Category: Metabolic Disorders

A New Bacterium Might Help Treat Type 2 Diabetes and Obesity

E. Coli bacteria. Image by CDC
E. Coli bacteria. Image by CDC

A newly discovered bacterium has been shown to have a possible link to type 2 diabetes and obesity, and may yield pathways to possible treatments.

It began when Patrice Cani, FNRS researcher at University of Louvain (UCLouvain), and his team repeatedly observed that a certain bacterium, Subdoligranulum, is usually lacking in obese and diabetic people, while it is systematically present in healthy people. Based on this, they decided to examine this family of bacteria.

Currently only one cultivated strain of this family is available in the world (the only known member of a large family) and was not the strain that was seen to be decreased in obese and diabetic people. This is not unusual: nearly 70% of bacteria in the intestine have not yet been identified — this is called the dark matter of the intestine.

In 2015, the team then set out to isolate the bacterium themselves in order to learn about its action on the human body, knowing that it is only present in healthy people. To find a second member of the family, the scientists spent two years searching, isolating and cultivating nearly 600 intestinal bacteria. 

All of this was in vain. Instead, the UCLouvain team uncovered a bacterium of a new, previously unknown kind. They named it Dysosmobacter welbionis: Dysosmo (“which smells bad”, in Greek), bacter (bacterium) is the bacterium which stinks, “Because, when you grow it, it has a slight odour,” they explained. Welbionis for WELBIO, the organisation in the Walloon region which funded this research.

The bacterium is peculiar for a number of reasons, including the fact that it produces butyrate. Though many other bacteria produce this colon cancer-promoting molecule, for example by strengthening the intestinal barrier and boost immunity. But the team also discovered that Dysosmobacter welbionis was less present in people with type 2 diabetes.

By analysing the microbiota from 12 000 faecal samples gathered from around the world, the UCLouvain scientists observed that the bacteria is present in 70% of the population. As to why such a widely prevalent bacteria was never discovered before, the answer likely lies in the improved cultivation techniques developed by the UCLouvain team.

The UCLouvain team including doctoral student Emilie Moens de Hase and post-doctoral fellow Tiphaine Le Roy then tested the action of Dysosmobacter welbionis in mice. The Results? The bacteria increased the number of mitochondria (a kind of power plants within cells that burns fat), thereby lowering sugar levels and weight, in addition to having strong anti-inflammatory effects. All these effects are very promising for type 2 diabetic and obese subjects and resemble those of Akkermansia, a beneficial bacterium that is at the heart of the research in Patrice Cani’s lab.

They also observed that the bacteria’s effects are not limited to the gut: Scientists have found that certain molecules produced by Dysosmobacter migrate around the body and have distant actions as well. This could explain the effects the bacteria have on the fat tissues, and also opens the doors for a possible impact on other diseases such as cancer. This is currently being investigated by the team.

The next step is to test the action of Dysosmobacter welbionis coupled with that of Akkermansia, in order to see if their association has cumulative effect on health, while always keeping in mind the fight against type 2 diabetes, inflammatory diseases, obesity and cancer. “That’s the fun of research: you dig for dinosaur bones and you end up finding a treasure,” Patrice Cani enthused.

Source: Université catholique de Louvain

Journal reference: Roy, T. L., et al. (2021) Dysosmobacter welbionis is a newly isolated human commensal bacterium preventing diet-induced obesity and metabolic disorders in mice. Gut. doi.org/10.1136/GUTJNL-2020-323778.

Zinc’s Surprising Role in Blood Pressure

Source: Wikimedia CC0

Researchers have discovered that a trace element, zinc, plays a previously unknown role in the regulation of blood pressure.

While the role of metals like potassium and calcium have been long known in this process, a new discovery about zinc’s critical and underappreciated role offers a potential new pathway for therapies to treat hypertension. While hypertension had been known to be associated with low zinc levels, it was not clear as to why.

The findings were published recently in Nature Communications.

The smooth muscle cells lining blood vessels regulate the speed at which the blood travels around the body. As smooth muscles contract, they narrow the artery, increasing blood pressure, and as the muscle relaxes, the artery expands and blood pressure falls. Too low a blood pressure, and the blood flow will be insufficient to sustain body tissues. If blood pressure is too high, the blood vessels risk being damaged or even ruptured.

“Fundamental discoveries going back more than 60 years have established that the levels of the calcium and potassium in the muscle surrounding blood vessels control how they expand and contract,” said lead author Ashenafi Betrie, PhD, and senior authors Scott Ayton, PhD, and Christine Wright, PhD, of the Florey Institute of Neuroscience and Mental Health and The University of Melbourne in Australia.

Specifically, the researchers explained, potassium regulates calcium in the muscle, and calcium is known to induce the narrowing of the arteries and veins that elevate blood pressure and restrict blood flow. Other cells surrounding the blood vessel, including endothelial cells and sensory nerves, also regulate the calcium and potassium within the muscle of the artery, and are themselves regulated by the levels of these metals contained within them.

“Our discovery that zinc is also important was serendipitous because we’d been researching the brain, not blood pressure,” said Dr Betrie. “We were investigating the impact of zinc-based drugs on brain function in Alzheimer’s disease when we noticed a pronounced and unexpected decrease in blood pressure in mouse models treated with the drugs.”

The investigators discovered that coordinated action by zinc within sensory nerves, endothelial cells and the muscle of arteries triggers lower calcium levels in the muscle of the blood vessel. This causes the vessel to relax, decreasing blood pressure and increasing blood flow. The scientists found that the brain and heart’s blood vessels were more sensitive to zinc than blood vessels in other areas of the body, warranting further research.

“Essentially, zinc has the opposite effect to calcium on blood flow and pressure,” said Dr Ayton. “Zinc is an important metal ion in biology and, given that calcium and potassium are famous for controlling blood flow and pressure, it’s surprising that the role of zinc hasn’t previously been appreciated.”

This research also explains the fact that the genes that control intracellular zinc levels are known to be associated with cardiovascular diseases including hypertension, and hypertension is also a known side effect of zinc deficiency.

“While there are a range of existing drugs that are available to lower blood pressure, many people develop resistance to them,” said Dr Wright, who added that a number of cardiovascular diseases, including pulmonary hypertension, are poorly treated by currently available therapies. “New zinc-based blood pressure drugs would be a huge outcome for an accidental discovery, reminding us that in research, it isn’t just about looking for something specific, but also about just looking.”

Source: Medical Xpress

‘Game-changing’ Weight Loss Drug Semaglutide Approved by FDA

Image source: Neonbrand on Unsplash

The US Food and Drug Administration approved a ‘game changing’ weight loss drug called Wegovy (semaglutide) for chronic weight management in adults with obesity or overweight.

This injection is the first drug for chronic weight management in adults with general obesity or overweight to be approved since 2014. The drug is indicated for chronic weight management in patients with a body mass index (BMI) of 27 kg/m2 or greater who have at least one weight-related ailment or in patients with a BMI of 30 kg/m2 or greater, and is to be used in conjunction with diet and exercise.

“Today’s approval offers adults with obesity or overweight a beneficial new treatment option to incorporate into a weight management program,” said John Sharretts, MD, deputy director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research. “FDA remains committed to facilitating the development and approval of additional safe and effective therapies for adults with obesity or overweight.”

Approximately 70% of American adults have obesity or overweight, and >67% of sub-Saharan Africans. This is a serious health issue linked to leading causes of death such as heart disease, stroke and diabetes, and also to increased risk of certain types of cancer. Losing 5% to 10% of body weight through diet and exercise has been associated with a reduced risk of cardiovascular disease in adult patients with obesity or overweight.

Wegovy works by mimicking a hormone called glucagon-like peptide-1 (GLP-1) that targets areas of the brain regulating appetite and food intake. The medication dose must be increased gradually over 16 to 20 weeks to 2.4 mg once per week to reduce gastrointestinal side effects.

The drug’s safety and efficacy were studied in four 68-week trials. Over 2600 patients received Wegovy for up to 68 weeks in these four studies and more than 1500 patients received placebo.

The largest placebo-controlled trial enrolled diabetes free adults with an average age of 46 years, and 74% of whom were female. The average body weight was 105 kg and average BMI was 38 kg/m2. Individuals receiving Wegovy lost an average of 12.4% of their initial body weight compared to individuals who received placebo. Another trial enrolled adults with type 2 diabetes. The average age was 55 years and 51% were female, with an average body weight of 100 kg and average BMI of 36 kg/m2. In this trial, individuals receiving Wegovy lost 6.2% of their initial body weight compared to the placebo group.

“The approval of Wegovy in the US brings great promise to people with obesity. Despite the best efforts to lose weight, many people with obesity struggle to achieve and maintain weight loss due to physiological responses that favour weight regain,” said Martin Holst Lange, executive vice president, Development at Novo Nordisk. “The unprecedented weight loss for an anti-obesity medication marks a new era in the treatment of obesity, and we now look forward to making Wegovy available to people living with obesity in the US”.

Unfortunately, the drug may be out of the reach of many people in need of it, with indications being that the medication may be charged at around US$1,300 a month.

Source: Food and Drug Administration

Tiny Implant Shelters Diabetes-curing Cells

Photo by Photomix Company from Pexels

A team of researchers have developed a miniscule device that allows them to implant insulin-secreting cells into diabetic mice, which secrete insulin in response to blood sugar without being destroyed by the immune system.

The findings are published in the journal Science Translational Medicine.

“We can take a person’s skin or fat cells, make them into stem cells and then grow those stem cells into insulin-secreting cells,” said co-senior investigator Jeffrey R Millman, PhD, an associate professor of medicine at Washington University. “The problem is that in people with Type 1 diabetes, the immune system attacks those insulin-secreting cells and destroys them. To deliver those cells as a therapy, we need devices to house cells that secrete insulin in response to blood sugar, while also protecting those cells from the immune response.”

Prof Millman, also an associate professor of biomedical engineering, had previously developed and honed a method to make stem cells and then grow them into insulin-secreting beta cells. Prof Millman previously used those beta cells to reverse diabetes in mice, but it was not clear how the insulin-secreting cells might safely be implanted into people with diabetes.

Prof Millman explained why the new device’s structure was so important.

“The device, which is about the width of a few strands of hair, is micro-porous—with openings too small for other cells to squeeze into—so the insulin-secreting cells consequently can’t be destroyed by immune cells, which are larger than the openings,” he said. “One of challenges in this scenario is to protect the cells inside of the implant without starving them. They still need nutrients and oxygen from the blood to stay alive. With this device, we seem to have made something in what you might call a Goldilocks zone, where the cells could feel just right inside the device and remain healthy and functional, releasing insulin in response to blood sugar levels.”

Millman’s laboratory collaborated with researchers from the laboratory of Minglin Ma, PhD, an associate professor of biomedical engineering at Cornell and the study’s other co-senior investigator. Prof Ma has been working to develop biomaterials that can help implant beta cells safely into animals and, eventually, people with Type 1 diabetes.

In recent years a number of implants have been tried to varying degrees of success. For this study, the team led by Prof Ma developed a nanofibre-integrated cell encapsulation (NICE) device. They filled those implants with insulin-secreting beta cells grown from stem cells and then implanted the devices into the abdomens of diabetic mice.

“The combined structural, mechanical and chemical properties of the device we used kept other cells in the mice from completely isolating the implant and, essentially, choking it off and making it ineffective,” Prof Ma explained. “The implants floated freely inside the animals, and when we removed them after about six months, the insulin-secreting cells inside the implants still were functioning. And importantly, it is a very robust and safe device.”

The cells in the implants continued to secrete insulin and control blood sugar in the mice for up to 200 days — even without any immunosuppressive drugs being administered.
“We’d rather not have to suppress someone’s immune system with drugs, because that would make the patient vulnerable to infections,” Prof Millman said. “The device we used in these experiments protected the implanted cells from the mice’s immune systems, and we believe similar devices could work the same way in people with insulin-dependent diabetes.”

Profs Millman and Ma stress that a considerable amount of work is needed before the device can be trialled in a clinical setting.

Source: Washington University School of Medicine in St Louis

Journal information: X. Wang et al., “A nanofibrous encapsulation device for safe delivery of insulin-producing cells to treat type 1 diabetes,” Science Translational Medicine (2021)

Spinal Stimulation Shines in Relief of Diabetic Neuropathic Pain

Photo by Zoltan Tasi on Unsplash

An implantable spinal cord stimulation device was effective at relieving diabetic neuropathy pain, according to a researcher presenting at an American Association of Clinical Endocrinology virtual meeting.

Presenting the trial results, Erika A Petersen, MD, of the University of Arkansas for Medical Sciences, said:  “This is the largest randomised controlled trial evaluating spinal cord stimulation for refractory painful diabetic neuropathy.”

In total, more than 85% of patients treated with 10 kHz stimulation were considered responders to treatment — experiencing 50% or greater reduction in pain. On top of that, 60% achieved remission, defined as a pain visual analog scale (VAS) of less than 3.0 cm for 6 consecutive months.

Meanwhile, those receiving only normal medical management saw no significant pain score reduction (7.0 at baseline vs 6.9 at 6 months). More than half of those conventionally treated experienced worsening of their pain, and only about 5% were responders to this type of treatment. Overall, only 1% of patients achieved pain remission with conventional medical management.

Beyond pain improvement, those receiving high frequency spinal cord stimulation plus medical management also saw a 62% improvement in neurological examination versus 3.3% of conventional treatment-only patients (P<0.001). The neurological examination included such as lower limb motor strength, light touch sensation and a 10-point foot assessment with a pinprick and 10-g monofilament.

Patients with the stimulation device also reported a reduction in dysesthaesias or uncomfortable sensations such as itching. They also reported a 62% improvement in sleep disturbances.

Overall, 92% patients in the stimulation group said they were satisfied with their treatment, compared with 6% of those on the conventional treatment group said the same.

The trial included 216 adults with painful analgesic-resistant diabetic neuropathy of the lower limbs. Half of participants received only conventional medical management, which included pharmacotherapies.

The other half of participants received 10-kHz SCS therapy. These participants received temporary stimulation for 5 to 7 days with percutaneous leads placed epidurally along T8 to T11. If 50% pain relief was achieved, they could have a permanent implantation of the pulse generator, usually in the low back.

In terms of safety, three infections occurred in the stimulation group, two of which required device removal.

There was no change in BMI or HbA1c in either group during the trial.

After the 6-month trial, 82% of patients on conventional treatment were eligible to crossover — meaning they had less than 50% pain relief, were dissatisfied with treatment, and the investigator agreed it was medically appropriate — and chose to receive the stimulation device.

In this extension phase, those with the stimulation device continued to experience pain relief, achieving an average VAS of 1.7 at 12 months out.

“The responder rate remained stable as well, with 86% at 12 months suggesting the attrition seen with other stimulation approaches is not a concern with 10 kHz stimulation,” said Petersen. “We will continue our follow-up to 24 months, with further evaluation of health economic data and other indicators.”

Source: MedPage Today

Journal information: Petersen E, et al “Neuromodulation for treatment of painful diabetic neuropathy – sustained benefits of 10kHz spinal cord stimulation in a randomized controlled trial” AACE 2021.

Familial High Cholesterol Often Eludes Genetic Testing

Image source: National Cancer Institute/Unsplash

Most familial hypercholesterolemia (FH) cases would go undetected if people were to rely on array-based genetic tests alone, a new study suggests.

FH predisposes people to elevated levels of LDL cholesterol, which can lead to premature coronary artery disease and early death.  

For example, the 23andMe test, which has a limited screen for only 24 known FH variants, would have missed over 60% of individuals with the autosomal dominant disorder. This figure was even worse for non-European ancestry individuals.

“Limited-variant screens may falsely reassure the majority of individuals at risk for FH that they do not carry a disease-causing variant, especially individuals of self-reported Black/African American and Hispanic ancestry,” according to Amy Sturm, of the Geisinger Genomic Medicine Institute in Danville, Pennsylvania, and colleagues.

In their study, limited-variant screening would miss nearly 94% and 85% of Black and Hispanic individuals with confirmed FH pathogenic variants. However this would be true for only a third of Ashkenazi Jewish people.

“The reduced yield of limited-variant screening could result in a major health care disparity for groups already affected by social and medical disenfranchisement that beget serious health disparities including a significantly higher rate of cardiovascular death among Black/African American individuals,” the investigators said.

“When FH is strongly clinical suspected, even if array-based FH reporting has negative results, a clinical genetic test should still be considered,” according to an accompanying note by JAMA Cardiology editors Pradeep Natarajan, MD, MMSc, of Massachusetts General Hospital and Harvard Medical School in Boston, and Elizabeth McNally, MD, PhD, of Northwestern University Feinberg School of Medicine in Chicago.

“Genetic databases overrepresent European ancestry populations and therefore make interpretation of genetic variation more accurate in these cohorts. However, even 64% of the FH mutations in European American individuals would have been missed by the 24-variant [test],” noted Drs Natarajan and McNally.

“Unfortunately, genetic testing for FH is underused, with 90% of affected individuals worldwide remaining undiagnosed and only 3.9% of patients with FH in the U.S. having a record of genetic testing,” noted Dr Sturm and colleagues.

“Recent expert statements recommend that patients suspected of having FH be offered genetic testing and that first-degree relatives of genetically positive individuals be screened for FH by lipid profile or genetic testing,” according to them.

Comprehensive genetic testing with next-generation sequencing (NGS) detects over 2000 potentially pathogenic variants within full genomes. Assay-based screens such as 23andMe only test for a small subset of known variants, and not the number present.

Both types of genetic tests for FH are available either in clinical settings or as a direct service to consumers.

“Whether testing is obtained directly by a consumer or through a clinical setting, those tested should consult with a genetic counselor or other qualified health care professional to fully understand the benefits and limitations of the different types of genetic testing for FH,” Sturm’s group urged.

For the study, the authors took deidentified NGS results, sourced from a single clinical laboratory, for gene panels of individuals receiving comprehensive genetic testing either for an FH indication (4563 participants) or as proactive health screening (6482 participants).

The researchers had tested both cohorts for more than 2000 possible variants in four FH-associated genes: LDLR, APOB, PCSK9, and LDLRAP1.

With the limited screening tests, only 8.4% of people with FH indication had a positive detection, compared to 27.0% for comprehensive NGS genotyping. In the proactive cohort of people with no clinical suspicion of FH, clinically significant FH variant prevalence was about one in 191 according to the comprehensive test.

A limitation was the researchers’ inability to confirm genetic testing results with medical and family histories.

Source: MedPage Today

Journal information: Sturm AC, et al “Limited-variant screening vs comprehensive genetic testing for familial hypercholesterolemia diagnosis” JAMA Cardiol 2021; DOI: 10.1001/jamacardio.2021.1301.

Only 1 in 10 Getting Full Diabetes Care in Developing Countries

 Only 1 in 10 people with diabetes in low- and middle-income countries are getting evidence-based, low-cost comprehensive care proven to reduce diabetes-related problems, according to a study published in Lancet Healthy Longevity

That comprehensive package of care – low-cost medicines to reduce blood sugar, blood pressure and cholesterol levels; and counseling on diet, exercise and weight – can help lower the health risks of under-treated diabetes. Those risks include future heart attacks, strokes, nerve damage, blindness, amputations and other disabling or fatal conditions.

The authors analysed data from recent surveys, examinations and tests of over 680 000 people between 25 and 64 worldwide. More than 37 000 had diabetes; more than half of them had a key biomarker of elevated blood sugar but had not yet received a diagnosis.

The researchers have provided their findings to the World Health Organization, which is developing efforts to scale up delivery of evidence-based diabetes care globally as part of an initiative known as the Global Diabetes Compact. The forms of diabetes-related care used in the study are all included in the 2020 WHO Package of Essential Noncommunicable Disease Interventions.

“Diabetes continues to explode everywhere, in every country, and 80% of people with it live in these low- and middle-income countries,” said lead author David Flood, MD, MSc, a National Clinician Scholar at the U-M Institute for Healthcare Policy and Innovation. “It confers a high risk of complications such as including heart attacks, blindness, and strokes. We can prevent these complications with comprehensive diabetes treatment, and we need to make sure people around the world can access treatment.”

Flood worked with senior author Jennifer Manne-Goehler, MD, ScD, of Brigham and Women’s Hospital and the Medical Practice Evaluation Center at Massachusetts General Hospital, to lead the analysis of detailed global data.

In addition to the main finding that 90% of the people with diabetes studied weren’t getting access to all six components of effective diabetes care, the study also finds major gaps in specific care.

For instance, while about half of all people with diabetes were taking a drug to lower their blood sugar, and 41% were taking a drug to lower their blood pressure, only 6.3% were receiving cholesterol-lowering medications. Less than a third had access to counseling on diet and exercise.

These findings show the need to scale-up proven treatment not only to lower glucose but also to address cardiovascular disease risk factors, such as hypertension and high cholesterol, in people with diabetes.

“Diabetes continues to explode everywhere, in every country, and 80% of people with it live in these low- and middle-income countries. We need to make sure people around the world can access treatment.” David Flood, MD, MSc.

Even when the authors focused on the people who had already received a formal diagnosis of diabetes, they found that 85% were taking a medicine to lower blood sugar, 57% for blood pressure, but only 9% for cholesterol. Nearly 74% had received diet-related counseling, and just under 66% had received exercise and weight counseling.

Taken together, less than one in five people with previously diagnosed diabetes were getting the full package of evidence-based care.

Economy and availability of care

The researchers found that generally, the lower the average income of the country and region,  the less evidence-based diabetes care was available.

The nations in the Oceania region of the Pacific had the highest prevalence of diabetes – both diagnosed and undiagnosed – but the lowest rates of diabetes-related care.

However some low-income countries had higher-than-expected rates of good diabetes care, said Dr Flood. The Latin America and Caribbean region had the second highest diabetes prevalence, but had much higher levels of care than Oceania.

Finding out what the countries with high-performing achievements in diabetes care are doing well could provide valuable insights for improving care elsewhere, the authors said. That even extends to informing care in high-income countries like the United States, which does not consistently deliver evidence-based care to people with diabetes.

The study also highlights differences in diabetes diagnoses in different regions and countries. Access to diagnosis enables people to receive diabetes care.

Women, people with higher levels of education and higher personal wealth, and people who are older or had high body mass index were more likely to be receiving evidence-based diabetes care. Diabetes in people with ‘normal’ BMI is not uncommon in low- and middle-income countries, suggesting more need to focus on these individuals, the authors noted.

The fact that cheap diabetes-related medications are available, and that people can cut risk through lifestyle changes, mean that cost should not be a major barrier, said Flood. In fact, studies have shown that the medications are cost-effective as a preventative measure.

Source: University of Michigan

Journal information: David Flood et al, The state of diabetes treatment coverage in 55 low-income and middle-income countries: a cross-sectional study of nationally representative, individual-level data in 680 102 adults, The Lancet Healthy Longevity (2021). DOI: 10.1016/S2666-7568(21)00089-1

Milk Consumption Does Not Raise Cholesterol Levels

Photo by ROBIN WORRALL on Unsplash

Regular consumption of milk is not associated with increased levels of cholesterol, according to new research.

A study published in the International Journal of Obesity analysed three large population studies and found that people who regularly drank high amounts of milk had lower levels of both ‘good’ and ‘bad’ cholesterol, although their BMI levels were higher than non-milk drinkers. Analysis of other large studies also suggests that regular milk drinkers had a 14% lower risk of coronary heart disease.

The team of researchers took a genetic approach to milk consumption by looking at a variation in the lactase gene associated with digestion of lactose. The study found that this gene variation for digesting lactose was a good identifier for people who consumed higher levels of milk.

“We found that among participants with a genetic variation that we associated with higher milk intake, they had higher BMI, body fat, but importantly had lower levels of good and bad cholesterol,” said Vimal Karani, Professor of Nutrigenetics and Nutrigenomics at the University of Reading said. “We also found that those with the genetic variation had a significantly lower risk of coronary heart disease. All of this suggests that reducing the intake of milk might not be necessary for preventing cardiovascular diseases.”

Contradictory research on the effect of high dairy intake and obesity and metabolic disorders was the motivation for the study. To exclude the effects of differences in sampling size, ethnicity and other factors, the team conducted a meta-analysis of data in up to 1.9 million people, including the UK Biobank and used the genetic approach to avoid confounding.

Even though the UK Biobank data showed that those with the lactase gene had an 11% reduced risk of type 2 diabetes, the study did not find a link between higher milk intake and increased likelihood of diabetes or related traits, such as glucose and inflammatory biomarkers.

“The study certainly shows that milk consumption is not a significant issue for cardiovascular disease risk even though there was a small rise in BMI and body fat among milk drinkers. What we do note in the study is that it remains unclear whether it is the fat content in dairy products that is contributing to the lower cholesterol levels or it is due to an unknown ‘milk factor’,” said Professor Karani.

Source: EurekaAlert

Journal information: Karani Santhanakrishnan Vimaleswaran et al, Evidence for a causal association between milk intake and cardiometabolic disease outcomes using a two-sample Mendelian Randomization analysis in up to 1,904,220 individuals, International Journal of Obesity (2021). DOI: 10.1038/s41366-021-00841-2

Rise in Obesity Impeding Cancer Fight

Though cancer death rates have fallen dramatically in the United States, those from obesity-related cancers are falling much more slowly.

In a study published this week in JAMA Network Open, researchers found that obesity-related cancer deaths are improving, but at a slowing pace.

Researchers at the University of North Carolina Gillings School of Global Public Health drew on mortality data for 50 million people, cancer deaths not associated with obesity — such as lung or skin cancer – are declining at a rate almost three times faster than obesity-related cancers, such as stomach, colorectal, uterine, thyroid and postmenopausal breast cancer.

“These are cancers where we could see even larger mortality improvements with creative and practical tools to combat obesity,” said study senior author Hazel B Nichols, PhD, associate professor in the Department of Epidemiology at the UNC Gillings School.

Most Americans are over the recommended body weight, and being overweight or obese puts them at risk for certain cancers.  

Extra body fat can lead to changes in the body that can contribute to cancer development, such as long-lasting inflammation and higher than normal levels of insulin and hormones that can fuel cell growth, according to the U.S. Centers for Disease Control and Prevention.

Discordant progress

Researchers use cancer death rates to track progress against cancer over time. The study authors set out to find out if obesity was stalling progress against cancer the way it did against heart disease. After 2011, heart disease mortality rates slowed their decline, a phenomenon which may be due to obesity.

“What was puzzling was that we didn’t see the same pattern of slower improvements when looking at cancer overall, which is surprising because obesity contributes to both cancer risk and heart disease risk,” said Dr Nichols. “When we focused on the differences between obesity-related cancers and non-obesity related cancers, we saw that improvements for obesity cancers were not as impressive — consistent with the pattern for heart disease.”

For example, the study showed that in 2011, 110 people out of 100 000 died from cancers not related to obesity. In 2018, the mortality rate for those cancers fell to 93.8 deaths per 100 00 people — a 2.29% annual decline.

During the same period, the decline for obesity-related cancers was much slower, changing from 58.4 to 54.9 deaths per 100 000 people, a rate of .83% — a rate one-third the decrease in non-obesity related cancers.

Obesity may also be contributing to more of the cancer deaths in the US. The study found that cancers not associated with obesity accounted for 66.8% of cancer deaths in 1999, decreasing to 62.6% in 2018.
The good news is that if we’re able to make these changes as a society, we will be able to improve the health of a nation. Christy Leigh Avery, PhD

Falls in cancer deaths are the result of fewer smokers, along with better screening and treatments, according to the American Cancer Society.

But the findings by UNC researchers reinforce the impact of obesity on cancer. 

“Obesity is a risk factor for many, but not all, types of cancer,” Nichols Dr said. “We need to make maintaining a healthy weight an obtainable goal for everyone in terms of safe public spaces, the availability and affordability of nutritious foods, and other structural factors. The good news is that if we’re able to make these changes as a society, we will be able to improve the health of a nation.”

Source: University of North Carolina

Journal information: Avery CL, Howard AG, Nichols HB. Comparison of 20-Year Obesity-Associated Cancer Mortality Trends With Heart Disease Mortality Trends in the US. JAMA Netw Open. 2021;4(5):e218356. doi:10.1001/jamanetworkopen.2021.8356

Enzyme’s Role in Kidney Disease Could Unlock New Therapies

Anatomic model of a kidney. Photo by Robina Weermeijer on Unsplash

University of South Australia (UniSA) researchers have discovered that a certain enzyme may help to curb chronic kidney disease, which affects nearly 10% of the world’s population.

This enzyme, known as NEDD4-2, is critical for kidney health, said UniSA Centre for Cancer Biology scientist Dr Jantina Manning.

Chronic kidney disease (CKD) is defined as the presence of kidney damage or reduced filtration rate, persisting for three months or more. It is a state of progressive loss of kidney function ultimately resulting in the need for dialysis or transplantation. 

Dr Manning and her colleagues, including Professor Sharad Kumar, Chair of the UniSA Centre for Cancer Biology, have shown in an animal study that there is a link between a high salt diet, low levels of NEDD4-2 and advanced kidney disease.

While a high salt diet can worsen some forms of kidney disease, it was not previously known that NEDD4-2 is involved in promoting this salt-induced kidney damage.

“We now know that both a high sodium diet and low NEDD4-2 levels promote renal disease progression, even in the absence of high blood pressure, which normally goes hand in hand with increased sodium,” says Dr. Manning.

The NEDD4-2 enzyme regulates the pathway required for sodium reabsorption in the kidneys to ensure correct levels of salt are maintained. If this enzyme is reduced or inhibited, increased salt absorption can result in kidney damage.

Even if people are on a low salt diet, they can get kidney damage if their levels of NEDD4-2 are low due to genetic causes.

Prof Kumar said the goal is to eventually to develop a drug that can raise NEDD4-2 levels in people who have CKD.

“We are now testing different strategies to make sure this protein is maintained at a normal level all the time for overall kidney health,” Prof Kumar said. “In diabetic nephropathy—a common cause of kidney disease—levels of NEDD4-2 are severely reduced. This is the case even when salt is not a factor.”

The study also revealed one other unexpected finding: that kidney disease induced by high salt diets is not always the result of high blood pressure.

“In a lot of cases, kidney disease is exacerbated by hypertension, so we wanted to investigate that link in our study. In fact, we found the complete opposite—that a high salt diet caused excessive water loss and low blood pressure. This is significant because it means that kidney disease can also happen in people who don’t have high blood pressure,” Dr Manning said.

A Lancet paper from 2020 estimated that about 700 million people—about 10% of the world’s population—suffer from chronic kidney disease, and has seen a 29% increase in the past 30 years. This massive surge in CKD is mainly due to the global obesity epidemic. Overweight and obesity lead to diabetes, one of the leading causes of CKD, along with high blood pressure. Between 1980 and 2014 there was a 300% increase in diabetes, according to World Health Organization statistics. This makes it one of the top 10 causes of death worldwide.

“Obesity and lifestyle are two main factors driving chronic kidney disease but there are other things at play as well,” said Dr Manning. “Acute kidney injuries, drugs taken for other conditions, high blood pressure and a genetic predisposition can also cause it.”

Source: Medical Xpress

Journal information: Jantina A. Manning et al. The ubiquitin ligase NEDD4-2/NEDD4L regulates both sodium homeostasis and fibrotic signaling to prevent end-stage renal disease, Cell Death & Disease (2021). DOI: 10.1038/s41419-021-03688-7