jueves, 28 de agosto de 2014

Obesity: exploring the causes, consequences and solutions

The World Health Organization estimates that global levels of obesity have doubled since 1980. In 2012, more than 40 million children under the age of 5 were estimated to be overweight or obese, which is an issue of serious concern as excess body weight is believed to be the driver of many non-communicable diseases, namely type 2 diabetes, cardiovascular disease and some types of cancer.
To tackle what is, in most cases, a preventable condition, there is increasing focus on research into understanding the mechanisms behind obesity, including our genetics and the influence of lifestyle and the environment. There is also now increased focus on introducing public health initiatives to aid long-term weight loss, which range from improving public, patient and healthcare provider education to policy reform regarding the sale of pre-packaged and processed foods.
To focus on these issues, BMC Medicine has launched an article collection that aims to explore the main contributing factors and possible solutions to tackle the worldwide impact of obesity.

Which are the culprits – sugars, starches or fats?

How much of what we eat makes us fat? This is an ongoing debate, fuelled most recently byRobert Lustig and his focus on sugar. On the question of sugar, a further debate arises – is itsucrose or fructose that has the most impact on obesity?
In an editorial to introduce the article collection in BMC MedicineJack Winkler, former Professor of Nutrition Policy at London Metropolitan University, and currently Director of Food & Health Research, discusses why it is so hard to measure which food components are associated with obesity.
Prof Winkler explains one of the many problems with this field is that data derived from large-scale studies depends on reliable and consistent reporting. However, this is a limiting factor simply because these studies rely on self-reported energy intake surveys, and as Prof Winkler reminds us, people are good at lying about how much they are actually eating.

The lies people tell about their food may be white lies, but they are large lies….. In one study of soft drinks, subjects in the National Diet and Nutrition Survey claimed to be drinking barely a quarter of the products that manufacturers reported they were selling

The consequences of obesity

There is no question that obesity places a burden on healthcare services. Earlier this year,Gillian Reeves and colleagues showed that elevated body mass index (BMI) in UK women is associated with increased hospital admissions equating to around 420,000 extra admissions annually, indicating that current obesity levels are directly impacting UK healthcare services.
Primary care physicians are usually the first in line to treat patients with obesity related diseases, although patients may not be visiting their GP to directly ‘treat’ their obesity. As David Haslam, a GP and physician specializing in obesity at the Centre for Obesity research explains, the role of primary care in managing obesity is complicated in the UK by ineffective or contradictory policies. In his commentary published as part of this article collection, Prof Haslam starkly points out:
“Obesity prevention has failed. If nobody in the UK gains another single ounce, there are enough already obese people to make epidemics of diabetes, then heart disease then premature death inevitable.”
Prof Haslam, who also serves as Chair of the National Obesity Forum, highlights that obesity can be most effectively managed by individualization of care, which should be implemented through effective screening and risk management. After all, not all patients will benefit from weight loss. Prof Haslam discusses the obesity paradox in his commentary, and recent evidence on this includes a meta-analysis we published this year by Wie Nie and colleagues, showing that an obesity paradox exists for pneumonia – i.e. obese individuals have an increased risk of pneumonia but a decreased risk of pneumonia mortality, indicating a survival advantage for obese individuals.
However, in most cases, obesity and diet are considered as a causal risk factor for chronic diseases such as type 2 diabetes. Recently, Elin Hall and colleagues showed that exposing pancreatic islet cells to the free fatty acid palmitate results in differential gene expression and epigenetic modifications, which may influence type 2 diabetes risk through impaired insulin secretion in these treated cells.
In an Opinion article, Naveed Sattar and Jason Gill discuss the plausible link between type 2 diabetes and ectopic fat around organs such as the liver and pancreas. In their article, they explain that studies have shown accumulation of ectopic fat around the liver leads to insulin resistance, and they also hypothesize that fat around the pancreas could lead to β-cell dysfunction. Prof Sattar and Dr Gill ask a very provocative question: can type 2 diabetes be reversed by loss of ectopic fat around key organs?

Taking action on obesity

So, what should be done about the rising levels of obesity? One of the physicians leading the issue is John Wass, a consultant physician and endocrinologist, and also Chair of the Working Party for Action on Obesity.
I interviewed Prof Wass about the goals of the working party, which aims to tackle the rise of obesity in the UK  by filling current gaps in knowledge and support within the healthcare and medical education systems. Prof Wass highlights that educating the public about healthy eating, and collaborations with the food industry on how to responsibly sell and label foods, is key to improving public health.
There is also ongoing debate about whether or not obesity should be considered as a disease. On this, Prof Wass explains that as obesity is a condition that needs to be actively managed it can be labelled as a disease, and unless it is recognized as such, prevention and management strategies will not be taken seriously.

Tomado de: 

miércoles, 27 de agosto de 2014

‘Prostate cancers’ not ‘prostate cancer’ – revealing the many faces of ‘one’ disease

New research published today in Genome Biology shows that RNA sequencing could lead the way towards more personalized treatments for prostate cancer. In this guest post, Dr Iain Frame, Director of Research at Prostate Cancer UK discusses what this could mean for patients and health services, and what more is needed to provide effective support and treatment for men with prostate cancer.
We are used to hearing and talking about prostate cancer as a single disease.  Albeit a disease with its tigers and pussycats – the tigers being the aggressive cancers that move out of the prostate gland to other parts of the body, and the pussycats being those cancers that may never cause any harm and won’t go on to kill.  But it’s never quite as simple as that is it?
More and more we hear clinicians and research scientists talk about ‘prostate cancers’ plural. This is largely down to the introduction of genomic sequencing which has allowed researchers to identify and examine large numbers of prostate tumors, which initiate and progress in different ways. Add to this, the genomic variations in the men themselves, and suddenly the world of detecting and treating cancers of the prostate becomes a lot more complicated – not that it was ever simple to begin with!
What the paper published today by Drs Collins and Wyatt from the Vancouver Prostate Centre does so well is apply state-of-the art RNA sequencing technology to a real life situation. So on top of the information we know at the whole genome level, they looked at which genes were being used and disrupted at the point when the tumor was collected. Being able to match this up with how these men and their tumors had responded to different treatments meant that the researchers could then see which treatments work best for the different tumor types.
So in theory, by knowing more about the tumor and the man who has the tumor, researchers will be able to develop more personalized or tailored treatments for individuals. As a result, clinicians will be armed with a much clearer idea as to which treatments will work most effectively and speculation will be a thing of the past.
However, there is a ‘but’.  The researchers here only looked at 25 tumors and were surprised by the sheer number of genomic differences between them. Forty-thousand  men are newly diagnosed with prostate cancer each year in the UK and there are 250,000 men in this country living with the disease – so how much variation will there be when the number of tumors examined in this way increases?
The challenge lies in how we translate this fantastically elegant research into real life benefits for these men and those at risk of prostate cancer.  And what’s more – let’s not kid ourselves that it is only prostate cancer that is looking to tailor treatments – every other disease is working to the same aim, putting tremendous pressure on health services, which will need to cope with the increased expense of diagnosing and managing disease at an individual level.
At Prostate Cancer UK, we strongly support the development of new tailored treatments for men with prostate cancer. However, allied to that aim is an ambition to be able to take some men out of the system – those men whose cancer will never spread.
We feel that alongside developing better treatments, the global research community needs to develop a more robust risk assessment tool that can be used in multi-ethnic populations, delivered through primary care reasonably simply and in a cost-effective way. By doing this in prostate cancer we should be able to concentrate limited healthcare resources on those who need it most – those with, or at high risk of, aggressive prostate cancers.
There is absolutely no doubt that this is a really exciting time for prostate cancer research.  The results from this research will help build a better picture of what is going on and I’m confident that in the future it can lead to important health benefits for men with, and at high risk of, aggressive prostate cancer.
But that fight needs resources – both financial and human – to succeed.  It is clear that we must keep building on research successes such as the one reported here,  but for this to be possible, more funding is needed to support more scientists through their research endeavors in order to achieve real benefits for men.

Tomado de blogs.biomedcentral.com

miércoles, 20 de agosto de 2014

Datos a largo plazo confirman los beneficios de las pruebas diagnósticas para la detección del cáncer de próstata

Datos a 13 años confirman los beneficios en términos de mortalidad, pero los investigadores dicen que todavía no se justifica realizar pruebas de detección a nivel poblacional
El Estudio aleatorizado europeo para la detección del cáncer de próstata (European Randomised study of Screening for Prostate Cancer, ERSPC) ha demostrado reducciones significativas en la mortalidad por el cáncer de próstata después de 9 y 11 años de seguimiento, pero las pruebas diagnósticas para la detección de la enfermedad aún son controvertidas debido a los acontecimientos adversos, como el sobrediagnóstico. Proporcionamos resultados actualizados sobre la mortalidad por cáncer de próstata con seguimiento hasta 2010, con análisis revisados a los 9, 11 y 13 años.
ERSPC es un ensayo multicéntrico, aleatorizado, con una base de datos centralizada predefinida, plan de análisis y grupo de edad principal (55-69 años), que evalúa las pruebas del antígeno específico de la próstata (prostate-specific antigen, PSA) en ocho países europeos. Se identificaron hombres elegibles de 50-74 años de edad a partir de registros poblacionales y se les asignó aleatoriamente, mediante números aleatorios generados por ordenador, a someterse a pruebas de detección de la enfermedad o a no realizarse ninguna intervención (control). Los investigadores no conocían las asignaciones de grupo. El criterio de valoración primario fue la mortalidad por cáncer de próstata en el grupo de edad principal. El análisis se realizó por intención de tratar. Realizamos un análisis secundario con corrección para el sesgo por selección debido a la no participación. En los centros franceses solo se comunicaron los datos de incidencia y no mortalidad a los 9 años de seguimiento. El estudio está registrado en Ensayos controlados actuales con el número ISRCTN49127736.
Con datos revisados a los 13 años de seguimiento, se diagnosticaron 7408 casos de cáncer de próstata en el grupo de intervención y 6107 casos en el grupo de control. La tasa de incidencia de cáncer de próstata entre los grupos de intervención y de control fue de 1,91 (IC 95% 1,83-1,99) después de 9 años (1,64 [1,58-1,69] incluida Francia), 1,66 (1,60-1,73) después de 11 años y 1,57 (1,51-1,62) después de 13 años. La tasa de mortalidad por cáncer de próstata fue de 0,85 (0,70-1,03) después de 9 años, 0,78 (0,66-0,91) después de 11 años y 0,79 (0,69-0,91) a los 13 años. La reducción absoluta del riesgo de muerte por cáncer de próstata a los 13 años fue de 0,11 por cada 1000 años-persona o de 1,28 por cada 1 000 hombres asignados aleatoriamente, lo que es equivalente a evitar una muerte por cáncer de próstata por cada 781 (IC 95 %490-1 929) hombres invitados a realizarse las pruebas de detección o uno por cada 27 (17-66) casos de cáncer de próstata adicionales detectados. Después del ajuste por no participación, la proporción de las tasas de mortalidad por cáncer de próstata en los hombres evaluados fue de 0,73 (IC 95% 0,61-0,88).
En esta actualización, el estudio ERSPC confirma una reducción sustancial en la mortalidad por cáncer de próstata atribuible a las pruebas de PSA, con un aumento sustancial del efecto absoluto a los 13 años en comparación con los hallazgos después de 9 y 11 años. Pese a nuestros hallazgos, aún se considera un prerrequisito la cuantificación adicional de daños y su reducción para que tenga lugar la introducción de las pruebas de detección a nivel poblacional
Tomado de Univadis


Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. The Lancet. 2014;doi:10.1016/S0140-6736(14)60525-0.

Test predicts future kidney stones

Having had one kidney stone increases the risk of having a second one. Although it is possible to take precautionary measures, they may be expensive, burdensome and cause side effects. A test, developed and presented by US physicians in the "Journal of the American Society of Nephrology" (JASN), can predict the risk of developing another kidney stone.
To develop the ROKS test (Recurrence Of Kidney Stone), researchers from the Mayo Clinic in Rochester analysed data from all adults residing in an area of Minnesota, who had experienced a first kidney stone between 1984 and 2003. Of the 2.239 people identified, 707 experienced at least one more kidney stone by 2012.
The following risk factors were determined from the information gathered: younger age, male, white race, family history, blood in urine, stone made of uric acid, obstructing stone in the kidney pelvis, additional non-obstructing stone, and past painful event associated with kidney stones even though a stone was not seen.
Using the test, predictions can be made on the probability of having another kidney stone at two, five or 10 years after the first one, said study leader Andrew Rule. "If we knew which patients were at high risk for another symptomatic kidney stone, then we could better advise patients on whether to follow stone prevention diets or take medications," he explained
Tomado de Univadis
Bibliografia: Rule AD et al. The ROKS Nomogram for Predicting a Second Symptomatic Stone Episode. J Am Soc Nephrol. 2014 Aug 7

miércoles, 13 de agosto de 2014

Descubren nuevos factores involucrados en el hígado graso

Investigadores del CNIO han descrito cómo las proteínas AP-1 regulan la acumulación de grasas en el hígado, característica de la enfermedad del hígado graso. La manipulación farmacológica de estas proteínas podría servir para el tratamiento de esta enfermedad en humanos.
Una de las enfermedades más prevalentes en las sociedades occidentales es la esteatosis hepática, también conocida como enfermedad del hígado graso (FLD en inglés), que afecta al 30% de la población adulta y se caracteriza por una acumulación de grasas en el hígado.

La FLD se asocia a una ingesta excesiva de alcohol y obesidad, y puede provocar insuficiencia hepática, diabetes e incluso cáncer. Hasta la fecha, no existen tratamientos farmacológicos para la enfermedad.

El Grupo de Genes, Desarrollo y Enfermedad del Centro Nacional de Investigaciones Oncológicas (CNIO), encabezado por Erwin Wagner, director del programa de la Fundación BBVA-CNIO de Biología Celular del Cáncer, ha descubierto nuevos factores, las proteínas AP-1, críticos en el desarrollo de la FLD.

Los resultados aparecen hoy en la portada de la revista Cell Metabolism, líder en el campo del metabolismo celular. El trabajo se ha desarrollado en colaboración con Johan Auwerx, de la Escuela Politécnica Federal de Lausanne, Suiza.
El hígado graso se asocia a una ingesta excesiva de alcohol y obesidad, y puede provocar insuficiencia hepática, diabetes e incluso cáncer.
El equipo del CNIO había observado que los hígados de los ratones obesos tenían niveles bajos de Fra1, proteína del tipo AP-1. Para conocer el porqué, los investigadores crearon ratones transgénicos que aumentaban o disminuían la producción de estas proteínas en el hígado y estudiaron sus consecuencias en la enfermedad.

Proteínas que eliminan la grasa hepática

“El aumento de las proteínas AP-1, como Fra1 o Fra2, fue capaz de prevenir la acumulación de grasa y la FLD en ratones. Sorprendentemente, el aumento de estas proteínas en ratones con obesidad y FLD hizo desaparecer por completo la grasa en el hígado, además de prevenir inflamación y daño hepático”, explica Sebastian Hasenfuss, primer autor del artículo.

Los investigadores también describen el mecanismo subyacente del efecto de estas proteínas sobre el metabolismo de las grasas. Según indica Wagner, “las proteínas AP-1 son reguladores maestros del metabolismo de las grasas”, y añade: “Estas proteínas controlan la captación en el hígado de las grasas procedentes del torrente sanguíneo".

El artículo afirma cómo otras proteínas relacionadas con Fra1, como c-Fos y JunD, ejercen efectos opuestos sobre el metabolismo de las grasas en el hígado. Los autores proponen que un desequilibrio entre el conjunto de estas proteínas podría ser clave en la patogénesis de la FLD.

Tomado de: intramed.net
Referencia bibliografica: Regulation of steatohepatitis and PPARγ signaling by distinct AP-1 dimers. Hasenfuss SC, Bakiri L, Thomsen MK, Williams EG, Auwerx J, Wagner EF. Cell Metabolism (2013) http://dx.doi.org/10.1016/j.cmet.2013.11.018