Arterial hypertension diagnosis: A problem? / Diagnóstico de hipertensión arterial: ¿un problema?

Introduction: Arterial hypertension (AHT), a leading risk factor in terms of attributable mortality, is a major public health problem, especially for primary care where most patients are diagnosed and followed up. Correct AHT diagnosis requires adequate theoretical knowledge and technical skills in physicians and nurses. The aim of this study was to evaluate the knowledge and skills used in initial AHT diagnosis by health professionals and to describe the factors that contribute to variability. Methodology: Cross-sectional observational study in a sample of 385 primary care physicians and nurses recruited in a Catalan health region. Using a validated questionnaire called ARC, we evaluated theoretical knowledge and analysed factors that may contribute to response variability. We also evaluated practical measurement skills using objective structured clinical examination tests. Results: Medical and nursing primary care professionals had deficient knowledge and skills for initial AHT diagnosis and measurement, despite self-perceiving their knowledge to be sufficient. However, professionals who had received postgraduate or other AHT training in the previous year scored better in the ARC questionnaire. Conclusions: The results of this study point to insufficient AHT expertise to ensure quality clinical practice, suggesting that ongoing theoretical and practical training needs to be improved. (AU)

Introducción: La hipertensión arterial (HTA) es un factor de riesgo destacado en términos de mortalidad atribuible, y un gran problema de salud pública, en especial para la atención primaria, donde se diagnostica y se realiza el seguimiento a la mayoría de los pacientes. El diagnóstico correcto de HTA requiere un conocimiento teórico y una competencia técnica adecuados por parte de médicos y enfermeros. El objetivo de este estudio fue evaluar el conocimiento y las competencias aplicados al diagnóstico inicial de HTA por parte de los profesionales sanitarios, así como describir los factores que contribuyen a la variabilidad. Metodología: Estudio observacional transversal de una muestra de 385 médicos y enfermeros de atención primaria seleccionados en una región sanitaria de Cataluña. Utilizando un cuestionario validado denominado ARC, evaluamos el conocimiento técnico y analizamos los factores que probablemente contribuyen a la variabilidad de la respuesta. También evaluamos las técnicas prácticas de medición utilizando una prueba de examen clínico objetivo. Resultados: Los profesionales médicos y enfermeros de atención primaria tenían un conocimiento deficiente para realizar el diagnóstico y la medición iniciales de HTA, a pesar de autopercibir que dicho conocimiento es suficiente. Sin embargo, los profesionales que recibieron formación de posgrado en HTA durante el último año obtuvieron una mejor puntuación en el cuestionario ARC. Conclusiones: Los resultados de este estudio señalan una experiencia insuficiente sobre HTA para garantizar una práctica clínica de calidad, lo cual demuestra que debe mejorarse la formación teórica y práctica continua. (AU)

Arterial hypertension diagnosis: A problem?

INTRODUCTION: Arterial hypertension (AHT), a leading risk factor in terms of attributable mortality, is a major public health problem, especially for primary care where most patients are diagnosed and followed up. Correct AHT diagnosis requires adequate theoretical knowledge and technical skills in physicians and nurses. The aim of this study was to evaluate the knowledge and skills used in initial AHT diagnosis by health professionals and to describe the factors that contribute to variability. METHODOLOGY: Cross-sectional observational study in a sample of 385 primary care physicians and nurses recruited in a Catalan health region. Using a validated questionnaire called ARC, we evaluated theoretical knowledge and analysed factors that may contribute to response variability. We also evaluated practical measurement skills using objective structured clinical examination tests. RESULTS: Medical and nursing primary care professionals had deficient knowledge and skills for initial AHT diagnosis and measurement, despite self-perceiving their knowledge to be sufficient. However, professionals who had received postgraduate or other AHT training in the previous year scored better in the ARC questionnaire. CONCLUSIONS: The results of this study point to insufficient AHT expertise to ensure quality clinical practice, suggesting that ongoing theoretical and practical training needs to be improved.

Respuesta a la carta al editor referida a «Importancia del conocimiento óptimo de los profesionales sanitarios en el diagnóstico inicial de la HTA para su valoración» / Reply: Importance of the optimal knowledge of healthcare professionals in the initial diagnosis of high blood pressure

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A new validated international questionnaire on health professionals' knowledge of hypertension diagnosis.

INTRODUCTION: Arterial hypertension is the main factor in attributable mortality. It is therefore considered one of the most important public health problems. Health professionals require special training and skills to make a diagnosis. No studies have been found in the literature search that use a validated instrument (questionnaire) to assess health professionals' theoretical and practical knowledge in diagnosing hypertension or measuring blood pressure. AIM: To design and validate an instrument for gauging health professionals' theoretical knowledge in measuring blood pressure for the initial diagnosis of hypertension. METHODOLOGY: Design, development, and validation of a questionnaire in three languages (English, Spanish, and Catalan) to assess knowledge based on the Rasch-item response theory model. RESULTS: A questionnaire in three languages was constructed and validated. It consisted of 23 questions on the theoretical knowledge of the initial diagnosis of hypertension and was called the ARC questionnaire. It met all the Rasch-IRT model criteria: item- and person-fit measurement, unidimensionality, local independence, invariance, targeting, and reliability. CONCLUSIONS: The ARC questionnaire is a validated tool that enables objective and uniform analyses of knowledge in the initial diagnosis of hypertension among medical and nursing professionals, comparing them over time. It allows for established strategies to be developed to enhance this knowledge.

A new validated international questionnaire on health professionals’ knowledge of hypertension diagnosis

Introduction: Arterial hypertension is the main factor in attributable mortality. It is therefore considered one of the most important public health problems. Health professionals require special training and skills to make a diagnosis. No studies have been found in the literature search that use a validated instrument (questionnaire) to assess health professionals’ theoretical and practical knowledge in diagnosing hypertension or measuring blood pressure. Aim: To design and validate an instrument for gauging health professionals’ theoretical knowledge in measuring blood pressure for the initial diagnosis of hypertension. Methodology: Design, development, and validation of a questionnaire in three languages (English, Spanish, and Catalan) to assess knowledge based on the Rasch-item response theory model. Results: A questionnaire in three languages was constructed and validated. It consisted of 23 questions on the theoretical knowledge of the initial diagnosis of hypertension and was called the ARC questionnaire. It met all the Rasch-IRT model criteria: item- and person-fit measurement, unidimensionality, local independence, invariance, targeting, and reliability. Conclusions: The ARC questionnaire is a validated tool that enables objective and uniform analyses of knowledge in the initial diagnosis of hypertension among medical and nursing professionals, comparing them over time. It allows for established strategies to be developed to enhance this knowledge.(AU)

Introducción: La hipertensión arterial es el principal factor de mortalidad atribuible. Es por eso que se considera uno de los problemas de salud pública más importantes. Los profesionales de la salud necesitan una formación y unas habilidades especiales para realizar un diagnóstico. En la literatura actual no se han encontrado estudios que utilicen un instrumento validado (cuestionario) para evaluar los conocimientos teóricos y prácticos de los profesionales de la salud en el diagnóstico de la hipertensión o medición de la tensión arterial. Objetivo: Diseñar y validar un instrumento para medir los conocimientos teóricos de los profesionales de la salud en la medida de la tensión arterial para el diagnóstico inicial de la hipertensión. Metodología: Diseño, desarrollo y validación de un cuestionario en tres idiomas (inglés, español y catalán) para evaluar los conocimientos basados en el modelo de Rasch (teoría de la respuesta al ítem). Resultados: Se construyó y validó un cuestionario en tres idiomas. Constaba de 23 preguntas sobre los conocimientos teóricos en el diagnóstico inicial de hipertensión que se denominó cuestionario ARC. Cumplió con todos los criterios del modelo Rasch-IRT: medición de ajuste (fit) al ítem y a la persona, unidimensionalidad, independencia local, invarianza, targeting y fiabilidad. Conclusiones: El cuestionario ARC es una herramienta validada que permite realizar análisis objetivos y uniformes de los conocimientos en el diagnóstico inicial de la hipertensión entre profesionales de medicina y de enfermería, comparándolos en el tiempo. Permite desarrollar estrategias establecidas para potenciar este conocimiento.(AU)

The gut mycobiome composition is linked to carotid atherosclerosis.

The mycobiotic component of the microbiota comprises an integral, yet under-researched, part of the gastrointestinal tract. Here, we present a preliminary study of the possible contribution of gut mycobiota to sub-clinical atherosclerosis in a well-characterised group of obese and non-obese subjects in association with the Framingham Risk Score (FRS) and carotid intima-media thickness (cIMT). From all taxa identified, the relative abundance of the phylum Zygomycota, comprising the family Mucoraceae and genus Mucor, was negatively associated with cIMT and this association remained significant after controlling for false discovery rate. Obese subjects with detectable Mucor spp. had a similar cardiovascular risk profile as non-obese subjects. Interestingly, the relative abundance of Mucor racemosus was negatively associated both with FRS and cIMT. Partial least square discriminant analyses modelling, evaluating the potential relevance of gut mycobiota in patients stratified by mean values of cIMT, showed that even a 1 component model had a high accuracy (0.789), with a high R2 value (0.51). Variable importance in projection scores showed that M. racemosus abundance had the same impact in the model as waist-to-hip ratio, high-density lipoprotein-cholesterol, fasting triglycerides or fasting glucose, suggesting that M. racemosus relative abundance in the gut may be a relevant biomarker for cardiovascular risk.

Neuroinflammation in obesity: circulating lipopolysaccharide-binding protein associates with brain structure and cognitive performance.

BACKGROUND/OBJECTIVES: Growing evidence implicates neuroinflammation in the pathogenesis of diet-induced obesity and cognitive dysfunction in rodent models. Obesity is associated with reduced white matter integrity and cognitive decline. Circulating lipopolysaccharide binding protein (LBP) concentration is known to be increased in patients with obesity. Here, we aimed to evaluate whether circulating LBP is associated longitudinally with white matter structure and cognitive performance according to obesity status. SUBJECTS/METHODS: This longitudinal study analyzed circulating LBP (ELISA), DTI-metrics (axial diffusivity (L1), fractional anisotropy (FA) and radial diffusivity (RD)) in specific regions of the white matter of 24 consecutive middle-aged obese subjects (13 women) and 20 healthy volunteers (10 women) at baseline and two years later. Digit Span Test (DST) was used as a measure of working memory/short-term verbal memory. RESULTS: Circulating LBP concentration was associated with FA and L1 values of several white matter regions both at baseline and follow-up. The associations remained significant after controlling for age, BMI, fat mass and plasma high sensitivity C-reactive protein. Importantly, the increase in LBP over time impacted negatively on FA and L1 values and on DST performance. CONCLUSIONS: Circulating LBP associates with brain white matter integrity and working memory/short-term verbal memory in both obese and non-obese subjects.

Decreased lipid metabolism but increased FA biosynthesis are coupled with changes in liver microRNAs in obese subjects with NAFLD.

BACKGROUND/OBJECTIVE: Many controversies regarding the association of liver miRNAs with obesity and nonalcoholic fatty liver diseases (NAFLD) call for additional validations. This study sought to investigate variations in genes and hepatic miRNAs in a sample of obese patients with or without NAFLD and human hepatocytes (HH). SUBJECTS/METHODS: A total of 60 non-consecutive obese women following bariatric surgery were recruited. Subjects were classified as NAFLD (n=17), borderline (n=24) and controls (n=19) with normal enzymatic profile, liver histology and ultrasound assessments. Profiling of 744 miRNAs was performed in 8 obese women with no sign of hepatic disease and 11 NAFLD patients. Additional validation and expression of genes related to de novo fatty acid (FA) biosynthesis, uptake, transport and ß-oxidation; glucose metabolism, and inflammation was tested in the extended sample. Induction of NAFLD-related genes and miRNAs was examined in HepG2 cells and primary HH treated with palmitic acid (PA), a combination of palmitate and oleic acid, or high glucose, and insulin (HG) mimicking insulin resistance in NAFLD. RESULTS: In the discovery sample, 14 miRNAs were associated with NAFLD. Analyses in the extended sample confirmed decreased miR-139-5p, miR-30b-5p, miR-122-5p and miR-422a, and increased miR-146b-5p in obese subjects with NAFLD. Multiple linear regression analyses disclosed that NAFLD contributed independently to explain miR-139-5p (P=0.005), miR-30b-5p (P=0.005), miR-122-5p (P=0.021), miR-422a (P=0.007) and miR-146a (P=0.033) expression variance after controlling for confounders. Decreased miR-122-5p in liver was associated with impaired FA usage. Expression of inflammatory and macrophage-related genes was opposite to decreased miR-30b-5p, miR-139-5p and miR-422a, whereas increased miR-146b-5p was associated with FABP4 and decreased glucose metabolism and FA mobilization. In partial agreement, PA (but not HG) led to decreased miR-139-5p, miR-30b-5p, miR-422a and miR-146a in vitro, in parallel with increased lipogenesis and FA transport, decreased glucose metabolism and diminished FA oxidation. CONCLUSION: This study confirms decreased liver glucose and lipid metabolism but increased FA biosynthesis coupled with changes in five unique miRNAs in obese patients with NAFLD.

Are nurses sufficiently well prepared to take on the detection of hypertension? / ¿Está el personal de enfermería lo suficientemente preparado para detectar la hipertensión?

The detection of arterial hypertension requires training and knowledge by the responsible health professional. The current guidelines recommend doctors and nurses to work together for the screening of hypertension. Objectives: To assess the level of knowledge among primary healthcare nurses’ in the screening of arterial hypertension. Methods: Descriptive, observational and transversal study. A random representative sample of 165 nurses working with adult patients in community-based primary healthcare centres were asked to complete an evaluation test of theoretical knowledge about hypertension. Higher scores indicated a greater knowledge about the detection of hypertension. Results: 32.1% of the participants obtained a score equal to or more than 72.7 which corresponded to the 75th percentile of correct answers. Nurses with lower scores were older, permanent employees with technical training studies. A higher age and technical training studies contributed independently to a lower score. In the multiple linear regression model, age and type of studies contributed independently to questionnaire's score variance. Conclusion: Currently, primary care nurses in the studied region do not have sufficient theoretical knowledge to detect hypertension. The results show the need to establish strategies to achieve the necessary knowledge for the implementation of a correct hypertension screening. For professional nurses, continuing education is essential to safe and effective nursing care

Antecedentes: La detección de la hipertensión arterial requiere formación y conocimientos por parte del profesional sanitario responsable. Las directrices actuales aconsejan a los doctores y enfermeros que trabajen juntos para diagnosticar la hipertensión. Objetivos: Evaluar el nivel de conocimiento entre el personal de enfermería de atención primaria para detectar la hipertensión arterial. Métodos: Estudio descriptivo, observacional y transversal. Se pidió a una muestra aleatoria de 165 enfermeros que trabajaban con adultos en centros de atención primaria que completaran una prueba de evaluación de sus conocimientos teóricos acerca de la hipertensión. Un resultado más alto indicaba un mayor conocimiento a la hora de detectar la hipertensión. Resultados: El 32,1% de los participantes obtuvo una puntuación igual o superior a 72,7, que se correspondía con el percentil 75 de respuestas correctas. El personal de enfermería con puntuación más baja fue el de los empleados más mayores, fijos y con estudios técnicos. La edad más avanzada y tener estudios de formación técnica contribuyeron de manera independiente a una menor puntuación. En el modelo de regresión lineal múltiple la edad y el tipo de formación contribuyeron de manera independiente a la variación del resultado. Conclusión: En la actualidad el personal de enfermería de atención primaria de la región estudiada no cuenta con suficientes conocimientos para detectar la hipertensión. Los resultados muestran la necesidad de establecer estrategias para alcanzar los conocimientos necesarios y poner en marcha un adecuado plan de diagnóstico de hipertensión. Para los enfermeros profesionales una formación continuada es clave para un cuidado seguro y eficaz

Genome-wide DNA methylation pattern in visceral adipose tissue differentiates insulin-resistant from insulin-sensitive obese subjects.

Elucidating the potential mechanisms involved in the detrimental effect of excess body weight on insulin action is an important priority in counteracting obesity-associated diseases. The present study aimed to disentangle the epigenetic basis of insulin resistance by performing a genome-wide epigenetic analysis in visceral adipose tissue (VAT) from morbidly obese patients depending on the insulin sensitivity evaluated by the clamp technique. The global human methylome screening performed in VAT from 7 insulin-resistant (IR) and 5 insulin-sensitive (IS) morbidly obese patients (discovery cohort) analyzed using the Infinium HumanMethylation450 BeadChip array identified 982 CpG sites able to perfectly separate the IR and IS samples. The identified sites represented 538 unique genes, 10% of which were diabetes-associated genes. The current work identified novel IR-related genes epigenetically regulated in VAT, such as COL9A1, COL11A2, CD44, MUC4, ADAM2, IGF2BP1, GATA4, TET1, ZNF714, ADCY9, TBX5, and HDACM. The gene with the largest methylation fold-change and mapped by 5 differentially methylated CpG sites located in island/shore and promoter region was ZNF714. This gene presented lower methylation levels in IR than in IS patients in association with increased transcription levels, as further reflected in a validation cohort (n = 24; 11 IR and 13 IS). This study reveals, for the first time, a potential epigenetic regulation involved in the dysregulation of VAT that could predispose patients to insulin resistance and future type 2 diabetes in morbid obesity, providing a potential therapeutic target and biomarkers for counteracting this process.

Are nurses sufficiently well prepared to take on the detection of hypertension?

BACKGROUND: The detection of arterial hypertension requires training and knowledge by the responsible health professional. The current guidelines recommend doctors and nurses to work together for the screening of hypertension. OBJECTIVES: To assess the level of knowledge among primary healthcare nurses' in the screening of arterial hypertension. METHODS: Descriptive, observational and transversal study. A random representative sample of 165 nurses working with adult patients in community-based primary healthcare centres were asked to complete an evaluation test of theoretical knowledge about hypertension. Higher scores indicated a greater knowledge about the detection of hypertension. RESULTS: 32.1% of the participants obtained a score equal to or more than 72.7 which corresponded to the 75th percentile of correct answers. Nurses with lower scores were older, permanent employees with technical training studies. A higher age and technical training studies contributed independently to a lower score. In the multiple linear regression model, age and type of studies contributed independently to questionnaire's score variance. CONCLUSION: Currently, primary care nurses in the studied region do not have sufficient theoretical knowledge to detect hypertension. The results show the need to establish strategies to achieve the necessary knowledge for the implementation of a correct hypertension screening. For professional nurses, continuing education is essential to safe and effective nursing care.

Circulating irisin levels and coronary heart disease: association with future acute coronary syndrome and major adverse cardiovascular events.

INTRODUCTION: Irisin is a newly discovered myokine, associated with 'browning' of the white adipose tissue, obesity, insulin resistance and metabolic syndrome. The purpose of this study is to evaluate circulating irisin as a predictor of acute coronary syndromes (ACSs) and major adverse cardiovascular events (MACE). METHODS: Sub-study 1: a case-control study, nested within the Veteran's Affairs Normative Ageing Study, evaluating circulating irisin levels in 88 ACS cases and 158 age- and sampling year-matched controls, as a predictor of ACS. Sub-study 2: a prospective cohort study, where 103 participants with established coronary artery disease were stratified by circulating irisin levels at the time they received percutaneous coronary interventions (PCIs) and were followed for the development of MACE. RESULTS: Study 1: there was no association between irisin levels and ACS in otherwise healthy individuals (odds ratio: 1.00 95% confidence interval: (0.99-1.00)). Study 2: the incidence of MACE was significantly lower in the first irisin tertile compared with the second and third (incidence rate 0 vs 0.92 (0.51-1.61) vs 0.57 (0.28-1.14) events per 1000 person-days; P < 0.01). This was primarily driven by the lower incidence of unstable angina (incidence rate 0 vs 0.61 (0.31-1.22) vs 0.43 (0.19-0.96) per 1000 person-days; P = 0.01). CONCLUSION: This is the first study to date that demonstrates that, although circulating irisin levels do not predict the development of ACS in healthy individuals, increased irisin levels are associated with the development of MACE in patients with established coronary artery disease after PCI.

Inflammation and insulin resistance exert dual effects on adipose tissue tumor protein 53 expression.

OBJECTIVE: The purpose of this study was to investigate the expression of human adipose tissue protein 53 (p53) in subjects who varied widely in terms of obesity and insulin resistance. We also analyzed different in vivo and in vitro models to try to comprehend the associations found in humans. METHODS: p53 was analyzed in human adipose and isolated adipocytes, in high fat-fed and GLP-1R KO mice, during in vitro adipogenesis, and in adipocytes after high glucose, rosiglitazone and inflammatory conditions. The effects of surgery-induced weight loss and ex vivo metformin were also evaluated. RESULTS: Omental (OM) p53 gene expression (+27%, P=0.001) and protein (+11%, P=0.04) were increased in obese subjects and high fat diet-induced obese mice (+86%, P=0.018). Although the obesity-associated inflammatory milieu was associated with increased OM p53, this was negatively related to insulin resistance and glycated hemoglobin, and positively with biomarkers for insulin sensitivity. Multiple linear regression analyses revealed that glycated hemoglobin (P<0.0001) and body mass index (P=0.048) contributed independently to explain 13.7% (P<0.0001) of the OM p53 variance. Accordingly, the improvement of insulin sensitivity with surgery-induced weight loss (+51%, P=0.01) and metformin (+42%, P=0.02) led to increased adipose p53. While the glucose-intolerant GLP-1R KO mice showed decreased mesenteric p53 (-45.4%, P=0.017), high glucose led to decreased p53 in pre-adipocytes (-27%, P<0.0001). Inflammatory treatments led to increased p53 (+35%, P<0.0001), while Rs downregulated this expression (-40%, P=0.005) in mature adipocytes. CONCLUSION: Inflammation and insulin resistance exert dual effects on adipose p53, which seems to be the final result of these opposing forces.

CIDEC/FSP27 and PLIN1 gene expression run in parallel to mitochondrial genes in human adipose tissue, both increasing after weight loss.

OBJECTIVE: FSP27 KO mice showed enhanced expression of mitochondrial genes, increased mitochondrial activity and smaller lipid droplets. Here, we aimed to investigate lipid droplet protein (CIDEC/FSP27 and perilipinA (PLIN1)) gene expression in human adipose tissue in association with obesity, insulin resistance and mitochondrial gene expression. DESIGN AND SUBJECTS: In cohort 1, CIDEC/FSP27, PLIN1, adipogenic (FASN, ACACA, PPARG, GLUT4) and mitochondrial (PPARGC1A, PPARGC1B, TFAM, MT-CO3) gene expression were analyzed in 171 adipose tissue samples (88 visceral adipose tissue (VAT) and 83 subcutaneous adipose tissue (SAT) depots) and in a time course experiment in human subcutaneous and visceral preadipocytes using real-time PCR. In cohort 2, the effects of bariatric surgery-induced weight loss were also evaluated in six caucasian morbidly obese women. Additionally, in cohort 2 FSP27 and PLIN1 protein levels were measured using western blotting. RESULTS: CIDEC/FSP27 (1.03±0.52 vs 0.49±0.23 relative gene expression unit (R.U.), P<0.0001) and PLIN1 (1.32±0.82 vs 0.63±0.42 R.U., P<0.0001) gene were significantly more expressed in SAT than in VAT. In VAT, CIDEC/FSP27 and PLIN1 gene expression decreased with body mass index, percent fat mass, fasting glucose, fasting insulin, HOMA and were positively associated with adipogenic (PPARG, GLUT4, FASN and ACACA) and mitochondrial biogenesis (PPARGC1A, PPARGC1B, TFAM and MT-CO3)-related genes. Mitochondrial gene expression increased during adipocyte differentiation in parallel to FSP27 and PLIN1 and other adipogenic genes. After bariatric surgery-induced weight loss, PLIN1 and CIDEC/FSP27 gene and protein expression in SAT increased significantly in parallel to adipogenic and mitochondrial genes. CONCLUSION: These findings suggest a positive functional interaction between CIDEC/FSP27, PLIN1 and mitochondrial biogenesis-related genes in human adipose tissue.

The lung innate immune gene surfactant protein-D is expressed in adipose tissue and linked to obesity status.

BACKGROUND: Surfactant protein-D (SFTPD) is a component of the lung innate immunity that enhances clearance of pathogens and modulates inflammatory responses. An inverse association of putative, lung-derived circulating SFTPD with obesity has been reported but no information is available concerning possible SFTPD gene expression in human adipose tissue. METHODS: SFTPD gene expression was analyzed in human omental (OM; n=156) and subcutaneous (SC; n=106) adipose tissue, and in isolated fat cells (n=12) in association with measures of obesity and glucose tolerance. RESULTS: SFTPD gene was expressed in human adipose tissue and adipocytes. This expression was decreased in OM and SC adipose tissue from obese subjects with (-47%, P<0.0001; and -37%, P=0.048) and without (-34%, P=0.001; and -22%, P=0.08; respectively) type 2 diabetes when compared with the control group. Indeed, OM SFTPD was inversely associated with body mass index (r=-0.33, P<0.0001), percent fat mass (r=-0.36, P<0.0001), waist perimeter (r=-0.26, P=0.002), diastolic blood pressure (r=-0.21, P=0.018) and fasting glucose (r=-0.21, P=0.012); and positively linked to the expression of insulin receptor substrate 1 (IRS1; r=0.25, P=0.004), perilipin A (PLIN; r=0.38, P=0.007) and fatty acid synthase (FASN; r=0.36, P<0.0001). Accordingly, increased SFTPD (4.5-fold, P=0.02) was detected in isolated adipocytes when compared with the stromal-vascular cell fraction, in parallel to IRS1, FASN and PLIN. CONCLUSIONS: Both OM and SC adipose tissue (mainly mature adipocytes) express SFTPD. This expression decreases with obesity and impaired glucose tolerance.

Thyroid hormone receptor alpha gene variants increase the risk of developing obesity and show gene-diet interactions.

OBJECTIVE: Thyroid hormone receptor-beta resistance has been associated with metabolic traits. THRA gene sequencing of an obese woman (index case) who presented as empirical thyroid hormone receptor-α (THRA) resistance, disclosed a polymorphism (rs12939700) in a critical region involved in TRα alternative processing. DESIGN AND SUBJECTS: THRA gene variants were evaluated in three independent europid populations (i) in two population cohorts at baseline (n=3417 and n=2265), 6 years later (n=2139) and (ii) in 4734 high cardiovascular risk subjects (HCVR, PREDIMED trial). RESULTS: The minor allele of the index case polymorphism (rs12939700), despite having a very low frequency (4%), was significantly associated with higher body mass index (BMI) (P=0.042) in HCVR subjects. A more frequent THRA polymorphism (rs1568400) was associated with higher BMI in subjects from the population (P=0.00008 and P=0.05) after adjusting for several confounders. Rs1568400 was also strongly associated with fasting triglycerides (P dominant=3.99 × 10(-5)). In the same sample, 6 years later, age and sex-adjusted risk of developing obesity was significantly increased in GG homozygotes (odds ratio 2.93 (95% confidence interval, 1.05-6.95)). In contrast, no association between rs1568400 and BMI was observed in HCVR subjects, in whom obesity was highly prevalent. This might be explained by the presence of an interaction (P <0.001) among the rs1568400 variant, BMI and saturated fat intake. Only when saturated fat intake was high (>24.5 g d(-1)), GG carriers showed a significantly higher BMI than A carriers after controlling for energy intake and physical activity. CONCLUSIONS: THRA gene polymorphisms are associated with obesity development. This is a novel observation linking the THRA locus to metabolic phenotypes.

Liver, but not adipose tissue PEDF gene expression is associated with insulin resistance.

OBJECTIVE: Recent studies linked circulating pigment epithelium-derived factor (PEDF) to obesity-associated insulin resistance, but the main source of circulating PEDF is unknown. We aimed to investigate liver and adipose tissue PEDF gene expression in association with obesity and insulin resistance. DESIGN, SUBJECTS AND METHODS: Three (two cross-sectional and one longitudinal) independent cohorts have been studied, for adipose tissue (n=80 and n=30) and liver gene expression (n=32 and n=14). Effects of high glucose and cytokines on HepG2 cell line were also investigated. PEDF gene expression and circulating PEDF were analyzed using real-time PCR and ELISA, respectively. RESULTS: In a first cohort of subjects, PEDF relative gene expression was higher in subcutaneous (SC) than in omental (OM) adipose tissue (P<0.0001) being also higher in mature adipocytes compared with stromo-vascular cells (P<0.0001). However, OM PEDF relative gene expression was decreased in morbidly obese subjects (P=0.01). Both OM PEDF and OM PEDF receptor (PEDFR) correlated positively with lipogenic and lipolytic genes, and with genes implicated in the lipid vacuole formation. Circulating PEDF levels were not associated with fat PEDF gene expression. In the second cohort, SC PEDF was decreased in subjects with type 2 diabetes and did not change significantly after weight loss. We next explored circulating PEDF in association with markers of liver-related insulin resistance injury (alanine aminotransferase, r=0.59, P=0.001). Interestingly, liver PEDF gene expression increased with obesity and insulin resistance in men, being significantly associated with fasting glucose and glycated hemoglobin in two independent cohorts. In fact, high glucose led to increased PEDF in HepG2 cells, while inflammatory stimuli present in the adipose tissue environment downregulated PEDF. CONCLUSION: Liver, but not adipose tissue, might be the source of increased circulating PEDF linked to insulin resistance.