Influence of Sociodemographic Variables and Healthy Habits on the Values of Insulin Resistance Indicators in 386,924 Spanish Workers.

BACKGROUND: Insulin resistance (IR) is an alteration of the action of insulin in cells, which do not respond adequately to this action, leading to an increase in blood glucose levels. IR produces a very diverse clinical picture and increases the cardiometabolic risk of the population that suffers from it. Among the factors that influence IR are genetics, unhealthy lifestyle habits, overweight, and obesity. The objective of this work was to determine how different sociodemographic variables and healthy habits influence the values of different scales that assess the risk of presenting IR in a group of Spanish workers. METHODS: An observational, cross-sectional, descriptive study was carried out in 386,924 workers from different Spanish regions. Different sociodemographic variables and lifestyle habits were studied (age, social class, educational level, smoking, Mediterranean diet, physical exercise) along with their association with four scales to evaluate the risk of insulin resistance (TyG index, TyG-BMI, METS-IR, TG/HDL-c). To analyse the quantitative variables, Student's t test was used, while the Chi-squared test was used for the qualitative variables. A multinomial logistic regression analysis was performed, calculating the odds ratio with its 95% confidence intervals. The accepted level of statistical significance was set at p < 0.05. RESULTS: In the multivariate analysis, all variables, except educational level, increased the risk of presenting high values on the IR risk scales, especially a sedentary lifestyle and low adherence to the Mediterranean diet. CONCLUSIONS: Our results demonstrate an association between the practice of regular physical exercise and a reduction in the risk of IR; a strong role of the Mediterranean diet as a protective factor for IR; an association between aging and increased IR, which has also been suggested in other studies; and, finally, a relationship between a low socioeconomic level and an increase in IR.

Relationship between Abdominal Volume Index and Body Adiposity Index and Scales of Insulin Resistance and Metabolic Syndrome.

Introduction, objectives: Obesity is a global health problem with a great negative impact on health. Among the pathologies caused by obesity are insulin resistance and metabolic syndrome, which constitute an increasingly common health problem in both developed and developing countries. The aim of this study was to examine the relationship between two scales that assess obesity-based on hip circumference-and metabolic syndrome (MetS) and insulin resistance risk scales as predictors of these alterations. MATERIALS, METHODS: A descriptive, cross-sectional study was carried out on 193,462 workers from different Spanish regions and work groups between January 2019 and September 2021. Abdominal volume index (AVI) and body adiposity index (BAI) were evaluated to assess obesity and its association with insulin resistance using three risk scales (TyG index, Triglycerides/HDL, and METS-IR), while their association with metabolic syndrome was determined using the NCEP ATP III, IDF, and JIS models. RESULTS: The results of the ROC curves to determine the predictive value of BAI and AVI in relation to the three criteria evaluated to calculate MetS in all instances presented a higher area under the curve (AUC) for AVI. The high values of AVI stand out for predicting MetS when applying the IDF criteria. The cut-off point in women was 13.70 with a Youden index of 0.802, whereas in men, the cut-off point was set at 17.59 with a Youden index of 0.672. Regarding the relationship of BAI and AVI with insulin resistance risk scales for both sexes, the AUC only revealed high values when using the METS-IR formula for both AVI and BAI. The AVI cut-off points to predict high values of insulin resistance risk scales in women were established at 13.12 with a Youden index of 0.722. In men, the cut-off point was 17.59, with a Youden index of 0.626. The BAI cut-off points in women were set at 33.88 with a Youden index of 0.748. In men, the cut-off point was 27.91, with a Youden index of 0.598. CONCLUSIONS: AVI demonstrated its value as a predictor of metabolic syndrome while exclusively applying the IDF criteria. AVI and BAI demonstrated their value as predictors of high values of insulin resistance risk scales only in the case of METS-IR. This predictive value is also higher in women.

Determination of the Level of Cardiovascular Risk in 172,282 Spanish Working Women.

Introduction, objectives: Although cardiovascular events have been traditionally associated mainly with men, some data reflect an increase in women, which may even exceed their male counterparts, constituting the leading cause of death in working women in Spain. The objective of this present study was to analyze the level of cardiovascular risk in Spanish working women by assessing the influence of age, type of work, and tobacco consumption. MATERIAL, METHODS: A descriptive cross-sectional study was carried out in 172,282 working women from different Spanish geographical areas and from different companies between January 2018 and June 2020. A range of variables and risk factors were assessed and various cardiovascular risk scales were used to analyze the data. RESULTS: An increase in cardiovascular risk was observed in the least qualified work groups, mainly corresponding to blue-collar workers, when using the SCORE or REGICOR risk equation. The prevalence of altered values for all the parameters analyzed (overweight and obesity, hypertension, dyslipidemia, diabetes, fatty liver, hepatic fibrosis, atherogenic indexes, and cardiovascular risk scales) was higher among blue-collar women. Age was the only factor that influenced all the cardiovascular risk scales studied, increasing risk when comparing the group of women aged 50 years and older with the others. CONCLUSIONS: Aging and belonging to the blue-collar job category meant worse results in the cardiovascular risk scales and in all the parameters analyzed. This is in line with numerous studies that argue that age and zip code are more influential than genetic code.

Relationship between Atherogenic Dyslipidaemia and Lipid Triad and Scales That Assess Insulin Resistance.

BACKGROUND: Atherogenic dyslipidaemia (AD) and lipid triad (LT) are characterised by high triglyceride levels together with low HDL and normal or high LDL cholesterol and are favoured by a persistent state of insulin resistance (IR), which increases the release of free fatty acids from abdominal adipose tissue. This alteration in the lipid profile favours the accelerated development of atherosclerosis, which is the most important cause of morbidity and mortality in all countries in the developed and developing world. One of the elements that plays a major role in the genesis of AD is IR. The aim of this study was to determine the relationship between variables that assess atherogenic risk (AD and LT) and scales that assess the risk of presenting insulin resistance. METHODS: A descriptive cross-sectional study of 418,343 workers was conducted to evaluate atherogenic dyslipidaemia and lipid triad; a relationship with three insulin resistance risk scales (Triglycerides/HDL, TyG index, METS-IR) was established. The usefulness of IR risk scales for predicting AD and LT was calculated by applying ROC curves, obtaining the area under the curve (AUC) and cut-off points with their sensitivity, specificity, and Youden index. Multivariate analysis was performed by binary logistic regression. RESULTS: The prevalence of high-risk values for insulin resistance with all of the scales is much higher in people with AD and LT compared to those without. The ROC curves present us with an AUC with the three insulin resistance risk scales for the two dyslipidaemias studied with figures ranging between 0.856 and 0.991, which implies that the results are good/very good. CONCLUSIONS: A relationship between atherogenic dyslipidaemia and the three insulin resistance risk scales assessed is revealed, with higher IR mean values and prevalence in people with atherogenic dyslipidaemia and lipid triad. The three scales make it possible to adequately classify the presence of AD and LT. The highest AUC is presented by the triglycerides/HDL scale, with a result close to 1. METS-IR is the most recommended formula to estimate insulin resistance.

Dietary Intervention on Overweight and Obesity after Confinement by COVID-19.

BACKGROUND: Obesity has become a public health problem in our society and is associated with many diseases, including type 2 diabetes mellitus, cardiovascular diseases, dyslipidemia, respiratory diseases, and cancer. Several studies relate weight loss in obese patients to improved anthropometric measurements and cardiometabolic risk. The objective of our study was to evaluate anthropometric changes, analytical parameters, insulin resistance, fatty liver, and metabolic scales, after a personalized weight loss program, through dietary advice to increase adherence to the Mediterranean diet and a motivational booster via mobile SMS messaging. METHODS: Intervention study on a sample of 1964 workers, in which different anthropometric parameters were evaluated before and after dietary intervention: the metabolic score of insulin resistance; non-alcoholic fatty liver disease using different scales; metabolic syndrome; atherogenic dyslipidemia; and the cardiometabolic index. A descriptive analysis of the categorical variables was performed, by calculating the frequency and distribution of the responses for each one. For quantitative variables, the mean and standard deviation were calculated, since they followed a normal distribution. Bivariate association analysis was performed by applying the chi-squared test (corrected by Fisher's exact statistic when conditions required it) and Student's t-test for independent samples (for comparison of means). RESULTS: The population subjected to the Mediterranean diet improved in all the variables evaluated at 12 months of follow-up and compliance with the diet. CONCLUSIONS: Dietary advice on a Mediterranean diet and its reinforcement with reminder messages through the use of mobile phones may be useful to improve the parameters evaluated in this study and reduce the cardiometabolic risk of patients.

Waist Circumference Is an Essential Factor in Predicting Insulin Resistance and Early Detection of Metabolic Syndrome in Adults.

BACKGROUND: Metabolic syndrome (Met-S) is considered one of the most important health problems of the 21st century. It includes a group of metabolic disorders that increase the risk of cardiovascular diseases such as overweight and obesity, elevated lipid profile and blood pressure and insulin resistance (IR). Based on the information mentioned above in which there seems to be a relationship between IR and Met-S, the objective of this work was twofold: on the one hand, to assess the relationship between the values of different insulin resistance risk scales and Met-S determined with three different scales, and on the other, to determine whether any of the components of Met-S predispose more to the appearance of IR. METHODS: A descriptive cross-sectional study of 418,343 workers. Waist circumference was measured and evaluated together with six formulas to assess the insulin resistance index. Categorical variables were evaluated by calculating the frequency and distribution of each one. For quantitative variables, mean and standard deviation were determined, and Student's t-test was applied, while for qualitative variables, the chi-square test was performed. The usefulness of the different risk scales for insulin resistance for predicting metabolic syndrome was evaluated using ROC curves, the area under the curve (AUC), as well as their cut-off points for sensitivity, specificity, and the Youden index. RESULTS: People with metabolic syndrome applying any criteria had higher values in the IR risk scales. The different IR scales made it possible to adequately classify people with metabolic syndrome. Of the three definitions of Met-S, the one that showed the greatest relationship with IR was IDF. CONCLUSIONS: Most risk scales for insulin resistance enable the presence of metabolic syndrome to be adequately classified, finding the best ones if the International Diabetes Federation (IDF) criteria are applied. Of the elements included in the Met-S, the one that seems to increase the risk of presenting IR the most is waist circumference; hence, the Met-S definition that is most related to IR is that of the IDF, which is the only one of the three in which a high value of waist circumference is necessary to be able to diagnose Met-S. Waist circumference can be considered the central essential component for detecting insulin resistance and, therefore, the early detection of metabolic syndrome.

Intratumor heterogeneity and clonal evolution in an aggressive papillary thyroid cancer and matched metastases.

The contribution of intratumor heterogeneity to thyroid metastatic cancers is still unknown. The clonal relationships between the primary thyroid tumors and lymph nodes (LN) or distant metastases are also poorly understood. The objective of this study was to determine the phylogenetic relationships between matched primary thyroid tumors and metastases. We searched for non-synonymous single-nucleotide variants (nsSNVs), gene fusions, alternative transcripts, and loss of heterozygosity (LOH) by paired-end massively parallel sequencing of cDNA (RNA-Seq) in a patient diagnosed with an aggressive papillary thyroid cancer (PTC). Seven tumor samples from a stage IVc PTC patient were analyzed by RNA-Seq: two areas from the primary tumor, four areas from two LN metastases, and one area from a pleural metastasis (PLM). A large panel of other thyroid tumors was used for Sanger sequencing screening. We identified seven new nsSNVs. Some of these were early events clonally present in both the primary PTC and the three matched metastases. Other nsSNVs were private to the primary tumor, the LN metastases and/or the PLM. Three new gene fusions were identified. A novel cancer-specific KAZN alternative transcript was detected in this aggressive PTC and in dozens of additional thyroid tumors. The PLM harbored an exclusive whole-chromosome 19 LOH. We have presented the first, to our knowledge, deep sequencing study comparing the mutational spectra in a PTC and both LN and distant metastases. This study has yielded novel findings concerning intra-tumor heterogeneity, clonal evolution and metastases dissemination in thyroid cancer.

Patterns of nucleotide and haplotype diversity at ICAM-1 across global human populations with varying levels of malaria exposure.

Malaria is one of the strongest selective pressures in recent human evolution. African populations have been and continue to be at risk for malarial infections. However, few studies have re-sequenced malaria susceptibility loci across geographically and genetically diverse groups in Africa. We examined nucleotide diversity at Intercellular adhesion molecule-1 (ICAM-1), a malaria susceptibility candidate locus, in a number of human populations with a specific focus on diverse African ethnic groups. We used tests of neutrality to assess whether natural selection has impacted this locus and tested whether SNP variation at ICAM-1 is correlated with malaria endemicity. We observe differing patterns of nucleotide and haplotype variation in global populations and higher levels of diversity in Africa. Although we do not observe a deviation from neutrality based on the allele frequency distribution, we do observe several alleles at ICAM-1, including the ICAM-1 (Kilifi) allele, that are correlated with malaria endemicity. We show that the ICAM-1 (Kilifi) allele, which is common in Africa and Asia, exists on distinct haplotype backgrounds and is likely to have arisen more recently in Asia. Our results suggest that correlation analyses of allele frequencies and malaria endemicity may be useful for identifying candidate functional variants that play a role in malaria resistance and susceptibility.

5-aza-2'-deoxycytidine has minor effects on differentiation in human thyroid cancer cell lines, but modulates genes that are involved in adaptation in vitro.

BACKGROUND: In thyroid cancer, the lack of response to specific treatment, for example, radioactive iodine, can be caused by a loss of differentiation characteristics of tumor cells. It is hypothesized that this loss is due to epigenetic modifications. Therefore, drugs releasing epigenetic repression have been proposed to reverse this silencing. METHODS: We investigated which genes were reinduced in dedifferentiated human thyroid cancer cell lines when treated with the demethylating agent 5-aza-2'-deoxycytidine (5-AzadC) and the histone deacetylase inhibitors trichostatin A (TSA) and suberoylanilide hydroxamic acid, by using reverse transcriptase-polymerase chain reaction and microarrays. These results were compared to the expression patterns in in vitro human differentiated thyrocytes and in in vivo dedifferentiated thyroid cancers. In addition, the effects of 5-AzadC on DNA quantities and cell viability were investigated. RESULTS: Among the canonical thyroid differentiation markers, most were not, or only to a minor extent, re-expressed by 5-AzadC, whether or not combined with TSA or forskolin, an inducer of differentiation in normal thyrocytes. Furthermore, 5-AzadC-modulated overall mRNA expression profiles showed only few commonly regulated genes compared to differentiated cultured primary thyrocytes. In addition, most of the commonly strongly 5-AzadC-induced genes in cell lines were either not regulated or upregulated in anaplastic thyroid carcinomas. Further analysis of which genes were induced by 5-AzadC showed that they were involved in pathways such as apoptosis, antigen presentation, defense response, and cell migration. A number of these genes had similar expression responses in 5-AzadC-treated nonthyroid cell lines. CONCLUSIONS: Our results suggest that 5-AzadC is not a strong inducer of differentiation in thyroid cancer cell lines. Under the studied conditions and with the model used, 5-AzadC treatment does not appear to be a potential redifferentiation treatment for dedifferentiated thyroid cancer. However, this may reflect primarily the inadequacy of the model rather than that of the treatment. Moreover, the observation that 5-AzadC negatively affected cell viability in cell lines could still suggest a therapeutic opportunity. Some of the genes that were modulated by 5-AzadC were also induced in nonthyroid cancer cell lines, which might be explained by an epigenetic modification resulting in the adaptation of the cell lines to their culture conditions.

Role of Epac and protein kinase A in thyrotropin-induced gene expression in primary thyrocytes.

cAMP pathway activation by thyrotropin (TSH) induces differentiation and gene expression in thyrocytes. We investigated which partners of the cAMP cascade regulate gene expression modulations: protein kinase A and/or the exchange proteins directly activated by cAMP (Epac). Human primary cultured thyrocytes were analysed by microarrays after treatment with the adenylate cyclase activator forskolin, the protein kinase A (PKA) activator 6-MB-cAMP and the Epac-selective cAMP analog 8-pCPT-2'-O-Me-cAMP (007) alone or combined with 6-MB-cAMP. Profiles were compared to those of TSH. Cultures treated with the adenylate cyclase- or the PKA activator alone or the latter combined with 007 had profiles similar to those induced by TSH. mRNA profiles of 007-treated cultures were highly distinct from TSH-treated cells, suggesting that TSH-modulated gene expressions are mainly modulated by cAMP and PKA and not through Epac in cultured human thyroid cells. To investigate whether the Epac-Rap-RapGAP pathway could play a potential role in thyroid tumorigenesis, the mRNA expressions of its constituent proteins were investigated in two malignant thyroid tumor types. Modulations of this pathway suggest an increased Rap pathway activity in these cancers independent from cAMP activation.

Complicaciones inmediatas derivadas del tratamiento antihipertensivo. A propósito de los estudios MEDIDA y HYVET / Short-term complications related to antihypertensive drugs. Reference to MEDIDA and HYVET studies

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Vómitos persistentes en mujer hipertensa / Persistent vomiting in a hypertensive woman

Numerosos documentos insisten en la necesidad deun control estricto de la presión arterial (PA). Contrasta la escasa información publicada al respecto de la reducción tensional estricta y sus potenciales consecuencias negativas. Presentamos una paciente con hipertensión arterial (HTA) crónica esencial en tratamiento farmacológico y dos ingresos hospitalarios por vómitos secundarios a hiponatremia (hNa+) por tiazidas. Discutimos las causas más comunes de hNa+ enel paciente hipertenso, igualmente con muy escasabibliografía. El caso expuesto ilustra varios errores comunes en la praxis clinica habitual: erróneo diagnóstico de HTA por incorrecta técnica de medida de laPA, inicio precoz de tratamiento farmacológico basadoúnicamente en valores de PA e inadecuado empleode la automedida domiciliaria de PA (AMPA). Todoello llevó a una iatrogenia y a la realización demaniobras invasivas en una paciente con una HTA debata blanca donde se echa de menos un abordaje menosfragmentario y más acorde con las guías terapéuticasen uso

Many documents stress the need for strict control ofblood pressure (BP) on the contrary to the scarce information published regarding strict tension reductionand its potential negative consequences.We present apatient suffering chronic essential AHT under drugtreatment and with two admissions to hospital dueto vomiting secondary to hyponatremia (hNa+) due tothiazides. We discuss the most common causes ofhNa+ in the hypertensive patient, this also being veryscarce in the literature. The case presented illustratesseveral common errors in the common clinical practice:erroneous diagnosis of AHT due to incorrect measurementtechnique of BP, early onset of drug treatmentonly based on BP values and inadequate use ofABPM. All of this led to an iatrogeny and conductionof invasive maneuvers in a female patient with whitecoat hypertension in whom a less fragmented approachand one more in agreement with the therapheuticguidelines in use should have been used

Complete fibular hemimelia: a long-term review of four cases.

Fibular hemimelia is a partial or total aplasia of the fibula, and is usually associated with other anomalies of the tibia, femur and foot. It represents the most frequent congenital defect of the long bones and is the most common skeletal deformity in the lower limbs. A retrospective study was made of four patients (three males and one female) with total aplasia of the fibula. The average follow-up was 15 years. Three patients were treated by successive tibial lengthenings; in one case amputation was carried out using the Syme technique. Lengthening required numerous operations and led to many complications, whereas the amputated case involved a single surgical operation without complications. The results of our cases and those reported in the literature suggest early amputation as the treatment of choice of Type II fibular hemimelia.

The peopling of São Tomé (Gulf of Guinea): origins of slave settlers and admixture with the Portuguese.

The geographic origins of African slave settlers and the Portuguese genetic contribution to the population of São Tomé (Gulf of Guinea) were assessed through the analysis of beta-globin haplotypes in 44 chromosomes bearing the betaS allele and through the study of the genetic variation in eight autosomal markers (APOA1, AT3, FY, LPL, OCA2, RB1, Sb19.3, and GC) informative for admixture in a sample of 224 individuals. The observed betaS haplotype distribution (36.4% Bantu, 52.3% Benin, 4.5% Cameroon, 4.5% Senegal, and 2.3% atypical) is in accordance with the historical information on the major geographic sources of slave settlers of São Tomé, although it captures a more important contribution of Central-West Africa regions than previously anticipated. European admixture, estimated to be 10.7 +/- 0.9%, has created a considerable level of genetic structure, as indicated by the finding of significant linkage disequilibrium between 33% of unlinked marker loci pairs. Recent admixture was found to have an important contribution to these values, since removal of individuals with Portuguese or Cape Verdian parents or grandparents from the sample dropped the miscegenation level to 6.5 +/- 0.8% and reduced significant linkage disequilibrium to 11% of unlinked marker pairs. Taken together, these results indicate that the peopling of São Tomé might have provided one of the first examples of the combination of diverse African contributions and European admixture that emerged from the overseas population relocations promoted by the Atlantic slave trade.