Tag Archives: obesity

Fruit discovery could provide new treatments for obesity, type 2 diabetes and cardiovascular disease

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May 12, 2016

A combination of two compounds found in red grapes and oranges could be used to improve the health of people with diabetes, and reduce cases of obesity and heart disease.

The find has been made by University of Warwick researchers who now hope that their discovery will be developed to provide a treatment for patients.

Professor Thornalley who led research said: “This is an incredibly exciting development and could have a massive impact on our ability to treat these diseases. As well as helping to treat diabetes and heart disease it could defuse the obesity time bomb.”

The research ‘Improved glycemic control and vascular function in overweight and obese subjects by glyoxalase 1 inducer formulation’ has been published in the journal Diabetes, and received funding from the UK’s innovation agency, Innovate UK. The project was a collaboration between the University of Warwick and University Hospitals Coventry and Warwickshire (UHCW) NHS Trust.

A team led by Paul Thornalley, Professor in Systems Biology at Warwick Medical School, studied two compounds found in fruits but not usually found together. The compounds are trans-resveratrol (tRES) – found in red grapes, and hesperetin (HESP) – found in oranges. When given jointly at pharmaceutical doses the compounds acted in tandem to decrease blood glucose, improve the action of insulin and improve the health of arteries.

The compounds act by increasing a protein called glyoxalase 1 (Glo1) in the body which neutralises a damaging sugar-derived compound called methylglyoxal (MG). MG is a major contributor to the damaging effects of sugar. Increased MG accumulation with a high energy diet intake is a driver of insulin resistance leading to type 2 diabetes, and also damages blood vessels and impairs handling of cholesterol associated with increased risk of cardiovascular diseases. Blocking MG improved health in overweight and obese people and will likely help patients with diabetes and high risk of cardiovascular disease too. It has already been proven experimentally that blocking MG improves health impairment in obesity and type 1 and type 2 diabetes.

Although the same compounds are found naturally in some fruits, the amounts and type required for health improvement cannot be obtained from increased fruit consumption. The compounds that increase Glo1 and are called a ‘Glo1 inducer’. Pharmaceutical doses for patients with obesity, diabetes and high risk of heart disease could be given to patients in capsule form.

Professor Thornalley increased Glo1 expression in cell culture. He then tested the formulation in a randomised, placebo-controlled crossover clinical trial.

Thirty-two overweight and obese people within the 18-80 age range who had a BMI between 25-40 took part in the trial. They were given the supplement in capsule form once a day for eight weeks. They were asked to maintain their usual diet and their food intake was monitored via a dietary questionnaire and they were also asked not to alter their daily physical activity. Changes to their sugar levels were assessed by blood samples, artery health measured by artery wall flexibility and other assessments by analysis of blood markers.

The team found that the highly overweight subjects who had BMIs of over 27.5 with treatment displayed increased Glo1 activity, decreased glucose levels, improved working of insulin, improved artery function and decreased blood vessel inflammation. There was no effect of placebo.

Professor Thornalley said: “Obesity, type 2 diabetes and cardiovascular disease are at epidemic levels in Westernised countries. Glo1 deficiency has been identified as a driver of health problems in obesity, diabetes and cardiovascular disease.”

“Diabetic kidney disease will be the initial target to prove effective treatment for which we are currently seeking commercial investors and partners. Our new pharmaceutical is safe and expected to be an effective add-on treatment taken with current therapy.

“The key steps to discovery were to focus on increasing Glo1 and then to combine tRES and HESP together in the formulation for effective treatment.

“As exciting as our breakthrough is it is important to stress that physical activity, diet, other lifestyle factors and current treatments should be adhered to.”

Professor Martin O Weickert, Consultant in Diabetes and Endocrinology at UHCW NHS Trust, and co-applicant for the grant, said: “We were really excited to participate in this study with Warwick Medical School, as taking part in world-leading research makes a real difference to our patients both now and in the future.

“As well as the positive effects for the UHCW patients who took part in the trial, we hope this study will lead to new treatments to help patients with diabetes and cardiovascular diseases all over the world.”

Prof. Thornalley and his team are now hoping manufacturers will want to explore the use of the compound as pharmaceutical products.

source: University of Warwick

Source: Fruit discovery could provide new treatments for obesity, type 2 diabetes and cardiovascular disease | Science Codex

Obesity less dangerous than 40 years ago

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May 11, 2016

New research from Denmark involving more than 100,000 individuals suggests that the excess risk of premature death associated with obesity has decreased over the past 40 years. All-cause mortality was higher in obese individuals than in normal weight individuals in 1976-78, but not in 2003-13.

Many try to lose weight to avoid diabetes and cardiovascular disease and hopefully live longer. This is often driven by recommendations from health care authorities and is further supported by the media and not least, by commercials often presenting normal weight or even thin people as ideal humans.

“The increased risk of all-cause mortality associated with obesity compared to normal weight decreased from 30% 1976-78 to 0% in 2003-13,” says principal investigator Dr. Shoaib Afzal, Herlev Hospital, Copenhagen University Hospital, Denmark.

This research has just been published in the Journal of the American Medical Association (JAMA).

What is the optimal BMI for lowest mortality?

The study also revealed changes in the BMI associated with the lowest all-cause mortality in three cohorts from Copenhagen, examined respectively in 1976-78, 1991-1994, and in 2003-2013 (all individuals were followed until 2014).

“The optimal BMI for the lowest mortality increased from 23.7 in 1976-78, through 24.6 in 1991-94, to 27 in 2003-13, while individuals with a BMI below or above the optimal value had higher mortality,” adds Shoaib Afzal.

“Compared to the 1970’s, today’s overweight individuals have lower mortality than so-called normal weight individuals. The reason for this change is unknown. However, these results would indicate a need to revise the categories presently used to define overweight, which are based on data from before the 1990’s” says senior author Clinical Professor Borge G. Nordestgaard, University of Copenhagen and Copenhagen University Hospital.

“Importantly, our results should not be interpreted as suggesting that now people can eat as much as they like, or that so-called normal weight individuals should eat more to become overweight. That said, maybe overweight people need not be quite as worried about their weight as before”, adds Nordestgaard.

Obesity and overweight are classified using Body Mass Index (BMI), calculated as weight in kilograms divided by height in meters squared. A BMI of 25-29.9 represents overweight, a BMI of 30 or greater represents obesity, while a BMI of 18.5-24.9 is considered normal weight. These categories are often used for recommendations on optimum weight.

Source: University of Copenhagen The Faculty of Health and Medical Sciences

Source: Obesity less dangerous than 40 years ago | Science Codex

BU study: Effects of obesity on death rates understated in prior research

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(BOSTON) — Researchers from the Boston University School of Public Health and the University of Pennsylvania have found that prior studies of the link between obesity and mortality are flawed because they rely on one-time measures of body mass index (BMI) that obscure the health impacts of weight change over time.

The study, published online in the journal Proceedings of the National Academy of Sciences, maintains that most obesity research, which gauges weight at only a single point in time, has underestimated the effects of excess weight on mortality. Studies that fail to distinguish between people who never exceeded normal weight and people of normal weight who were formerly overweight or obese are misleading because they neglect the enduring effects of past obesity and fail to account for the fact that weight loss is often associated with illness, the researchers said.

When such a distinction is made, the study found, adverse health effects grow larger in weight categories above the normal range, and no protective effect of being overweight is observed.

“The risks of obesity are obscured in prior research because most of the studies only incorporate information on weight at a single point in time,” said lead author Andrew Stokes, assistant professor of global health at BUSPH. “The simple step of incorporating weight history clarifies the risks of obesity and shows that they are much higher than appreciated.”

Stokes and co-author Samuel Preston, professor of sociology at the University of Pennsylvania, tested a model that gauged obesity status through individuals’ reporting of their lifetime maximum weight, rather than just a ‘snapshot’ survey weight. They found that the death rate for people who were normal weight at the time of survey was 27 percent higher than the rate for people whose weight never exceeded that category.

They also found a higher prevalence of both diabetes and cardiovascular disease among people who had reached a higher-than-normal BMI and then lost weight, compared to people who remained in a high BMI category.

Stokes and Preston argue that using “weight histories” in studies of obesity and mortality is important for two reasons. One reason is that obesity at a particular age may predispose people to illness, regardless of subsequent weight loss. The other is that weight loss is often caused by illness.

The researchers used data from the large-scale 1988-2010 National Health and Nutrition Examination Survey, linking the data to death certificate records through 2011. The survey asked respondents to recall their maximum lifetime weight, as well as recording their weight at the time of the survey.

Of those in the normal-weight category at the time of the survey, 39 percent had transitioned into that category from higher-weight categories.

The study used statistical criteria to compare the performance of various models, including some that included data on weight histories and others that did not. The researchers found that weight at the time of the survey was a poor predictor of mortality, compared to models using data on lifetime maximum weight.

“The disparity in predictive power between these models is related to exceptionally high mortality among those who have lost weight, with the normal-weight category being particularly susceptible to distortions arising from weight loss,” the researchers said. “These distortions make overweight and obesity appear less harmful by obscuring the benefits of remaining never obese.”

The study comes amid controversy over the relationship between obesity and mortality, with some recent studies indicating that excess weight is a protective factor in health. One such study, a major meta-analysis in 2013 led by a researcher with the Centers for Disease Control and Prevention, indicated that being overweight was associated with lower mortality, and that slight obesity conferred no excess risk of death.

A number of past studies have shown that people who lose weight have higher rates of death than those who maintain their weight over time. Part of the reason for that disparity is that illness may be a cause of weight loss, through decreased appetite or increased metabolic demands. Few studies have adequately accounted for that source of bias, Stokes and Preston noted.

They urged more research using weight histories, saying such an approach had proven valuable in studies of smoking, which distinguish between former and current smokers and those who have never smoked.

Source: Boston University Medical Center

Source: BU study: Effects of obesity on death rates understated in prior research | Science Codex

New study describes how glucose regulation enables malignant tumor growth | Science Codex

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COLUMBUS, Ohio — A new study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) identifies a key pathway used by cancer cells to make the lipids by integrating oncogenic signaling, fuel availability and lipid synthesis to support cell division and rapid tumor growth.

The researchers identified a critical molecule in that pathway that, if blocked, might cripple lipid production by cancer cells and slow tumor growth. This approach would be a new strategy for treating a lethal type of brain cancer called glioblastoma multiforme, as well as other malignancies. This discovery also has significant therapeutic implications on other metabolic disorders with deregulated lipid metabolism, such as atherosclerosis, obesity and diabetes.

The study discovered that activation of the epidermal growth factor receptor (EGFR), which triggers enhanced uptake of glucose, leads to a chemical change in a molecule called SCAP. This enables SCAP to transport a second molecule called SREBP, and this leads to the activation of genes that regulate the production and uptake of lipids. SREBPs are key proteins for regulating lipid metabolism.

The researchers published their findings in the journal Cancer Cell Nov. 9, 2015.

Source: New study describes how glucose regulation enables malignant tumor growth | Science Codex