Pre-diabetes induces ultrastructural alterations in the large blood vessel aorta in rats / La prediabetes induce alteraciones ultraestructurales en la aorta de los grandes vasos sanguíneos en ratas

Excessive consumption of carbohydrate and fat increases the risk of cardiovascular disease. We sought to determine the potential ultrastructural alterations in large blood vessels induced by a high fat and fructose diet (HFD) in a rat model of prediabetes. Rats were either fed with HFD (model group) or a standard laboratory chow (control group) for 15 weeks before being sacrificed. The harvested thoracic aorta tissues were examined using transmission electron microscopy (TEM), and blood samples were assayed for biomarkers of pre-diabetes.TEM images showed that HFD induced profound pathological changes to the aortic wall layers, tunica intima and tunica media ultrastructures in the pre-diabetic rats as shown by apoptotic endothelial cells with pyknotic nuclei, damaged basal lamina, deteriorated smooth muscle cells that have irregular plasma membranes, shrunken nucleus with clumped nuclear chromatin, damaged mitochondria and few cytoplasmic lipid droplets and vacuoles. In addition, HFD significantly (p<0.05) decreased adiponectin and increased biomarkers of lipidemia, glycaemia, inflammation, oxidative stress, vascular injury such as soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion protein 1 (sVCAM-1), endothelin-1 (ET-1), and coagulation and thrombosis such as Von Willebrand factor (vWF), and plasminogen activator inhibitor-1 (PAI-1), compared to normal levels of these parameters in the control group. Thus, we demonstrated that feeding rats with a HFDisable to develop a pre-diabetic animal model that is useful to study the aortic ultrastructural alterations.

El consumo excesivo de carbohidratos y grasas aumenta el riesgo de enfermedades cardiovasculares. Intentamos determinar las posibles alteraciones ultraestructurales en los grandes vasos sanguíneos, inducidas por una dieta alta en grasas y fructosa (HFD) en un modelo de rata de prediabetes. Las ratas se alimentaron con HFD (grupo modelo) o una comida de laboratorio estándar (grupo de control) durante 15 semanas antes de ser sacrificadas. Los tejidos de la aorta torácica recolectados se examinaron mediante microscopía electrónica de transmisión (TEM) y las muestras de sangre se analizaron para detectar biomarcadores de prediabetes. Las imágenes TEM mostraron que HFD indujo cambios patológicos profundos en las capas de la pared aórtica, túnica íntima y túnica media en la ratas pre-diabéticas como lo muestran las células endoteliales apoptóticas con núcleos picnóticos, lámina basal dañada, células musculares lisas deterioradas que tienen membranas plasmáticas irregulares, núcleo encogido con cromatina nuclear aglomerada, mitocondrias dañadas y pocas gotitas lipídicas citoplásmicas y vacuolas. Además, HFD presentó disminución significativa de adiponectina (p <0,05), y aumento de biomarcadores de lipidemia, glucemia, inflamación, estrés oxidativo, lesión vascular como la molécula de adhesión intercelular soluble 1 (sICAM-1), proteína de adhesión de células vasculares soluble 1 (sVCAM-1), endotelina 1 (ET-1), y la coagulación y la trombosis, como el factor de Von Willebrand (vWF), y el inhibidor del activador del plasminógeno-1 (PAI -1), en comparación con los niveles normales de estos parámetros en el grupo de control. Por tanto, la alimentación de ratas con HFD es capaz de desarrollar un modelo animal prediabético que es útil para estudiar las alteraciones ultraestructurales aórticas.

Comparison of Urine Albumin-to-Creatinine Ratio (ACR) Between ACR Strip Test and Quantitative Test in Prediabetes and Diabetes

BACKGROUND: Albuminuria is generally known as a sensitive marker of renal and cardiovascular dysfunction. It can be used to help predict the occurrence of nephropathy and cardiovascular disorders in diabetes. Individuals with prediabetes have a tendency to develop macrovascular and microvascular pathology, resulting in an increased risk of retinopathy, cardiovascular diseases, and chronic renal diseases. We evaluated the clinical value of a strip test for measuring the urinary albumin-to-creatinine ratio (ACR) in prediabetes and diabetes. METHODS: Spot urine samples were obtained from 226 prediabetic and 275 diabetic subjects during regular health checkups. Urinary ACR was measured by using strip and laboratory quantitative tests. RESULTS: The positive rates of albuminuria measured by using the ACR strip test were 15.5% (microalbuminuria, 14.6%; macroalbuminuria, 0.9%) and 30.5% (microalbuminuria, 25.1%; macroalbuminuria, 5.5%) in prediabetes and diabetes, respectively. In the prediabetic population, the sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the ACR strip method were 92.0%, 94.0%, 65.7%, 99.0%, and 93.8%, respectively; the corresponding values in the diabetic population were 80.0%, 91.6%, 81.0%, 91.1%, and 88.0%, respectively. The median [interquartile range] ACR values in the strip tests for measurement ranges of 300 mg/g were 9.4 [6.3-15.4], 46.9 [26.5-87.7], and 368.8 [296.2-575.2] mg/g, respectively, using the laboratory method. CONCLUSIONS: The ACR strip test showed high sensitivity, specificity, and negative predictive value, suggesting that the test can be used to screen for albuminuria in cases of prediabetes and diabetes.

Gestational prediabetes: a new term for early prevention.

Women with gestational diabetes mellitus (GDM) have higher rates of foetal macrosomia, shoulder dystocia and pregnancy-induced hypertension, and are at higher risk of developing type 2 diabetes. Herein, we introduce a new conceptual term, “gestational prediabetes”, which requires the absence of diabetes before pregnancy, and the presence of blood glucose levels (or a related marker) in early pregnancy that are higher than normal, but not yet high enough to meet the diagnostic criteria for GDM. Identifying women with gestational prediabetes might be done in early pregnancy (e.g., 12 weeks’ gestation) using conventional glycaemic testing, assessment of visceral abdominal adiposity or hepatic fat by ultrasonography, or measuring serum sex hormone-binding globulin or adiponectin. However, none of these approaches has been systematically compared to conventional predictors, such as maternal body mass index or waist circumference. Any early-pregnancy predictor of gestational prediabetes risk needs to have low cost, ease of administration, and a short turnaround time. The theoretical advantage of identifying women with gestational prediabetes would be to “prevent” the onset of GDM (and its inherent risks to the pregnancy) in a timelier manner. One sensible starting point would be an intervention to prevent early excessive weight gain in pregnancy, which is currently being evaluated by two randomized clinical trials. In addition, early intervention could offset the need for resource-intense GDM management or insulin therapy.

Insulinorresistencia e hígado graso no alcohólico, ¿existe relación causa-efecto entre ambas condiciones? / Insulin-resistance and non-alcoholic fatty liver, is there a cause-effect relationship between both conditions?

La insulinorresistencia y el síndrome de insulinorresistencia constituyen la causa primaria mas importante dentro de la etiopatogenia del hígado graso no alcohólico, conjuntamente con la obesidad y la diabetes mellitus tipo 2. La insulinorresistencia puede ser causa y a la vez consecuencia de la enfermedad hepática. La prevalencia del hígado graso no alcohólico documentada en trabajos realizados en países desarrollados es la siguiente: el hígado graso no alcohólico simple tiene una prevalencia de un 20 a 23 por ciento, aumentando en los pacientes con hipertransaminasemia persitente, en los que se puede observar una prevalencia entre 21 y 63 por ciento, y la prevalencia de esteatohepatitis oscila entre un 2 y un 3 por ciento de la población. Es bueno señalar que esta prevalencia va en aumento conjuntamente con el aumento de la prevalencia del síndrome de insulinorresistencia, la obesidad y la diabetes mellitus tipo 2. El hígado graso no alcohólico constituye la causa mas frecuente de hipertransaminasemia persistente, de hepatopatía crónica y de cirrosis hepßtica idiopática. La edad igual o superior a 40 años, la presencia de insulinorresistencia, de síndrome de insulinorresistencia, de obesidad y de diabetes mellitus tipo 2, ensombrecen el pronóstico de los pacientes con hígado graso no alcohólico, por lo que la presencia de estos factores antes mencionados son considerados factores de mal pronóstico en el paciente con hígado graso no alcohólico(AU)

Insulin resistance and the insulin resistance syndrome are the more significant main cause in pathogeny of non-alcoholic fatty liver, together with obesity and type 2 diabetes mellitus. Insulin resistance may be the cause and the consequence of hepatic disease. Prevalence of non-alcoholic fatty liver documented in papers performed in developing countries is at follow: from a 20 percent to 23 percent, increase in patients presenting with persistent high level of transaminase, in which it is possible to observe a prevalence between 21 percent and 63 percent, and prevalence of steatohepatitis fluctuates between 2 percent and 3 percent of population. We must to mark that this prevalence is increasing together with the prevalence increase of insulin resistance syndrome, obesity, and type 2 diabetes mellitus. The non-alcohol fatty liver is the more frequent cause of a persistent high level of transaminase, of chronic liver disease, and of idiopathic liver cirrhosis. An age similar or higher than 40 years, presence of insulin resistance, insulin resistance syndrome, obesity, and type 2 diabetes mellitus darken the prognosis of patients presenting with non-alcoholic fatty liver, so the presence of above mentioned factors is considered as a poor prognosis factors in patient presenting non-alcoholic fatty liver(AU)

Diabete Melito Gestacional: dose ideal de insulina utilizada durante o terceiro trimestre de gestação e resultados perinatais / Gestational Diabetes Mellitus: ideal insulin dose used in the third trimester of gestation

Objetivo: Avaliar a dose ideal de insulina utilizada no tratamento do diabete melito gestacional (DMG) durante o terceiro trimestre da gestação e os resultados perinatais. Métodos: Foram avaliados, retrospectivamente,prontuários e carteiras de pré-natal de 104 gestantes com diagnóstico de DMG, com gestação única, que necessitaramde insulinoterapia durante o terceiro trimestre. O período do estudo foi de agosto de 2005 até julho de 2006. Foi utilizada inicialmente 0,9UI/kg/dia, dividida em quatro tomadas ao dia, com doses iguais de insulina regular pré-prandial e NPH ao deitar. A dose foi ajustada conforme os resultados das glicemias capilares, considerandovalores normais: jejum 60-90mg/dl, 1 hora pósprandial 60-120mg/dl e 3 horas da manhã 70-100mg/dl.Resultados: A dose média total de insulina foi de 76,7UI (DP=24,6), utilizando uma média de 0,97UI/kg/dia (DP=0,22UI) para o controle glicêmico. A dose antes do café (AC) foi significantemente maior (p<0,01)que a dose antes do almoço (AA), antes do jantar (AJ) e ao deitar (AD). A dose AA não difere da dose AJ (p=0,07) e é maior que a dose ao deitar (p=0,01). A dose AC foi de 30%, AA 25%, AJ 24% e AD 21% da dose total. O peso médio dos recém-nascidos foi 3.237g (DP=424g), com 10,6% de grande para a idade gestacional (GIG) e 16,3% hipoglicemia neonatal. Não houveóbito perinatal. Conclusão: A dose mais adequada para esta população durante o terceiro trimestre de gestação foi de 0,97UI/kg/dia, com um excelente resultado perinatal.

Objective: To evaluate the insulin dose for the management of gestational diabetes mellitus (GDM) duringthe third trimester of gestation.Methods: A hundred and four promptuaries of single-gestation patients diagnosed GDM and who neededinsulin therapy during the third trimester were analysed retrospectively in the study. The study was carried outfrom August, 2005 to July, 2006. At first, 0,9UI/kg/day was used divided into four doses a day, with equal regularinsulin pre-prandial and NPH bed time doses. The dose was adjusted according capillary glicemy testing results, considering normal values: before breakfast (BB) 60-90mg/dl, 1 hour pos-prandial 60-120mg/dl and at 3a.m. 70-100mg/dl. Results: Total insulin dose was 76,7UI (DP: 24,6),using an average of 0,97UI/kg/day (DP=0,22UI) for glucose level control. The dose before breakfast (BB) wassignificantly higher (p<0,01) than the dose before lunch (BL), before dinner (BD) and bed time (BT). No differencewas found in the doses BL or before BD (p=0,77) and it´s higher than the dose BT (p=0,01). Doses were BB 30%, BL 25%, BD 24% and BT 21% of the totaldose. Average birth weight was 3237g (DP=424g), with 10,6% large for gestational age (LGA) and 16,3% neonatal hypoglycemia. No perinatal deaths were reported. Conclusion: The most adequate dose for this group duringthe third trimester of gestation was 0,97UI/kg/day, with an excelent perinatal result.