Monday, July 22, 2019
‘More Plants, Less Meat, Less Diabetes,’ New Analysis Indicates
Middle-aged people who ate more plant-based foods — mainly semi-vegetarians but also vegetarians and vegans — were less likely to develop type 2 diabetes than their peers who ate more meat, fish, eggs, and dairy, in a large meta-analysis.
Overall, people with the highest versus lowest intake of any plant-based foods had a 23% lower risk of developing type 2 diabetes, independent of body mass index (BMI), in a 2- to 28-year follow-up, the new data show.
And those with the highest versus lowest intake of healthy plant-based foods — that is, fruits, vegetables, whole grains, legumes, and nuts — had a 30% lower risk of incident diabetes.
“To our knowledge, the present study provides the most comprehensive evidence on the association between plant-based dietary patterns and incidence of type 2 diabetes,” Frank Qian, MPH, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, and colleagues summarize, in their article published online July 22 in JAMA Internal Medicine.
They acknowledge that this meta-analysis of nine observational studies in high-income countries cannot show cause and effect, and intake was based on (mainly one-time) self-reported replies to a food frequency questionnaire.
Nevertheless, “owing to the overall low feasibility of randomized clinical trials directly testing plant-based dietary patterns for the prevention of type 2 diabetes,” the study supports “a possible protective role of these dietary patterns against the development of type 2 diabetes,” they write.
Participants in the category of greatest adherence to a plant-based diet still consumed roughly 1.7 to 3.9 servings/day of dairy, eggs, fish, or meat, they note, so additional studies are needed to see if reducing this further would increase health benefits.
More Plants, Less Meat Still Achievable Even in ‘Food Deserts’
The takeaway message is simple, Kim Allan Williams, Sr, MD, cardiology division chief, Rush University Medical Center, Chicago, Illinois, told Medscape Medical News in an email: “More plants. Less meat. Less diabetes.”
“Meat and especially processed meat,” he stressed, “is associated with more diabetes, heart failure, cancer, hypertension, stroke, hyperlipidemia, heart attacks, and death.”
Also invited to comment, Michelle L. O’Donoghue, MD, MPH, associate professor of medicine, Harvard Medical School, and a cardiologist at Brigham and Women’s Hospital, Boston, Massachusetts, agrees that the findings “contribute to a growing body of research that a diet rich in plants and low in animal intake may help to reduce the risk of developing many chronic Western diseases including type 2 diabetes.”
Intriguingly, some studies have even suggested that a plant-based diet may actually help reverse type 2 diabetes, says O’Donoghue, who writes a blog for theheart.org | Medscape Cardiology.
And there are simple steps people can take to improve their diet, she said, to shift it more towards healthy plant-based sources, even if they live in a so-called “food desert.”
Similarly, Michelle McMacken, MD, assistant professor, NYU School of Medicine, and director, Bellevue Hospital Weight Management Clinic, New York City, told Medscape Medical News in an email that the study findings “should inspire clinicians to consider recommending a more plant-based eating pattern to their patients.”
Can a Plant-Based Diet Prevent Diabetes?
As background, Qian and colleagues explain that it is not clear if eating a more vegetarian-type diet might ward off type 2 diabetes.
To investigate this, they performed a meta-analysis of nine studies in five US cohorts (Nurses’ Health Study I and II, Adventists Health Study I and II, and Health Professionals Follow-up Study) and four other cohorts from around the world in Greece (ATTICA), Singapore (Singapore Chinese Health Study), the Netherlands (Rotterdam Study), and Taiwan (Tzu Chi Health Study).
The analysis included 307,099 participants with a mean age of 36 to 65 years and a mean BMI of 23 to 36.7 kg/m2. Of these, 23,544 participants were diagnosed with diabetes during follow-up.
Overall, participants with a higher versus lower adherence to a plant-based diet had a reduced risk of incident type 2 diabetes (relative risk [RR], 0.77; 95% CI 0.71 – 0.84), after adjusting for risk factors such as BMI, age, smoking, and family history of diabetes.
In four cohorts with more detailed information, participants with a higher versus lower adherence to a “healthy plant-based diet” had an even greater reduced risk of the outcome (RR, 0.70; 95% CI, 0.62 – 0.79).
Nutrient Content of Plant-Based Foods Matters
O’Donoghue says emerging evidence is contributing to new dietary theories.
“We are only now beginning to understand that carbs shouldn’t be shouldering all the blame” for risk of type 2 diabetes, she explains.
“Certainly, processed or refined carbohydrates and sugars may contribute to inflammation and disease development,” she continued.
“However, we are finding that a plant-based diet that reduces or eliminates animal intake while increasing intake of healthy whole grain carbohydrates may actually have very favorable effects.”
At the same time, “the [nutrient] quality of the food we eat is crucial, and that was reflected in the findings of the current study,” where nutrient-rich plant-based foods provided greater benefit than nutrient-poor plant-based foods.
Moreover, diets such as the Mediterranean diet emphasize the intake of fruits and vegetables and may also offer clinical benefit for patients unwilling to fully commit to a plant-based diet.
And although a ketogenic diet may lead to weight loss, the data are very mixed regarding its effects on inflammation, lipid parameters, and disease progression, so this should not be recommended as a first-line strategy, she advises.
Sustained efforts are needed to inform people about the importance of good nutrition for good health, according to O’Donoghue, and it is imperative that efforts are increased to provide healthier food choices in schools.
Unfortunately, many people living in “food deserts” in low-income communities still have limited access to fresh, wholesome fruits and vegetables, or these foods are too expensive.
However, “even in the absence of fresh produce,” she said, “patients can still make healthier choices at the grocery store with canned vegetables and healthier grains, [and] more affordable or free grocery delivery is also becoming a reality in many parts of the country.”
McMacken agrees: “Patients can be counseled to look in their local grocery stores for healthy and inexpensive plant-based foods, such as dried or canned legumes (beans, chickpeas, and lentils), whole grains (brown rice, oats, barley), frozen vegetables, and fresh produce that is in season,” while reducing consumption of highly processed foods.
Possible Mechanisms
Several mechanisms may explain the study findings, Qian and colleagues suggest.
Plant-based foods “contain fiber, vitamins and minerals, antioxidants, phenolic compounds, and unsaturated fatty acids,” they note, which “improve insulinsensitivity and blood pressure, reduce long-term weight gain, and ameliorate systemic inflammation — pathways involved in the cause of type 2 diabetes.”
On the other hand, “these diets also deemphasize or avoid red and processed meats, which have been shown to adversely affect risk of type 2 diabetes, possibly owing to their high heme iron or dietary cholesterol contents.”
“Further experimental evidence,” the researchers conclude, “could help provide insights into other novel pathways that could mediate the beneficial association between plant-based dietary patterns and type 2 diabetes.”
The study was supported by grants from the National Institutes of Health. Qian and Williams have reported no relevant financial disclosures. Disclosures for the other authors are listed in the article. O’Donoghue has reported receiving research grants from Merck, GlaxoSmithKline, Eisai, AstraZeneca, and Janssen. McMacken currently serves on the advisory board for Nutrinic and as faculty for Sustainable Diet.
JAMA Int Med. Published online July 22, 2019. Abstract.
Gum Disease Bacteria a Novel Treatment Target for Alzheimer’s?
As more disappointing results emerge from anti-amyloid drug trials in Alzheimer’s disease (AD), there is growing interest in novel treatment approaches for this condition.
One such approach is based on the hypothesis that Porphyromonas gingivalis (Pg), the bacteria involved in periodontal disease, may cause AD. The biopharmaceutical company Cortexyme Inc is testing this theory with an investigational agent COR388, which targets gingipains, the toxic proteases released by Pg.
Early results show the drug is well tolerated and promising in terms of biomarker findings. Organizers hope that a phase 2/3 trial of the treatment now under way will provide definitive efficacy results.
Dr Michael Detke
“Our findings suggest that there’s hope for a new and very different approach to Alzheimer’s disease”, Michael Detke, MD, PhD, chief medical officer for Cortexyme, told Medscape Medical News.
The findings were presented here at the Alzheimer’s Association International Conference (AAIC) 2019.
Downstream Inflammation
The gingipain hypothesis assumes that Pg is a key etiologic agent in AD. The thinking is that the infection causes downstream inflammation and signs of AD such as tau tangles, and amyloid-beta.
Research has already found that people with periodontal disease are at higher risk for AD. Some studies have shown that gum disease precedes AD, which dispels the idea that the bacteria is an effect of AD rather than a cause, said Detke.
The most important causal data come from a mouse model of AD, he said. “Several studies show that if you put Pg in the mouth of a mouse, it causes all the signs of Alzheimer’s disease.”
Studies have also shown that most patients with AD have Pg present in the brain. In collaboration with other groups, Detke’s team compared brain bank samples of patients with AD and age-matched controls who did not have AD. They found that the AD patients were statistically significantly more likely to have been infected with Pg.
“Almost 100% of the samples from Alzheimer’s patients had Pg, and about one third or maybe 40% of the control brains had Pg,” Detke said.
It makes sense that some individuals without AD would have the infection, as the hallmark pathological signs of the disease appear about 20 years before clinical symptoms, said Detke.
Several factors likely determine why one individual with Pg gets AD while another with the pathogen does not. For instance, it may be that some individuals have better blood–brain barrier function or a better immune response.
“This is pretty common in the infectious disease area,” said Detke. He noted that while the Helicobacter pylori (H pylori) bacteria is closely linked to ulcers, only about 10% of those with the bacteria actually get an ulcer.
Cognitive Advantage
For the study, the investigators administered cognitive tests to a small sample of subjects with mild to moderate AD — 6 taking COR388 (50 mg of the oral drug twice daily) and 3 taking placebo.
One of these tests examined change from baseline to 28 days on the mini-mental state exam (MMSE). Here, subjects taking COR388 had about a 1-point improvement while those on placebo worsened by about half a point. The improvement in the treatment group almost reached statistical significance (P = .052).
In addition, the study results showed beneficial trends in other cognitive tests.
The researchers also examined blood levels of RANTES, a key inflammatory biomarker. Levels of RANTES dropped by about 30% in the treated group (P<.01 vs placebo). They also investigated cerebrospinal fluid (CSF) levels of ApoE fragments, a marker of gingipain activity in the brain.
“We know that ApoE is chopped up into fragments in the brains of people with Alzheimer’s, and we know that those fragments cause neuro toxicity,” said Detke.
If COR388 is affecting Pg, this should reduce the number of these fragments. Again, investigators found a 30% reduction in CSF ApoE fragments in the AD group (P <.05).
The drug was well tolerated in phase 1 a/b single ascending dose (SAD), and multiple ascending dose (MAD) studies. There were only a few side effects such as headache and dizziness, and these were mild. Detke noted that there seemed to be a higher rate of side effects in the placebo group.
“This drug targets a bacterial protein. It’s not supposed to, and doesn’t seem to, be hitting anything in the human body, so you would expect it to be safe and have minimal side effects.”
Detke’s team is reaching out to possible collaborators to try to determine if Pg is linked to dementias other than AD. “That’s definitely possible and we’re exploring it,” he said.
The company has launched the phase 2/3 GingipAIN inhibitor (GAIN) for treatment of Alzheimer’s disease trial. The study includes 570 patients with mild to moderate AD (MMSE score 12-22) at 100 sites in the US and Europe.
Subjects have been randomly assigned to placebo or to a low (40 mg twice daily) or high dose (80 mg twice daily) of COR388, for 48 weeks, after which there will be a 6-week safety follow-up.
“The 40 mg dose produces levels in humans that are comparable to, or a little higher than, blood levels in mice that worked,” said Detke.
“We have chosen 40 mg to be sort of minimally effective and then 80 mg should produce blood levels that are at least twice that level, but both doses are still well within the safety range.”
Although the study is not enrolling based on the presence or absence of gum disease, about half the sites will include dental assessments of participants, said Detke.
Results of the GAIN study are expected in late 2021.
New Avenues
Asked to comment on this new research for Medscape Medical News, Rebecca Edelmayer, PhD, director of scientific engagement at the Alzheimer’s Association, said “it’s a new way of thinking” about treating AD.
“It’s highlighting some of the new avenues, new ways, that we are continuing to try to build and foster a pipeline of innovation for developing new treatments for Alzheimer’s disease,” she said.
However, much of the data related to a bacterial link to AD “is still very preliminary” and “we have to learn more”, said Edelmayer.
“We still need a lot more evidence to prove any kind of causality.”
The role of infectious agents in AD — including bacteria and viruses — is a hot topic in neuroscience. The AAIC 2019 hosted what organizers billed as a “robust discussion on this emerging provocative topic” as well as a related press briefing. The panel included noted experts in the field.
While some speakers agreed there’s evidence suggesting microbes and/or viruses in the brain may trigger immune reactions related to the buildup of amyloid plaques and tau tangles, others sounded a cautionary note.
One of these was Michael Heneka, MD, PhD, professor of Clinical Neuroscience, Department of Neurodegenerative Diseases and Geriatric Psychiatry/Neurology, University of Bonn Medical Center, and the German Center for Neurodegenerative Disease. Heneka said several questions need to be answered before antibacterial therapies should be tested in patients.
“For example, the precise time point in the pathogenesis of Alzheimer’s at which bacteria may enter the brain needs to be determined, since these phenomena may present just late-stage events,” Heneka said in a statement released by the Alzheimer’s Association.
“Furthermore, it remains elusive how bacteria would overcome the intrinsic innate immune defense of microglia that usually shield the brain from such invasion.”
The research related to the role of infectious agents in AD “reinforces the complexity of Alzheimer’s Disease” and highlights the importance of sharing data across the research community, Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, said in the press release.
“No stone should be left unturned,” Carrillo said, “in the vigorous search for better treatments, prevention, and a cure for Alzheimer’s Disease.”
The study was funded by Cortexyme. Detke is an employee of Cortexyme.
Alzheimer’s Association International Conference (AAIC) 2019: Abstract 35428. Presented July 17, 2019.
‘Ditch opioid ‘negotiating class’ plan; let state AGs handle it’
Cities and counties around the U.S. have sued opioid drugmakers and distributors over their alleged role in a nationwide crisis, and plaintiffs recently proposed a “negotiating class” to help the sides reach a settlement. But that idea isn’t helping, two experts say.
Instead, it’s an idea the parties shouldn’t sink time into, former Connecticut Deputy Attorney General Perry Zinn Rowthorn told FiercePharma. Rowthorn, along with Connecticut’s former Attorney General George Jepsen, this week wrote an op-ed in the Cleveland Plain Dealer picking apart the proposal.
The upshot of their argument: State attorneys general, which are running their own investigations and lawsuits, are better equipped to negotiate a settlement favorable to all the plaintiffs involved.
Why? The experts, who are now partners at Shipman & Goodwin’s attorneys general practice, argue the proposal forces municipalities to decide upfront whether they want to take part in the process—before they know anything about a potential settlement.
The proposal would also apply to every city and county in the U.S.—24,500 jurisdictions in all, many of which haven’t actually sued the opioid makers. Those that haven’t might not be aware of their opt-in or opt-out rights. They might even ignore the class notices altogether.
So, while the proposal would require a 75% affirmative vote for a settlement, only those plaintiffs that choose to opt in would vote. That in turn means a small number of localities could play an outsized role in a major national issue. It’s not the way governments around the country should set policy, the attorneys general argue.
Instead of spending time on the “negotiating class” idea, the experts argue state attorneys general are more equipped to negotiate a settlement. If attorneys general reach a deal, cities and counties could join in.
The lawsuits are part of what Rowthorn called the “most complicated piece of litigation that really anyone has seen, frankly.” Thousands of cities and counties have sued opioid companies, while state attorneys general around the country are pressing their own probes and lawsuits.
Meanwhile, the defendants themselves don’t like the proposal. In a court filing, the drugmakers and distributors involved brought up some of the same arguments. According to the defendants’ lawyers, the idea doesn’t comply with federal class action law, and any deal the sides reach would face years of scrutiny on appeal. In the end, an appeals court could send the parties back to “square one,” they wrote.
Now, Rowthorn said there’s no consensus about how the issue will proceed.
As the multidistrict litigation plays out in Cleveland, Oklahoma recently finished a trial against Johnson & Johnson after securing settlements with Teva Pharmaceutical and Purdue Pharma. The state argues J&J played a “kingpin” role in opioid distribution there that led to a crisis. J&J says the facts don’t match up with Oklahoma’s allegations.
A judge is set to rule soon on the case in a decision that will reverberate around the country as it will represent the first ruling either for or against a drugmaker on the issue.
J&J aims to torpedo thousands of talc cases with one high-stakes hearing
Johnson & Johnson faces about 14,200 lawsuits alleging harm from talc, and Monday marks its next big test.
In a New Jersey courtroom, the drugmaker plans to challenge expert evidence set to be presented at trial—and the judge’s decision will determine the fate of most of the outstanding lawsuits.
That evidence is key to 85% of the cases grouped for consideration in J&J’s home state. If the court decides the plaintiffs’ expert evidence can’t be used in court, then “there’s nowhere for these cases to go,” a lawyer for J&J told the Wall Street Journal.
Apparently, the company has high hopes for the outcome. “[W]hen folks have a chance to really look at the facts in these cases, they see that the product is safe and that the company acted responsibly,” CFO Joe Wolk told analysts on the company’s Q1 earnings call last week.
The talc plaintiffs argue J&J’s products caused them to develop cancer and that the company hid the risks from the public.
Meanwhile, at a federal court in Delaware, J&J on Friday fell short in its attempt to combine 2,400 state lawsuits from around the country in the court where several units for its supplier Imerys filed for bankruptcy.
U.S. District Judge Maryellen Noreika rejected the company’s request to move those cases to her court. Among her laundry list of reasons: The cases don’t have much to do with Imerys bankruptcy proceedings. Plus, moving them would overburden her court while impeding their progress in courts around the country, she wrote.
A J&J spokeswoman said the company is “disappointed” with the decision because the company’s request, if granted, “would have streamlined the process for reviewing current cases and increased overall efficiency for all parties involved.”
The drugmaker faces about 14,200 lawsuits alleging harm from its talc powder, and only a fraction of those cases have played out in a trial. So far, in numerous verdicts, juries have together awarded billions in damages. But as a spokeswoman said last month, every verdict against J&J that’s made it through appeals has been overturned.
Aside from the talc injury cases, the company now faces a criminal investigation over its public statements in defense of the iconic product, Bloomberg reported earlier in July.
Intec cut to Perform by Oppenheimer
Oppenheimer analyst Jay Olson downgraded Intec Pharma Ltd. (NASDAQ: NTEC) from Outperform to Perform.
The analyst commented, “The Ph3 ACCORDANCE study comparing NTEC’s Accordion Pill Carbidopa/Levodopa (AP-CD/LD) to Immediate Release (IR-CD/LD) failed to detect a statistically significant difference on the primary endpoint of OFF-time change from baseline in patients with Parkinson’s disease (PD). While these are top-line results and we await details, we believe this failure is a major setback for NTEC and remove AP-CD/LD from our model, thereby updating our revenue and earnings estimates for NTEC. Besides PD, NTEC still has additional opportunities with other drugs including proprietary partnerships with Novartis and Merck. Because we are uncertain about the read across from AP-CD/LD to other AP applications in different diseases beyond PD, we downgrade NTEC to Perform from Outperform and remove our PT at this time.”
Gilead announces new late-stage data on HIV med Biktarvy
Gilead Sciences (GILD +0.3%) announces results from two Phase 3 clinical trials evaluating Biktarvy (bictegravir 50 mg/emtricitabine 200mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) in women and drug-resistant HIV patients who switched from other treatments. The data were presented at the International AIDS Society Conference on HIV Science in Mexico City.
In one study, at week 96, 99.5% of women who received Biktarvy throughout the study duration and 98.5% of women who switched to Biktarvy at week 48 maintained virologic suppression without developing treatment-emergent resistance.
Results from the other study in patients who switched to Biktarvy from DTG+F/TAF or DTG-F/TDF regimens for 48 weeks, including some with prior resistance to NTRTs, NNRTIs and/or protease inhibitors, showed its non-inferiority (no worse than) to DTG+F/TAF at week 48. No participants with pre-existing NRTI resistance mutations has HIV RNA greater than 50 c/mL.
Biktarvy is not yet approved for treating HIV in patients with known drug resistance.
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