinlagerung (Ödembildung), schwerwiegende, chronische Infektionserkrankungen mit Fieber, Sepsis, ausgeprägten Entzündungsreaktion, fortgeschrittene Lebererkrankungen und Funktionseinbußen der Nieren, die eine Nierenersatztherapie notwendig macht. Nicht teilnehmen sollten auch Patienten, die dauerhaft systemisch Glukocortikoide nehmen, deren Energiehaushalt durch eine hochgradige Einschränkung ihrer Bewegungsfähigkeit z.B. stark beeinflusst wird oder Patienten des Diabetes Typ 1 oder Typ 2 während einer Schwangerschaft. Die Teilnehmer mit Typ 2-Diabetes fühlen sich signifikant unwohler mit ihrem Körpergewicht und schätzten es auch als zu hoch ein als die Teilnehmer mit Typ 1-Diabetes. Passend zu dem hohen eingeschätzten Krankheitswert des Übergewichts beim Typ 2-Diabetes, assoziierten diese Patienten das Körpergewicht mit früheren wie auch zukünftigen gesundheitlichen Problemen. Obwohl Typ 2-Diabetiker eher Gewichtsabnahmen begannen, waren diese in der Vergangenheit nur mäßig erfolgreich gewesen. Die Änderungsbereitschaft das Gewicht zu reduzieren, bleibt dennoch bei den Teilnehmern mit Typ 2-Diabetes bestehen und zeigte sich ausgeprägter bei diesen Teilnehmern. Hingegen waren die Gewichtsreduktionsversuche bei den Teilnehmern mit Typ 1-Diabetes öfter von Erfolg gekrönt als bei den Teilnehmern mit (...)

Regulatory RNA binding molecules : implication for diabetes pathogenesis

Le glucose est notre principale source d'énergie. Après un repas, le taux de glucose dans le sang (glycémie) augmente, ce qui entraine la sécrétion d'insuline. L'insuline est une hormone synthétisée au niveau du pancréas par des cellules dites bêta. Elle agit sur différents organes tels que les muscles, le foie ou le tissu adipeux, induisant ainsi le stockage du glucose en vue d'une utilisation future.¦Le diabète est une maladie caractérisée par un taux élevé de glucose dans le sang (hyperglycémie), résultant d'une incapacité de notre corps à utiliser ou à produire suffisamment d'insuline. A long terme, cette hyperglycémie entraîne une détérioration du système cardio-vasculaire ainsi que de nombreuses complications. On distingue principalement deux type de diabète : le diabète de type 1 et le diabète de type 2, le plus fréquent (environ 90% des cas). Bien que ces deux maladies diffèrent sur beaucoup de points, elles partagent quelques similitudes. D'une part, on décèle une diminution de la quantité de cellules bêta. Cette diminution est cependant partielle dans le cas d'un diabète de type 2, et totale dans celui d'un diabète de type 1. D'autre part, la présence dans la circulation de médiateurs de l'inflammation nommés cytokines est décelée aussi bien chez les patients de type 1 que de type 2. Les cytokines sont sécrétées lors d'une inflammation. Elles servent de moyen de communication entre les différents acteurs de l'inflammation et ont pour certaines un effet néfaste sur la survie des cellules bêta.¦L'objectif principal de ma thèse a été d'étudier en détail l'effet de petites molécules régulatrices de l'expression génique, appelées microARNs. Basé sur le fait que de nombreuses publications ont démontré que les microARNs étaient impliqués dans différentes maladies telles que le cancer, j'ai émis l'hypothèse qu'ils pouvaient également jouer un rôle important dans le développement du diabète.¦Nous avons commencé par mettre des cellules bêta en culture en présence de cytokines, imitant ainsi un environnement inflammatoire. Nous avons pu de ce fait identifier les microARNs dont les niveaux d'expression étaient modifiés. A l'aide de méthodes biochimiques, nous avons ensuite observé que la modulation de certains microARNs par les cytokines avaient des effets néfastes sur la cellule bêta : sur sa production et sa sécrétion d'insuline, ainsi que sur sa mort (apoptose). Nous avons en conséquence pu démontrer que ces petites molécules avaient un rôle important à jouer dans le dysfonctionnement des cellules bêta induit par les cytokines, aboutissant au développement du diabète.¦-¦La cellule bêta pancréatique est une cellule endocrine présente dans les îlots de Langerhans, dans le pancréas. L'insuline, une hormone sécrétée par ces cellules, joue un rôle essentiel dans la régulation de la glycémie. Le diabète se développe si le taux d'insuline relâché par les cellules bêta n'est pas suffisant pour couvrir les besoins métaboliques corporels. Le diabète de type 1, qui représente environ 5 à 10% des cas, est une maladie auto-immune qui se caractérise par une réaction inflammatoire déclenchée par notre système immunitaire envers les cellules bêta. La conséquence de cette attaque est une disparition progressive des cellules bêta. Le diabète de type 2 est, quant à lui, largement plus répandu puisqu'il représente environ 90% des cas. Des facteurs à la fois génétiques et environnementaux sont responsables d'une diminution de la sensibilité des tissus métabolisant l'insuline, ainsi que d'une réduction de la sécrétion de l'insuline par les cellules bêta, ce qui a pour conséquence le développement de la maladie. Malgré les différences entre ces deux types de diabète, ils ont pour points communs la présence d'infiltrat immunitaire et la diminution de l'état fonctionnel des cellules bêta.¦Une meilleure compréhension des mécanismes aboutissant à l'altération de la cellule bêta est primordiale, avant de pouvoir développer de nouvelles stratégies thérapeutiques capables de guérir cette maladie. Durant ma thèse, j'ai donc étudié l'implication de petites molécules d'ARN, régulatrices de l'expression génique, appelées microARNs, dans les conditions physiopathologiques qui aboutissent au développement du diabète. J'ai débuté mon étude par l'identification de microARNs dont le niveau d'expression était modifié lorsque les cellules bêta étaient exposées à des conditions favorisant à la fois le développement du diabète de type 1 (cytokines) et celui du diabète de type 2 (palmitate). Nous avons découvert qu'une modification de l'expression des miR-21, -34a et -146a était commune aux deux traitements. Ces changements d'expressions ont également été confirmés dans deux modèles animaux : les souris NOD qui développent un diabète s'apparentant au diabète de type 1 et les souris db/db qui développent plutôt un diabète de type 2. Puis, à l'aide de puces à ADN, nous avons comparé l'expression de microARNs chez des souris NOD pré-diabétiques. Nous avons alors retrouvé des changements au niveau de l'expression des mêmes microARNs mais également au niveau d'une famille de microARNs : les miR-29a, -29b et -29c. De manière artificielle, nous avons ensuite surexprimé ou inhibé en conditions physiopathologiques l'expression de tous ces microARNs et nous nous sommes intéressés à l'impact d'un tel changement sur différentes fonctions de la cellule bêta comme la synthèse et la sécrétion d'insulinè ainsi que leur survie. Nous avons ainsi pu démontrer que les miR-21, -34a, -29a, -29b, -29c avaient un effet délétère sur la sécrétion d'insuline et que la surexpression de tous ces microARNs (excepté le miR-21) favorisait la mort. Finalement, nous avons démontré que la plupart de ces microARNs étaient impliqués dans la régulation d'importantes voies de signalisation responsables de l'apoptose des cellules bêta telles que les voies de NFKB, BCL2 ou encore JNK.¦Par conséquent, nos résultats démontrent que les microARNs ont un rôle important à jouer dans le dysfonctionnement des cellules bêta lors de la mise en place du diabète.

Risk prediction of prevalent diabetes in a Swiss population using a weighted genetic score--the CoLaus Study.

AIMS/HYPOTHESIS: Several susceptibility genes for type 2 diabetes have been discovered recently. Individually, these genes increase the disease risk only minimally. The goals of the present study were to determine, at the population level, the risk of diabetes in individuals who carry risk alleles within several susceptibility genes for the disease and the added value of this genetic information over the clinical predictors. METHODS: We constructed an additive genetic score using the most replicated single-nucleotide polymorphisms (SNPs) within 15 type 2 diabetes-susceptibility genes, weighting each SNP with its reported effect. We tested this score in the extensively phenotyped population-based cross-sectional CoLaus Study in Lausanne, Switzerland (n = 5,360), involving 356 diabetic individuals. RESULTS: The clinical predictors of prevalent diabetes were age, BMI, family history of diabetes, WHR, and triacylglycerol/HDL-cholesterol ratio. After adjustment for these variables, the risk of diabetes was 2.7 (95% CI 1.8-4.0, p = 0.000006) for individuals with a genetic score within the top quintile, compared with the bottom quintile. Adding the genetic score to the clinical covariates improved the area under the receiver operating characteristic curve slightly (from 0.86 to 0.87), yet significantly (p = 0.002). BMI was similar in these two extreme quintiles. CONCLUSIONS/INTERPRETATION: In this population, a simple weighted 15 SNP-based genetic score provides additional information over clinical predictors of prevalent diabetes. At this stage, however, the clinical benefit of this genetic information is limited.

Mise en place d'un programme de prévention et de prise en charge du diabète en Suisse: le point de vue des patients et des professionnels de la santé [Implementation of a diabetes disease management program in Switzerland: patients' and healthcare professionals' point of view].

BACKGROUND: A reorganization of healthcare systems is required to meet the challenge of the increasing prevalence of chronic diseases, e.g. diabetes. In North-America and Europe, several countries have thus developed national or regional chronic disease management programs. In Switzerland, such initiatives have only emerged recently. In 2010, the canton of Vaud set up the "Diabetes Cantonal Program", within the framework of which we conducted a study designed to ascertain the opinions of both diabetic patients and healthcare professionals on the elements that could be integrated into this program, the barriers and facilitators to its development, and the incentives that could motivate these actors to participate. METHODS: We organized eight focus-groups: one with diabetic patients and one with healthcare professionals in the four sanitary areas of the canton of Vaud. The discussions were recorded, transcribed and submitted to a thematic content analysis. RESULTS: Patients and healthcare professionals were rather in favour of the implementation of a cantonal program, although patients were more cautious concerning its necessity. All participants envisioned a set of elements that could be integrated to this program. They also considered that the program could be developed more easily if it were adapted to patients' and professionals' needs and if it used existing structures and professionals. The difficulty to motivate both patients and professionals to participate was mentioned as a barrier to the development of this program however. Quality or financial incentives could therefore be created to overcome this potential problem. CONCLUSION: The identification of the elements to consider, barriers, facilitators and incentives to participate to a chronic disease management program, obtained by exploring the opinions of patients and healthcare professionals, should favour its further development and implementation.

Diabetes care in Switzerland: good, but perfectible: a population-based cross-sectional survey.

BACKGROUND: While Switzerland invests a lot of money in its healthcare system, little is known about the quality of care delivered. The objective of this study was to assess the quality of care provided to patients with diabetes in the Canton of Vaud, Switzerland. METHODS: Cross-sectional study of 406 non-institutionalized adults with type 1 or 2 diabetes. Patients' characteristics, diabetes and process of care indicators were collected using a self-administered questionnaire. Process indicators (past 12 months) included HbA1C check among HbA1C-aware patients, eye assessment by ophtalmologist, microalbuminuria check, feet examination, lipid test, blood pressure and weight measurement, influenza immunization, physical activity recommendations, and dietary recommendations. Item-by-item (each process of care indicator: percentage of patients having received it), composite (mean percentage of recommended care: sum of received processes of care / sum of possible recommended care), and all-or-none (percentage of patients receiving all specified recommended care) measures were computed. RESULTS: Mean age was 64.4 years; 59% were men. Type 1 and type 2 diabetes were reported by 18.2% and 68.5% of patients, respectively, but diabetes type remained undetermined for almost 20% of patients. Patients were treated with oral anti-diabetic drugs (50%), insulin (23%) or both (27%). Of 219 HbA1C-aware patients, 98% reported ≥ one HbA1C check during the last year. Also, ≥94% reported ≥ one blood pressure measurement, ≥ one weight measurement or lipid test, and 68%, 64% and 56% had feet examination, microalbuminuria check and eye assessment, respectively. Influenza immunization was reported by 62% of the patients.The percentage of patients receiving all processes of care ranged between 14.2%-16.9%, and 46.6%-50.7%, when considering ten and four indicators, respectively. Ambulatory care utilization showed little use of multidisciplinary care, and low levels of participation in diabetes-education classes. CONCLUSIONS: While routine processes-of-care were performed annually in most patients, diabetes-specific risk screenings, influenza immunization, physical activity and dietary recommendations were less often reported; this was also the case for multidisciplinary care and participation in education classes. There is room for diabetes care improvement in Switzerland. These results should help define priorities and further develop country-specific chronic disease management initiatives for diabetes.