ABSTRACT
La diabetes tipo 2 (DT2) es elevada en Yucatán; 52% de los afectados presentan falla al tratamiento con sulfonilureas y metformina. Una posible explicación es por polimorfismos en los genes IRS1, CAPN10, PPARG2, involucrados en la disfunción de la célula b pancreática y respuesta baja a la acción de insulina. Se determinó la asociación de los polimorfismos Gly972Arg, SNP43 y Pro12Ala con el riesgo a la falla al tratamiento con sulfonilurea y metformina, en pacientes con DT2 de Yucatán, México. Se estudiaron ciento treinta y dos pacientes, clasificados con base al control de la hiperglucemia con sulfonilureas y metformina, en grupos de respondedores (HbA1c<8%) y no respondedores (HbA1c > 8%) al tratamiento. De cada sujeto, se obtuvieron datos demográficos, antropométricos, clínicos y metabólicos. Los polimorfismos se identificaron mediante el análisis del ADN por PCR/RFLP y PCR/OAL. Se calcularon las frecuencias genotípicas y alélicas y el equilibrio de Hardy-Weinberg. Se analizó estadísticamente con X² y regresión logística múltiple (Epi-Info 2000 y SPSS versión 12). Se observó diferencia significativa (p = 0,027) en el riesgo a la falla al tratamiento 4,69 veces mayor en sujetos obesos con genotipo AA SNP43, comparado con sujetos con genotipo GA: X² (OR= 4,69, IC: 1,15-20,59) y regresión logística múltiple, p= 0,048, (OR= 3,72, IC: 1,009-13,718). Se identificó interacción entre el genotipo AA y el IMC>27 (p=0,009). Los hallazgos sugieren que el polimorfismo SNP43 podría influir en la respuesta al tratamiento con sulfonilureas y metformina, con expresión dependiente de obesidad.
In Yucatán, 52% of patients with type 2 diabetes (DT2) present secondary failure to treatment associated with sulphonylurea and metformin. A possible explanation may be due to polymorphisms in the genes IRS1, CAPN10, PPARG2, which are involved in pancreatic b cell dysfunction and a poor response to the action of insulin. The association of the polymorphisms Gly972Arg, SNP43, and Pro12Ala, of the genes IRS1, CAPN10, PPARG2, with the risk of failure to sulphonylurea and metformin therapies was determinated in patients with DT2 in Yucatán, México. One hundred and thirty and two subjects with DT2 were classified in groups of responders (HbA1c< 8%) and non-responders (HbA1c> 8%) to the treatment, according to the control of hyperglucemia with sulphonylurea and metformin. Demographic, anthropometric and metabolic data were obtained from each subject. The polymorphisms were identified by means of DNA analysis by PCR/RFLP and PCR/OAL. Genotypic and allelic frequencies and the Hardy-Weinberg equilibrium were determined. Statistical analyses consisted of X² and multiple logistic regression tests (Epi-Info 2000 and SPSS version 12). Obese subjects carrying the genotype AA SNP43 showed 4.69 times more risk of failure to respond to treatment (p=0.027), when compared with subjects sharing GA genotype: X² (OR= 4.69, IC: 1.15-20.59) and multiple logistic regression, p= 0.048, (OR= 3.72, IC: 1.009-13.718). The interaction between genotype AA and the BMI> 27 showed also a significant difference (p=0.009). The findings suggest the fact that polymorphism SNP43 may influence the response to treatment with sulphonylurea and metformin, the expression being dependent on obesity.
Subject(s)
Humans , Male , Female , Sulfonylurea Compounds/therapeutic use , Metformin/therapeutic use , Polymorphism, GeneticABSTRACT
Objetivo: Describir la metodología de análisis de múltiples transcritos con técnicas de microarreglo en biopsias simultáneas de tejido muscular, adiposo y sangre en un mismo individuo, como parte de la estandarización del estudio GEMM (Genética de las Enfermedades Metabólicas en México). Material y métodos: Se incluyó a cuatro sujetos con índice de masa corporal (IMC) entre 20 y 41. Se registró estatura, talla y composición corporal. Se realizó biopsia muscular (vasto lateral), de tejido adiposo subcutáneo y muestra de sangre completa. El ARN total fue extraído de los tejidos y amplificado para análisis de microarreglos. Resultados: De 48 687 potenciales transcritos, 39.4% fue detectable en al menos uno de los tejidos. La expresión de leptina no fue detectable en linfocitos, débilmente expresada en músculo, alta expresión en el tejido adiposo y correlacionó con el IMC. El GLUT4 también ilustra la especificidad para el músculo sin verse afectado por el IMC. La concordancia en la expresión de transcritos fue 0.70 (p<0.001) para los tres tejidos. Conclusiones: Fue factible cuantificar simultáneamente la expresión genética de miles de transcritos, hubo concordancia en la expresión entre diferentes tejidos obtenidos en un mismo individuo, y confiabilidad del método al reproducir las relaciones biológicas esperadas. El estudio GEMM podrá analizar las correlaciones de los transcritos expresados dentro de un órgano y luego entre diferentes tejidos, y proveerá endofenotipos cuantitativos novedosos que proporcionarán un amplio panorama de información sobre las enfermedades metabólicas, incluyendo obesidad y diabetes tipo 2.
OBJECTIVE: We describe the methodology used to analyze multiple transcripts using microarray techniques in simultaneous biopsies of muscle, adipose tissue and lymphocytes obtained from the same individual as part of the standard protocol of the Genetics of Metabolic Diseases in Mexico: GEMM Family Study. METHODS: We recruited 4 healthy male subjects with BM1 20-41, who signed an informed consent letter. Subjects participated in a clinical examination that included anthropometric and body composition measurements, muscle biopsies (vastus lateralis) subcutaneous fat biopsies anda blood draw. All samples provided sufficient amplified RNA for microarray analysis. Total RNA was extracted from the biopsy samples and amplified for analysis. RESULTS: Of the 48,687 transcript targets queried, 39.4% were detectable in a least one of the studied tissues. Leptin was not detectable in lymphocytes, weakly expressed in muscle, but overexpressed and highly correlated with BMI in subcutaneous fat. Another example was GLUT4, which was detectable only in muscle and not correlated with BMI. Expression level concordance was 0.7 (p< 0.001) for the three tissues studied. CONCLUSIONS: We demonstrated the feasibility of carrying out simultaneous analysis of gene expression in multiple tissues, concordance of genetic expression in different tissues, and obtained confidence that this method corroborates the expected biological relationships among LEPand GLUT4. TheGEMM study will provide a broad and valuable overview on metabolic diseases, including obesity and type 2 diabetes.
Subject(s)
Humans , Male , Adult , Lymphocytes , Muscle, Skeletal , Gene Expression Profiling/methods , Subcutaneous Fat , Subcutaneous Fat/chemistry , Lymphocytes/chemistry , Mexico , Muscle, Skeletal/chemistry , RNAABSTRACT
Nutritional genomics forms part of the genomic sciences and addresses the interaction between genes and the human diet, its influence on metabolism and subsequent susceptibility to develop common diseases. It encompasses both nutrigenomics, which explores the effects of nutrients on the genome, proteome and metabolome; and nutrigenetics, that explores the effects of genetic variations on the diet/disease interaction. A number of mechanisms drive the gene/diet interaction: elements in the diet can act as links for transcription factor receptors and alter intermediary concentrations, thereby modifying chromatin and impacting genetic regulation; affect signal pathways, regulating phosphorylation of tyrosine in receptors; decrease signaling through the inositol pathway; and act through epigenetic mechanisms, silencing DNA fragments by methylation of cytosine. The signals generated by polyunsaturated fatty acids are so powerful that they can even bypass insulin mediated lipogenesis, stimulated by carbohydrates. Some fatty acids modify the expression of genes that participate in fatty acid transport by lipoproteins. Nutritional genomics has myriad possible therapeutic and preventive applications: in patients with enzymatic deficiencies; in those with a genetic predisposition to complex diseases such as dyslipidemia, diabetes and cancer; in those that already suffer these diseases; in those with altered mood or memory; during the aging process; in pregnant women; and as a preventive measure in the healthy population.
Subject(s)
Female , Humans , Pregnancy , Dietetics/methods , Genetic Predisposition to Disease/prevention & control , Metabolic Diseases/diet therapy , Nutrigenomics , Chronic DiseaseABSTRACT
Three leptospirosis cases with lung involvement are reported from the Yucatan Peninsula, Mexico. All three patients were admitted to the intensive care unit due to acute respiratory failure. Treatment with antibiotics resulted in favorable evolution despite the negative prognosis. Leptospirosis should be included in the differential diagnosis of patients with fever and lung involvement.
Analisamos três casos de leptospirose com envolvimento pulmonar na Península Yucatán, México. Os três pacientes com seqüelas pulmonares entraram na unidade de cuidados intensivos devido à insuficiência respiratória grave. Todos os casos evoluíram favoravelmente ao tratamento com antibióticos, apesar do prognóstico negativo. Leptospirose deve ser incluída no diagnóstico diferencial de pacientes com febre e comprometimento pulmonar.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Young Adult , Hemorrhage/microbiology , Leptospirosis/diagnosis , Lung Diseases/microbiology , Enzyme-Linked Immunosorbent Assay , Hemorrhage/diagnosis , Hemorrhage/drug therapy , Immunoglobulin G/blood , Leptospira interrogans/immunology , Leptospirosis/drug therapy , Lung Diseases/diagnosis , Lung Diseases/drug therapy , Severity of Illness Index , Young AdultABSTRACT
La obesidad se asocia con un estado inflamatorio implicado en el desarrollo de aterosclerosis y resistencia a la insulina. Los macrófagos son claves en la génesis de estos procesos. La obesidad induce la acumulación de macrófagos en el tejido adiposo. Los macrófagos producen muchas de las moléculas inflamatorias secretadas por el tejido adiposo. Las proteínas quimioatrayentes de monocitos (MCP) y sus receptores son fundamentales en la respuesta inflamatoria y en el reclutamiento de células inmunes en sitios de inflamación. La expresión en el tejido adiposo de una MCP, la quimiocina del ligando 2 del motif C-C (CCL2 o MCP1), está incrementada en proporción a la adiposidad. El receptor 2 de quimiocina del motif C-C (CCR2) regula el reclutamiento y quimiotaxis de monocitos y macrófagos, es necesario para las respuestas inflamatorias dependientes de macrófagos y para el desarrollo de aterosclerosis. Ya que el receptor CCR2 regula las respuestas inflamatorias locales, se ha postulado que las MCP, actuando a través de su receptor CCR2, podrían regular la inflamación inducida por la obesidad en el tejido adiposo. Este documento se enfoca en dilucidar los mecanismos moleculares y genéticos que permiten reclutar y retener macrófagos en el tejido adiposo.
Obesity is associated with a complex systemic inflammatory reaction that has been associated with the development of atherosclerosis and insulin resistance. Obesity also induces macrophage accumulation in adipose tissue. Macrophages produce many of the pro inflammatory molecules released by adipose tissue and have been implicated in the development of obesity-induced adipose tissue inflammation. Monocyte chemoattractant proteins (MCPs) and their receptors play key roles in the development of inflammatory responses and are crucial for the recruitment of immune cells towards inflammation sites. Adipose tissue expression of at least 1 MCP, C-C motif chemokine ligand-2 (CCL2 or MCP1), increases in proportion to adiposity. The C-C motif chemokine receptor-2 (CCR2) regulates monocyte and macrophage recruitment and is necessary for macrophage-dependent inflammatory responses and the development of atherosclerosis. Because CCR2 regulates monocyte and macrophage chemotaxis and local inflammatory responses, it has been hypothesized that monocyte chemoattractant molecules acting through CCR2 might regulate obesity-induced inflammation in adipose tissue. Our study focuses on the molecular and genetic mechanisms that recruit and retain macrophages in adipose tissue.
Subject(s)
Humans , Insulin Resistance , Macrophages/physiology , Obesity/immunology , Obesity/metabolism , Adipose Tissue, White/physiology , Obesity/drug therapy , /physiology , /physiologyABSTRACT
A leptospirosis clinical-epidemiological study was made in humans and reservoirs in the state of Yucatßn, MÚxico. Interviews and serological analyses were made on 400 persons from an open population, 439 probable cases of leptospirosis and 1060 animal reservoirs (cows, pigs, dogs, rats and opossums). IgM Leptospira DipstickTM and Microscopic Agglutination Test (MAT) was used to detect human antibodies to leptospiras and serovar respectively. Leptospirosis incidence in humans was 2.2/100,000 inhab. in 1998, 0.7/100,000 in 1999 and 0.9/100,000 in 2000. Overall seroprevalence was 14.2 percent, relatively unchanged from seroprevalences observed 20 years ago. Highest seropositivity was found in people over 56 years of age, predominating males over females. Predominant serovars in the open population were tarassovi, hardjo, pomona and panama. Leptospirosis cases were most frequent in rural areas, and the anicteric course predominated over the icteric. The panama, icterohaemorrhagiae and pomona serovars predominated in both anicteric and icteric courses. Dogs, pigs and rodents had the highest seropositivity among the reservoirs. Contact with rodents and natural water sources were significant factors (p ú 0.05). Human cases (74 percent) occurred during the rainy season. It is concluded that leptospirosis is still a serious illness with important clinical and epidemiological implications in the state of Yucatßn, Mexico
Subject(s)
Animals , Humans , Male , Female , Adolescent , Adult , Middle Aged , Disease Reservoirs , Leptospirosis , Incidence , Leptospirosis , Mexico , Seroepidemiologic StudiesABSTRACT
Se presentan los casos de dos mujeres con hipogonadismo hipogonadotrópico y trastornos olfatorios. El diagnóstico de síndrome de Kallmann fue corroborado en ambos casos con imágenes de Resonancia Magnética que mostraron aplasia de los bulbos olfatorios en un caso, e hipoplasia en el otro. Se destaca la función de la Resonancia Magnética para la demostración inequívoca por imagen del defecto olfatorio. Se comenta la presencia clínica y se hace una revisión de la literatura