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1.
Salud ment ; 46(2): 69-82, Mar.-Apr. 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1450417

RESUMO

Abstract Introduction The COVID-19 pandemic caused the cessation of academic activities from the face-to-face format to confinement and virtual classes, in which little is studied about its effect on mental health. Objective Determine levels of depression, anxiety, and stress in medical students in Mexico and Colombia during the COVID-19 pandemic. Furthermore, depression, anxiety, and stress were compared by gender, education status, and country. Method A cross-sectional study was carried out with 426 medical students. Data was collected using an online survey containing the Depression, Anxiety, Stress Scale (DASS-21) questionnaire. Results Overall scores for depression, anxiety, and stress were 6.7 ± 1.2, 8.8 ± 1.2, and 5.6 ± 1.2, respectively. Females had significantly higher overall scores for depression (.24-fold increase), anxiety (.25-fold increase), and stress (.40-fold increase) than males (p ≤ .01). The risk for anxiety and stress by school year showed that basic years were associated with higher scores than advanced years (.25 and .38-fold increase, respectively). For females, starting medical school did show an increased risk of depression when compared to male students in their basic years (.38-fold increase). Lastly, students from Mexico had an increased risk for depression and anxiety (p ≤ .022 and p ≤ .004, respectively) but not for stress (p ≤ .402), when compared to students from Colombia. Discussion and conclusion Significant anxiety and depression were observed in medical students from Mexico and Colombia. Factors associated with an increased risk of depression and anxiety are students in their basic years as well as being female.


Resumen Introducción La pandemia de COVID-19 provocó el cese de las actividades académicas desde el formato presencial al confinamiento de las clases virtuales, de las que poco se ha estudiado sobre su efecto en la salud mental. Objetivo Determinar los niveles de depresión, ansiedad y estrés en estudiantes de medicina de México y Colombia durante la pandemia de COVID-19; además de comparar depresión, ansiedad y estrés por género, nivel educativo y país. Método Se realizó un estudio transversal con 426 estudiantes de medicina. Los datos se recopilaron mediante una encuesta en línea que contenía el cuestionario DASS-21. Resultados Las puntuaciones generales de depresión, ansiedad y estrés fueron 6.7 ± 1.2, 8.8 ± 1.2 y 5.6 ± 1.2, respectivamente. Las mujeres tuvieron puntajes generales significativamente más altos para depresión (.24-fold increase), ansiedad (.25-fold increase) y estrés (.40-fold increase). El riesgo de ansiedad y estrés por año escolar mostró que los años básicos se asociaron con puntajes más altos que los estudiantes en años los avanzados (.25 y .38-fold increase). Para las mujeres, cursar años básicos mostró un mayor riesgo de depresión en comparación con los estudiantes varones (.38-fold increase). Por último, los estudiantes mexicanos tuvieron un mayor riesgo de depresión y ansiedad (p ≤ .022 y p ≤ .004, respectivamente) pero no de estrés (p ≤ .402) en comparación con los estudiantes Colombianos. Discusión y conclusión Se observó ansiedad y depresión significativas en estudiantes de medicina mexicanos y colombianos. Los factores asociados a un mayor riesgo de depresión y ansiedad fueron; ser estudiante en años básicos además de ser mujer.

2.
J Acad Nutr Diet ; 123(6): 933-952.e1, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36634870

RESUMO

BACKGROUND: Microbiome therapies (probiotic, prebiotic, and synbiotics) have been proposed as adjuvants in the control of central obesity; however, their results for patients with type 2 diabetes (T2D) remain inconclusive. OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the effect of microbiome therapies on central obesity as measured by waist circumference (WC), and to evaluate the effect of microbiome therapies for glycemic parameters (fasting glucose [FPG], fasting insulin [FPI], hemoglobin A1c [HbA1c], and insulin resistance [HOMA1-IR]) in patients with T2D. METHODS: SCOPUS, Pubmed, EBSCO, and LILACS databases were searched for studies that investigated the effect of microbiome therapies on WC up to June 1, 2022. Heterogeneity was determined using Cochran's Q test and quantified using the inconsistency index. The random effects model was used to calculate the pooled difference in means (DM) and 95% confidence intervals (95%CI). Egger's test and Beggs-Muzamar's test were used to assess publication bias. RESULTS: Fifteen reports were included (443 treated and 387 controls). Overall, a significant decrease in WC was found (DM = -0.97 cm; 95% confidence interval [95%CI] = -1.74 to -0.20; P = 0.014); however, when stratified by type of microbiome therapy, only probiotics significantly decreased WC (DM = -0.62 cm; 95%CI = -1.00 to -0.24; P = 0.002). No effect was observed for prebiotics and synbiotics. With respect to glycemic parameters, HbA1c, FPG, and HOMA1-IR significantly decrease with microbiome therapies (P ≤ 0.001). When stratified by the type of therapy, for probiotic treatments, HbA1c, FPG, and HOMA1-IR scores decrease (P < 0.001). For prebiotic treatments, HbA1c and FPG (P ≤ 0.001) levels decrease, whereas FPI increased (P = 0.012). Synbiotic treatments were only associated with an increase in FPI (P = 0.031). CONCLUSION: Findings indicate that using probiotics alone improved WC in patients with T2D. Both probiotics and prebiotics decreased HbA1c and FPG; however, prebiotics and synbiotics resulted in an increase in FPI. The formulation of the therapy (single vs multi) had no difference on the effect.


Assuntos
Diabetes Mellitus Tipo 2 , Microbiota , Probióticos , Simbióticos , Humanos , Diabetes Mellitus Tipo 2/terapia , Obesidade Abdominal/terapia , Hemoglobinas Glicadas , Circunferência da Cintura , Ensaios Clínicos Controlados Aleatórios como Assunto , Probióticos/uso terapêutico , Prebióticos , Obesidade
3.
Int J Mol Sci ; 23(19)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36232479

RESUMO

Oxidative stress plays an important role in vascular complications observed in patients with obesity and Type 2 Diabetes (T2D). Xanthine oxidase (XO) breaks down purine nucleotides into uric acid and contributes to the production of reactive oxygen species (ROS). However, the relationship between XO activity and glucose homeostasis in T2D subjects with obesity is unclear. We hypothesized that disordered glucose levels are associated with serum XO activity in overweight women and men with T2D and without hyperuricemia. We studied serum XO activity in women and men with and without T2D. Our results show that serum XO activity was greater in T2D patients with body mass index (BMI) ≥ 25 kg/m2 than in those with BMI < 25 kg/m2 (p < 0.0001). Sex-based comparative analyses of overweight T2D patients showed that serum XO activity correlated with homeostasis model assessment of ß-cell function (HOMA-ß), fasting plasma glucose (FPG), and hemoglobin A1C in overweight T2D women but not in overweight T2D men. In addition, as compared to overweight T2D men, women had higher high-sensitivity C-reactive protein (hs-CRP) levels. However, overweight T2D men had higher XO activity and uric acid levels than women. Our results suggest that XO activity is higher in overweight T2D patients, especially in men, but is more sensitive to disordered glucose levels in overweight women with T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Sobrepeso , Glicemia/análise , Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 2/complicações , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Obesidade/complicações , Sobrepeso/complicações , Nucleotídeos de Purina , Espécies Reativas de Oxigênio/metabolismo , Ácido Úrico , Xantina Oxidase/metabolismo
4.
Lasers Med Sci ; 37(9): 3537-3549, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36063232

RESUMO

Undiagnosed type 2 diabetes (T2D) remains a major public health concern. The global estimation of undiagnosed diabetes is about 46%, being this situation more critical in developing countries. Therefore, we proposed a non-invasive method to quantify glycated hemoglobin (HbA1c) and glucose in vivo. We developed a technique based on Raman spectroscopy, RReliefF as a feature selection method, and regression based on feed-forward artificial neural networks (FFNN). The spectra were obtained from the forearm, wrist, and index finger of 46 individuals. The use of FFNN allowed us to achieve an error in the predictive model of 0.69% for HbA1c and 30.12 mg/dL for glucose. Patients were classified according to HbA1c values into three categories: healthy, prediabetes, and T2D. The proposed method obtained a specificity and sensitivity of 87.50% and 80.77%, respectively. This work demonstrates the benefit of using artificial neural networks and feature selection techniques to enhance Raman spectra processing to determine glycated hemoglobin and glucose in patients with undiagnosed T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Humanos , Hemoglobinas Glicadas , Diabetes Mellitus Tipo 2/diagnóstico , Glucose , Glicemia , Análise Espectral Raman , Redes Neurais de Computação
5.
Eur J Clin Nutr ; 76(12): 1646-1656, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35418606

RESUMO

Probiotics are shown to alter the microbiota, leading to a favorable environment, in which weight loss and metabolic parameters are improve. However, the results on probiotics' effect on specific types of central adipose tissues, mainly visceral (VAT) and subcutaneous adipose tissue (SAT), are conflicting. Therefore, we conducted a systematic review, aimed to evaluate the effects of probiotics on VAT and SAT. PubMed, SCOPUS, EBSCO, and LILACS databases were searched for studies that investigated the effect of probiotics on VAT and SAT. Fixed effects were used to calculate the pooled difference in means (DM) and 95% confidence intervals (95%CI). Fourteen publications met the inclusion criteria, which consisted of 1523 participants. For VAT, overall, there was a significant decrease (DM = -3.63 cm2, 95% CI: -5.08 to -2.17, p < 0.001). When stratified by type of probiotic, single Bifidobacterium (DM = -4.49 cm2, 95% CI:-7.37 to -1.61, p = 0.002) and single Lactobacillus probiotics (DM = -3.84 cm2, 95% CI:-5.74 to -1.93, p < 0.001) resulted in significant reductions. Mixed probiotics had no effect. For SAT, overall, there was a significant decrease (DM = -2.91 cm2, 95% CI:-4.82 to -1.01, p = 0.003), and when stratified by type of probiotic, single Lactobacillus (DM = -3.39 cm2, 95% CI:-5.90 to -0.88, p = 0.008) and mixed probiotics (DM = -5.97 cm2, 95% CI:-10.32 to -1.62, p = 0.007) resulted in a significant decrease. Single Bifidobacterium probiotics had no effect. Using meta-regression, no association was observed between the total daily probiotic dose and VAT or SAT reduction. This study shows that probiotics have a beneficial effect on central adiposity. Single Lactobacillus-based probiotics reduced VAT and SAT, whereas Bifidobacterium-based probiotics reduce VAT.


Assuntos
Gordura Intra-Abdominal , Probióticos , Humanos , Gordura Intra-Abdominal/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Gordura Subcutânea , Tecido Adiposo
6.
Rev Med Inst Mex Seguro Soc ; 59(6): 490-499, 2021 11 01.
Artigo em Espanhol | MEDLINE | ID: mdl-34908382

RESUMO

Background: In Mexico there is little information regarding the link between metabolic syndrome (MetS), socioeconomic status (SES) and quality of life (QoL). Objective: To assess the association between subjects who are at high risk of developing MetS with SES and QoL. Material and methods: Patients attending UMF-2 IMSS or Centro Urbano-SSA Clínica-1 were asked to participate. Anthropometric measures were collected, the AMAI, SF12, and ESF-I questionnaire where apply for SES, QoL, and MetS, respectively. Association were determined by calculating Spearman's rho and the risk (odds ratio and 95% confidence-interval) was assessed using logistic regression. Results: The difference of SES (193 ± 53 vs. 124 ± 50) and QoL (86.3 ± 14.8 vs. 56.0±25.4) questionnaires were significantly between low-risk and high-risk groups, respectively (p < 0.001). There was a negative correlation between ESF-I and SES (rho = -0.623, p < 0.001) as well as the QoL (rho = -0.719, p < 0.001). MetS risk was augmented by decreasing SES (C+: OR = 6.4, 95%IC: 3.2-13.0; D: OR = 66.1, 95%IC: 23.2-188.3), whereas increasing QoL attenuated it (OR = 0.93, 95%CI: 0.91-0.94). However, QoL mitigated the effect of SES (C+: OR = 4.5, 95%IC: 2.1-9.6; D: OR = 11.9, 95%IC: 3.8-37.6). Conclusions: Lower QoL and SES increased the risk of MetS in Central Mexico; however, improving the QoL can mitigated the effect SES has on developing MetS.


Introducción: en México existe escasa información respecto al vínculo entre el síndrome metabólico (MetS), el nivel socioeconómico (NSE) y la calidad de vida (CdV) de la población. Objetivo: evaluar la asociación entre sujetos que tienen alto riesgo de desarrollar MetS con NSE y CdV. Material y métodos: se invitó a participar a pacientes de la UMF-2 del IMSS y del Centro Urbano-SSA Clínica-1. Se recolectaron medidas antropométricas y se aplicaron los cuestionarios AMAI, SF12 y ESF-I para NSE, CdV y MetS, respectivamente. La asociación se determinó calculando rho de Spearman. El riesgo se evaluó mediante regresión logística (razon de momios e intervalo de confianza del 95%). Resultados: la diferencia entre NSE (193 ± 53 frente a 124 ± 50) y CdV (86.3 ± 14.8 frente a 56.0 ± 25.4) fue significativa entre los grupos de bajo y alto riesgo, respectivamente (p < 0.001). Hubo una fuerte correlación negativa entre las puntuaciones de la ESF-I y NSE (rho = -0.623, p < 0.001) así como con la CdV (rho = -0.719, p < 0.001). El riesgo de MetS aumentó al disminuir el NSE (C+: OR = 6.4, IC95%: 3.2 - 13.0; D: OR = 66.1, IC95%: 23.2 - 188.3), mientras que el aumento de la CdV lo atenuó (OR = 0.93, IC95%: 0.91 - 0.94). Interesantemente, la CdV mitigó el efecto del NSE (C+: OR = 4.5, IC95%: 2.1 - 9.6; D: OR = 11.9, IC95%: 3.8 - 37.6). Conclusión: Una menor CdV y NSE aumentan el riesgo de MetS en la región centro de México; sin embargo, el aumento en la CdV podría disminuir el efecto que tiene el NSE en el desarrollo de MetS.


Assuntos
Síndrome Metabólica , Qualidade de Vida , Humanos , Modelos Logísticos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , México/epidemiologia , Classe Social
7.
Rev. Méd. Inst. Mex. Seguro Soc ; 59(6): 490-499, dic. 2021. tab, grap
Artigo em Espanhol | LILACS | ID: biblio-1355275

RESUMO

Introducción: en México existe escasa información respecto al vínculo entre el síndrome metabólico (MetS), el nivel socioeconómico (NSE) y la calidad de vida (CdV) de la población. Objetivo: evaluar la asociación entre sujetos que tienen alto riesgo de desarrollar MetS con NSE y CdV. Métodos: se invitó a participar a pacientes de la UMF-2 del IMSS y del Centro Urbano-SSA Clínica-1. Se recolectaron medidas antropométricas y se aplicaron los cuestionarios AMAI, SF12 y ESF-I para NSE, CdV y MetS, respectivamente. La asociación se determinó calculando rho de Spearman. El riesgo se evaluó mediante regresión logística (razon de momios e intervalo de confianza del 95%). Resultados: la diferencia entre NSE (193  53 frente a 124  50) y CdV (86.3  14.8 frente a 56.0  25.4) fue significativa entre los grupos de bajo y alto riesgo, respectivamente (p < 0.001). Hubo una fuerte correlación negativa entre las puntuaciones de la ESF-I y NSE (rho = -0.623, p < 0.001) así como con la CdV (rho = -0.719, p < 0.001). El riesgo de MetS aumentó al disminuir el NSE (C+: OR = 6.4, IC95%: 3.2 - 13.0; D: OR = 66.1, IC95%: 23.2 - 188.3), mientras que el aumento de la CdV lo atenuó (OR = 0.93, IC95%: 0.91 - 0.94). Interesantemente, la CdV mitigó el efecto del NSE (C+: OR = 4.5, IC95%: 2.1 - 9.6; D: OR = 11.9, IC95%: 3.8 - 37.6). Conclusión: Una menor CdV y NSE aumentan el riesgo de MetS en la región centro de México; sin embargo, el aumento en la CdV podría disminuir el efecto que tiene el NSE en el desarrollo de MetS.


Background: In Mexico there is little information regarding the link between metabolic syndrome (MetS), socioeconomic status (SES) and quality of life (QoL) Objective: To assess the association between subjects who are at high risk of developing MetS with SES and QoL. Methods: Patients attending UMF-2 IMSS or Centro Urbano-SSA Clínica-1 were asked to participate. Anthropometric measures were collected, the AMAI, SF12, and ESF-I questionnaire where apply for SES, QoL, and MetS, respectively. Association were determined by calculating Spearman's rho and the risk (odds ratio and 95% confidence-interval) was assessed using logistic regression. Results: The difference of SES (193  53 vs. 124  50) and QoL (86.3  14.8 vs. 56.025.4) questionnaires were significantly between low-risk and high-risk groups, respectively (p < 0.001). There was a negative correlation between ESF-I and SES (rho = -0.623, p < 0.001) as well as the QoL (rho = -0.719, p < 0.001). MetS risk was augmented by decreasing SES (C+: OR = 6.4, 95%IC: 3.2-13.0; D: OR = 66.1, 95%IC: 23.2-188.3), whereas increasing QoL attenuated it (OR = 0.93, 95%CI: 0.91-0.94). However, QoL mitigated the effect of SES (C+: OR = 4.5, 95%IC: 2.1-9.6; D: OR = 11.9, 95%IC: 3.8-37.6).


Assuntos
Humanos , Masculino , Feminino , Qualidade de Vida , Grupos de Risco , Saúde Pública , Síndrome Metabólica , Associação , Modelos Logísticos , México
8.
Med. clín (Ed. impr.) ; 157(9): 409-417, noviembre 2021. tab, graf
Artigo em Inglês | IBECS | ID: ibc-215646

RESUMO

Objectives: Chronological age confers an increased risk for cardiovascular disease; however, chronological age does not reflect the subject's current health status. Therefore, we assessed whether Metabolic age (Met-age), based on free fat mass, is a predictor of cardiovascular risk (CVR).MethodsSubjects attending either IMSS UMF-2 or CUSC-1 were asked to participate. CVR was assessed using the waist-to-height ratio (WHtR), whereas Met-age was determined using the TANITA bio-analyser (model: BC-545F Fitscan). The strengthen of association was determined by calculating Pearson's r and predictability was determined by the area-under-a-receiver-operating characteristic curve (AUC).Results284 subjects participated in this study, of which 61.6% had increased CVR. As expected, the chronological age was significantly higher in the CVR(+) group than the CVR(−) group (47.3±14.4 v. 35.2±12.7, respectively, p<.001) as well as Met-age (59.3±15.5 v. 34.3±14.3, respectively, p<.001). There was a strong association between WHtR and Met-age (r=.720, p<.001) and a moderate association for chronological age (r=.407 p<.001); however, the correlation between WHtR and Met-age was significantly better than chronological age (Z=−5.91, p<.01). Met-age was a good predictor of CVR (AUC=.88, 95%CI: .83–.92, p<.001), whereas chronological age was a fair predictor (AUC=.72, 95%CI: .66–.78, p<.001). However, Met-age showed a higher discriminatory capacity for CVR than chronological age (z=−4.597, p<.001).ConclusionsHere, we determined that Met-age correlated with a CVR index, WHtR, and was able to predict subjects with increased CVR better than chronological age. (AU)


Objetivos: La edad cronológica confiere un mayor riesgo a la enfermedad cardiovascular; sin embargo, la edad cronológica no refleja el estado de salud actual del individuo. Por lo tanto, evaluamos si la edad metabólica (Met-age), basada en masa de grasa libre, es un factor predictivo del riesgo cardiovascular (RCV).MétodosSe solicitó su participación a individuos que asistían a IMSS UMF-2 o CUSC-1. Se evaluó el RCV utilizando el índice cintura-altura (ICA), mientras que Met-age se determinó utilizando el bioanalizador TANITA (modelo: Bc-545F Fitscan). La fuerza de asociación se determinó calculando la r de Pearson, y la predictibilidad se determinó mediante el índice de área bajo la curva (AUC).ResultadosDoscientos ochenta y cuatro sujetos participaron en este estudio, de los cuales el 61,6% reflejó un aumento del RCV. Como se esperaba, la edad cronológica fue significativamente mayor en el grupo del RCV+ que en el grupo del RCV− (47,3±14,4 vs. 35,2±12,7, respectivamente; p<0,001), así como en Met-age (59,3±15,5 vs. 34,3±14,3, respectivamente; p <0,001). Se produjo una fuerte asociación entre el ICA y la Met-age (r=0,720; p<0,001) y una asociación moderada con la edad cronológica (r=0,407; p<0,001); sin embargo, la correlación entre el ICA y la Met-age fue significativamente mejor que la edad cronológica (Z=−5,91; p<0,01). La Met-age fue un buen predictor del RCV (AUC=0,88, IC 95%: 0,83-0,92; p<0,001), mientras que la edad cronológica fue un factor predictivo moderado (AUC=0,72; IC 95%: 0,66-0,78; p<0,001). Sin embargo, la Met-age mostró una mayor capacidad discriminatoria para identificar el RCV que la edad cronológica (z=−4,597; p<0,001).ConclusionesEn este estudio determinamos que la Met-age se correlacionó con el índice ICA del RCV, y fue capaz de predecir sujetos con RCV mejor que la edad cronológica. (AU)


Assuntos
Humanos , Índice de Massa Corporal , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Cardiopatias , Circunferência da Cintura , Fatores de Risco , México
9.
Reumatol Clin (Engl Ed) ; 17(8): 447-455, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34625147

RESUMO

OBJECTIVE: We performed a meta-analysis to determine the effect Interleukin-6 (IL-6) promoter polymorphism (-174 G>C, -572 G>C, and -597 G>A) have on the development rheumatoid arthritis (RA) by ethnicity. MATERIAL AND METHODS: PubMed, EBSCO, LILACS, and Scopus databases were searched for studies exploring the association between any IL6 polymorphisms and RA until November 2018. Genotype distributions were extracted and, depending on the level heterogeneity, determined by the ψ2-based Q test and the Inconsistency Index (I2), fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. RESULTS: From 708 identified publications, 33 were used in this analysis. For the -174 polymorphism, Asians (ORheterozygous=7.57, 95%CI: 2.28-25.14, ORhomozygous=5.84, 95%CI: 2.06-16.56, ORdominant=7.21, 95%CI: 2.30-22.63, ORrecessive=5.04, 95%CI: 1.78-14.28, ORallelic=6.60, 95%CI: 2.26-19.28, p<.05) and Middle East countries (ORheterozygous=2.30, 95%CI: 1.10-4.81, ORdominant=2.27, 95%CI: 1.22-4.22, ORallelic=2.29, 95%CI: 1.24-4.23, p<.05) were associated with a significant risk of developing RA. Whereas, for Latinos, the C-allele was associated with a benefit (ORhomozygous=0.26, 95%CI: .08-.82, ORrecessive=.25, 95%CI: .08-.80, p<.05). For the -572 polymorphism, Asians demonstrated a significant association for the homozygous and recessive genetic models (8 studies, ORhomozygous=1.56, 95%CI: 1.16-2.09, ORrecessive=1.63, 95%CI: 1.08-2.45, p<.05). For the -597 polymorphism, no association was observed. CONCLUSIONS: Here, the -174 G>C polymorphism increased the risk of developing RA in Asians and Middle East populations. Interestingly, for Latinos, the polymorphism was associated with a benefit. For the -572 polymorphism, only the Asian population showed an increased risk of developing RA for the CC genotype.


Assuntos
Artrite Reumatoide , Interleucina-6/genética , Artrite Reumatoide/genética , Etnicidade/genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único
10.
J Drug Assess ; 10(1): 97-105, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34676131

RESUMO

OBJECTIVE: Receptor activator of NF-κß ligand (RANKL) is crucial for the development of hepatic insulin resistance and poor glucose uptake; therefore, inhibiting RANKL with Denosumab could improve fasting plasma glucose (FPG) and insulin (FPI). METHODS: A systematic review was conducted to evaluate the effects of Denosumab on glycemic parameters. PubMed, SCOPUS, EBSCO, and LILACS databases were searched for studies that investigated the effect of Denosumab on FPG, glycated hemoglobin (HbA1c), FPI, and Homeostatic Model Assessment for Insulin Resistance (HOMA1-IR). The pooled standard difference in means (SDM) and 95% confidence intervals (95%CI) were calculated. The results were stratified into (1) Normal Glucose Tolerance (NGT) and (2) Impaired Glucose Tolerance (IGT). RESULTS: Six publications (1203 participants) were included. There was a significant association between Denosumab and FPG (SDM = -0.388, 95%CI: -0.705 to -0.070, p = .017) and with HOMA1-IR (SDM = -0.223, 95%CI: -0.388 to -0.058, p = .008), but not for HbA1c and FPI. When stratified by glucose tolerance, the association between Denosumab and FPG, HbA1c, and HOMA1-IR was present for the IGT group. Lastly, Denosumab had a time-dependent effect on HbA1c (slope = -0.037, 95%CI: -0.059 to -0.015, p < .005). CONCLUSIONS: Denosumab significantly improved glycemic parameters. This outcome was more prominent for subjects with compromised glucose tolerance, positing that Denosumab can be used as a treatment to improve glucose metabolism for persons with pre-diabetes and diabetes.

11.
J Diabetes Complications ; 35(9): 107974, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34210601

RESUMO

BACKGROUND: Evidence implicates tumor necrosis factor (TNF) in the pathophysiology of Type 2 Diabetes (T2D) through unclear mechanisms. We hypothesized that disordered glycemic control leads to TNF activation and increases in soluble-TNF (sTNF) and its receptors-1 (sTNFR1) and -2 (sTNFR2). METHODS: We characterized 265 T2D and non-diabetic Latin American subjects and assessed the relationship between the TNF system and fasting plasma glucose (FPG), hemoglobin-A1C (A1C), insulin (FPI), C-peptide and HOMA-Beta. RESULTS: sTNF and sTNFR2 but not sTNFR1 levels were higher in T2D than non-diabetics (P<0.0001). In T2D, sTNFR2 was associated with A1C and C-peptide (R2=0.354, b=0.504, P<0.0001; b=0.167, P=0.049). Also, T2D patients with disordered glycemic control had increased sTNFR2 levels that correlated with FPG (Rho:0.393, P<0.001), A1C (Rho:0.451, P<0.001) and HOMA-Beta (Rho:-0.308, P=0.005); events not observed in T2D patients with adequate glycemic control. Furthermore, sex-based comparative analyses of T2D patients showed that women compared to men had higher sTNFR2 levels (P=0.017) that correlated with FPG, A1C, FPI and HOMA-Beta. CONCLUSIONS: Disordered glycemic control is associated with sTNF and sTNFR2. sTNFR2 levels were higher in T2D women than men. Thus, increased sTNFR2 levels may be an important biomarker for disordered glucose and inflammatory complications in T2D patients and women in particular.


Assuntos
Diabetes Mellitus Tipo 2 , Controle Glicêmico , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Fator de Necrose Tumoral alfa/sangue , Peptídeo C , Diabetes Mellitus Tipo 2/complicações , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino
12.
Arq. bras. oftalmol ; 84(3): 249-257, May-June 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1248973

RESUMO

ABSTRACT Purpose: Paraoxonase-1 activity is associated with age-related macular degeneration. Two polymorphisms (L55M and Q192R) were shown to increase paraoxonase-1 activity and have been implicated in the development of age-related macular degeneration. The results of studies that have examined these polymorphisms are conflicting, showing no effect, as well as increased or decreased risk. Therefore, this meta-analysis was conducted to determine the effect of these polymorphisms on age-related macular degeneration. Methods: PubMed, EBSCO, LILACS, and Scopus databases, as well as and the retrieved bibliographies of publications were searched for case-control studies that examined for paraoxonase-1 polymorphisms and age-related macular degeneration. Data were analyzed using the Comprehensive Meta-Analysis Version 2.2 and the NCSS Statistical Version 2020 software. Genotype distributions were extracted and, depending on the level of heterogeneity, fixed effects or random effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. Results: Overall, for the L55M polymorphism, none of the genetic models demonstrated a significant association. However, for non-Asian populations, a significant association was determined for the heterozygous and dominant genetic models (ORrange=1.24-1.27, p<0.05). For the Asian population, the heterozygous, dominant, and allelic genetic models demonstrated a benefit/protective factor (ORrange=0.29-0.35, p<0.05). For the Q192R polymorphism, none of the genetic models demonstrated a significant association. However, when the cohort was grouped by ethnicity, a significant association was determined in the Asian population for the recessive and allelic genetic models (ORrange=1.63-2.08, p<0.05). However, for the non-Asian population, there was no association observed. Also, there was no identifiable risk when the cohort was stratified into exudative and non-exudative cases. Conclusions: The paraoxonase-1L55M polymorphism increases the risk of developing age-related macular degeneration in non-Asian populations, whereas in Asian populations, the polymorphism exerts a protective effect. However, for the paraoxonase-1 Q192R polymorphism, only the Asian population demonstrated a risk of developing age-related macular degeneration.(AU)


RESUMO Objetivo: A atividade da paraoxonase1 está associada à degeneração macular relacionada à idade. Dois polimorfismos (L55M e Q192R) mostraram aumentar a atividade da paraoxonase1 e foram implicados no desenvolvimento da degeneração macular relacionada à idade. Os estudos que examinaram esses polimorfismos apresentaram resultados conflitantes: nenhum efeito, risco aumentado ou diminuído. Assim, esta meta-análise foi realizada para determinar o efeito desses polimorfismos na degeneração macular relacionada à idade. Métodos: Foi feita uma busca nos bancos de dados PubMed, EBSCO, LILACS e SCOPUS, bem como nas bibliografias compiladas das publicações, buscando-se estudos caso-controle que tivessem analisado os polimorfismos da paraoxonase1 e a degeneração macular relacionada à idade. Os dados foram analisados com software Comprehensive Meta-Analysis, versão 2.2, e NCSS Statistical, versão 2020. As distribuições de genótipos foram extraídas e, dependendo do nível de heterogeneidade, modelos de efeitos fixos ou aleatórios foram utilizados para calcular razões de probabilidade (RPs) combinadas, com intervalos de confiança de 95% (IC 95%) para os modelos genéticos heterozigoto, homozigoto, dominante, recessivo e alélico. Resultados: Em geral, nenhum dos modelos genéticos demonstrou associação significativa para o polimorfismo L55M. Entretanto, em populações não asiáticas, foi determinada uma associação significativa para os modelos genéticos heterozigoto e dominante (RPfaixa=1,24-1,27, p<0,05). Para a população asiática, os modelos heterozigoto, dominante e alélico mostraram um fator benéfico ou protetor (RPfaixa=0,29-0,35, p<0,05). Para o polimorfismo Q192R, nenhum dos modelos genéticos demonstrou qualquer associação significativa. Porém, quando a coorte foi agrupada por etnia, determinou-se uma associação significativa na população asiática para os modelos genéticos recessivo e alélico (RPfaixa=1,63-2,08, p<0,05). Contudo, nenhuma associação foi observada para a população não asiática. Não houve risco identificável quando a coorte foi estratificada em exsudativa e não exsudativa. Conclusões: Determinamos que o polimorfismo L55M da paraoxonase1 de fato aumenta o risco de desenvolvimento de degeneração macular relacionada à idade em populações não asiáticas, enquanto que em populações asiáticas, esse polimorfismo tem um efeito protetor. Porém, para o polimorfismo Q192R da paraoxonase1, apenas a população asiática demonstrou risco de desenvolver degeneração macular relacionada à idade.(AU)


Assuntos
Humanos , Polimorfismo Genético , Arildialquilfosfatase , Degeneração Macular/etiologia , Etnicidade
13.
High Blood Press Cardiovasc Prev ; 28(3): 263-270, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33666897

RESUMO

INTRODUCTION: Every 10 years, an adult's basal metabolic rate (BMR), independent of their BMI, decreases 1-2% due to skeletal muscle loss, thus decreasing an adult's energy requirement and promoting obesity. Increased obesity augments the risk of developing Metabolic Syndrome (MetS); however, an adult's healthy lifestyle, which increases BMR, can mitigate MetS development. To compare different BMRs for certain ages, Metabolic age (Met-age) was developed. AIM: To assess the association between Met-age and MetS and to determine if Met-age is an indicator of high-risk individuals for MetS. METHODS: Four hundred thirty-five attendees at 2 clinics agreed to participate and gave signed informed consent. MetS risk was assessed by the ESF-I questionnaire. Met-age was determined using a TANITA bio-analyzer. Strengthen of association was determined by calculating Spearman's rho and predictability was evaluated by the area-under-a-receiver-operating characteristic curve (AUC). Difference-in-age (DIA) = [chronological age - Met-age]. RESULTS: There was a difference between the low-risk (n = 155) and the high-risk (n = 280) groups' Met-age (37.8±16.7 v. 62.9±17.3) and DIA (1.3±17.4 v. - 10.5±20.8, p < 0.001). There was a positive correlation between the ESF-I questionnaire and Met-age (rho = - 0.624, p < 0.001) and a negative correlation for DIA (rho = - 0.358, p < 0.001). Met-age was strongly predictive (AUC = 0.84, 95% CI 0.80-0.88), suggesting a 45.5 years cutoff (sensitivity = 83.2%, specificity = 72.3%). DIA was a good predictor (AUC = 0.68, 95% CI 0.63-0.74) with a - 11.5 years cutoff (sensitivity = 52.5%, specificity = 82.8%). CONCLUSION: Met-age highly associated with and is an indicator of high-risk individuals for MetS. This would suggest that increases in Met-age are associated with augmented MetS severity, independent of the individual's chronological age.


Assuntos
Metabolismo Basal , Síndrome Metabólica/metabolismo , Adulto , Fatores Etários , Envelhecimento , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Fatores de Risco
14.
Arq Bras Oftalmol ; 84(3): 249-257, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33567022

RESUMO

PURPOSE: Paraoxonase-1 activity is associated with age-related macular degeneration. Two polymorphisms (L55M and Q192R) were shown to increase paraoxonase-1 activity and have been implicated in the development of age-related macular degeneration. The results of studies that have examined these polymorphisms are conflicting, showing no effect, as well as increased or decreased risk. Therefore, this meta-analysis was conducted to determine the effect of these polymorphisms on age-related macular degeneration. METHODS: PubMed, EBSCO, LILACS, and Scopus databases, as well as and the retrieved bibliographies of publications were searched for case-control studies that examined for paraoxonase-1 polymorphisms and age-related macular degeneration. Data were analyzed using the Comprehensive Meta-Analysis Version 2.2 and the NCSS Statistical Version 2020 software. Genotype distributions were extracted and, depending on the level of heterogeneity, fixed effects or random effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. RESULTS: Overall, for the L55M polymorphism, none of the genetic models demonstrated a significant association. However, for non-Asian populations, a significant association was determined for the heterozygous and dominant genetic models (ORrange=1.24-1.27, p<0.05). For the Asian population, the heterozygous, dominant, and allelic genetic models demonstrated a benefit/protective factor (ORrange=0.29-0.35, p<0.05). For the Q192R polymorphism, none of the genetic models demonstrated a significant association. However, when the cohort was grouped by ethnicity, a significant association was determined in the Asian population for the recessive and allelic genetic models (ORrange=1.63-2.08, p<0.05). However, for the non-Asian population, there was no association observed. Also, there was no identifiable risk when the cohort was stratified into exudative and non-exudative cases. CONCLUSIONS: The paraoxonase-1L55M polymorphism increases the risk of developing age-related macular degeneration in non-Asian populations, whereas in Asian populations, the polymorphism exerts a protective effect. However, for the paraoxonase-1 Q192R polymorphism, only the Asian population demonstrated a risk of developing age-related macular degeneration.


Assuntos
Arildialquilfosfatase , Degeneração Macular , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único
15.
Acta Diabetol ; 58(4): 475-484, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33394132

RESUMO

AIMS: Osteoprotegerin (OPG) has been associated with Charcot Neuroarthropathy (CN); however, three studied OPG polymorphisms (1181C > G, 245A > C and 950 T > C) have yielded conflicting results. Therefore, this meta-analysis was conducted to determine the difference in serum OPG concentrations between healthy controls and diabetics with and without CN and the effect OPG polymorphisms have on CN development. METHODS: PubMed, LILAC, SCOPUS, and EBSCO databases and retrieved publications' bibliographies were searched for studies that examined for OPG and CN. Depending on the heterogeneity, fixed or random effects were used to calculate the pooled odds ratio (OR) or standard difference in means (SDM) with 95% confidence intervals (95%CI) for 5 genetic models (heterozygous, homozygous, dominant, recessive, and allelic) and serum concentrations, respectively. RESULTS: Seven publications (12 studies) demonstrated that serum OPG concentrations were more elevated in subjects with CN (SDM = 0.719, 95%CI = 0.555-0.883, p < 0.001). When CN was compared to healthy controls or diabetics, the difference was more prominent for healthy controls (SDM = 1.043, 95%CI = 0.676-1.409, p < 0.001) than diabetics (SDM = 0.639, 95%CI = 0.456-0.821, p < 0.001) and the SDM difference was significant (p = 0.013). Using 6 publications (9 studies), neither the 1181C > G or the 950 T > C polymorphisms showed any significant associations for any genetic model. For the 245A > C polymorphism, only the homozygous genetic model showed a significant association between the polymorphism and CN (OR = 2.850, 95%CI: 1.051-7.729, p = 0.040). CONCLUSIONS: Here, we determined a potential correlation between the CN and serum OPG concentrations and that only the CC genotype of the 245A > C polymorphism showed an increased risk of developing CN.


Assuntos
Artropatia Neurogênica/genética , Osteoprotegerina/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Artropatia Neurogênica/epidemiologia , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Heterozigoto , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Osteoprotegerina/sangue , Polimorfismo de Nucleotídeo Único
16.
Med Clin (Barc) ; 157(9): 409-417, 2021 Nov 12.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33067009

RESUMO

OBJECTIVES: Chronological age confers an increased risk for cardiovascular disease; however, chronological age does not reflect the subject's current health status. Therefore, we assessed whether Metabolic age (Met-age), based on free fat mass, is a predictor of cardiovascular risk (CVR). METHODS: Subjects attending either IMSS UMF-2 or CUSC-1 were asked to participate. CVR was assessed using the waist-to-height ratio (WHtR), whereas Met-age was determined using the TANITA bio-analyser (model: BC-545F Fitscan). The strengthen of association was determined by calculating Pearson's r and predictability was determined by the area-under-a-receiver-operating characteristic curve (AUC). RESULTS: 284 subjects participated in this study, of which 61.6% had increased CVR. As expected, the chronological age was significantly higher in the CVR(+) group than the CVR(-) group (47.3±14.4 v. 35.2±12.7, respectively, p<.001) as well as Met-age (59.3±15.5 v. 34.3±14.3, respectively, p<.001). There was a strong association between WHtR and Met-age (r=.720, p<.001) and a moderate association for chronological age (r=.407 p<.001); however, the correlation between WHtR and Met-age was significantly better than chronological age (Z=-5.91, p<.01). Met-age was a good predictor of CVR (AUC=.88, 95%CI: .83-.92, p<.001), whereas chronological age was a fair predictor (AUC=.72, 95%CI: .66-.78, p<.001). However, Met-age showed a higher discriminatory capacity for CVR than chronological age (z=-4.597, p<.001). CONCLUSIONS: Here, we determined that Met-age correlated with a CVR index, WHtR, and was able to predict subjects with increased CVR better than chronological age.


Assuntos
Doenças Cardiovasculares , Índice de Massa Corporal , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco de Doenças Cardíacas , Humanos , Fatores de Risco , Circunferência da Cintura , Razão Cintura-Estatura
17.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32505641

RESUMO

OBJECTIVE: We performed a meta-analysis to determine the effect Interleukin-6 (IL-6) promoter polymorphism (-174 G>C, -572 G>C, and -597 G>A) have on the development rheumatoid arthritis (RA) by ethnicity. MATERIAL AND METHODS: PubMed, EBSCO, LILACS, and Scopus databases were searched for studies exploring the association between any IL6 polymorphisms and RA until November 2018. Genotype distributions were extracted and, depending on the level heterogeneity, determined by the ψ2-based Q test and the Inconsistency Index (I2), fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. RESULTS: From 708 identified publications, 33 were used in this analysis. For the -174 polymorphism, Asians (ORheterozygous=7.57, 95%CI: 2.28-25.14, ORhomozygous=5.84, 95%CI: 2.06-16.56, ORdominant=7.21, 95%CI: 2.30-22.63, ORrecessive=5.04, 95%CI: 1.78-14.28, ORallelic=6.60, 95%CI: 2.26-19.28, p<.05) and Middle East countries (ORheterozygous=2.30, 95%CI: 1.10-4.81, ORdominant=2.27, 95%CI: 1.22-4.22, ORallelic=2.29, 95%CI: 1.24-4.23, p<.05) were associated with a significant risk of developing RA. Whereas, for Latinos, the C-allele was associated with a benefit (ORhomozygous=0.26, 95%CI: .08-.82, ORrecessive=.25, 95%CI: .08-.80, p<.05). For the -572 polymorphism, Asians demonstrated a significant association for the homozygous and recessive genetic models (8 studies, ORhomozygous=1.56, 95%CI: 1.16-2.09, ORrecessive=1.63, 95%CI: 1.08-2.45, p<.05). For the -597 polymorphism, no association was observed. CONCLUSIONS: Here, the -174 G>C polymorphism increased the risk of developing RA in Asians and Middle East populations. Interestingly, for Latinos, the polymorphism was associated with a benefit. For the -572 polymorphism, only the Asian population showed an increased risk of developing RA for the CC genotype.

18.
Diagnostics (Basel) ; 10(3)2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32138353

RESUMO

. Urinary albumin excretion remains the key biomarker to detect renal complications in type 2 diabetes. As diabetes epidemy increases, particularly in low-income countries, efficient and low-cost methods to measure urinary albumin are needed. In this pilot study, we evaluated the performance of Raman spectroscopy in the assessment of urinary albumin in patients with type 2 diabetes. The spectral Raman analysis of albumin was performed using artificial urine, at five concentrations of albumin and 24 h collection urine samples from ten patients with Type 2 Diabetes. The spectra were obtained after removing the background fluorescence and fitting Gaussian curves to spectral regions containing features of such metabolites. In the samples from patients with type 2 diabetes, we identified the presence of albumin in the peaks of the spectrum located at 663.07, 993.43, 1021.43, 1235.28, 1429.91 and 1633.91 cm-1. In artificial urine, there was an increase in the intensity of the Raman signal at 1450 cm-1, which corresponds to the increment of the concentrations of albumin. The highest concentration of albumin was located at 1630 cm-1. The capability of Raman spectroscopy for detection of small concentrations of urinary albumin suggests the feasibility of this method for the screening of type 2 diabetes renal complications.

19.
Genet Mol Biol ; 42(3): 549-559, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31188929

RESUMO

Our objective was to determine the association between the methylenetetrahydrofolate reductase polymorphisms (C677T and A1298C) and the risk of developing acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), acute myeloid leukemia (AML), and multiple myelomas (MM) in Latinos. PubMed, SCOPUS, EBSCO, LILACS, and other Latin-specific databases were searched for case-control studies that investigated the association between these polymorphisms and hematologic malignancies until November 2017. Genotype distributions were extracted and either fixed-effects or random-effects models were used to calculate the pooled crude odds ratios (ORs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. No publication bias was detected by the Begg-Mazumdar's test and Egger's test. From 290 publications, we identified 15 studies on the C677T polymorphism and 13 studies on the A1298C polymorphism. We observed a significant decrease in risk for the C677T polymorphism (OR range=0.54-0.75, p<0.01) and a significant increase in risk for the A1298C polymorphism (OR range=1.28-2.52, p<0.05) in developing ALL for all genetic models. No associations were determined for CML, AML, or MM for either polymorphism. This meta-analysis demonstrated that the A1298C polymorphism was associated with an increased risk of developing ALL, whereas the C677T polymorphism was associated with a decreased risk (protective factor) in the Latino population.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31093233

RESUMO

OBJECTIVE: To determine the reliability of a non-laboratorial questionnaire, the Encuesta de Identificación de Sujetos Metabólicamente Comprometidos en Fase-I (ESF-I) for identifying Metabolic Syndrome among a population in central Mexico. METHODS: Clinical and biochemical parameters were collected for 232 participants from 1 June 2012 - 31 August 2013. Three definitions of Metabolic Syndrome (Harmonizing, National Cholesterol Education Program Expert Panel and Adult Treatment Panel III [ATPIII], and International Diabetes Federation [IDF]) were used to allocate subjects to either the normal or Metabolic Syndrome positive (MetS+) group. The predictability of the questionnaire was determined by the Area-Under-the-Receiver-Operating Characteristic curve (AUC). Youden's index was calculated and the highest score was considered the optimal cutoff value. Cohen´s kappa (κ) was calculated to determine the level of agreement between the ESF-I questionnaire (max score: 15 based on 15 items) and Metabolic Syndrome. RESULTS: From 53.8% - 60.7% of the participants were determined to be MetS+. The average questionnaire score was significantly higher in the MetS+ group for each definition (4.0 vs. 8.0, P < 0.05). The ESF-I questionnaire was predictive for the Harmonizing definition (AUC = 0.841, 95%CI: 0.790 - 0.892), the ATPIII definition (AUC = 0.827, 95%CI: 0.774 - 0.880), and the IDF definition (AUC = 0.836, 95%CI: 0.785 - 0.887). A cutoff value of 7 was determined for each definition; therefore, the cohort was re-categorized based on questionnaire results. There was a strong agreement between the ESF-I questionnaire and MetS (Harmonizing: accuracy = 77.6%, κ = 0.554; ATPIII: accuracy = 74.1%, κ = 0.489; IDF: accuracy = 74.6%, κ = 0.495, P < 0.001). CONCLUSION: The ESF-I questionnaire can identify MetS+ patients, and therefore, lead to earlier diagnoses, reduced number of consultations, and lower costs with easier application.

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