The gonadal expression pattern of lipocalin­2 and 24p3 receptor is modified in the gonads of the offspring of obese rats.

Obesity represents a global health and economic burden, affecting millions of individuals worldwide. This pathology is associated with a chronic low­grade inflammatory state that is partially responsible for the development of other cardiometabolic complications. Clinical studies have reported an association between high circulating levels of lipocalin­2 (Lcn2) and increased body weight. Additionally, there is scientific evidence demonstrating the impact of maternal obesity on fetal programming. The latter and the fact that the authors previously found that Lcn2 and its receptor (24p3R) are expressed in the gonads of wild­type rats, led to the analysis of their mRNA profile and cellular localization in gonads collected from the offspring of obese rats at 21 days postconception (dpc), and 0, 2, 4, 6, 12, 20 and 30 days postnatal (dpn) in the present study. Semi­quantitative PCR revealed a statistically significant downregulation of Lcn2 and 24p3R mRNA at 21 dpc in the ovaries (P<0.01) and testicles (P<0.001) of the offspring of obese mothers. At 30 dpn, the relative expression of Lcn2 mRNA decreased significantly in the ovaries of the experimental group (P<0.05), while Lcn2 mRNA expression was not detectable in testicles. Regarding 24p3R, its mRNA was only significantly decreased at 21 dpc in ovaries of pups of obese mothers. At 30 dpn, the change in females was not significant. Conversely, in testicles, 24p3R mRNA levels increased slightly in the experimental group at 30 dpn. The Lcn2 protein signal was less intense in gonadal tissue sections from 30 dpn offspring of obese rats (P<0.001), whereas the 24p3R signal was downregulated in ovaries (P<0.001) and slightly upregulated in testicles. It was concluded that maternal obesity changes the expression of Lcn2 and 24p3R in the gonads of the offspring of obese rats, possibly through fetal programming. The consequences of this dysregulation for the offspring's gonadal function remains to be determined.

Association of common polymorphisms in the VEGFA and SIRT1 genes with type 2 diabetes-related traits in Mexicans.

INTRODUCTION: Genetic variants have been replicated for association with type 2 diabetes mellitus (T2D) and many of them with diabetes-related traits. Because T2D is highly prevalent in Mexico, this study aimed to test the association of CDKN2A/B, PPARGC1A, VEGFA, SIRT1 and UCP2 gene polymorphisms (rs10811661, rs8192678, rs2010963, rs7896005 and rs659366 respectively) with metabolic traits in 415 unrelated Mexican mestizos with T2D under three models of inheritance. MATERIAL AND METHODS: A total of 415 unrelated Mexican mestizos were genotyped by TaqMan assays. Triglycerides, cholesterol, glucose, high-density lipoprotein cholesterol (HDL-C), insulin and anthropometric measurements were determined and the HOMA-IR was calculated. Association studies were tested by the Kruskal-Wallis test, linear regression, statistical power analysis, Bonferroni correction, paired SNP analysis, and physical interaction by GeneMANIA. RESULTS: All polymorphisms were in Hardy-Weinberg equilibrium, and the association by genotype with T2D-related traits displayed nominal significance for rs8192678 with glucose (p = 0.023) and triglycerides (p = 0.013); rs2010963 with diastolic blood pressure (DBP) (p = 0.012) and cholesterol (p = 0.013); rs7896005 with DBP (p = 0.012) and insulin (p = 0.011); and rs659366 with cholesterol (p = 0.034), glucose (p = 0.031) and triglycerides (p = 0.028); and the association of rs2010963 with HDL-C (p = 0.0007) was significant. Linear regression performed with three models of inheritance, adjusted by age + sex + BMI and corrected with Bonferroni, showed a significant association of rs2010963 with HDL-C in an additive model (p = 0.007); and rs7896005 was significantly associated with DBP in the recessive model (p = 0.006). CONCLUSIONS: Rigorous analysis evidenced the association of VEGFA rs2010963 and SIRT1 rs7896005 with HDL-C and DBP respectively; these traits are known predictors of cardiovascular complications, which increase the risk of cardiovascular diseases in this population.

The ADRA2A rs553668 variant is associated with type 2 diabetes and five variants were associated at nominal significance levels in a population-based case-control study from Mexico City.

Type 2 diabetes (T2D) is a disease with a prevalence of 9.4% in Mexicans. Its etiology is complex involving environmental and genetic factors. The aim of this study was to analyse the association between PPARG rs1801282, PPARGC1A rs8192678, VEGFA rs2010963, ADRA2A rs553668, KCNQ1 rs2237892, SIRT1 rs7896005, IGF2BP2 rs4402960, and UCP3 rs3781907 single nucleotide variants (SNVs) with T2D and metabolic traits in a case-control study of a population from Mexico City. A total of 831 blood samples of non-diabetic, with healthy control participants (416) and individuals with T2D (415) were collected over a five-year period. After DNA extraction, genotyping was performed with TaqMan probes using real-time PCR. The genotypes were analysed for association with T2D in linear and logistic regressions adjusting for age, sex, and body mass index using the dominant, recessive, and additive models with a Bonferroni correction for multiple comparisons p < 0.001 and for association with related T2D traits fixed with a p < 2.3 × 10-4. The univariate analysis gives a significant (p < 1 × 10-4) for sex, triglycerides, and HOMA-IR. Significant association with T2D was found for ADRA2A rs553668 under the recessive model (OR = 3.640 and 95% CI of 2.330-5.690 (p < 1 × 10-4); statistical power 0.999) and under the additive model (OR = 1.640 and 95% CI of 1.340-2.000 (p < 1 × 10-4); statistical power 0.997). Variants PPARG rs1801282, PPARGC1A rs8192678, SIRT1 rs7896005, IGF2BP2 rs4402960 and UCP3 rs3781907 were nominally associated (p > 0.001 and <0.050). Results describe association of ADRA2A rs553668 with T2D in a Mexican population. Variants with nominal association with T2D require to be replicated in additional Mexican populations.

[Gender differences in lipocalin 2 plasmatic levels are correlated with age and the triglyceride/high-density lipoprotein ratio in healthy individuals]. / Las diferencias de género en los niveles plasmáticos de la lipocalina 2 se correlacionan con la edad y con la proporción de triglicéridos y lipoproteínas de alta densidad en individuos sanos.

INTRODUCTION: The increment of lipocalin 2, also called neutrophil gelatinase-associated lipocalin, plasmatic levels is associated with cardiometabolic and nefrologic alterations. Nonetheless, there is much controversy about lipocalin 2 plasmatic concentrations among healthy individuals. AIM: The aim of this study was to quantify lipocalin 2 in plasma of healthy men and women and to assess a possible correlation with cardiometabolic risk factors. METHODS: Fifty-three subjects (24 men and 29 women) were included. By means of an ELISA, a higher concentration of lipocalin 2 was observed in men than in women (91 ± 9 vs. 57 ± 7 ng/ml). Such difference was statistically significant (p < 0.0001). RESULTS: Lipocalin 2 levels were significantly correlated with body mass index, homeostasis model assessment index-insulin resistance index, triglycerides, high-density lipoprotein, and age. CONCLUSION: Lipocalin 2 plasmatic concentrations present a gender-specific profile in healthy subjects and its circulating levels appear to be age-dependent and associated with several cardiometabolic risk factors, including the triglycerides/high-density lipoprotein cholesterol ratio, which has proven to be a reliable marker for cardiometabolic risk among the global population.

Lipocalin-2 plasmatic levels are reduced in patients with long-term type 2 diabetes mellitus.

BACKGROUND: De-regulation of adipocytokines synthesis and secretion appears to be involved in the pathogenesis of different metabolic diseases. AIMS: We assessed a possible association between plasmatic levels of lipocalin-2 (LCN2) and type 2 diabetes mellitus (T2DM), as well as among levels of LCN2 and those of adiponectin, ghrelin, leptin and resistin, in Mexican diabetic patients. SUBJECTS AND METHODS: Fifty-three healthy individuals and fifty-three with long-term T2DM were included. Measurements from all patients for BMI, fasting glucose, insulin, lipids and adipocytokine profiles were obtained. RESULTS: Comparison of data between the corresponding for diabetic subjects and those of healthy individuals showed significant differences in every anthropometric and metabolic parameter analyzed (P < 0.001). In diabetic subjects, lipocalin-2 and ghrelin plasmatic levels were statistically diminished (P < 0.001) in comparison with the levels registered in healthy subjects. In conclusion, in this study we found that LCN2 plasmatic levels are reduced in Mexican subjects with long-term diabetes and this reduction in circulating concentrations is similar to the one reported for anti-inflammatory adipocytokines, which suggests that lipocalin-2 is somehow involved in insulin resistance and cardiometabolic alterations through an uncharacterized mechanism generated by the inflammation process.

Importance of maternal diabetes on the chronological deregulation of the intrauterine development: an experimental study in rat.

We investigated whether maternal diabetes induced in rats using streptozotocin (STZ) on Day 5 of pregnancy affects the intrauterine developmental timeline. A total of 30 pregnant Sprague-Dawley diabetic rats (DRs) and 20 control rats (CRs) were used to obtain 21-day fetuses (F21) and newborn (NB) pups. Gestational age, weight, and body size were recorded as were the maxillofacial morphometry and morphohistological characteristics of the limbs. In DRs, pregnancy continued for ∼1.7 days, and delivery occurred 23 days postcoitus (DPC). In this group, the number of pups was lower, and 13% had maxillofacial defects. F21 in the DR group had lower weights and were smaller; moreover, the morphological characteristics of the maxillofacial structures, derived from the neural crest, were discordant with their chronological gestational age, resembling 18- to 19-day-old fetuses. These deficiencies were counterbalanced in NB pups. We conclude that hyperglycemia, which results from maternal diabetes and precedes embryo implantation, deregulates the intrauterine developmental timeline, restricts embryo-fetal growth, and primarily delays the remodeling and maturation of the structures derived from neural crest cells.

A discrete-time recurrent neurofuzzy network for black-box modeling of insulin dynamics in diabetic type-1 patients.

In this work we present a data-driven modeling of the insulin dynamics in different in silico patients using a recurrent neural network with output feedback. The inputs for the identification is the rate of insulin (microU/dl/min) applied to the patient, and blood glucose concentration. The output is insulin concentration (microU/ml) present in the blood stream. Once completed the off-line modeling, this model could be used for on-line monitoring of the insulin concentration for a better treatment. The learning law of the recurrent neural network is inspired by adaptive observer theory, and proven to be convergent in the parameters and stable in the Lyapunov sense, even with only 13 samples available. Simulation results are shown to validate the presented modeling.

Los segmentos cardíacos primitivos, su implicación en la cardiogénesis normal aplicada a la cardiología pediátrica / Involvement of the primitive cardiac segments in the normal cardiogenesis. Its importance in the pediatric cardiology

The ample development of diagnostic echocardiography in pediatric cardiology has demanded precise knowledge of the abnormal anatomy of hearts that present congenital cardiac diseases. As a result, the information on morphologic and molecular aspects of cardiac embryogenesis has become fundamental to understand the anomalous anatomy of the malformed hearts. Based on these facts, in this paper we reviewed normal cardiogenesis, integrating the new information obtained experimentally in the chick embryo and from classic descriptive knowledge in humans. The age at which each cardiac segment appears is specified. At the same time, the changes in shape, relationships and position of these cardiac segments are detailed. Some implications of this process in the production of congenital cardiac defects and the importance of some specific genes are also discussed. This information is useful in the diagnosis of congenital cardiac diseases, as well as in discussing their embryogenesis. It is also beneficial in studying the possible mechanisms and genes implicated in normal morphogenesis of cardiac chambers, septa and valves. All this knowledge is important to plan strategies to avoid the production of this type of congenital pathologies.

[Effect of maternal diabetes on human and rat fetal development]. / Efecto de la diabetes materna en el desarrollo fetal de humanos y ratas.

Diabetes is a genetically determined metabolic disease with fasting hyperglycemia due to relative or absolute absence of insulin. With the use of exogenous insulin, successful gestations are now possible. Nevertheless, there are still severe problems associated, such as spontaneous abortion, perinatal mortality and congenital malformations. Caudal regression syndrome, disclosure of the neural tube and cardiovascular alterations are the most common malformations. Gestational diabetes can induce increased fetal corporal fat and macrosomia with hyperinsulinemia, hypoglycemic, hypoxia, metabolic acidosis and perinatal death. During adult life, diabetic mothers' children can develop obesity, glucose intolerance and type 2 diabetes. In order to study fetuses' alterations during diabetic gestations we now have animal models of diabetes. Maternal diabetes in rats alters fetal development in a very similar manner to that of humans. Although we do not accurately know the pathogenic mechanism by which diabetes produces fetuses' abnormal development, hyperglycemia and hyperketonemia had been mentioned to have predominant roles. Hyperglycemia damages DNA and increases oxidative stress and hyperketonemia increases the rate of embryo malformations. The addition of antioxidants such as C and E vitamins can reduce this damage. During adult life, diabetic rats' cubs have alterations in glucose metabolism and in reproductive function. The understanding of mechanisms by which maternal diabetes affects fetuses development, can help us to prevent complications and improve mothers' and children's life quality.

Evaluation of the effects of nateglinide on postprandial glycemia in patients with type 2 diabetes mellitus: a multicenter, multinational, non-randomized, non-controlled Latin American study.

One hundred and sixteen Latin American type 2 diabetic patients previously only on a diet were enrolled in this multicenter, multinational, nonrandomized, noncontrolled study. Only 109 completed the study. After 8 weeks of treatment with 120 mg of nateglinide, administered prior to each meal, the postprandial (2 h) glucose concentration decreased to 85.11 +/- 5.65 mg/dl (p < 0.0001), and HbA(1c) values decreased to 1.06 +/- 0.10% (p < 0.0001). No response differences were detected in relation to age, gender, or ethnicity, but we did encounter a better response in recently diagnosed patients (

Diabetes mellitus. Enfoques fisiopatológicos moderados para una epidemia mundial / Diabetes mellitus. Modern physiopathological approaches for a world epidemic

En la actualidad la diabetes es una causa principal de morbilidad y mortalidad. Cálculos recientes sugieren que la diabetes se está acercando con rapidez a proporciones endémicas y se estima que el número de diabéticos será de 220 millones hacia el año 2010. La diabetes tipo 2 representa alrededor del 95 por ciento de los casos. Este trabajo revisa nuevos enfoques para el manejo de la diabetes mellitus, a fin de reducir la incidencia de complicaciones.

Perfiles de glucosa e insulina en pacientes con hepatitis crónica por virus C / Glucose and insulin profiles on patients with chronic C hepatitis

Con objeto de estudiar el comportamiento de los perfiles de glucosa e insulina en pacientes con hepatitis crónica por virus C (HCV), se incluyeron once pacientes con edad promedio de 47.5 años e índice de masa corporal de 23.8 por ciento 1.4. Cinco de ellos eran diabéticos. Su diabetes apareció años después de la hepatitis. El grupo control estuvo compuesto por 12 sujetos sanos con edad promedio de 42.8 años e índice de masa corporal de 24.1 ñ 1.2. Los pacientes tuvieron hepatitis crónica con diferentes grados de daño hepático, pero sin cirrosis. Las cifras de glucosa en ayunas fueron 119.9 ñ 43.4 mg/dL para el grupo de pacientes y 91.9 ñ 3.6 mg/dL para el control. Los niveles de insulina de ayunas fueron 28.1 ñ 17 µU/mL para el grupo de pacientes y 12.9 ñ 3.9 µU/mL para el control. Los valores posprandiales de insulina fueron 38.5 ñ 38 µU/mL para el grupo de pacientes y 51.04 ñ 27 µU/mL para el control. Los valores poprandiales de glucosa fueron 146.9 ñ 118 mg/dL para el grupo de pacientes y 104 ñ 15 mg/mL para el control. En cuanto a la glucosa y a la insulina, el grupo de pacientes no mostró diferencias significativas cuando sus valores de ayuno se compararon versus los posprandiales, contrario a lo que sucedió en el control (p < 0.01 y p< 0.005). Se sugiere que en pacientes con HCV se efectúen periódicamente mediciones de glucemia de ayuno y posprandiales para detectar oportunamente alteraciones de hiperglucemia

Efecto de la diabetes inducida sobre la reproducción y el desarrollo / Effect of induced diabetes upor reproduction and development

La diabetes mellitus es una enfermedad con una gran morbilidad y mortalidad, por lo que sus efectos se han estudiado en relación con los diversos órganos a los que afecta, sin ser la función reproductora la excepción. Para lograr esto, se ha recurrido a utilizar diversos animales como modelos experimentales, a los que se les induce diabetes. Se han descrito diversas sustancias para inducir la diabetes en animales, siendo la estretptozotocina (STZ) la que ha demostrado mayor eficacia. La STZ es un antibiótico producido por Streptomyces achromogenes, el cual tiene selectividad por las células beta del páncreas, destruyéndolas a través de la fragmentación del DNA. Se ha comprobado que la STZ diluida en amortiguador, estabilizada durante dos horas aproximadamente y almacenada a 6ºC, tiene una gran capacidad inductora de diabetes, sobre todo en especies como la rata, el ratón y el hamster. En ratas con diabetes inducida las alteraciones reproductivas se han asociado con alteraciones a nivel del eje hipotálamo-hipófisis-gónada, tanto por disminución de secreción de GnRH, como por deficiente secreción de LH, FSH y prolactina, así como por alteraciones a nivel gonadal y producción de hormonas esteroideas (testosterona, estrógenos y progesterona). Esto trae como consecuencia en ratas machos, la menor producción de espermatozoides, así la disminución en la movilidad de los mismos. En el caso de las hembras, las principales alteraciones son atrofia avárica, foliculogénesis anormal, insuficiencia del cuerpo lúteo, involución uterina y problemas asociados con el mantenimiento de la gestación. En diversos estudios se ha observado la prevalencia de malformaciones congénitas en los productos de ratas con diabetes inducida con STZ, siendo las más frecuetnes retraso en el desarrollo, alteraciones en el cierre del tubo neural, alteraciones cardiaca y micrognatias, entre otros

Plan de alimentación en la diabetes mellitus gestacional / Meal planning during gestational diabetes mellitus

El propósito de este artículo es proporcionar de forma accesible, tanto al médico como a la paciente con diabetes mellitus gestacional, los conocimientos básicos acerca de la composición y contenido calórico de los nutrientes, su organización y equivalencia en el sistema y listas de intercambio de alimentos, de tal forma que dependiendo de los requerimientos calóricos del embarazo y de la actividad física que se desarrolle, facilite la elaboración del plan de alimentación (con gran diversidad de menús) para que la paciente con diabete mellitus logre un buen control metabólico (cifras de glucosa dentro de los límites normales) y disminuya así el riesgo de morbimortalidad perinatal

Diabetes mellitus, resistencia a la insulina y enfermedades crónicas del hígado / Diabetes mellitus, resistance to insulin and chronic diseases of the liver

Se analizan los cambios que ocurren en el metabolismo de la glucosa en pacientes con hepatopatías crónicas. La sensibilidad a la insulina está disminuida en los pacientes con cirrosis hepática, incluso antes de que la intolerancia a la glucosa se haga manifiesta. La resistencia a la insulina reside en el músculo y mayormente resulta de un defecto en la síntesis del glucógeno. La diabetes mellitus en los pacientes con cirrosis y resistencia a la insulina es el resultado de un defecto progresivo en la secreción de insulina con el desarrollo de resistencia a la insulina por el hígado, lo que conduce a la hiperglucemia de ayuno.

Conceptos básicos en cronobiomedicina / Basic concepts in chronobiomedicine

Los seres vivientes se caracterizan por exhibir fenómenos cíclicos que les permiten interactuar con ellos mismos y con otros seres. Los principales objetivos de la cronobiología son la cuantificación de la variabilidad de estos fenómenos cíclicos, así como de los fenómenos rítmicos que les permiten sus interacciones; esto se lleva a cabo por medio de la determinación estadística (cronas) de la estructura temporal (cronoma) de cada organismo. La aplicación y desarrollo de estudios cronobiológicos en el ser humano constituyen la cronobiomedicina.

Pruebas de laboratorio útiles para el control de la diabetes mellitus: hemoglobina glucosilada / Laboratory tests used in diabetes mellitus control: glycosilated hemoglobin

La diabetes mellitus es una enfermedad crónica que requiere del cuidado médico constante y de la educación tanto del paciente como de sus familiares. Para su control, el médico se apoya en unas serie de pruebas de laboratorio entre las cuales la hemoglobina glucosilada (HbA1C) juega un papel importante. Esta prueba tiene la ventaja de monitorear las condiciones metabólicas del paciente en las ocho semanas precedentes permitiendo así conocer con mayor certeza la calidad del control de la diabetes. La determinación de hemoglobina glucosilada se debe realizar cada tres o cuatro meses y los valores estimados como normales son de 3 a 6 por ciento