TIME diabetes

How Diabetes Harms the Brain

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ALFRED PASIEKA/SCIENCE PHOTO LIB—Getty Images/Science Photo Libra

Diabetes can damage a number of organs, from the eyes to the kidneys and the heart. Now there’s fresh evidence that unchecked blood sugar can affect the brain as well, which may lead to drops in cognitive functions

When blood sugar levels start to climb in diabetes, a number of body systems are harmed—and that list includes the brain, since studies have linked diabetes with a higher risk of stroke and dementia. Now, a new study published in the journal Neurology reports that changes in blood vessel activity in the brains of diabetics may lead to drops in cognitive functions and their ability to perform daily activities.

Dr. Vera Novak, associate professor of neurology at Harvard Medical School and Beth Israel Deaconess Medical Center, and her colleagues followed a group of 65 older people. About half had type 2 diabetes, and half did not. After two years, the diabetic patients had lower scores on cognitive tests compared to when they began, while people without diabetes showed little change on the tests.

MORE: The Strange Way a Diabetes Drug May Help Skin Scars

What drove the decline, says Novak, were changes in the brains of the diabetic patients. Diabetes can cause blood vessels to be less responsive to the ebb and flow of demand in different parts of the brain. Normally, flexible vessels will swell slightly to increase blood flow and oxygen to areas that are more intensely active, such as regions involved in memory or higher reasoning during intellectual tasks. But unchecked blood sugar can make these vessels less malleable and therefore less responsive.

“When doing any task, from cognition to moving your fingers, you need to increase blood flow to that specific area of the brain,” says Novak. “With diabetes, however, that vasodilation ability is reduced, so you have fewer resources to perform any task.”

MORE: Statins May Seriously Increase Diabetes Risk

In the study, Novak measured the changes in the flexibility of the blood vessels and found that among the diabetic patients, their flexibility declined, while it remained essentially the same for those without the condition. When blood sugar levels fluctuate as they do among people with diabetes, it can damage cells and nerves and trigger inflammation. What’s concerning, says Novak, is that these changes occurred even among people who were taking medication and had their diabetes under relatively good control. “Blood sugar control alone cannot treat [cognitive declines] associated with diabetes,” Novak says. “We need a new medication to improve [blood vessel] reactivity, cognition and brain function in diabetics.”

Her group is continuing to study ways that brain function can be improved by addressing the health of blood vessels; one method they are investigating involves using insulin inhaled through the nose or blood pressure medications to get brain vessel activity back to normal.

Figuring out whether such therapies can improve the brain function among people with diabetes is critical, since more people are diagnosed with the disease earlier in life, including in childhood. In previous studies, Novak and her colleagues showed that people with diabetes have brains that look five years older than those of similar-aged controls; for children with the disease, that could take a drastic toll on their cognitive skills as they age. “We really don’t have any treatment for cognitive decline in diabetes,” she says, “because the brain is not listed as an organ of risk for this disease. So we need more research and evidence like this.”

TIME health

The Woman Who Made Death a Conversation Starter

Elisabeth Kubler-Ross
Lyn Alweis—Post Archive/Getty Images Elisabeth Kubler-Ross in 1983

July 8, 1926: Elisabeth Kübler-Ross, the psychiatrist who pioneered treatment for people with terminal illness, is born

The idea that the dying might have something to teach the living seems self-evident. After all, as the psychiatrist Elisabeth Kübler-Ross put it, in a 1969 profile in LIFE Magazine, who better to offer instruction on “the ultimate human crisis” than those in the midst of it?

“When I wanted to know what it was like to be schizophrenic,” Dr. Kübler-Ross told TIME earlier the same year, “I spent a lot of time with schizophrenics. Why not do the same thing? We will sit together with dying patients and ask them to be our teachers.”

And yet the medical community reacted as though she’d suggested interviewing ghosts about the afterlife (which, to some degree, she later did). The institutional hush surrounding terminal illness was so deeply rooted by the 1960s that Kübler-Ross’s suggestion came as a shocking breach of protocol.

“The reaction of physicians ranged from annoyance to overt hostility,” TIME attested.

Kübler-Ross, born in Switzerland on this day, July 8, in 1926, was not deterred. Her seminar at the University of Chicago’s Billings Hospital, begun in 1965, featured terminally ill patients as lecturers—and helped lift the taboo on frank discussions of death in hospitals across the country. In her bestselling 1969 book, On Death and Dying, she compiled the insights she gleaned from these patients, most notably her conclusion that they typically struggled through five stages at the end of life: denial, anger, bargaining, depression, and acceptance.

While other researchers have questioned whether the five-stage model accurately depicts the experience of dying (or grieving in general), few deny that Kübler-Ross’s work led to improvements in the way terminally ill patients were treated. As she revealed, they didn’t necessarily appreciate being ignored in hospitals or tiptoed around by relatives and friends.

TIME summarized Kübler-Ross’s conclusion that “…the patient who is not officially told that his illness is fatal always discovers the truth anyway, and may resent the deception, however well meant.” The story goes on:

The dying are living too, bitter at being prematurely consigned—by indifference, false cheerfulness and isolation—to the bourn of the dead. It is not death they fear, but dying, a process almost as painful to see as to endure, and one on which society—and even medicine—so readily turns its back.

Kübler-Ross’s seminars lifted terminally ill patients out of their isolation, at least for a time, and gave them a platform to share their fears and their hopes. (Even those who made it to the acceptance stage rarely gave up hope, according to TIME.)

Just as importantly, the seminars gave Kübler-Ross’s students a glimpse into the part of life that remains one of our culture’s best-kept secrets. As LIFE concluded in 1969, “It is very much as if, while watching the others come to an understanding with death, they begin to move toward understandings of their own.”

Read more from 1969, here in the TIME archives: Dying: Out of Darkness

TIME pharma deals

Ireland’s Horizon Pharma Launches Hostile, $3 billion Bid For U.S. Rival

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JEAN-CHRISTOPHE VERHAEGEN—AFP/Getty Images

Offer represents a 42% premium over Depomed's Monday closing price

Ireland’s Horizon Pharma is bringing its $3 billion takeover offer for U.S. rival Depomed directly to the company’s shareholders after being rebuffed in its attempts to negotiate with Depomed’s management.

Horizon’s hostile bid for Depomed, announced on Tuesday, values the Newark, Calif.-based specialty pharmaceutical company at $29.25 per share, which represents a 42% premium over Depomed’s Monday closing price. Depomed’s share price jumped nearly 40% on the news of Horizon’s offer.

The Irish manufacturer of drugs to treat arthritis and other inflammatory diseases said in a press release that it made “repeated attempts” to enter into deal discussions with Depomed’s management and board starting in March, only to have those advances and its takeover offer rejected. Depomed makes a range of pain treatments and products that treat conditions related to the central nervous system. Horizon believes the deal would increase sales for both companies’ products while the five different drugs Depomed currently has on the market would nearly double the size of Horizon’s current portfolio.

“The strategic and financial benefits of our proposal are highly compelling,” Horizon CEO and chairman Timothy Walbert said in a statement. Walbert added that his company’s proposal offers “substantial long-term value for Depomed’s shareholders,” whom he encouraged to urge the Depomed board to enter deal discussions.

If the two companies are able to reach an agreement, it would represent the latest in a string of deals for Horizon, which paid $660 million for Vidara Therapeutics International last year and also acquired Hyperion Therapeutics for $1.1 billion earlier this year. The pharma industry in general has seen more than its share of dealmaking recently, with deal volume and value on the rise in the first quarter of 2015, led by mega-mergers such as AbbVie’s $21 billion purchase of Pharmacyclics and Pfizer’s $17 billion acquisition of Hospira.

TIME Aging

Here’s Why You May Be Aging Faster Than Your Friends

Researchers zero in on more than a dozen factors that can predict how fast you’re aging — and have some ideas about what makes people age more slowly

We all have friends who were born in the same year but look years younger (or older) than we do. Now researchers say that such perceptions aren’t just about outward appearances but about something deeper—the different pace at which each of us ages, and what that means for our health.

In a study published in the Proceedings of the National Academy of Sciences, scientists led by Daniel Belsky, an assistant professor of medicine at the Duke University School of Medicine’s division of geriatrics, describe a panel of 18 measures tested in 20- and 30-year olds that showed how quickly they are aging. The markers proved to be a good indicator of physiological age; they mirrored the biological effects of aging found in older people. But they were also good markers of physical age, meaning that those who aged faster also looked older, according to unbiased assessments by random people looking at their photos.

MORE: The Cure for Aging

Most studies on aging, and the factors that affect aging, come from investigations of older populations, says Belsky. And in most cases, the chronic diseases or physiological changes that come with aging are already well established in these groups. But it’s clear that aging doesn’t happen overnight; rather, it occurs gradually over a period of decades, much like water affects the shape of riverbanks or stones over time. It’s not obvious on a day-to-day basis, but can be dramatic if several years have passed.

In the study, 954 people born in 1972 or 1973 in Dunedin, New Zealand, agreed to participate in a study that followed them from age 26 to age 38. Each participant agreed to be tested on a range of 18 different factors that earlier studies have linked to aging, including blood pressure, lung function, cholesterol, body mass index, inflammation and the integrity of their DNA. Based on their scores on these measures, researchers calculated a biological age for each volunteer. They did this again when the people in the study were 32 and 38 years old, and combined them to calculate the pace at which each person was aging.

MORE: This Diet Has Been Linked to a Longer Life—Again

Some people were biologically older and aging faster than others, despite being the same chronological age. Not only that, but the researchers showed, by giving the 20- and 30-somethings the same tests of balance and thinking skills that gerontologists give for older adults, that these aging changes were the same as those occurring later in life.

Though some people really were biologically older than they are, the good news is that some were younger than their chronological age and aging more slowly than they should be. Comparing the slower and faster aging groups should reveal some hints about how to keep aging in check. And of the factors that influence aging, says Belsky, the vast majority, as much as 80%, aren’t genetic and therefore well within our control. (Even the 20% that’s DNA-based is modifiable to some extent.) “This is just the beginning,” he says. “The next step is to figure out what knowing this information helps us to do. One of the things it can help us do is identify the causes of accelerated aging so that we might slow it down. And the other thing it can help us do is evaluate therapies that slow down aging.”

MORE: Eat Better and Stress Less: It’ll Make Your Cells (and Maybe You) Live Longer

Having a way to measure, relatively accurately, the pace at which people age provides a good way of tracking whether any anti-aging treatment works or not. Some of those keys to youth likely won’t be surprising; given the 18 factors that the scientists studied, they will probably involve habits like having a healthy diet that’s low in fat and salt, maintaining a healthy weight, reducing stress, having a strong immune system and getting regular exercise. Not smoking, or quitting smoking may also play a role. To find out, Belsky says he will continue to follow the study group and re-evaluate them again when they are 45. The researchers are charting the participants’ diet, exercise and other behaviors. “We can start to evaluate which behaviors are working to slow down aging,” he says, by seeing which changes slow down the pace of aging. “It’s a tremendous opportunity to begin to sort things out.”

TIME medicine

FDA Approves New Cystic Fibrosis Drug

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Gregory Bull—AP In this March 4, 2015 photo, research scientist Tony Huang works in a laboratory at Vertex Pharmaceuticals Inc. in San Diego.

It will cost more than $250,000 a year

(WASHINGTON)—Federal health officials have approved a new combination drug for the most common form of cystic fibrosis, the debilitating inherited disease that causes internal mucus buildup, lung infections and early death. But it will come at a steep price — more than $250,000 for a year’s treatment.

The Food and Drug Administration cleared the twice-a-day pill from Vertex Pharmaceuticals Inc. for a variation of cystic fibrosis that affects about 8,500 people in the U.S. who are 12 years and older. The approval notice was posted to the agency’s website Thursday.

The new drug — to be sold as Orkambi — is Vertex’s follow-up to its breakthrough pill Kalydeco, which became the first drug to treat the underlying cause of cystic fibrosis in 2012. Orkambi combines Kalydeco with a new drug ingredient, lumacaftor.

Kalydeco is only approved for a cluster of rare cystic fibrosis forms that affect about 2,000 patients who are 2 years old and up.

About 30,000 Americans live with cystic fibrosis, which is caused by variety of genetic mutations passed from parents to their children. The disease causes sticky mucus to buildup in the lungs and other organs, which leads to infections, digestive problems and eventually death.

Vertex said Orkambi will cost $259,000 per year. That’s less than the $311,000 annual price tag for Kalydeco.

Dr. Robert Giusti of New York University’s Langone Medical Center noted that half of all U.S. cystic fibrosis patients have the form targeted by Orkambi, which occurs when a child inherits two copies of a certain genetic mutation — one from each parent. He expects the FDA will eventually expand the drug’s approval to patients as young as 6, increasing the number of people who could benefit.

“This is really exciting because this is a disease that causes a 1 to 2 percent deterioration each year in lung function of patients,” said Giusti, who directs the center’s cystic fibrosis program. “Now they have a therapy available to potentially reverse that effect.”

In the 1950s, children with cystic fibrosis seldom survived long enough to complete elementary school. Due to improvements in care, the typical cystic fibrosis patient today can expect to survive into their early 40s, according to the Cystic Fibrosis Foundation.

Prior to the approval of Kalydeco, drugs used to treat cystic fibrosis focused on controlling symptoms — such as opening up lung airways and breaking up mucus. Kalydeco was the first drug to target the underlying genetic defect that causes the disease.

Expectations for Vertex’s new drug have been tempered by study results that, while statistically significant, were not as dramatic as those first reported with Kalydeco. In company trials, patients treated with Orkambi for six months reported a 2.5 to 3 percent improvement in lung function, a key measure for cystic fibrosis patients. That improvement met the FDA’s standards for effectiveness, but did not equal results seen with Kalydeco, which improved lung function by about 10 percent.

Company officials have pointed out the differences in the forms of the disease targeted by the two drugs. Kalydeco was developed for patients who have a problem with a protein on their cell walls, which doesn’t properly balance the flow of water and salt from the cell. Orkambi targets patients with two problems — the protein does not reach the cell wall and, once there, does not work properly.

Shares of Vertex rose $5.07, or 4 percent, to close at $131.26 in trading Thursday. Its shares are up almost 34 percent over the past year.

Vertex’s cystic fibrosis drugs grew out of a long-term partnership with the Cystic Fibrosis Foundation. Vertex Pharmaceuticals Incorporated received roughly $120 million in research and funding from the foundation, culminating in the 2012 approval of Kalydeco. The twice-a-day pill had sales of $464 million last year, according to the Cambridge, Massachusetts company.

Last November the Cystic Fibrosis Foundation sold its royalty rights to Kalydeco and Orkambi for $3.3 billion.

TIME public health

First Person Dies of Measles in U.S. Since 2003

The death is the first in Washington since 1990

(SEATTLE) — Washington state health officials say measles caused the death of a woman from the northwest part of the state in the spring — the first measles death in the U.S. since 2003 and the first in Washington since 1990.

The measles infection was discovered during an autopsy.

Washington State Department of Health spokesman Donn Moyer says the woman was hospitalized in Clallam County for several health conditions before being moved to the University of Washington Medical Center in Seattle, where she died. He says officials are withholding her age to protect her identity, but she wasn’t elderly.

Officials didn’t say whether the woman was vaccinated, but they did note she had a compromised immune system.

Moyer says the woman likely was exposed to measles at the Clallam County medical facility. Clallam County had an outbreak of five cases this year.

TIME Obesity

Injecting This Drug Helps Patients Lose Weight

Daily shots of liraglutide (Saxenda), recently approved by the FDA, helps overweight or obese patients lose weight

In a study published in the New England Journal of Medicine, researchers say that the only injectable weight loss drug approved by the Food and Drug Administration (FDA) helps people to lose more than 12 pounds, more than twice as much as people taking a placebo.

The study is one of several that the FDA considered before approving the drug in 2014. It included data on 3,731 patients who were randomly assigned to take liraglutide or a placebo for just over a year. The trial continued to follow the patients for another year, and that data will be published soon.

MORE: This Pill Can Trick the Body Into Losing Weight, Study Finds

Liraglutide is similar to an already approved drug to treat type 2 diabetes, but is used in higher doses for weight loss. The drug mimics the effects of a hormone that works in the gut to signal the brain that you’ve eaten enough and feel full. As a diabetes drug, it helps the beta cells in the pancreas release insulin to keep blood sugar levels in check. In the NEJM study, none of the patients had diabetes, although some were pre-diabetic, and the FDA says liraglutide for weight loss should not be used together with the diabetes drug, also made by Novo Nordisk.

According to the study’s lead author, Dr. Xavier Pi-Sunyer, director of the obesity research center at Columbia University, liraglutide works as well as phentermine-topiramate (Qsymia), which doctors believe works by suppressing appetite. They key to making any weight loss medication effective, he says, is combining it with diet and exercise changes as well, which is what the participants in the study did. One advantage of liraglutide is that it can be used by women in their child-bearing years.

So far, the side effects of litaglutide, which include nausea, diarrhea, gall bladder abnormalities and pancreatitis, were minimal and did not outweigh the benefits of weight loss. But in approving the drug, the FDA asked the company to continue to study the drug to ensure that the adverse events remain within an acceptable range.

TIME medicine

Study Suggests Clue to Strange Link Between Swine Flu Vaccine and Narcolepsy

The immune system may have misidentified a protein in the vaccine

(WASHINGTON) — One vaccine used in Europe during the 2009 swine flu pandemic was linked to rare cases of a baffling side effect — the sleep disorder narcolepsy. Now new research offers a clue to what happened.

The vaccine Pandemrix never was used in the United States, and was pulled off the market abroad, but reports of narcolepsy in Finland and several other countries sparked questions globally about flu shot safety.

On Wednesday, an international team of researchers reported the problem may have been a case of mistaken identity by the immune system.

Narcolepsy is an incurable disorder that interferes with normal sleep cycles, leaving people chronically sleepy during the daytime and apt to abruptly fall asleep. No one knows what causes it, although patients have very low levels of a brain chemical named hypocretin that’s important for wakefulness. One theory is that a particular gene variant makes people susceptible, and that some environmental trigger, maybe an infection, pushes them over the edge.

About a year after mass vaccinations began against a new strain of H1N1 flu, called swine flu at the time, some European countries reported rare cases of narcolepsy in recipients of GlaxoSmithKline’s Pandemrix but not in people given other flu vaccines. Research found narcolepsy patients had that genetic predisposition, but no other explanation.

In the new study, Dr. Lawrence Steinman of Stanford University and colleagues found that the H1N1 virus contains a protein that is structurally similar to part of a brain cell receptor for that wakefulness chemical. They wondered if the flu-fighting antibodies generated by the Pandemrix vaccine might also latch onto those narcolepsy-linked receptors, leading to damage.

Colleagues in Finland sent blood samples that had been stored from 20 people diagnosed with vaccine-associated narcolepsy. Sure enough, 17 harbored antibodies capable of reacting both to flu and to those narcolepsy-linked receptors, Steinman’s team reported in the journal Science Translational Medicine. Recipients of another European vaccine, Novartis’ Focetria, didn’t harbor those cross-reactive antibodies.

Pandemrix contained much higher levels of the flu protein than Focetria, possibly because the two flu shots were made from different H1N1 subtypes, the researchers found.

The study doesn’t prove the link, Steinman stressed, calling for more research. It’s not clear how the antibodies could have gotten into the brain.

Moreover, some unvaccinated people who caught the flu harbor the antibodies, too, he said, and a study from China found H1N1 infection itself may increase narcolepsy risk.

It’s a plausible theory, said Dr. William Schaffner, a flu vaccine expert at Vanderbilt University who wasn’t involved in the new research.

Importantly, “this would also appear to be a solvable problem,” with manufacturing techniques to ensure that future vaccines don’t contain too much cross-reactive protein, he said.

However the narcolepsy puzzle turns out, the flu kills tens of thousands of people every year. “It’s really important to get vaccinated against flu,” Steinman said.

 

TIME medicine

How This Common Drug Can Have Lasting Effects on Kids

Antibiotics are prescribed for a range of childhood ailments, from ear to throat infections. But the drugs may be changing kids’ health in potentially unwelcome ways

In a study published in Nature Communications, scientists document the possible long-term effects of antibiotics when they’re used early in life. Their study involved mice, but the team used the drugs in doses and treatment regimens that mimic those frequently administered in young children.

Dr. Martin Blaser, professor of medicine and microbiology at New York University Langone Medical Center, and his colleagues tested three different antibiotic regimens: one involving amoxicillin, another involving macrolides and a final one that combined the two. They compared these animals to mice that received a placebo. The mice got antibiotics 10 to 15 days after birth, then again 27 days later and finally after day 39. They lived for 160 days, at which point they were sacrificed and their gut bacteria were studied.

MORE: Here’s What Eating Nothing But McDonalds for 10 Days Does to Your Gut Bacteria

Compared to the mice taking the placebo, the antibiotic-treated animals had less diverse communities of bacteria, and the proportions of the bugs living in their guts were also different. The macrolides seemed to have the biggest effect on reducing microbial richness, while amoxicillin led to abnormally large bones. The changes in the microbiome persisted even to the animals’ death, nearly four months after their last antibiotic dose.

“There are really long-term, probably permanent effects on the microbiome from antibiotics,” says Blaser. “We showed changes in the richness and the community structure, and also the genes present in the bacteria.”

MORE: Antibiotics Before Age 2 Increase Risk of Childhood Obesity

What this means for humans still isn’t clear from this study, but the findings do provide hints. Other studies that have analyzed the potential effects of antibiotics found that children receiving more rounds of the drugs because of early infections tend to be heavier and are more likely to be obese as adolescents and adults. And the earlier children are exposed to the drugs, the more likely their metabolism is to be affected.

Blaser notes that antibiotics are a necessary and potentially life-saving treatment for some, but for many infections, their risks might be greater than their benefits. “If what we found in mice is true for human children, then this is yet another reason to be cautious in using antibiotics,” he says. “We know there are kids who are severely ill who must have antibiotics. But there is a larger number of kids who are only mildly ill. The question is, what proportion of them really need antibiotics?” Based on the animal data, he says, the first two to three years of life are particularly important for development, and doctors and parents should be judicious about prescribing antibiotics during this sensitive time.

TIME medicine

Minnesota Takes Half Step Toward Legalizing Marijuana

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Getty Images

Pills and oils are approved, but smoking marijuana remains prohibited

Minnesota eased a statewide ban on medical marijuana products Wednesday, approving the use of pills and oils for seriously ill patients, while upholding a ban on products that can be smoked.

Under the new law, users will be able to use liquid and pill extracts of marijuana plants, provided they are suffering from serious conditions such as epilepsy, HIV and cancer, the Associated Press reports. The law also restricts sales to only eight dispensaries within the state.

While legalization advocates hailed the new rules as a step forward, they argued that Minnesota’s approach was unusually restrictive, potentially excluding patients living in rural areas or on tight budgets from obtaining the drugs.

[AP]

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