INDICADORES NUTRICIONALES, CLÍNICOS Y BIOQUÍMICOS ASOCIADOS A ESTADOS INFLAMATORIOS Y PREDICTIVOS DE DIABETES MELLITUS TIPO 2 EN INDIVIDUOS EN RIESGO: PAPEL DE LÍPIDOS POLIINSATURADOS DIETARIOS

Diabetes mellitus tipo 2 y otras patologías relacionadas con un estado proinflamatorio crónico (hipertensión arterial, aterosclerosis, enfermedad de Alzheimer y cáncer ) se producen en ciertos individuos, debido a la acumulaciòn de alteraciones en el organismo, a través del tiempo. El propósito de este proyecto es elaborar índices confiables, clínicos y bioquímicos que podrían servir como marcadores de perturbaciones en el organismo que pueden ser indicadores fiables de la manifestación clínica de diabetes mellitus tipo 2 y si estos parámetros son modificables por hábitos dietarios saludables y práctica de ejercicios físicos. Estas medidas simples y económicas podrían ser empleadas efectivamente para evitar o posponer la aparición de diabetes mellitus tipo 2 en sujetos en riesgo.

Doença arterial coronariana subclínica em pacientes com Diabetes Mellitus tipo 1 em hemodiálise

FUNDAMENTO: A aterosclerose ocorre mais cedo em pacientes com diabetes mellitus tipo 1 (DM-1) e a doença arterial coronariana (DAC) constitui a mais importante causa de morte. OBJETIVO: Avaliar a prevalência e as características anatômicas da DAC em pacientes com DM-1 e insuficiência renal crônica, submetidos à diálise. MÉTODOS: Este é um estudo descritivo de 20 pacientes com DM-1 submetidos à diálise sem DAC conhecida. A DAC foi avaliada através de angiografia coronariana quantitativa (ACQ) e ultra-som intravascular (USIV). A ACQ foi realizada em todas as lesões >30%, visualmente Todos os segmentos proximais de 18 mm das artérias coronárias foram analisados por USIV. Todos os outros segmentos coronarianos com estenose >30% também foram analisados. RESULTADOS: A angiografia detectou 29 lesões >30% em 15 pacientes (75%). Onze (55%) das lesões eram >50% e 10 (50%) >70%. Treze pacientes tiveram as 3 principais artérias avaliadas pelo USIV. A aterosclerose estava presente em todos os pacientes e em todos os 51 segmentos proximais de 18 mm analisados. Esses segmentos significam que a medida do diâmetro dos vasos apresentava-se significantemente maior no USIV do que na ACQ, em todos os vasos. As imagens do ISIV de 25 (86,2%) das 29 lesões >30% foram obtidas. Placas fibróticas eram comuns (48%) e 60% apresentavam remodelamento intermediário de vasos. CONCLUSÃO: A DAC estava presente em todos os vasos de todos os pacientes com diabete tipo 1 submetidos a hemodiálise. Esses achados estão de acordo com outros estudos de autópsia, angiografia e USIV. Além disso, eles indicam a necessidade de estudos adicionais epidemiológicos e de imagem, para um melhor entendimento e tratamento de uma condição clínica complexa e grave que afeta jovens indivíduos.

Lipoproteína (a) está associada com níveis basais de insulina em pacientes com Diabetes Mellitus tipo 2

FUNDAMENTO: Ainda não foi claramente estabelecido se a resistência/deficiência insulínica leva diretamente à aterogênese ou através de sua associação com outros fatores de risco como os níveis de lipoproteína (a)[Lp(a)]. OBJETIVO: O objetivo do estudo foi estabelecer a relação entre os níveis basais de insulina, lípides e lipoproteína (a) em pacientes com diabetes mellitus (DM) tipo 2. MÉTODOS: Amostras de sangue foram colhidas em jejum e os níveis de insulina, lipoproteína (a), colesterol total (CT), triglicérides (TG), lipoproteína de baixa densidade (LDL-C), lipoproteína de alta densidade (LDL-C), glicose e hemoglobina glicada (HbA1c) foram medidos em 60 pacientes com DM tipo 2 e 28 indivíduos saudáveis. Nós dividimos os pacientes em dois grupos baseados nos níveis basais de insulina: > 10 µIU/ml e < 10 µIU/ml. RESULTADOS: Os níveis de insulina eram mais altos nos indivíduos diabéticos do que nos controles [p < 0,05]. Os níveis de CT (p< 0,01), LDL-C (p< 0,05), razão CT/HDL (p< 0,01), e TG (p< 0,05) eram mais altos e os níveis de HDL- C eram significantemente mais baixos em ambos os grupos de diabéticos, quando comparados aos controles. Os níveis de Lp(a) eram significantemente mais baixos em diabéticos com insulina basal > 10 µIU/ml comparados com aqueles que apresentavam insulina basal < 10 µIU/ml (p < 0.05). A análise de regressão mostrou uma relação significante da Lp(a) com os níveis de insulina (r = 0,262, p < 0,05) e razão Insulina/Glicose(r = 0,257, p < 0,05). CONCLUSÃO: Os níveis de Lp(a) se correlacionam inversamente com os níveis de insulina em pacientes com DM tipo 2. Os níveis de Lp(a) podem ser um dos fatores de risco cardiovascular em pacientes com DM tipo 2 com maior duração da doença. (Arq Bras Cardiol 2009;93(1):28-33)

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 (...)

Congenital heart disease in pregnancies complicated by maternal diabetes mellitus. An international clinical collaboration, literature review, and meta-analysis.

PURPOSE: Investigation of the incidence and distribution of congenital structural cardiac malformations among the offspring of mothers with diabetes type 1 and of the influence of periconceptional glycemic control. METHODS: Multicenter retrospective clinical study, literature review, and meta-analysis. The incidence and pattern of congenital heart disease in the own study population and in the literature on the offspring of type 1 diabetic mothers were compared with the incidence and spectrum of the various cardiovascular defects in the offspring of nondiabetic mothers as registered by EUROCAT Northern Netherlands. Medical records were, in addition, reviewed for HbA(1c) during the 1st trimester. RESULTS: The distribution of congenital heart anomalies in the own diabetic study population was in accordance with the distribution encountered in the literature. This distribution differed considerably from that in the nondiabetic population. Approximately half the cardiovascular defects were conotruncal anomalies. The authors' study demonstrated a remarkable increase in the likelihood of visceral heterotaxia and variants of single ventricle among these patients. As expected, elevated HbA(1c) values during the 1st trimester were associated with offspring fetal cardiovascular defects. CONCLUSION: This study shows an increased likelihood of specific heart anomalies, namely transposition of the great arteries, persistent truncus arteriosus, visceral heterotaxia and single ventricle, among offspring of diabetic mothers. This suggests a profound teratogenic effect at a very early stage in cardiogenesis. The study emphasizes the frequency with which the offspring of diabetes-complicated pregnancies suffer from complex forms of congenital heart disease. Pregnancies with poor 1st-trimester glycemic control are more prone to the presence of fetal heart disease.

Cytomegalovirus infection and new-onset post-transplant diabetes mellitus.

We analyzed data from all consecutive kidney transplant patients at our institution between April 2003 and October 2006. We found 15 cases of late-onset cytomegalovirus (CMV) infection, two of which developed concurrent post-transplant diabetes mellitus (PTDM). In these two cases, PTDM was transient and normal glucose tolerance was achieved after an eight-wk therapeutic course of oral valganciclovir. These findings suggest that CMV infection after organ transplantation may be associated with concurrent PTDM. The distinct causative relationship is yet to be determined.

Potassium channel alterations mediate peripheral nerve hyperexcitability in a mouse model of type 2 diabetes mellitus

Diabetes mellitus (DM) is a major cause of peripheral neuropathy. More than 220 million people worldwide suffer from type 2 DM, which will, in approximately half of them, lead to the development of diabetic peripheral neuropathy. While of significant medical importance, the pathophysiological changes present in DPN are still poorly understood. To get more insight into DPN associated with type 2 DM, we decided to use the rodent model of this form of diabetes, the db/db mice. During the in-vivo conduction velocity studies on these animals, we observed the presence of multiple spiking followed by a single stimulation. This prompted us to evaluate the excitability properties of db/db peripheral nerves. Ex-vivo electrophysiological evaluation revealed a significant increase in the excitability of db/db sciatic nerves. While the shape and kinetics of the compound action potential of db/db nerves were the same as for control nerves, we observed an increase in the after-hyperpolarization phase (AHP) under diabetic conditions. Using pharmacological inhibitors we demonstrated that both the peripheral nerve hyperexcitability (PNH) and the increased AHP were mostly mediated by the decreased activity of Kv1-channels. Importantly, we corroborated these data at the molecular level. We observed a strong reduction of Kv1.2 channel presence in the juxtaparanodal regions of teased fibers in db/db mice as compared to control mice. Quantification of the amount of both Kv1.2 isoforms in DRG neurons and in the endoneurial compartment of peripheral nerve by Western blotting revealed that less mature Kv1.2 was integrated into the axonal membranes at the juxtaparanodes. Our observation that peripheral nerve hyperexcitability present in db/db mice is at least in part a consequence of changes in potassium channel distribution suggests that the same mechanism also mediates PNH in diabetic patients. ∗Current address: Department of Physiology, UCSF, San Francisco, CA, USA.

Syndrome métabolique, diabète sucré et vulnérabilité: une approche "syndémique" de la maladie chronique [Metabolic syndrome, diabetes mellitus and vulnerability: a syndemic approach of chronic diseases].

The pandemic metabolic syndrome is generally attributed to our lifestyle. The current therapeutic strategies are centered on the behavioral changes and pharmacotherapy. A deeply analysis reveals the importance of the socio-cultural determinants with a "dose-responses effect according to the socio-economic level. The "syndemic" theory, which puts at the same level the socio-cultural environment, the behaviors and biomedecine, suggests a more holistic approach. This theory suggests introducing other partners of care, such cultural-mediators and welfare workers trained in the care, to have finally an approach centered on the roots of the causes. The healthcare networks centered on the management of the costs of health should not forget the socio-cultural dimension, unless wanting to select the good cases.

Renal responses to three types of renin-angiotensin system blockers in patients with diabetes mellitus on a high-salt diet: a need for higher doses in diabetic patients?

Objective Activation of the renal renin-angiotensin system in patients with diabetes mellitus appears to contribute to the risk of nephropathy. Recently, it has been recognized than an elevation of prorenin in plasma also provides a strong indication of risk of nephropathy. This study was designed to examine renin-angiotensin system control mechanisms in the patient with diabetes mellitus.Methods We enrolled 43 individuals with type 2 diabetes mellitus. All individuals were on a high-salt diet to minimize the contribution of the systemic renin-angiotensin system. After an acute exposure to captopril (25 mg), they were randomized to treatment with either irbesartan (300 mg) or aliskiren (300 mg) for 2 weeks.Results All agents acutely lowered blood pressure and plasma aldosterone, and increased renal plasma flow and glomerular filtration rate. Yet, only captopril and aliskiren acutely increased plasma renin and decreased plasma angiotensin II, whereas irbesartan acutely affected neither renin nor angiotensin II. Plasma renin and angiotensin II subsequently did increase upon chronic irbesartan treatment. When given on day 14, irbesartan and aliskiren again induced the above hemodynamic, renal and adrenal effects, yet without significantly changing plasma renin. Irbesartan at that time did not affect plasma angiotensin II, whereas aliskiren lowered it to almost zero.Conclusion The relative resistance of the renal renin response to acute (irbesartan) and chronic (irbesartan and aliskiren) renin-angiotensin system blockade supports the concept of an activated renal renin-angiotensin system in diabetes, particularly at the level of the juxtaglomerular cell, and implies that diabetic patients might require higher doses of renin-angiotensin system blockers to fully suppress the renal renin-angiotensin system. J Hypertens 29: 2454-2461 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Causas específicas de mortalidad en una cohorte de pacientes con diabetes mellitus tipo 2

La diabetis mellitus és un trastorn metabòlic a causa del dèficit de secreció d'insulina i a un augment de la seva resistència perifèrica. En el present estudi es van determinar les causes específiques de mortalitat en pacients amb diabetis mellitus. Es va observar que la mortalitat cardiovascular segueix sent la principal causa de mort en pacients amb diabetis metllitus tipus 2, seguida de la mortalitat per neoplàsies. La mortalitat total i específica per patologia cardiovascular o per neoplàsies va ser significativament superior en els pacients homes.