Obesity-related fertility issues may be improved by correcting blood sugar levels

 Reproductive hormone levels in females with obesity may be partially restored by lowering blood glucose levels, leading to improved fertility, according to a study published in the Journal of Endocrinology

The study indicates that altered levels of reproductive hormones in a well-established mouse model of obesity may be partially restored by a common type 2 diabetes medication that reduces blood glucose levels. Many women with obesity that experience fertility issues also have altered levels of reproductive hormones. Currently there is no effective therapy to address this. Development of a therapy that not only improves women’s’ metabolic health but also treats obesity-related infertility would be a significant advancement, with the potential to improve many people’s quality of life.

 

Although fertility problems are well established in women with obesity, there remains a lack of effective and targeted treatments to address them. Obesity is a growing health epidemic, which means more women are being affected by reproductive difficulties. Obesity-related fertility issues are complex but evidence suggests that, in part, they may be linked to changes in energy metabolism, which lead to altered levels of reproductive hormones that can then disrupt the menstrual cycle and ovulation. People with obesity are at a greater risk of developing type 2 diabetes and often have high blood glucose levels, as well as other metabolic changes.

 

The MC4R gene knock-out (KO) mouse is a well-characterised model of obesity, which also exhibits irregular reproductive cycles with altered hormone levels that lead to declining fertility. The mouse reproductive cycle is similar to that of humans, in that the profile of hormone level changes is analogous, although it is much shorter in duration, so the MC4R KO mouse is a good, representative model for initial investigations of metabolic and reproductive function in obesity. 

 

Dapagliflozin is a drug commonly used to treat type 2 diabetes, where it reduces blood glucose levels and improves other markers of metabolic health but its effects on reproductive health and fertility have yet to be investigated.

 

In this study, Professor Chen and colleagues at the University of Queensland in Australia, investigated the effects of dapagliflozin treatment on metabolic health and reproductive hormone levels in the MC4R mouse model of obesity. After just 8 weeks of treatment blood glucose levels were normal, body weight was reduced, the reproductive cycle was normalised and levels of reproductive hormones and ovulation were partially restored, compared with non-treated mice.

 

“We often see low fertility in women with obesity in clinical practice”, comments primary author, Dr Cui, a visiting fellow from Chengdu Women and Children Hospital in China, “so this research provides hope for a future, effective treatment.”

 

Professor Chen comments, “These data suggest that normalising blood glucose metabolism with dapagliflozin in obesity may be a promising route for at least partially restoring reproductive function. This could improve fertility in women where no other successful therapy is currently available.”

 

However, Professor Chen cautions, “Although encouraging, these studies were conducted in mice and much more work needs to be done to confirm that these findings could be replicated effectively in women. However, people with obesity are at much greater risk of developing type 2 diabetes, so the known health benefits of correcting blood glucose levels may be extended to also improving fertility in those affected.”

 

The team now intend to further investigate the therapeutic benefits of using dapagliflozin to improve reproductive function by examining the molecular pathways involved, which could identify better targets for future fertility treatment in women.

 

Europeans join call for more to be done to tackle obesity

People from across Europe are being urged to support a call for EU Member States to do more to tackle the region’s growing obesity epidemic.

The action is being organised to coincide with European Obesity Day which takes place on Saturday 20 May and is being promoted via a European Obesity Day website page https://www.europeanobesityday.eu/get-involved/please-join-call-action/. Everyone who pledges their support can also download a certificate of acknowledgement.

Europe's leading organisation responsible for research into obesity, the European Association for the Study of Obesity (EASO), has warned that EU Member States need to do more to tackle the growing obesity epidemic, or they could face crippling costs of providing medical care in the future.  

They are also urging people to reduce the stigma around obesity and to do more to support those who have it.

According to EASO, too few European countries have effective strategies in place to tackle obesity, and some have none at all. “Despite the growing epidemic, many plans consist only of collections of vague goals rather than concrete measures,” says  EASO President, Professor Hermann Toplak.

“To be effective, Member States need to have comprehensive strategies that cover all aspects of weight management. These should include the promotion of healthier lifestyles and the reduction in demand and consumption of excessive amounts of high-calorie food and drinks, as well as the treatment of obesity to help prevent the many other diseases on which it impacts,” he said.

Type 2 diabetes, cardiovascular diseases and several forms of cancer are among the non-communicable diseases (NCDs) and chronic conditions attributable to excess weight.

To help facilitate cooperation between EU Member States and to inspire them to do more, EASO organised a major conference in Brussels this week (on Wednesday 10 May).  More than 100 national policymakers, representatives from the European Institutions, the WHO, and healthcare specialists attended to discuss the challenges they face and to share examples of best practice.

EASO’s 32 member associations and more than 70 collaborating centres will be marking European Obesity Day at a national level by staging events over the coming week to create greater awareness and understanding of obesity.  The initiatives range from walks and fun runs to free public health checks and consultations with healthcare professionals.

In line with the theme for European Obesity Day 2017, Tackling Obesity Together, people across all EU member states are being encouraged to participate.

According to World Health Organisation, obesity is one of the greatest public health challenges of the 21st century. Its prevalence has tripled in many countries in Europe since the 1980s.

Several reports have shown that if the number of overweight people and those with obesity continues to increase at the same rate,  it will affect more than half of all European citizens by 2030. In some countries, it may be as high as 90%. 

Five obesity myths busted at the start of the JanUary campaign

 At the start of JanUary, Dr. James Brown of Aston University sets out five common misconceptions about obesity and healthy living. Formerly National Obesity Awareness Week, the JanUary campaign aims to encourage people to eat right, lose weight and work on their fitness.

Dr. James Brown, Lecturer in Biology and Biomedical Science in the School of Life and Health Sciences at Aston University, commented:

“With increased awareness among the general public regarding obesity, many people are looking to adopt healthier lifestyles. But, despite our best intentions, it’s all too easy to set about this in the wrong way. Initiatives like JanUary help to ensure our self-improvement drive doesn’t go to waste, bringing much-needed attention to reassessing our eating and exercising habits. First off, people should learn what works and what doesn’t.”

To mark the start of JanUary, Dr. James Brown busts five common myths surrounding our health:

1. Myth: In order to lose weight, I simply need to increase the amount of exercise that I do.

• Exercise on its own is unlikely to have a significant impact on weight loss. The most successful regime for losing weight should combine exercise and dieting. Dieting alone is the next best approach, followed by a focus on exercise to sustain weight loss.

2. Myth: Carbohydrates are bad and, in order to become healthier, I need to cut them out of my diet completely.

• Taken as part of a healthy diet, carbohydrates are not at all bad. In fact, many of the healthiest foods, such as fruits and vegetables, are rich in carbs. It is the processed and added sugars in some types of carbs – white bread, for example – that are most damaging and should be avoided.

3. Myth: Low fat foods are my best option for a healthy diet.

• This often isn’t the case because many processed low fat foods, such as yoghurt, are actually high in sugar to ensure they are palatable. If people opt for low fat foods, they should ensure they come without additives.

4. Myth: My child may be overweight now, but this is likely to be puppy fat and I am sure he or she will lose this extra weight in later life.

• Being overweight as a child is closely associated with obesity in later life. Parents should monitor their children’s weight, and ensure they have the right diet and exercise routine to prevent them from becoming obese.

5. Myth: The only way I can truly lose weight and avoid obesity is to invest in a gym membership and make sure I work out twice a week.

• There are alternative, potentially more effective ways to do this, such as ‘exercise snacking’. This involves multiple bouts of exercise for short periods during the day, such as 10 minutes after breakfast, lunch and dinner – a method that has be shown to control blood sugar better than a single, continuous workout.

Obesity in Focus at Diabetes Professional Care

Obesity is set to take centre stage at this year’s Diabetes Professional Care, with industry experts presenting the very latest thinking on the subject as part of its new dedicated Obesity in Practice area. The two-day, free-to-attend, 7 stream CPD accredited show will also host an obesity led discussion and will feature some of the most innovative obesity focused technologies and solutions on the market.

Toby Baker, Event Director at Diabetes Professional Care, comments: “The UK is currently ranked as having the highest levels of obesity in Europe, with more than 1 in 4 adults being classified as obese. Over the next 20 years, the number of obese adults in the UK is forecast to soar to around 26 million people, which will cause millions more cases of type 2 diabetes, heart disease and cancer. This is a subject that needs to be addressed and quickly. We hope that our dedicated Obesity in Practice zone, educational conference streams, practical workshops and cutting-edge suppliers, provide the perfect platform from which we can all learn and share knowledge in order to help combat this devastating condition.”   

New for 2016, Obesity in Practice is a specialist area at Diabetes Professional Care, dedicated to the entire obesity spectrum. Industry leading speakers will be taking to the stage to discuss the most relevant and current hot topics, including the NHS’ five-year plan, hydration, bariatric surgery, the obesity crisis and the effect obesity has on diabetes.

Chairing the presentations within the Obesity in Practice zone and delivering its welcome presentation will be Tam Fry, spokesperson for the National Obesity Forum, Expert Advisory Team Member with Action On Sugar and Patron of the Child Growth Foundation.

Those wanting to know more about the NHS’ plans to counteract the obesity problem, will not want to miss the talk titled ‘The NHS’ Five Year Forward View’. The talk will detail a marked shift in focus towards diabetes and obesity prevention. Plus, it will also discuss the latest obesity guidelines and outline Central Government Funding.

One proposed response to the obesity crisis is bariatric surgery. Dimitri Pournaras, Clinical Fellow in Upper Gastrointestinal and Bariatric Surgery at Musgrave Park Hospital will look at why the NHS should do more bariatric surgery and detail just how much we should be doing.

Medical experts and campaigners criticised the Government’s recent childhood obesity strategy, calling it weak and embarrassing, and accused policymakers of throwing away the best chance to tackle the culture of unhealthy eating that is crippling the NHS. With this in mind Jenny Rosborough, Registered Nutritionist (Public Health) and Campaign Manager at Action on Sugar, will analyse what role the government and the food and drink industry play in tackling obesity.

Research suggests that water could be the secret weapon in the fight against the obesity, with statistics finding obese people and those with higher body mass indexes are more likely to be inadequately hydrated. Professor Tom Sanders, Emeritus Professor of Nutrition and Dietetics at Kings College London will follow up this theme during his presentation titled: ‘Obesity and Hydration – am I hungry or am I thirsty?’

Carolyn Pallister, Dietitian & Public Health Manager at Slimming World will explore the role the commercial sector plays in supporting weight management in patients and in reducing health risks. Whilst, Andrew Shanahan, Journalist, Entrepreneur & Director of Man v Fat, will detail ‘MAN v FAT Football - Can The Beautiful Game Solve The Obesity Crisis?’.

In addition to the Obesity in Practice zone, the show will also host The Live Debate, an interactive discussion, which will see several leading authorities examine the hot topic of: ‘Food for Thought - What Should a Diabetes Patient Eat?’ Taking place on day two of the show, the panel will include: Dr Trudi Deakin, Chief Executive at X-PERT Health, Dr Ian Lake, GP and PWD Type 1 and Arjun Panesar, CEO at Diabetes.co.uk. Acting as facilitator and chairing the debate will be Dr Mike Sadler and John Grummit, Vice President at International Diabetes Federation.

The panel will be fielding questions from the audience and challenging each other on all things obesity orientated, covering everything from government nutritional guidance and surgery through to how much onus should be placed on the patient. 

Artificial hip joints and obesity: Risk of complications rises with BMI but benefits predominate

Every tenth patient who receives an artificial hip joint in Europe is obese. This is a big challenge for orthopaedic surgery because a person who is overweight has to expect complications. In the meantime, there are an increasing number of ways of improving the safety and success of implanted hip prostheses in obese patients. “From a medical standpoint, it is sensible to implant an artificial hip even in an extremely obese person if he or she needs one. It is an effective way to re-establish the mobility of individuals with serious cases of arthrosis. Otherwise, the alternatives would be: chronic pain, disability and even the need for nursing care.” This was the conclusion of Prof Sébastien Lustig from Croix-Rousse University Hospital in Lyon, France and Prof Sébastien Parratte from Aix Marseille University in Marseille, France, at the 17th Congress of the European Federation of National Societies for Orthopaedics and Traumatology (EFORT) in Geneva.

The higher the BMI, the bigger the risk

According to a Swiss study, obese individuals with a body mass index (BMI) of 35kg/m² and up are candidates who risk follow-up operations and infections. An evaluation of data from 2,500 knee replacement procedures indicates that patients with a BMI from this level upward have twice as many revisional surgeries as others do and suffer from serious infections twice as often.

Prof Lustig: “Obesity is not just a biomechanical problem but also a biological one. It is true that every pound of joints bearing body weight is subject to a load of four to six pounds. Yet the effect of being overweight is much more complex and always has to be kept in mind in orthopaedic surgery.” In the meantime, we know that there is a complex interplay between obesity on the one hand and metabolic syndrome and cardiovascular diseases on the other. They promote inflammatory processes and cartilage degeneration, which play a part in the origination of arthroses. Diabetes, one of the typical co-morbidities of obesity, increases the risk of infection in hip replacement surgeries by ten percent. It is therefore imperative that this condition be effectively treated prior to surgery. Other actions to avoid infection are quitting smoking prior to surgery, special preparation of the skin and the use of bone cement with antibiotics. They are especially important in the event of severe obesity.

Preoperative counselling should address the topic of weight reduction

The information given to the patient prior to hip replacement surgery is a co-determinant of the success of that surgery. Prof Parratte: “There is no official weight limit for the implantation of prosthetic joints. Nonetheless, in cases of morbid obesity, i.e. a BMI from 40 kg/m², it would be advisable for the patient to lose weight prior to surgery.” The surgeons should therefore sit down with the patients and go through all risks that might occur if they fail to lose weight prior to surgery. Moreover, the possible ways of reducing weight should be discussed – if necessary also surgical options such as gastric banding. Prior to replacement surgery, patients must also be told what they can and cannot do with the new hip joint. Prof Lustig: “The risk of dislocation is higher for obese individuals in particular compared to people whose weight is in the normal range. It is also assumed that aseptic loosening of artificial hips occurs more frequently in obese patients. This condition is caused especially by abraded particles or a lack of initial stability in the implant. Prof Lustig: “The type of artificial hip joint that has proven effective for preventing hip dislocation is one with high offset, decreased cup abduction and larger head diameter.”

Surgical techniques must fit the situation

Finally, the suitable surgical techniques play an important role in the success of procedures. Prof Parratte: “Surgeons operating on obese patients should select the surgical approach with which they are most familiar. Minimal invasive surgeries are not indicated in any case.” As the number of obese individuals needing joint replacement will increase in the future, special surgical techniques could become established. One recommendation, for instance, is that orthopaedic surgeons use tailor-made patient-specific templates as a guide when putting prostheses in place. This approach boosts accuracy while reducing blood loss and surgery time. It likewise helps in correctly dimensioning the incisions and implants in patients with a high BMI. With patient-specific templates, the mechanical axis can be restored more reliably as well.

Kanazawa University research: Mechanism revealed linking liver disease and obesity

 Kanazawa University researchers find similarities in the impeded signalling between central insulin activity and glucose production in the liver for both obese mice and mice that have had the vagus nerve removed. The results are published in Cell Reports, March 2016.

The vital role of insulin in controlling glucose production is often disrupted in people suffering from obesity, a condition approaching global epidemic levels. Previous work has shown that central insulin action suppresses glucose production in the liver by increasing levels of the ligand interleukin 6 (IL-6) in the liver. The ligand activates the transcription factor STAT3, which in turn suppresses gene expression of glucose-producing enzymes. However, how the liver communicates with central nervous system and the vagus nerve, which controls unconscious processes like digestion, has so far not been understood. Now a collaboration of researchers in Japan led by Hiroshi Inoue at Kanazawa University’s Institute for Frontier Science Initiative (InFiniti) has identified the molecular mechanism for this communication.

Acetylcholine is the main neurotransmitter in the vagus nerve. It also suppresses IL-6 via the α7-nicotinic acetylcholine receptor. The researchers administered insulin and monitored subsequent vagal nerve activity, as well as IL-6 levels in a type of white blood cell in the liver known as “Kupffer cells”. They noticed a decrease in vagal nerve activity accompanied by increases in IL-6 in the Kupffer cells, resulting in decreased glucose production.

The researchers then investigated the effects of administering methyllycaconitine, which prevents α7-nicotinic acetylcholine receptor activity, as well as removal of the vagal nerve. They found that while STAT3 phosphorylation and IL-6 expression in the liver increased only slightly the IL-6/STAT3 signalling response to administered insulin was lost.

The researchers compared the response in lean and obese mice and found that the administered insulin “failed to elicit changes in vagus nerve activity of high-fat diet-induced obese mice.” They conclude, “These findings suggest that the aberrant regulation of Kupffer cells via the vagus nerve and α7-nAchR-mediated cholinergic action by central insulin action may have a significant role in the pathogenesis of chronic hepatic inflammation in obesity and of dysregulation of hepatic glucose production.”

Background

Glucose metabolism

Insulin is a hormone responsible for maintaining glucose levels and regulating glucose production in the liver. It also interacts with the central nervous system to regulate glucose metabolism. These metabolic processes include glucose oxidation to release ATP - which powers cells – glucose storage as glycogen, and the production of fatty acids and other substances.

Obesity-related diseases

Excessive body weight and insufficient exercise has been linked to insulin resistance, which can develop into a lack of insulin and type 2 diabetes. The surge in global obesity levels has been reflected in the numbers of people suffering from type 2 diabetes, a disease that is reported to cause over a million deaths each year. In 2014 90% of the 387 million cases of diabetes registered were type 2 and this is expected to increase to 587 million by 2035.

Obesity is also closely linked to inflammation and cancer of the liver. Interleukin 6 is a cytokine that can cause inflammation. The researchers found that the ability of the vagus nerve to regulate IL-6 expression was impeded in high-fat diet-induced obese mice. As well as the detrimental effects on glucose homeostasis, the results of this research suggest a molecular mechanism that links obesity to liver inflammation. Administration of neostigmine – which has a cholinergic action – suppressed expression of inflammatory cytokines in the Kupffer cells of obese insulin-resistant mice.

Enzyme potential target for fight against obesity and diabetes

Removing an enzyme that controls bile acid and hormone levels significantly protects female mice from weight gain, according to a new study presented today at the Society for Endocrinology annual conference in Edinburgh. The finding offers a new a therapeutic target in the fight against obesity.

Steroid hormones and bile acids have multiple functions that affect appetite, physical activity and how energy is used and stored in the body. For example, the sex hormone oestrogen (a steroid) has previously shown to decrease women’s appetite while firing up their metabolism and levels of physical activity. Bile acids are important to digest fats in diets, without which animals could not make the most out of a fatty food’s calorific content.

The enzyme 5β-Reductase helps generate bile acid and clears excess levels of steroid hormones in the human body.

In this study, researchers from the University of Oxford compared the effects of feeding wild mice a high calorie, fat-rich diet with mice that lacked the ability to make 5β-Reductase over a period of 30 weeks.

Female mice without 5β-Reductase gained 42% less weight than the wild mice (15.8g vs 27.2g respectively), while males in both experimental groups gained the same amount of weight. Female mice without 5β-Reductase also stored less fat around the gonads, vital organs and under their skin compared to wild mice, while also being more sensitive to insulin and better at controlling their blood glucose levels.

“The gender-specific health outcomes of our experiment are interesting but poorly understood”, said lead author of the study Dr Laura Gathercole. “It could be that lacking this key enzyme means female mice are less able to extract energy from their food, spend more energy to power their metabolism, or both at the same time”.

“Tweaking steroid and bile acid levels has significant health implications and so 5β-Reductase could be an important potential therapeutic target in metabolic disease”, she continued.

The researchers next steps are to pinpoint the mechanisms behind the phenomenon, which could provide insights into the different ways males and females regulate their energy and metabolisms.

Lack of sleep is linked to obesity, new evidence shows

Can lack of sleep make you fat? A new paper which reviews the evidence from sleep restriction studies reveals that inadequate sleep is linked to obesity. The research, published in a special issue of the The American Journal of Human Biology, explores how lack of sleep can impact appetite regulation, impair glucose metabolism and increase blood pressure. "Obesity develops when energy intake is greater than expenditure. Diet and physical activity play an important part in this, but an additional factor may be inadequate sleep," said Dr Kristen Knutson, from the University of Chicago. "A review of the evidence shows how short or poor quality sleep is linked to increased risk of obesity by de-regulating appetite, leading to increased energy consumption."
Dr Knutson accumulated evidence from experimental and observational studies of sleep. Observational studies revealed cross-sectional associations between getting fewer than six hours sleep and increased body mass index (BMI) or obesity.
The studies revealed how signals from the brain which control appetite regulation are impacted by experimental sleep restriction. Inadequate sleep impacts secretion of the signal hormones ghrelin, which increases appetite, and leptin, which indicates when the body is satiated. This can lead to increased food intake without the compensating energy expenditure.
"In the United States 18% of adults are estimated to get less than 6 hours of sleep, which equates to 53 million short sleepers who may be at risk of associated obesity," said Knutson. "Poor sleeping patterns are not random and it is important to consider the social, cultural and environmental factors which can cause inadequate sleep so at-risk groups can be identified."
The evidence suggests the association between inadequate sleep and higher BMI is stronger in children and adolescents. It also shows that sleep deficiency in lower socioeconomic groups may result in greater associated obesity risks.
The majority of the studies Dr Knutson examined came from Western countries, which highlights the need for more research to understand sleep's role in disease risk. However other research papers in the special issue focus on obesity in the United Arab Emirates, Samoa, and Brazil.
"These findings show that sleeping poorly can increase a person's risk of developing obesity, diabetes, high blood pressure or heart disease," concluded Knutson. "Future research should determine whether efforts to improve sleep can also help prevent the development of these diseases or improve the lives of patients with these conditions."

**Source: Wiley-Blackwell

Obesity Accounts for 21 Percent of U.S. Health Care Costs, Study Finds

Obesity now accounts for almost 21 percent of U.S. health care costs -- more than twice the previous estimates, reports a new Cornell University study.

The research, which is the first to show the causal effect of obesity on medical care costs, uses new methods and makes a stronger case for government intervention to prevent obesity, the authors say in the January issue of the Journal of Health Economics.

The study reports that an obese person incurs medical costs that are $2,741 higher (in 2005 dollars) than if they were not obese. Nationwide, that translates into $190.2 billion per year, or 20.6 percent of national health expenditures. Previous estimates had pegged the cost of obesity at $85.7 billion, or 9.1 percent of national health expenditures.
"Historically we've been underestimating the benefit of preventing and reducing obesity," said lead author John Cawley, Cornell professor of policy analysis and management and of economics. "Obesity raises the risk of cancer, stroke, heart attack and diabetes. For any type of surgery, there are complications with anesthesia, with healing [for the obese]. … Obesity raises the costs of treating almost any medical condition. It adds up very quickly."
The new study, conducted with Chad Meyerhoefer of Lehigh University, estimates the effect of obesity on medical expenses by treating the heritable component of weight as a natural experiment. Previous research simply reported the difference between the medical expenses of heavier and lighter people, which is a misleading estimate of the causal effect because obese and non-obese individuals differ in so many ways. Cawley explains, "For example, I could have injured my back at work, and that may have led me to gain weight. The injury could have led to a lot of health care costs that are due to my back, not my obesity."
The research provides hard evidence for policymakers to use in cost-effectiveness analysis when deciding whether and how much to fund obesity prevention programs, Cawley said. Since previous studies have underestimated the medical costs of obesity, the economic rationale for governments to intervene and reduce obesity has been underappreciated.

**Published in "SCIENCE DAILY"