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1.
Sci Rep ; 12(1): 19645, 2022 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-36385623

RESUMO

Policies in sunny countries, such as those in the Mediterranean area, do not promote vitamin D supplementation despite some studies might suggest the high prevalence of sub-optimal levels. The objective was to determine the vitamin D levels by 25-hydroxyvitamin D (25(OH)D) of a Mediterranean population and their characteristics. This population-based study included a database of public health system from all individuals living in Catalonia > 18 years who had some measure of 25(OH)D between January 2018 and April 2021. More than half million people were classified based on 25(OH)D measurements to study their characteristics. Three vitamin D categories were created: < 20 ng/ml deficiency, 20-30 ng/ml insufficiency and > 30 ng/ml optimal. Less than 10% of the population residing in Catalonia had recent 25(OH)D determinations and the majority of determinations were in ≥ 45 years and in women. Around 80% of young people with determination had sub-optimal levels but the prevalence of vitamin D supplementation prescription increased with age which was associated with better values of 25(OH)D. In a Mediterranean area 25(OH)D determinations were low despite the high prevalence of suboptimal levels in the population with recent determination. In addition, the measurements were especially concentrated in people ≥ 45 years of age and in women who were, in addition, the groups to whom the most vitamin D supplementation was prescribed. On the contrary, young people presented few determinations of 25(OH)D and, although majority of them showed sub-optimal levels, vitamin D supplementation was not prescribed in most cases.


Assuntos
Deficiência de Vitamina D , Feminino , Humanos , Adolescente , Deficiência de Vitamina D/epidemiologia , Vitamina D , Vitaminas , Calcifediol , Grupos Raciais
2.
Pediatr. aten. prim ; 24(93)ene. - mar. 2022. tab
Artigo em Espanhol | IBECS | ID: ibc-210309

RESUMO

Introducción: el gold standard para el diagnóstico de reflujo ácido en Pediatría es la pHmetría 24 horas. La ecografía ha demostrado ser una técnica incruenta y existen pocos estudios que la comparen con la pHmetría. Métodos: estudio prospectivo, observacional y analítico. Se realizó estudio ecográfico a pacientes con indicación de pHmetría, y previa a esta. Se determinaron variables ecográficas propuestas por el grupo de ecografía de la SEGHNP (Gomes 1991 modificado), considerando la presencia de reflujo ácido patológico si tenía dos o más parámetros alterados. Resultados: se incluyeron 32 pacientes, 68,8% (n = 22) varones, entre 1 mes y 13 años. Tenían pHmetría patológica el 59,3% (n = 19). El diagnóstico de reflujo por ecografía según lo propuesto por la SEGHNP no se relacionó con el diagnóstico de reflujo ácido por pHmetría (p = 0,169). La ecografía presentó una sensibilidad de 60% y una especificidad del 61,5%, con valor predictivo positivo (VPP) de 70,58% y valor predictivo negativo de 53,3%. Al analizar cada variable ecográfica y compararla con la presencia de reflujo por pHmetría no hubo datos significativos. Sin embargo, un ángulo de Hiss patológico y una longitud del esófago abdominal menor de 1,3 cm se asociaron estadísticamente con reflujo ácido por pHmetría (p = 0,033), obteniendo un VPP, cociente de probabilidad positivo y probabilidad preprueba positiva altos (88,9%; 5,47; 89,1%, respectivamente), con proporción de falsos positivos bajo (7,7%). Conclusión: en nuestra población estudiada, los criterios ecográ9 (AU)ficos propuestos por la SEGHNP no se relacionan con pHmetría patológica, pero si la presencia de un esófago abdominal menor de 1,3 cm junto a un ángulo de Hiss mayor de 110°


Introduction: the gold standard for diagnosis of acid reflux in paediatric patients is 24-hour pH monitoring. Ultrasound is a non-invasive technique and few studies have compared it with pH monitoring.Methods: prospective, observational and analytical study. We performed an ultrasound examination in patients in whom pH monitoring was indicated before performance of the latter test. We analysed the sonographic variables proposed by the Ultrasound Group of the SEGHNP (modified Gomes 1991 criteria), with 2 or more abnormal sonographic parameters indicating the presence of pathological acid reflux.Results: the study included 32 patients, 68.8% (n = 22) male, aged 1 month to 13 years. The results of pH monitoring were pathological in 59.3% (n = 19). We did not find an association between the sonographic diagnosis of reflux according to the criteria proposed by SEGHNP and the diagnosis of reflux based on pH monitoring (p = 0.169). We found a sensitivity of 60% and a specificity of 61.5% with the use of ultrasound, with a positive predictive value (PPV) of 70.58% and a negative predictive value of 53.3%. When we compared each ultrasound variable separately to the presence of reflux determined by pH monitoring, we did not find any significant associations. However, we found a statistically significant association between the combination of an angle of His in the pathological range and an abdominal oesophagus length of less than 1.3 cm on ultrasound and the detection of acid reflux by pH monitoring (p = 0.033), with a high PPV, positive likelihood ratio and pre-test probability (88.9%, 5.47 and 89.1%, respectively) and a low false-positive rate (7.7%).Conclusion: in our sample, we did not find an association between the... (AU)


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Refluxo Gastroesofágico/diagnóstico por imagem , Ultrassonografia , Concentração de Íons de Hidrogênio , Sensibilidade e Especificidade , Estudos Prospectivos , Manometria
3.
Sci Rep ; 11(1): 16453, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385479

RESUMO

Our aim was to evaluate whether fatty liver index (FLI) is associated with the risk of type 2 diabetes (T2DM) development within the Spanish adult population and according to their prediabetes status; additionally, to examine its incremental predictive value regarding traditional risk factors. A total of 2260 subjects (Prediabetes: 641 subjects, normoglycemia: 1619 subjects) from the Di@bet.es cohort study were studied. Socio-demographic, anthropometric, clinical data and survey on habits were recorded. An oral glucose tolerance test was performed and fasting determinations of glucose, lipids and insulin were made. FLI was calculated and classified into three categories: Low (< 30), intermediate (30-60) and high (> 60). In total, 143 people developed diabetes at follow-up. The presence of a high FLI category was in all cases a significant independent risk factor for the development of diabetes. The inclusion of FLI categories in prediction models based on different conventional T2DM risk factors significantly increase the prediction power of the models when all the population was considered. According to our results, FLI might be considered an early indicator of T2DM development even under normoglycemic condition. The data also suggest that FLI could provide additional information for the prediction of T2DM in models based on conventional risk factors.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Adulto , Biomarcadores/metabolismo , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
4.
Clin Nutr ; 40(5): 2587-2598, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33932804

RESUMO

BACKGROUND: Fish could play a role in preventing type 2 diabetes (T2D) but there has been little specification about the type of fish and the preventive mechanism involved in its health claim. The sardine is a source of omega-3 and taurine that, in isolation or in synergy, would produce T2D-delaying through different molecular mechanism. HYPOTHESIS: The consumption of twice a week of sardine, during one year would reduce T2D-developing risk in a population with prediabetes (preDM) and old age. DESIGN: 152 subjects with fasting glucose between 100-124 mg/dL aged ≥65 yo were recruited from three primary care centers in Barcelona and were randomly distributed among two interventional groups: control group (CG) and sardine group (SG). Both groups received same T2D-prevention nutritional during a year but only SG had to add 200 g of sardine per week. All variables were collected before to start and at the end of the diet. (ClinicalTrials.gov: NCT03557541). RESULTS: 152 people were randomized into CG (n=77) and SG (n=75) with 18 and 12 drop outs respectively. Subjects in SG, significantly compared to CG, decreased percentage classified-individuals in a very high risk group to develop T2D according to FINDRISC (p=0.035). In addition to increasing HDL-cholesterol and adiponectin and decreasing triglycerides (p<0.05) and blood pressure (<0.05), SG showed a lower HOMA-IR (p=0.032). The consumption of sardine characteristics nutrients as omega-3, EPA and DHA, vitamin D, fluorine and taurine were higher for SG (p<0.05). These results agreed with the increased of taurine, fatty acid (FA) omega-3 and bile acids circulating metabolites (p<0.05). Changes erythrocyte membrane FA were detected only in SG with a decrease of 5 omega-6 FA (p<0.001) and an increase of 3 omega-3 FA types (p<0.001). CONCLUSION: We conclude that a year T2D-prevention diet with sardine supplementation has a greater protective effect against developing T2D and CV events.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Dieta , Peixes , Estado Pré-Diabético , Idoso , Animais , Glicemia , Pressão Sanguínea , Composição Corporal , Ingestão de Energia , Feminino , Humanos , Masculino
5.
Acta pediatr. esp ; 78(3/4): e171-e174, mar.-abr. 2020. ilus
Artigo em Espanhol | IBECS | ID: ibc-202531

RESUMO

La desnutrición neonatal supone uno de los principales retos diagnósticos en la práctica diaria. Ante un neonato con desnutrición será necesario descartar las causas que con más frecuencia pueden producirla, pero también sospechar otras más inusuales como es la infección por el virus de la inmunodeficiencia humana. Se presenta el caso de un neonato varón de 27 días de vida que presentaba una desnutrición neonatal grave, realizándose el diagnóstico diferencial del mismo y una revisión bibliográfica a propósito del tema


Neonatal malnutrition is one of the main diagnostic challenges in the daily practice. It will always be necessary to discard the causes that more frequently can produce it, but also is important to take into account other more unusual causes. We present the case of a 27-day-old male neonate with severe neonatal malnutrition and we make a differential diagnosis and a literature review of the subject


Assuntos
Humanos , Masculino , Recém-Nascido , Desnutrição/virologia , Doenças do Recém-Nascido/virologia , Infecções por HIV/complicações , Transmissão Vertical de Doenças Infecciosas , Doenças do Recém-Nascido/tratamento farmacológico , Desnutrição/tratamento farmacológico
6.
Acta pediatr. esp ; 78(3/4): e144-e146, mar.-abr. 2020. ilus
Artigo em Espanhol | IBECS | ID: ibc-202542

RESUMO

Candida albicans es un hongo frecuentemente aislado en la cavidad oral, aunque sólo produce infección en determinados casos. Una entidad rara, principalmente en la edad pediátrica, asociada a este microorganismo es la lengua vellosa negra, una patología benigna y autolimitada pero que puede alertar por su alto impacto estético. Presentamos el caso de un preescolar varón de dos años con enfermedad inflamatoria intestinal en tratamiento inmunosupresor y antibiótico por un absceso perianal, que acude a consulta por presentar lengua negra


Candida albicans is a fungus frequently localized in oral cavity. In spite of that, it only produces disease in certain cases. A rare presentation form associated with this microorganism, mainly in pediatric age, is the black hairy tongue, a benign and self-limited pathology that can alert for its high aesthetic impact. We present the case of a two-year-old male who has black tongue in the context of inflammatory bowel disease treated with immunosuppressant and antibiotic drugs for a perianal abcess


Assuntos
Humanos , Masculino , Pré-Escolar , Língua Pilosa/microbiologia , Candida albicans/isolamento & purificação , Língua Pilosa/tratamento farmacológico , Fluconazol/uso terapêutico , Antifúngicos/uso terapêutico , Nistatina/uso terapêutico
7.
Sci Rep ; 10(1): 2765, 2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066839

RESUMO

Our aim was to determine the incidence of type 2 diabetes mellitus in a nation-wide population based cohort from Spain (di@bet.es study). The target was the Spanish population. In total 5072 people older than 18 years,were randomly selected from all over Spain). Socio-demographic and clinical data, survey on habits (physical activity and food consumption) and weight, height, waist, hip and blood pressure were recorder. A fasting blood draw and an oral glucose tolerance test were performed. Determinations of serum glucose were made. In the follow-up the same variables were collected and HbA1c was determined. A total of 2408 subjects participated in the follow-up. In total, 154 people developed diabetes (6.4% cumulative incidence in 7.5 years of follow-up). The incidence of diabetes adjusted for the structure of age and sex of the Spanish population was 11.6 cases/1000 person-years (IC95% = 11.1-12.1). The incidence of known diabetes was 3.7 cases/1000 person-years (IC95% = 2.8-4.6). The main risk factors for developing diabetes were the presence of prediabetes in cross-sectional study, age, male sex, obesity, central obesity, increase in weight, and family history of diabetes. This work provides data about population-based incidence rates of diabetes and associated risk factors in a nation-wide cohort of Spanish population.


Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Obesidade/epidemiologia , Adulto , Idoso , Glicemia , Pressão Sanguínea , Peso Corporal , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/patologia , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Jejum , Feminino , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/patologia , Fatores de Risco , Espanha/epidemiologia
8.
Clin Nutr ; 39(2): 524-532, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30876826

RESUMO

BACKGROUND: Prediabetes and old age are both high risk factors for developing Type 2 Diabetes (T2D), while obesity is one of the most important factors triggering the disease. Nutritional interventions are the most effective tool for preventing T2D, as they improve different biochemical and anthropometric outcomes and growth-promoting/inhibiting gut microbiota populations. However, to date there are no specific dietary recommendations to stop the development of T2D in elderly groups, for whom hypocaloric diets and other commonly used weight-loss programs could be considered dangerous. The objective of our study, thus, was to understand the impact of dietary patterns on T2D risk as related to gut microbiota profile in obese and non-obese elderly prediabetic subjects. METHODS: A cross-sectional study was performed in 182 subjects ≥65 years old with prediabetes, divided into obese (OB) or non-obese (NOB) subgroups, and their risk of developing T2D was measured according to FINDRISK score and biochemical parameters. Also, clusters into different dietary patterns in each group by PCA analysis was related with gut microbiota, which was analyzed from stool samples by qPCR. The creation of clusters was used to re-evaluate T2D risk. RESULTS: OB was at higher risk of developing T2D and showed worse metabolic outcomes. Unhealthier and healthier dietary pattern clusters were observed for both OB (OB-6 and OB-5 respectively) and NOB (NOB-2 and NOB-3 respectively) groups. Results obtained from the gut microbiota showed that only Prevotella was higher in NOB, but when comparisons were made between clusters, a clear relation with dietary pattern was observed; showing in healthier dietary clusters a decrease in Prevotella, an increase of Faecalibacterium prausnitzii and an increase in lactic acid bacteria. T2D risk was greater in the obese group between unhealthier dietary clusters. No difference between healthier dietary clusters was observed. CONCLUSION: A healthy dietary pattern and the growth-promoting beneficial and growth-inhibiting disadvantageous gut microbiota populations linked to it provide protection against the development of T2D in an obese population with advanced age and preDM.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Dieta Saudável/métodos , Microbioma Gastrointestinal/fisiologia , Obesidade/epidemiologia , Idoso , Comorbidade , Estudos Transversais , Dieta Saudável/estatística & dados numéricos , Feminino , Humanos , Masculino , Medição de Risco , Espanha/epidemiologia
9.
Oncogene ; 38(28): 5739, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31053808

RESUMO

The original microRNA hybridization data for this article, which has been available for the scientific community upon request, has now been deposited in the GEO repository under accession number GSE124432.

10.
J Bone Oncol ; 13: 123-135, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30591866

RESUMO

Adjuvant bisphosphonates improve disease outcomes in postmenopausal early breast cancer (EBC) but the long-term effects are poorly described. The AZURE trial (ISRCTN79831382) was designed to determine whether adjuvant zoledronic acid (ZOL) improves disease outcomes in EBC. Previous analyses showed no effect on overall outcomes but identified benefits in postmenopausal women. Here we present the long-term risks and benefits of adjuvant ZOL with 10-years follow-up. PATIENTS AND METHODS: 3360 patients with stage II/III breast cancer were included in an academic, international, phase III, randomized, open label trial. Patients were followed up on a regular schedule until 10 years. Patients were randomized on a 1:1 basis to standard adjuvant systemic therapy +/- intravenous ZOL 4 mg every 3-4 weeks x6, and then at reduced frequency to complete 5 years treatment. The primary outcome was disease free survival (DFS). Secondary outcomes included invasive DFS (IDFS), overall survival (OS), sites of recurrence, skeletal morbidity and treatment outcomes according to primary tumor amplification of the transcription factor, MAF. Pre-planned subgroup analyses focused on interactions between menopausal status and treatment effects. RESULTS: With a median follow up of 117 months [IQR 70.4-120.4), DFS and IDFS were similar in both arms (HRDFS  = 0.94, 95%CI = 0.84-1.06, p = 0.340; HRIDFS  = 0.91, 95%CI = 0.82-1.02, p = 0.116). However, outcomes remain improved with ZOL in postmenopausal women (HRDFS  = 0.82, 95%CI = 0.67-1.00; HRIDFS  = 0.78, 95%CI = 0.64-0.94). In the 79% of tested women with a MAF FISH negative tumor, ZOL improved IDFS (HRIDFS  = 0.75, 95%CI = 0.58-0.97) and OS HROS  = 0.69, 95%CI = 0.50-0.94), irrespective of menopause. ZOL did not improve disease outcomes in MAF FISH + tumors. Bone metastases as a first DFS recurrence (BDFS) were reduced with ZOL (HRB-DFS  = 0.76, 95%CI = 0.63-0.92, p = 0.005). ZOL reduced skeletal morbidity with fewer fractures and skeletal events after disease recurrence. 30 cases of osteonecrosis of the jaw in the ZOL arm (1.8%) have occurred. CONCLUSIONS: Disease benefits with adjuvant ZOL in postmenopausal early breast cancer persist at 10 years of follow-up. The biomarker MAF identified a patient subgroup that derived benefit from ZOL irrespective of menopausal status.

11.
Rev. calid. asist ; 32(4): 234-239, jul.-ago. 2017. ilus
Artigo em Espanhol | IBECS | ID: ibc-164253

RESUMO

Un proceso asistencial integrado (PAI) es una herramienta cuyo propósito es aumentar la efectividad de las actuaciones clínicas a través de una mayor coordinación y garantía de continuidad asistencial. Los PAI sitúan al paciente como el eje central de la organización asistencial. Se definen como el conjunto de actividades que realizan los proveedores de la atención sanitaria con la finalidad de incrementar el nivel de salud y el grado de satisfacción de la población que recibe los servicios. La elaboración de un PAI precisa analizar el flujo de actividades, la interrelación entre profesionales y dispositivos asistenciales y las expectativas del paciente. En este artículo se presenta y se discute la metodología para la elaboración de un PAI, así como los factores de éxito para su definición y su efectiva implantación. Se explica también, a modo de ejemplo, el reciente PAI para hipoglucemias en personas con diabetes mellitus tipo 2 elaborado por un equipo multidisciplinar y avalado por varias sociedades científicas (AU)


An Integrated Healthcare Pathway (PAI) is a tool which has as its aim to increase the effectiveness of clinical performance through greater coordination and to ensure continuity of care. PAI places the patient as the central focus of the organisation of health services. It is defined as the set of activities carried out by the health care providers in order to increase the level of health and satisfaction of the population receiving services. The development of a PAI requires the analysis of the flow of activities, the inter-relationships between professionals and care teams, and patient expectations. The methodology for the development of a PAI is presented and discussed in this article, as well as the success factors for its definition and its effective implementation. It also explains, as an example, the recent PAI for Hypoglycaemia in patients with Type 2 Diabetes Mellitus developed by a multidisciplinary team and supported by several scientific societies (AU)


Assuntos
Humanos , Terapias Complementares/organização & administração , Terapias Complementares/normas , Assistência ao Paciente/normas , Hipoglicemia/diagnóstico , Hipoglicemia/terapia , Diabetes Mellitus Tipo 2/epidemiologia , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Garantia da Qualidade dos Cuidados de Saúde/normas , Diabetes Mellitus Tipo 2/prevenção & controle , Protocolos Clínicos
12.
Rev Calid Asist ; 32(4): 234-239, 2017.
Artigo em Espanhol | MEDLINE | ID: mdl-28283260

RESUMO

An Integrated Healthcare Pathway (PAI) is a tool which has as its aim to increase the effectiveness of clinical performance through greater coordination and to ensure continuity of care. PAI places the patient as the central focus of the organisation of health services. It is defined as the set of activities carried out by the health care providers in order to increase the level of health and satisfaction of the population receiving services. The development of a PAI requires the analysis of the flow of activities, the inter-relationships between professionals and care teams, and patient expectations. The methodology for the development of a PAI is presented and discussed in this article, as well as the success factors for its definition and its effective implementation. It also explains, as an example, the recent PAI for Hypoglycaemia in patients with Type 2 Diabetes Mellitus developed by a multidisciplinary team and supported by several scientific societies.


Assuntos
Procedimentos Clínicos , Prestação Integrada de Cuidados de Saúde/métodos , Diabetes Mellitus Tipo 2/complicações , Humanos , Hipoglicemia/etiologia , Hipoglicemia/terapia , Espanha
13.
Sci Rep ; 6: 19223, 2016 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-26771085

RESUMO

Transcriptional and signaling networks establish complex cross-regulatory interactions that drive cellular differentiation during development. Using microarrays we identified the gene encoding the ligand Wnt9a as a candidate target of Neurogenin3, a basic helix-loop-helix transcription factor that functions as a master regulator of pancreatic endocrine differentiation. Here we show that Wnt9a is expressed in the embryonic pancreas and that its deficiency enhances activation of the endocrine transcriptional program and increases the number of endocrine cells at birth. We identify the gene encoding the endocrine transcription factor Nkx2-2 as one of the most upregulated genes in Wnt9a-ablated pancreases and associate its activation to reduced expression of the Wnt effector Tcf7l2. Accordingly, in vitro studies confirm that Tcf7l2 represses activation of Nkx2-2 by Neurogenin3 and inhibits Nkx2-2 expression in differentiated ß-cells. Further, we report that Tcf7l2 protein levels decline upon initiation of endocrine differentiation in vivo, disclosing the downregulation of this factor in the developing endocrine compartment. These findings highlight the notion that modulation of signalling cues by lineage-promoting factors is pivotal for controlling differentiation programs.


Assuntos
Organogênese , Pâncreas/embriologia , Pâncreas/metabolismo , Proteína 2 Semelhante ao Fator 7 de Transcrição/metabolismo , Proteínas Wnt/deficiência , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Contagem de Células , Células Endócrinas/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Inativação de Genes , Proteína Homeobox Nkx-2.2 , Proteínas de Homeodomínio/genética , Camundongos , Modelos Biológicos , Proteínas do Tecido Nervoso/metabolismo , Organogênese/genética , Pâncreas/anatomia & histologia , Pâncreas/citologia , Fenótipo , Transdução de Sinais , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Fatores de Transcrição/genética , Proteínas de Peixe-Zebra
14.
Mol Endocrinol ; 28(9): 1558-70, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25058603

RESUMO

Human genetic studies have revealed that the T minor allele of single nucleotide polymorphism rs7903146 in the transcription factor 7-like 2 (TCF7L2) gene is strongly associated with an increased risk of diabetes by 30%-40%. Molecular and clinical studies are of great importance for understanding how this unique variation in TCF7L2 influences type 2 diabetes (T2D) onset and progression. At the molecular level, some studies have been performed in diabetic mice and pancreatic islets from healthy human donors. Whereas TCF7L2 mRNA levels are up-regulated in islets, protein levels are down-regulated. We performed studies on TCF7L2 splicing, mRNA expression, and protein levels in immortalized human lymphocytes from nondiabetic individuals and T2D patients carrying the C/C or the at-risk T/T genotype. Our results show differential expression of TCF7L2 splice variants between nondiabetic and T2D patients carrying the at-risk genotype, as well as differences in protein levels. Therefore, we investigated the regulation of splice variants, and our results propose that splicing of exon 4 is under control of the serine-arginine-rich factor transformer 2 ß (TRA2B). Finally, we studied the endoplasmic reticulum stress pathways, looking for a posttranslational explanation. We saw a shift in the activation of these pathways between nondiabetic individuals and T2D patients carrying the at-risk genotype. These results suggest that, in human immortalized lymphocytes carrying the at-risk T/T genotype, first the differential expression of TCF7L2 splice variants implies a regulation, at least for exon 4, by TRA2B and second, the differential protein levels between both T/T carriers point to a different activation of endoplasmic reticulum stress pathways.


Assuntos
Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Regulação da Expressão Gênica , Biossíntese de Proteínas , Proteína 2 Semelhante ao Fator 7 de Transcrição/metabolismo , Transcrição Gênica , Idoso , Alelos , Processamento Alternativo , Sítios de Ligação , Éxons , Feminino , Genótipo , Glucose/metabolismo , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores de Estrogênio/metabolismo , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética
15.
Obesity (Silver Spring) ; 22(3): 698-704, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23804579

RESUMO

OBJECTIVE: This study compares the patterns of visceral (VIS) and subcutaneous (SC) adipose tissue (AT)-derived metabolites from non-obese (BMI 24-26 kg/m2) and obese subjects (BMI > 40 kg/m2) with no major metabolic risk factors other than BMI. METHODS: SC- and VIS- AT obtained from obese (Ob) and non-obese (NOb) subjects during surgery were incubated to obtain their metabolites. Differences related to obesity or anatomical provenances of AT were assessed using an untargeted metabolomics approach based on gas chromatography-mass spectrometry. RESULTS: The overall effect of obesity on the metabolite profile resulted more remarkable than the effect of regional AT. Only the depletion of 2-ketoisocaproic (2-KIC) acid reached statistical significance for the SC-AT alone, although it was observed in both depots. Obesity induced more significant changes in several amino acids levels of the VIS-AT metabolites. On the one hand, higher released levels of glutamine and alanine were detected in the VIS- obese AT, whereas on the other, the VIS- obese AT presented a diminished uptake of essential amino acids (methionine, threonine, lysine), BCAAs, leucine, and serine. CONCLUSION: This study shows that obesity markedly affects the amino acid metabolic signature of the AT before the clinical onset of other significant metabolic alterations aside from BMI.


Assuntos
Distribuição da Gordura Corporal , Gordura Intra-Abdominal/metabolismo , Metaboloma , Obesidade Mórbida/metabolismo , Adulto , Aminoácidos/metabolismo , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Gordura Subcutânea/metabolismo
16.
Oncogene ; 33(23): 3054-63, 2014 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-23851508

RESUMO

Matrix metalloproteinases (MMPs) have been traditionally implicated in cancer progression because of their ability to degrade the extracellular matrix. However, some members of the MMP family have recently been identified as proteases with antitumor properties. Thus, it has been described that collagenase-2 (MMP-8) has a protective role in tumor and metastasis progression, but the molecular mechanisms underlying these effects are unknown. We show herein that Mmp8 expression causes a decrease in miR-21 levels that in turn leads to a reduction in tumor growth and lung metastasis formation by MDA-MB-231 (4175) breast cancer cells. By using both in vitro and in vivo models, we demonstrate that the mechanism responsible for these MMP-8 beneficial effects involves cleavage of decorin by MMP-8 and a subsequent reduction of transforming growth factor ß (TGF-ß) signaling that controls miR-21 levels. In addition, miR-21 downregulation induced by MMP-8 increases the levels of tumor suppressors such as programmed cell death 4, which may also contribute to the decrease in tumor formation and metastasis of breast cancer cells overexpressing this metalloproteinase. These findings reveal a new signaling pathway for cancer regulation controlled by MMP-8, and contribute to clarify the molecular mechanisms by which tumor-defying proteases may exert their protective function in cancer and metastasis.


Assuntos
Neoplasias da Mama/metabolismo , Decorina/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Metaloproteinase 8 da Matriz/metabolismo , MicroRNAs/metabolismo , Animais , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Metástase Neoplásica , RNA Interferente Pequeno/farmacologia , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Ann Nutr Metab ; 62(4): 339-46, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23838479

RESUMO

BACKGROUND AND AIMS: Mediterranean diet (MedDiet) is causally related to diabetes and is a dietary pattern recommended to individuals with diabetes. We investigated MedDiet adherence in individuals with prediabetes and unknown (PREDM/UKDM) or known diabetes (KDM) compared to those with normal glucose metabolism (NORMAL). METHODS: This was a national, population-based, cross-sectional, cluster-sampling study. MedDiet adherence was scored (MedScore, mean ± SD 24 ± 5) using a qualitative food frequency questionnaire. Logistic regression was used to examine the association between MedScore and PREDM/UKDM or KDM versus control subjects. RESULTS: We evaluated 5,076 individuals. Mean age was 50 years, 57% were female, 826 (582/244) were PREDM/UKDM, 478 were KDM and 3,772 were NORMAL. Mean age increased across MedScore tertiles (46, 51 and 56 years, p < 0.0001). Higher age-adjusted adherence to MedDiet (5-unit increment in the MedScore) was associated with lower and nondifferent odds (OR, 95% CI) of prevalent PREDM/UKDM (0.88, 0.81-0.96, p = 0.001) and KDM (0.97, 0.87-1.07, p = 0.279), respectively, compared to individuals in the NORMAL group. CONCLUSIONS: In a representative sample of the whole Spanish population, MedDiet adherence is independently associated with PREDM/UKDM. Therapeutic intervention may be, in part, responsible for the lack of differences in adherence observed between the KDM and NORMAL groups. However, reverse causation bias cannot be ruled out in cross-sectional studies.


Assuntos
Glicemia/análise , Diabetes Mellitus/epidemiologia , Dieta Mediterrânea , Cooperação do Paciente , Estado Pré-Diabético/epidemiologia , Adulto , Idoso , Análise de Variância , Estudos de Casos e Controles , Estudos Transversais , Inquéritos sobre Dietas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Espanha/epidemiologia
18.
Eur J Clin Nutr ; 67(9): 911-6, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23859999

RESUMO

BACKGROUND: Despite the marked increase in cardiovascular risk factors in Spain in recent years, the prevalence and incidence of cardiovascular diseases have not risen as expected. Our objective is to examine the association between consumption of olive oil and the presence of cardiometabolic risk factors in the context of a large study representative of the Spanish population. SUBJECTS AND METHODS: A population-based, cross-sectional, cluster sampling study was conducted. The target population was the whole Spanish population. A total of 4572 individuals aged ≥ 18 years in 100 clusters (health centers) were randomly selected with a probability proportional to population size. The main outcome measures were clinical and demographic structured survey, lifestyle survey, physical examination (weight, height, body mass index, waist, hip and blood pressure) and oral glucose tolerance test (OGTT) (75 g). RESULTS: Around 90% of the Spanish population use olive oil, at least for dressing, and slightly fewer for cooking or frying. The preference for olive oil is related to age, educational level, alcohol intake, body mass index and serum glucose, insulin and lipids. People who consume olive oil (vs sunflower oil) had a lower risk of obesity (odds ratio (OR)=0.62 (95% confidence interval (CI)=0.41-0.93, P=0.02)), impaired glucose regulation (OR=0.49 (95% CI=0.28-0.86, P=0.04)), hypertriglyceridemia (OR=0.53 (95% CI=0.33-0.84, P=0.03)) and low HDL cholesterol levels (OR=0.40 (95% CI=0.26-0.59, P=0.0001)). CONCLUSIONS: The results show that consumption of olive oil has a beneficial effect on different cardiovascular risk factors, particularly in the presence of obesity, impaired glucose tolerance or a sedentary lifestyle.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Intolerância à Glucose/sangue , Intolerância à Glucose/dietoterapia , Óleos de Plantas/administração & dosagem , Adulto , Idoso , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , Peso Corporal , Doenças Cardiovasculares/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Análise por Conglomerados , Estudos Transversais , Feminino , Teste de Tolerância a Glucose , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/prevenção & controle , Insulina/sangue , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/prevenção & controle , Razão de Chances , Azeite de Oliva , Prevalência , Fatores de Risco , Comportamento Sedentário , Espanha/epidemiologia , Óleo de Girassol , Triglicerídeos/sangue
20.
Int J Endocrinol ; 2012: 872305, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22848215

RESUMO

Objective. To evaluate the association between diabetes mellitus and health-related quality of life (HRQOL) controlled for several sociodemographic and anthropometric variables, in a representative sample of the Spanish population. Methods. A population-based, cross-sectional, and cluster sampling study, with the entire Spanish population as the target population. Five thousand and forty-seven participants (2162/2885 men/women) answered the HRQOL short form 12-questionnaire (SF-12). The physical (PCS-12) and the mental component summary (MCS-12) scores were assessed. Subjects were divided into four groups according to carbohydrate metabolism status: normal, prediabetes, unknown diabetes (UNKDM), and known diabetes (KDM). Logistic regression analyses were conducted. Results. Mean PCS-12/MCS-12 values were 50.9 ± 8.5/ 47.6 ± 10.2, respectively. Men had higher scores than women in both PCS-12 (51.8 ± 7.2 versus 50.3 ± 9.2; P < 0.001) and MCS-12 (50.2 ± 8.5 versus 45.5 ± 10.8; P < 0.001). Increasing age and obesity were associated with a poorer PCS-12 score. In women lower PCS-12 and MCS-12 scores were associated with a higher level of glucose metabolism abnormality (prediabetes and diabetes), (P < 0.0001 for trend), but only the PCS-12 score was associated with altered glucose levels in men (P < 0.001 for trend). The Odds Ratio adjusted for age, body mass index (BMI) and educational level, for a PCS-12 score below the median was 1.62 (CI 95%: 1.2-2.19; P < 0.002) for men with KDM and 1.75 for women with KDM (CI 95%: 1.26-2.43; P < 0.001), respectively. Conclusion. Current study indicates that increasing levels of altered carbohydrate metabolism are accompanied by a trend towards decreasing quality of life, mainly in women, in a representative sample of Spanish population.

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