Dr. Villagran-Orellana, Marcelo

Objective: The aim of this study was to identify which anthropometric measurement (body mass index [BMI], waist circumference [WC], or waist-to-height ratio [WHtR]) is a better predictor of type 2 diabetes and hypertension in the Chilean population. Methods: The study included 13 044 participants (59.7% women) from the Chilean National Health Surveys conducted in 2003, 2009-2010, and 2016-2017. BMI, WC, and WHtR were the anthropometric measurements evaluated. Hypertension was defined as systolic blood pressure ≥140 mm Hg and diastolic blood pressure -90 mm Hg or on medication for hypertension. Diabetes was defined as fasting glucose -7 mmol/L or on medication for diabetes. The receiver operating characteristics (ROC) curve and the area under curve (AUC) were computed to derive the specificity and sensitivity using a bootstrapping approach. Results: Compared with BMI and WC, WHtR was the anthropometric measurement with the highest AUC curve in both sexes for hypertension (AUC for women: 0.70; 95% confidence interval [CI], 0.67-0.73; AUC for men: 0.71; 95% CI, 0.69-0.74) and diabetes (AUC for women: 0.71; 95% CI, 0.66-0.77; AUC for men: 0.71; 95% CI, 0.67-0.76). The sex-specific cutoff points of WHtR to predict hypertension were 0.59 and 0.55 for women and men, respectively. Those used to predict diabetes were 0.60 and 0.58 for women and men, respectively. Conclusion: WHtR was a better predictor of hypertension and diabetes than BMI and WC in Chile. The definition of cutoff points specific for the Chilean population could be implemented in future screening programs aiming to identify high-risk individuals.

La obesidad es una enfermedad inflamatoria, crónica, recurrente, progresiva y de etiología multifactorial, que afecta a más 650 millones de personas en el mundo. La carga física, emocional y económica que genera la obesidad no solo guarda relación con sus manifestaciones clínicas, sino también por su impacto a nivel sistémico y a largo plazo. En Chile, el crecimiento económico, la urbanización y la globalización han modificado profundamente el modo de vivir de la población lo que ha favorecido un ambiente obesogénico. Sin embargo, ¿qué factores han repercutido en el desarrollo de obesidad en Chile? ¿cuál ha sido el rol de cada uno de estos factores en el aumento de la prevalencia de esta patología? En la parte 1 de esta revisión discutiremos los principales factores no modificables que han repercutido en su desarrollo, desde la transición epidemiológica que vivió el país en la década de los 70, hasta las patologías endocrinas relacionadas.

Vitamin C is a water-soluble antioxidant associated with the prevention of the common cold and is also a cofactor of hydrolases that participate in the synthesis of collagen and catecholamines, and in the regulation of gene expression. In cancer, vitamin C is associated with prevention, progression, and treatment, due to its general properties or its role as a pro-oxidant at high concentration. This review explores the role of vitamin C in cancer clinical trials and the aspects to consider in future studies, such as plasmatic vitamin C and metabolite excretion recording, and metabolism and transport of vitamin C into cancer cells. The reviewed studies show that vitamin C intake from natural sources can prevent the development of pulmonary and breast cancer, and that vitamin C synergizes with gemcitabine and erlotinib in pancreatic cancer. In vitro assays reveal that vitamin C synergizes with DNA-methyl transferase inhibitors. However, vitamin C was not associated with cancer prevention in a Mendelian randomized study. In conclusion, the role of vitamin C in the prevention and treatment of cancer is still an ongoing area of research. It is necessary that new phase II and III clinical trials be performed to collect stronger evidence of the therapeutic role of vitamin C in cancer.

Los factores del estilo de vida podrían promover un envejecimiento saludable. Objetivo: Investigar la asociación entre la actividad física (PA), comportamiento sedentario y deterioro cognitivo en chilenos mayores adultos. Material y Métodos: Se incluyeron 1.390 participantes de la Encuesta Nacional de Salud (2009-2010). El Mini-mental El examen estatal se utilizó para diagnosticar el deterioro cognitivo. La actividad física y el comportamiento sedentario fueron evaluados con Cuestionario Global de Actividad Física (GPAQ). Regresión Logística se realizó para investigar las asociaciones. Resultados: Comparados con adultos mayores con niveles más bajos de PA (< 48 min/día), aquellos con niveles medios (48-248 min/día) y más altos (>248 min/día) de PA tuvieron menores probabilidades de deterioro cognitivo (Odds ratio (OR): 0,57 [95% IC: 0,32; 0,83], p < 0,01, respectivamente). Los participantes que informaron que pasaban más de 8 horas al día sentados tenían una alta probabilidad de deterioro cognitivo en comparación con aquellos que pasaban < 4 horas/ día (OR: 3,70 [IC 95%: 1,37; 6,03], p = 0,01). Conclusiones: Tanto la PA como el comportamiento sedentario se asociaron independientemente con el deterioro cognitivo independiente de los principales factores de confusión en adultos mayores chilenos.

Type 2 diabetes Mellitus (T2DM) prevalence has significantly increased worldwide in recent years due to population age, obesity, and modern sedentary lifestyles. The projections estimate that 439 million people will be diabetic in 2030. T2DM is characterized by an impaired β-pancreatic cell function and insulin secretion, hyperglycemia and insulin resistance, and recently the epigenetic regulation of β-pancreatic cells differentiation has been underlined as being involved. It is currently known that several bioactive molecules, widely abundant in plants used as food or infusions, have a key role in histone modification and DNA methylation, and constituted potential epidrugs candidates against T2DM. In this sense, in this review the epigenetic mechanisms involved in T2DM and protein targets are reviewed, with special focus in studies addressing the potential use of phytochemicals as epidrugs that prevent and/or control T2DM in vivo and in vitro. As main findings, and although some controversial results have been found, bioactive molecules with epigenetic regulatory function, appear to be a potential replacement/complementary therapy of pharmacological hypoglycemic drugs, with minimal side effects. Indeed, natural epidrugs have shown to prevent or delay the T2DM development and the morbidity associated to dysfunction of blood vessels, eyes and kidneys due to sustained hyperglycemia in T2DM patients.

Background: Genetic variants within the FTO gene have been associated with increased adiposity and metabolic markers; however, there is limited evidence regarding the association of FTO gene variants with physical activity-related variables. The authors aimed to investigate the association of the rs17817449 single-nucleotide polymorphism of FTO with physical activity, sedentary time, and cardiorespiratory fitness in Chilean adults. Methods: A total of 409 participants from the GENADIO study were included and genotyped for the rs17817449 single-nucleotide polymorphism of FTO in this cross-sectional study. Physical activity and sedentary time were measured with ActiGraph accelerometers. Cardiorespiratory fitness was assessed using the Chester step test. The associations were assessed by using multivariate regression analyses. Results: No associations were found for FTO variant with physical activity levels and cardiorespiratory fitness. The risk allele (G) of the FTO was found to be associated with sedentary time in the minimally adjusted model (β = 19.7 min/d; 95% confidence interval, 4.0 to 35.5, per each copy of the risk allele; P = .006), but the association was no longer significant when body mass index was included as a confounder (P = .211). Conclusion: The rs17817449 single-nucleotide polymorphism of the FTO gene was not associated with the level of physical activity, cardiorespiratory fitness, and sedentary behaviors in Chilean adults.

Alternariol is a toxic metabolite of Alternaria fungi and studies have shown multiple potential pharmacological effects. To outline the anticancer effects and mechanisms of alternariol and its derivatives based on database reports, an updated search of PubMed/MedLine, ScienceDirect, Web of Science, and Scopus databases was performed with relevant keywords for published articles. The studies found to suggest that this mycotoxin and/or its derivatives have potential anticancer effects in many pharmacological preclinical test systems. Scientific reports indicate that alternariol and/or its derivatives exhibit anticancer through several pathways, including cytotoxic, reactive oxygen species leading to oxidative stress and mitochondrial dysfunction-linked cytotoxic effect, anti- inflammatory, cell cycle arrest, apoptotic cell death, genotoxic and mutagenic, anti-proliferative, autophagy, and estrogenic and clastogenic mechanisms. In light of these results, alternariol may be one of the hopeful chemotherapeutic agents.

Antecedentes. El receptor de melanocortina 4 (MC4R) participa en el control del apetito a nivel del sistema nervioso central, a través de la vía de la leptina-melanocortina. Se ha reportado asociación entre diferentes polimorfismos del gen MC4R y la obesidad; sin embargo, existen escasos estudios del polimorfismo de nucleótido simple (SNP) rs483145 de este gen. Objetivo. Investigar su prevalencia y asociación con marcadores de adiposidad en adultos chilenos. Métodos. La prevalencia del SNP rs483145, del gen MC4R, fue determinada en 259 participantes del estudio Genes, Ambiente, Diabetes y Obesidad (GENADIO) mediante reacción en cadena de la polimerasa (PCR) en tiempo real. La asociación del alelo de riesgo de MC4R (A) con marcadores de adiposidad (peso corporal, índice de masa corporal, porcentaje de masa grasa, perímetro de cadera, perímetro de cintura e índice cintura/cadera), se realizó mediante análisis de regresión lineal y fue ajustada por variables de confusión (sociodemográficas y de actividad física) mediante 3 modelos estadísticos. Resultados. Se determinó que la prevalencia del alelo de riesgo (A) del SNP rs483145 del gen MC4R es del 24,5% en la población adulta chilena incluida en este estudio, sin encontrar asociación con ninguno de los marcadores de adiposidad estudiados, tanto en modelos ajustados como sin ajustar.

Background: Fat-mass-associated-gene (FTO) is associated with higher energy intake and specific food preferences. Aim: To investigate the association of the FTO genotype with energy intake, macronutrient and alcohol consumption. Material and Methods: Four hundred and nine participants of the GENADIO (Genes, Environment, Diabetes and Obesity) study were included. Energy intake, macronutrient and alcohol consumption were the outcomes of interest. The association of FTO (rs9939609) genotype with these outcomes was investigated using linear regression analyses, adjusting for confounding variables. Results: After adjusting for socio-demographic factors, being a carrier of the risk allele for the FTO gene was associated with a higher energy intake (173 kcal per each extra copy of the risk variant [95% confidence intervals (CI): 45; 301], (P = 0.008). After adjusting for lifestyle factors and body mass index, the association was slightly attenuated but remained significant (144 kcal [95% CI: 14; 274], p = 0.030). Conclusions: The FTO genotype is associated with a higher energy intake. (Rev Med Chile 2018; 146: 1252-1260)

Chile tiene una de las tasas de obesidad más altas del mundo. Se estima que para el año 2030 las muertes atribuidas a esta enfermedad alcanzarían a 204 mil personas, incrementándose además los costos económicos asociados a esta patología. Las causas y los factores de riesgo asociados al desarrollo de obesidad son diversos. Sin embargo, existe consenso que una de las maneras más eficaces de prevenir y/o disminuir su prevalencia es abordando los factores de riesgo modificables, a través del fomento de hábitos de vida saludable con un enfoque integral, centrados en la alimentación saludable, práctica de actividad física, prevención del tabaquismo y consumo de alcohol, como también en el cuidado de la salud mental del individuo. No obstante, el desafío es cómo hacer realidad estos buenos propósitos. En este contexto, el objetivo de esta revisión, parte 2, fue investigar los principales factores modificables, con énfasis en los factores individuales, que han repercutido en el desarrollo de obesidad: desde una mirada global hasta el caso particular de Chile.