Obesity

Posted on Obesity, Rheumatoid arthritis

Research shows obesity is associated with worse flare symptoms and quality of life in people with early rheumatoid arthritis

Obesity
Obesity

A recent study from Hospital for Special Surgery (HSS) and others has found a correlation between obesity and more severe disease flare symptoms that negatively affect quality of life in patients with early rheumatoid arthritis (RA), a systemic, autoimmune, inflammatory disorder affecting multiple joints in the body. The study will be presented at ACR Convergence 2023, the annual meeting of the American College of Rheumatology.

RA is usually treated with a combination of medications to relieve swelling and pain while regulating the immune system. Joint surgery to relieve pain and disability, including joint replacement, may also be considered when these nonsurgical methods fail to provide lasting benefit.

“If a person with RA is experiencing frequent flares, weight could be a contributing factor,” said study principal investigator Vivian P. Bykerk, BSc, MD, FRCPC, a rheumatologist at HSS. “It may be helpful for patients to talk with their doctor about how to lose weight.”

To conduct their research, investigators used data from the prospective RA registry study called the Consortium of Early ArThritis CoHorts-USA Study (CATCH-US). This study, conducted at HSS and Johns Hopkins School of Medicine, recruited participants with at least two swollen joints and early or recent onset rheumatoid arthritis (symptoms ≤12/≤24 months) between December 2014 and May 2023. The researchers collected baseline characteristics and patient reported outcomes at each visit.

In this study, flares were determined using the OMERACT RA-Flare Questionnaire (RA-FQ), a patient-reported outcomes tool that assesses symptoms of pain, stiffness, fatigue, impacts on physical function, and impacts on social participation. Items in this tool are scored from 0 to 10, with 0 being best and 10 worst. All five scores are summed for an overall score range of 0 to 50. Investigators also collected an Evaluator Global Assessment (EGA) score, indicating rheumatoid arthritis clinical disease activity; this was scored by the enrolling rheumatologist between 0 (not active) and 10 (very active). Using a multivariable linear regression model, the investigators tested the correlation between body mass index (BMI) and RA-FQ scores, considering EGA scores and demographic factors such as age, sex, and ethnicity as covariates.

There were 134 participants in the study; 85% were female, 71% were white, and 87% were non-Hispanic. Almost half (46%) were overweight or obese. The median age was 47.3 years, and the median BMI was 24.3.

“Our key finding was that there was a linear relationship between having a higher BMI and having a higher RA-FQ score,” said lead study author Margaret Butler, a research assistant in the Department of Medicine at HSS. “As BMI got higher, RA-FQ scores increased as well, indicating that the patient would have poorer outcomes. Having a higher BMI also predicted worse scores in each of the five individual categories except physical function. The relationship was even more pronounced when you separated patients by healthy BMI, overweight BMI, and obese BMI, with patients having an obese BMI having worse RA-FQ scores compared to the other two groups.”

The researchers say that clinicians should consider patients’ BMI and RA-FQ scores when formulating treatment plans for RA flares. “Doctors should encourage patients to lose weight, if determined to be the root cause of frequent flare ups to avoid prescribing additional medications to control symptoms,” said Dr. Bykerk. “Losing weight for people with RA is a difficult problem because they have lost significant muscle mass, and that is our metabolic-driving tissue. To lose weight, patients have to build muscle and have a more nourishing, high-protein diet. We need programs to help patients do this.”

A previous study by the researchers revealed that fewer patients with RA go into remission if they are obese or overweight. Future studies will examine whether BMI influences RA flares throughout the course of the disease.

Posted on Obesity

Obesity is linked to neurodegeneration through insulin resistance.

Obesity linked to neurodegeneration through insulin resistance

Sugar fly. Artistic rendering generated by DALL.E the prompt used is “The drawing of the fruit fly Drosophila in a dark background in the style of Seurat”. The researchers fed fruit flies high sugar diets and examined the effect on brain function. CREDIT Akhila Rajan created this image using DALL-E and owns it. They are making it available under CC-BY 4.0 (CC-BY 4.0, https://creativecommons.org/licenses/by/4.0/)

Researchers led by Mroj Alassaf at the Fred Hutchinson Cancer Research Center in the United States have discovered a link between obesity and neurodegenerative disorders like Alzheimer’s disease. Using the common fruit fly, the research shows that a high-sugar diet — a hallmark of obesity — causes insulin resistance in the brain, which in turn reduces the ability to remove neuronal debris, thus increasing the risk of neurodegeneration. Publishing November 7th in the open access journal PLOS Biology, the research will impact therapies designed to reduce the risk of developing neurodegenerative diseases.

Although obesity is known to be a risk factor for neurodegenerative disorders like Alzheimer’s disease and Parkinson’s disease, exactly how one leads to the other remains a mystery. The new study focused on answering this question by taking advantage of the similarity between humans and fruit flies. Having previously shown that a high-sugar diet leads to insulin resistance in the peripheral organs of flies, the researchers now turned to their brains. Specifically, they examined glial cells because microglial dysfunction is known to lead to neural degeneration.

Levels of the protein PI3k indicate how much a cell is able to respond to insulin. The researchers found that the high sugar diet led to reduced PI3k levels in glial cells, indicating insulin resistance. They also looked at the fly equivalent of microglia, called ensheathing glia, whose primary function is to remove neural debris, such as degenerating axons. They observed that these glia had low levels of the protein Draper, indicating impaired function. Further tests revealed that artificial reduction of PI3k levels led to both insulin resistance and low Draper levels in ensheathing glia. Finally, they showed that after actually damaging olfactory neurons, the ensheathing glia could not remove the degenerating axons in the flies on the high sugar diet because their Draper levels did not increase.

The authors add, “Using fruit flies, the authors establish that high-sugar diets trigger insulin resistance in glia, disrupting their ability to clear neuronal debris. This study provides insight into how obesity-inducing diets potentially contribute to the increased risk of neurodegenerative disorders.”

Posted on Mindfulness, Obesity, Weight Loss

Practicing mindfulness can help people make heart-healthy eating choices

Practicing mindfulness focused on healthy eating can be good for the heart, a new study shows, because it improves self-awareness and helps people stick to a heart-healthy diet.

When people who had elevated blood pressure participated in an eight-week mindfulness-based blood pressure reduction program for the study, they significantly improved their scores on measures of self-awareness and adherence to a heart-healthy diet compared to a control group. The results were published in JAMA Network Open.

“Participants in the program showed significant improvement in adherence to a heart-healthy diet, which is one of the biggest drivers of blood pressure, as well as significant improvements in self-awareness, which appears to influence healthy eating habits,” said lead study author Eric B. Loucks, an associate professor of epidemiology, behavioral and social sciences, and director of the Mindfulness Center at Brown University.

Loucks said the study helps explain the mechanism by which a customized mindfulness training program adapted toward improving diet can affect blood pressure.

“Improvements in our self-awareness, of how different foods make us feel, of how our body feels in general, as well as our thoughts, emotions and physical sensations around eating healthy as well as unhealthy food, can influence people’s dietary choices,” he said.

High blood pressure, a major cause of cardiovascular disease, is the single most important risk factor for early death worldwide, according to a recent report by the World Health Organization, leading to an estimated 10.8 million avoidable deaths every year. The important thing to note about those avoidable deaths, Loucks said, is that there is ample research supporting effective strategies to control and prevent hypertension.

“Almost everyone has the power to control blood pressure through changes in diet and physical activity, adherence to antihypertensive medications, minimizing alcohol intake and monitoring stress reactivity,” he said.

A heart-focused mindfulness program

The mindfulness-based blood pressure reduction program used in the study, which Loucks developed in 2014, trains participants in skills such as meditation, yoga, self-awareness, attention control and emotion regulation. What makes the program unique, he said, is that participants learn how to direct those skills toward behaviors known to lower blood pressure.

The MB-BP plan consisted of a group orientation session, eight 2.5-hour weekly group sessions and one day-long retreat, as well as recommended home practice for 45 minutes, six days a week. The program was led by trained instructors with expertise in cardiovascular disease etiology, treatment and prevention. Classes were held in Providence, R.I., at Brown University and at a health center in a lower-income, urban neighborhood.

The study compared two groups, totaling 201 participants. The 101 people in the test group were a part of the 8-week MB-BP program, which included personalized feedback and education about hypertension risk factors; mindfulness training of participants in relationship to hypertension risk factors (including mindful eating); and behavior change support. The “usual care” control group received educational brochures on controlling high blood pressure. Both groups received a home blood-pressure monitoring device with usage training, and options for referral to primary care physicians.

The researchers focused on participant adherence to the DASH (Dietary Approaches to Stop Hypertension) program, a balanced eating plan rich in fruits, vegetables, whole grains and low-fat dairy, intended to create a heart-healthy eating style for life. Despite its effectiveness, adherence to the DASH diet is typically low.

After six months, the mindfulness group showed a 0.34-point improvement in the DASH diet score. Loucks explained that this effect can be interpreted as equivalent for a participant shifting from a vegetable intake approaching recommended levels (2-3 servings) to recommended levels (at least 4 servings), or making similar shifts across another component of the DASH score. The control group showed a -0.04-point change in DASH diet score.

The mindfulness group also showed a 0.71-point improvement in the average interoceptive awareness (which is the process of sensing and interpreting signals from one’s own body) score compared to six months prior, which outperformed the control group by a significant 0.54 points.

The authors said the trial results offer evidence that an adapted mindfulness training program for participants with high blood pressure that targets diet and self-awareness significantly improves both.

“The program gives participants the tools to make heart-healthy diet changes that can lower their blood pressure and decrease their risk of cardiovascular disease,” Loucks said.

The researchers are studying different “doses” of the program (for example, shorter program lengths, fewer sessions), as well as factors influencing the implementation of the MB-BP plan in a real-world setting — including eligibility for health insurance coverage, accessibility for different patient groups and flexibility for physicians.

Posted on Obesity, Weight Loss

The naturally occurring peptide may tackle obesity-related conditions’ ‘root cause’.

Naturally occurring peptide may tackle the ‘root cause’ of obesity-related conditions
Naturally occurring peptide may tackle the ‘root cause’ of obesity-related conditions

Research shows that a peptide (small protein) called PEPITEM could provide a revolutionary approach to reducing the risk of type 2 diabetes and other obesity-related diseases such as hepatic steatosis (fatty liver). 

The researchers used an animal model of obesity to investigate whether PEPITEM, delivered by a slow-release pump, could prevent or reverse the effects that a high fat diet has on the pancreas.  Excitingly, the results showed that administration of PEPITEM significantly reduced the enlargement of insulin-producing cells in the pancreas and also significantly reduced immune cell migration into various tissues. 

The research team was led by Dr Helen MCGettrick and Dr Asif Iqbal from the University of Birmingham’s Institute of Inflammation and Ageing and Institute of Cardiovascular Sciences.  Dr McGettrick said: “We have found a new therapeutic approach that could provide new drugs to tackle the root cause of obesity-related conditions by preventing the damage caused by systemic inflammation.

PEPITEM was first identified in 2015 by Birmingham researchers who described its role in the adiponectin-PEPITEM pathway, which is involved in controlling the onset and severity of auto-immune and chronic inflammatory diseases. 

Obesity causes complex and dramatic changes in metabolism in adipose (fat) tissue, damage to the pancreas, reduced insulin sensitivity and eventually the hyperglycaemia that underpins type 2 diabetes.  It also causes a low-level inflammatory response across the boyd, encouraging white blood cells to enter into many tissues including the visceral adipose tissue (fat stored deep inside the body wrapped around the organs, including the liver and gut) and peritoneal cavity (a thin membrane that encompasses the gut). 

The latest research, published in Clinical and Experimental Immunology, shows that the adiponectin-PEPITEM pathway also connects obesity, the low-level inflammatory response that is driven by it, and changes in the pancreas that precede diabetes. 

The results showed that dosing with PEPITEM while the mice were on a high fat diet significantly reduced the enlargement of insulin-producing beta cells in the pancreas and the number of white blood cells in the visceral adipose tissue and peritoneal cavity, compared to controls. 

The researchers also looked at the potential of PEPITEM to reverse the changes brought on by obesity, by feeding the animals a high fat diet prior to treating with PEPITEM.  Excitingly, they saw similar results.  Dr Asif Iqbal commented: “Until now we have understood very little about how the inflammation that accompanies obesity drives pathology.  These results show us that PEPITEM can both prevent and reverse the impact that obesity has on metabolism.  The next stage is to translate these exciting results into therapeutics that can be used in humans.”

Professor Ed Rainger from Birmingham’s Institute of Cardiovascular Sciences led the team that first identified PEPITEM.  He commented: “We are all very excited about these latest results.  PEPITEM is a naturally occurring peptide.  We have already shown it has effects on several organs and now for the first time, we have shown that PEPITEM is effective

Posted on Diabetes, Diet, Obesity

More evidence that sugary drinks cause weight gain

More evidence that sugary drinks cause weight gain
More evidence that sugary drinks cause weight gain

A review of dozens of studies from the last decade, led by researchers at the University of Toronto and Harvard University, recently found that sugar-sweetened beverages promote weight gain in children and adults.

The review, published in the American Journal of Clinical Nutrition, is the largest and most thorough analysis to date of research on sweetened drinks, and overweight and obesity — both of which heighten risks for diabetes, heart disease, some cancers and other diseases.

Vasanti Malik led the study, with colleagues in Toronto and Boston. Malik is an assistant professor of nutritional sciences at U of T’s Temerty Faculty of Medicine and the Joannah & Brian Lawson Centre for Child Nutrition. She spoke with writer Jim Oldfield about the findings, and take-aways for public policy and personal health.

Why do this study now?

Our last meta-analysis on this topic was 2013. You want to update a meta-analysis every five to 10 years anyway, but especially in this area because there has been so much new research the last decade. Evidence has continued to accumulate showing associations among sugar-sweetened beverages, or SSBs as we call them, and weight and chronic disease. And it’s very important to have an updated synthesis of that evidence, especially for public policy. The Canada Food Guide is clear on the need to limit SSBs and recommends water as the drink of choice, and added sugar intake including SSBs has declined in Canada, in part due to public policies. But levels here are still too high. As well, the USDA Dietary Guidelines for Americans are arguably not as strong, and with U.S. policymakers coming together soon to discuss the 2025 guidelines, our study will be an important piece of evidence to inform their work. 

What did your study show?

We expected to find a positive association between SSBs and weight gain, among adults and children, and in cohort studies and randomized clinical trials. And that was exactly what we found. We analyzed 85 studies, which totalled over half a million participants. In cohort studies, which follow people over long periods of time, each serving-per-day increase in SSBs was associated with a 0.42-kg (almost one-pound) higher body weight in adults. In children, we saw a 0.07-unit higher body-mass index (just under one-twelfth of a BMI unit). Perhaps most striking, findings from our dose-response analysis showed that weight gain increases with increasing levels of SSB intake, in both children and adults. A dose–response relationship provides strongevidence for a cause-and-effect relationship.  

How much weight gain might one drink a day lead to over time?

Well, we estimated that associated change in body weight over a one-year period. For adults, one additional 12-ounce serving a day was linked to a 0.20-kg higher body weight (about half a pound) in one year. Over 10 years, that could be about five pounds. In children, we observed a 0.03-unit higher BMI for each additional daily serving of SSBs over a one-year period. Although these results may seem modest, weight gain is a gradual process, with adults averaging about one pound (0.45 kg) of weight gain per year. So, limiting SSB consumption could be an effective way to prevent age-related weight gain. Limiting SSB intake among children is also an important strategy to help them develop healthy lifestyle habits and weight trajectories.

How common is excess consumption of these drinks?

It’s very common. Sugar-sweetened beverages include sodas, fruit drinks, sports and energy drinks, and they are the largest source of added sugar in the North American diet. Moreover, the rise in consumption of these drinks has mirrored the epidemic of overweight and obesity. In 2016, almost two billion adults were estimated as having overweight and 650 million had obesity. Even more worrying, the rate of increase in obesity in children and adolescents is now greater than in adults. The prevalence of childhood obesity has increased more than four-fold globally since the 1970s, which is truly alarming.

What are some of the health effects of SSBs?

A typical 12-ounce serving of an SSB contains over 140 calories and more than eight teaspoons of sugar. That nearly reaches the recommended daily limit for added sugar, which is no more than 10 per cent of total calories, or about 200 calories for a 2000-calorie per day diet. These drinks are sugar in liquid form. They’re usually made with table sugar, high-fructose corn syrup or other sweeteners that provide calories, and are digested rapidly, more so than sugar consumed as a solid. This bolus of glucose increases blood sugar levels, which triggers a glycemic response that over time can lead to insulin resistance and diabetes. The fructose component also floods the liver, which can cause lipogenesis (creation of fat), which puts a person on the path to fatty liver and metabolic disease. Fructose also increases uric acid, which contributes to insulin resistance and risk for cardiovascular and other diseases. Insulin spikes from the glycemic response can result in an appetite cascade and over-eating, as can excess insulin in the blood over longer periods. Some evidence shows that SSBs activate the dopaminergic reward system in the brain and encourage addictive behaviour, and that they alter the gut microbiome, but we need more research on those effects.

Are you optimistic, given these effects and the research evidence?  

Intake levels of SSBs have come down in the developed world. We’re still seeing increases in the developing world, but taxes in some of those countries are working. Thailand introduced a tax that has reduced consumption, as has Mexico and South Africa. At least 85 countries now have a tax on SSBs, which in part reflects the World Health Organization’s stand on this issue. In Canada, Newfoundland introduced a tax recently, and several U.S. regions and cities have had a tax for years, in response to public health efforts, more awareness and advocacy. The general effect of these taxes is reduced intake, and the revenues can be put toward further public health measures and health care. Other changes will help in Canada and elsewhere as well, such as limiting marketing to children, and better front-of-pack and nutrition labels. All these efforts will push intake down, but it’s important to remember that as that happens, people need access to clean, safe drinking water as an alternative. That’s an ongoing challenge globally, and in many parts of Canada, that we really need to address.

Vasanti Malik holds a Canada Research Chair in Nutrition and Chronic Disease Prevention at the University of Toronto, and an adjunct position in Nutrition at the Harvard T.H. Chan School of Public Health. Michelle Nguyen, a doctoral student at U of T, conducted the study analysis and wrote the paper.