Tag Archives: diabetes
The aging global population is the greatest challenge faced by 21st-century healthcare systems. Even COVID-19 is, in a sense, a disease of aging. The risk of death from the virus roughly doubles for every nine years of life, a pattern that is almost identical to a host of other illnesses. But why are old people vulnerable to so many different things?
It turns out that a major hallmark of the aging process in many mammals is inflammation. By that, I don’t mean intense local response we typically associate with an infected wound, but a low grade, grinding, inflammatory background noise that grows louder the longer we live. This “inflammaging” has been shown to contribute to the development of atherosclerosis (the buildup of fat in arteries), diabetes, high blood pressure , frailty, cancer and cognitive decline.
Now a new study published in Nature reveals that microglia — a type of white blood cells found in the brain — are extremely vulnerable to changes in the levels of a major inflammatory molecule called prostaglandin E2 (PGE2). The team found that exposure to this molecule badly affected the ability of microglia and related cells to generate energy and carry out normal cellular processes.
Fortunately, the researchers found that these effects occurred only because of PGE2’s interaction with one specific receptor on the microglia. By disrupting it, they were able to normalize cellular energy production and reduce brain inflammation. The result was improved cognition in aged mice. This offers hope that the cognitive impairment associated with growing older is a transient state we can potentially fix, rather than the inevitable consequence of aging of the brain. Levels of PGE2 increase as mammals age for a variety of reasons — one of which is probably the increasing number of cells in different tissues entering a state termed cellular senescence. This means they become dysfunctional and can cause damage to tissue by releasing PGE2 and other inflammatory molecules.
But the researchers also found that macrophages — another type of white blood cells related to microglia — from people over the age of 65 made significantly more PGE2 than those from young people. Intriguingly, exposing these white blood cells to PGE2 suppressed the ability of their mitochondria — the nearest thing a cell has to batteries — to function. This meant that the entire pattern of energy generation and cellular behavior was disrupted.
Although PGE2 exerts its effects on cells through a range of receptors, the team were able to narrow down the effect to interaction with just one type (the “EP2 receptor” on the macrophages). They showed this by treating white blood cells, grown in the lab, with drugs that either turned this receptor on or off. When the receptor was turned on, cells acted as if they had been exposed to PGE2. But when they were treated with the drugs that turned it off, they recovered. That’s all fine, but it was done in a petri dish. What would happen in an intact body?
The researchers took genetically modified animals in which the EP2 receptor had been removed and allowed them to grow old. They then tested their learning and memory by looking at their ability to navigate mazes (something of a cliche for researchers) and their behavior in an “object location test.” This test is a bit like someone secretly entering your house, swapping your ornaments around on the mantelpiece and then sneaking out again. The better the memory, the longer the subject will spend looking suspiciously at the new arrangement, wondering why it has changed.
It turned out that the old genetically modified mice learned and remembered just as well as their young counterparts. These effects could be duplicated in normal old mice by giving them one of the drugs that could turn the EP2 receptor off for one month. So it seems possible that inhibiting the interaction of PGE2 with this particular receptor may represent a new approach to treating late-life cognitive disorders.
From the outset of the pandemic, data coming out of early coronavirus hot spots like China, Italy, and New York City foretold that certain groups of people would be more vulnerable to Covid-19. The disease hit older people and people with underlying medical conditions the hardest. As early as February, diabetes had emerged as one of the conditions associated with the highest risk. In one large study out of China, people with diabetes were more than three times as likely to die of Covid-19 than the overall population.
But that’s not what brought four diabetes experts from Australia and the United Kingdom onto a Zoom call back in April. They were supposed to just be catching up—a virtual tea among friends. But talk soon turned to something strange that they’d been seeing in their own hospitals and hearing about through the grapevine. The weird thing was that people were showing up in Covid-19 wards, after having tested positive for the virus, with lots of sugar in their blood. These were people with no known history of diabetes. But you wouldn’t know it from their lab results.
After that call, the experts reached out to colleagues in other countries to see if they’d seen or heard of similar cases. They had. Acute viral infections of all sorts can stress the body, causing blood sugar levels to rise. So that in itself wasn’t unusual, says Francesco Rubino, a bariatric surgeon and diabetes researcher at King’s College in London, who was on that first Zoom call. “What we were seeing and hearing was a little bit different.”
Doctors around the world had described to him strange situations in which Covid-19 patients were showing symptoms of diabetes that didn’t fit the typical two-flavor manifestation of the disease. In most people with type 1 diabetes, their immune cells suddenly turn traitorous, destroying the cells in the pancreas that produce insulin—the hormone that allows glucose to exit the bloodstream and enter cells. People with type 2 diabetes have a different problem; their body slowly becomes resistant to the insulin it does produce. Rubino and his colleagues were seeing blended features of both types showing up spontaneously in people who’d recently been diagnosed with Covid-19.
“That was the first clinical puzzle,” he says. For clues to an explanation, Rubino and his colleagues looked to ACE2, the protein receptor that SARS-CoV-2 uses to invade human cells. It appears in the airways, yes, but also in other organs involved in controlling blood sugar, including the gut. Doctors in China discovered copies of the coronavirus in the poop of their Covid-19 patients. And a meta-analysis found that gastrointestinal symptoms plague one out of 10 Covid-19 sufferers.
In the last few decades, scientists have discovered that the gut is not the passive digestive organ once thought. It actually is a major endocrine player—responsible for producing hormone signals that talk to the pancreas, telling it to make more insulin, and to the brain, ordering it to make its owner stop eating. If the coronavirus is messing with these signals, that could provide a biological basis for why Covid-19 would be associated with different forms of diabetes, including hybrid and previously unknown manifestations of the disease. Rubino is one of a growing number of researchers who think that the relationship between the coronavirus and diabetes is actually a two-way street. Having diabetes doesn’t just tip the odds toward contracting a worse case of Covid-19. In some people, the virus might actually trigger the onset of diabetes, and the potential for a lifetime of having to manage it.
Using induced pluripotent stem cells produced from the skin of a patient with a rare, genetic form of insulin-dependent diabetes called Wolfram syndrome, researchers transformed the human stem cells into insulin-producing cells and used the gene-editing tool CRISPR-Cas9 to correct a genetic defect that had caused the syndrome. They then implanted the cells into lab mice and cured the unrelenting diabetes in those mice.
The findings, from researchers at Washington University School of Medicine in St. Louis, suggest the CRISPR-Cas9 technique may hold promise as a treatment for diabetes, particularly the forms caused by a single gene mutation, and it also may be useful one day in some patients with the more common forms of diabetes, such as type 1 and type 2.
Wolfram syndrome is caused by mutations to a single gene, providing the researchers an opportunity to determine whether combining stem cell technology with CRISPR to correct the genetic error also might correct the diabetes caused by the mutation. Patients with Wolfram syndrome develop diabetes during childhood or adolescence and quickly require insulin-replacement therapy, requiring insulin injections multiple times each day. Most go on to develop problems with vision and balance, as well as other issues, and in many patients, the syndrome contributes to an early death.
Researchers at Washington University School of Medicine in St. Louis have transformed stem cells into insulin-producing cells. They used the CRISPR gene-editing tool to correct a defect that caused a form of diabetes, and implanted the cells into mice to reverse diabetes in the animals. Shown is a microscopic image of insulin-secreting beta cells (insulin is green) that were made from stem cells produced from the skin of a patient with Wolfram syndrome.
“This is the first time CRISPR has been used to fix a patient’s diabetes-causing genetic defect and successfully reverse diabetes,” said co-senior investigator Jeffrey R. Millman, PhD, an assistant professor of medicine and of biomedical engineering at Washington University. “For this study, we used cells from a patient with Wolfram syndrome because, conceptually, we knew it would be easier to correct a defect caused by a single gene. But we see this as a stepping stone toward applying gene therapy to a broader population of patients with diabetes.”
The study is published online in the journal Science Translational Medicine.
Chronic inflammation, which results when old age, stress or environmental toxins keep the body’s immune system in overdrive, can contribute to a variety of devastating diseases, from Alzheimer’s and Parkinson’s to diabetes and cancer.
Now, scientists at the University of California, Berkeley, have identified a molecular “switch” that controls the immune machinery responsible for chronic inflammation in the body. The finding, which appears online in the journal Cell Metabolism, could lead to new ways to halt or even reverse many of these age-related conditions.
“My lab is very interested in understanding the reversibility of aging,” said senior author Danica Chen, associate professor of metabolic biology, nutritional sciences and toxicology at UC Berkeley. “In the past, we showed that aged stem cells can be rejuvenated. Now, we are asking: to what extent can aging be reversed? And we are doing that by looking at physiological conditions, like inflammation and insulin resistance, that have been associated with aging-related degeneration and diseases.”
In the study, Chen and her team show that a bulky collection of immune proteins called the NLRP3 inflammasome — responsible for sensing potential threats to the body and launching an inflammation response — can be essentially switched off by removing a small bit of molecular matter in a process called deacetylation.
Overactivation of the NLRP3 inflammasome has been linked to a variety of chronic conditions, including multiple sclerosis, cancer, diabetes and dementia. Chen’s results suggest that drugs targeted toward deacetylating, or switching off, this NLRP3 inflammasome might help prevent or treat these conditions and possibly age-related degeneration in general.
“This acetylation can serve as a switch,” Chen said. “So, when it is acetylated, this inflammasome is on. When it is deacetylated, the inflammasome is off.”
As we learn more and more about health, well-being, and all the factors that affect both, inflammation has become a major player in the conversation. Linked with symptoms ranging from bloating and acne to more serious things like depression and cancer, chronic inflammation, researchers believe, could continue to increase in prevalence. But a new vaccine offers hope for the future of preventing inflammatory diseases.
The vaccine, which is currently for animals, was developed by Institut Cochin in France. Researchers already knew about a connection between inflammation, gut health, and the protein flagellin: Flagellin essentially allows into the rest of the body, resulting in inflammation, and while antibodies exist within that intestinal barrier to help prevent leaky gut, it’s harder to keep all the bacteria contained if your microbiome is out of balance. Researchers hypothesized they could boost the flagellin antibodies within the gut, thereby keeping harmful bacteria from spreading into the body. They administered a flagellin vaccine to mice by injecting it directly into their intestinal lining, spurring the production of the flagellin-fighting antibodies. Chronic inflammation is thought to be related to 60% of deaths worldwide, due to its connection to stroke, diabetes, cancer, and more. This vaccine could be a game-changer if scientists are able to replicate the findings in a version for humans, which researcher Benoît Chassaing says they’re working on.
“This vaccine strategy can be envisaged in humans, because such abnormalities of the microbiota have been observed in patients with inflammatory and metabolic diseases. With this in mind, we are currently working on a means of locally administering flagellin to the intestinal mucosa,” he says.
They’re also looking into testing the vaccine on animals that already have chronic inflammatory diseases, to see if it can be used for inflammatory treatment, as opposed to just prevention. But until such a vaccine for humans exists, there are lots of ways to combat inflammation naturally. If you’re still looking for more information, check out the Ultimate Guide to Inflammation class.. When inflammation was induced, the unvaccinated mice became obese, and the vaccinated mice did not. Immunization quelled intestinal inflammation by lowering levels of the flagellin-expressing bacteria in their microbiota, intestines, and intestinal lining.
An injection has helped reduce body weight and glucose levels in patients with diabetes and obesity in four weeks. The findings came from a small study in which patients lost on average 4.4kg and the treatment led to substantial improvements to their blood glucose, with some patients’ reducing to near-normal levels.Obesity is a common problem in the UK and it is estimated that one in four adults are obese. One of the most common types of weight loss surgery is a procedure known as gastric bypass surgery, which can be very effective in keeping excess weight off and improving blood sugar levels in diabetics. However, some patients decide against surgery and the procedure can cause complications such as abdominal pain, chronic nausea, vomiting and debilitating low blood sugar levels.
Previous research by Imperial College London suggested that one of the reasons why gastric bypass surgery works so well is because three specific hormones originating from the bowels are released in higher levels. This hormone combination, called ‘GOP’ for short, reduces appetite, causes weight loss and improves the body’s ability to use the sugar absorbed from eating. Researchers wanted to see if infusing patients with the GOP hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin and peptide YY, to mimic the high levels seen after surgery, could aid weight loss and reduce high glucose levels. Fifteen patients were given the GOP treatment for four weeks using a pump that slowly injects the GOP mixture under the skin for 12 hours a day, beginning one hour before breakfast and disconnecting after their last meal of the day. Patients also received dietetic advice on healthy eating and weight loss from a dietician.
“Obesity and type 2 diabetes can lead to very serious and potentially life-threatening conditions such as cancer, stroke and heart disease. There is a real need to find new medicines so we can improve and save the lives of many patients, said Tricia Tan, Professor of Practice (Metabolic Medicine & Endocrinology) at Imperial College London and lead author of the study. “Although this is a small study our new combination hormone treatment is promising and has shown significant improvements in patients’ health in only four weeks. Compared to other methods the treatment is non-invasive and reduced glucose levels to near-normal levels in our patients”, she adds.
People with chronic diseases like arthritis, diabetes and heart disease may one day forego the daily regimen of pills and, instead, receive a scheduled dosage of medication through a grape-sized implant that is remotely controlled.
Researchers from Houston Methodist successfully delivered continuous, predetermined dosages of two chronic disease medications using a nanochannel delivery system (nDS) that they remotely controlled using Bluetooth technology. The nDS device provides controlled release of drugs without the use of pumps, valves or a power supply for possibly up to year without a refill for some patients. This technology will be tested in space next year.
A proof-of-concept paper recently published in Lab on a Chip (online June 25) explains how the Houston Methodist nanomedicine researchers accomplished long-term delivery of drugs for rheumatoid arthritis and high blood pressure, medications that are often administered at specific times of the day or at varying dosages based on patient needs.
Nanomedicine scientists at Houston Methodist Research Institute created a remote-controlled implantable nanochannel drug delivery system (nDS) the size of a grape
“We see this universal drug implant as part of the future of health care innovation. Some chronic disease drugs have the greatest benefit of delivery during overnight hours when it’s inconvenient for patients to take oral medication. This device could vastly improve their disease management and prevent them from missing doses, simply with a medical professional overseeing their treatment remotely,” said Alessandro Grattoni, Ph.D., corresponding author and chair of the department of nanomedicine at Houston Methodist Research Institute.
Grattoni and the Houston Methodist researchers have worked on implantable nanochannel delivery systems to regulate the delivery of a variety of therapies for medical issues ranging from HIV-prevention to cancer. As basic research progresses with the remote-controlled device, the Houston Methodist technology is planned for extreme remote communication testing on the International Space Station in 2020. The team hopes that one day the system will be widely available to clinicians to treat patients remotely via telemedicine. This could provide both an improvement in the patients’ quality of life and a reduction of cost to the health care system.
‘In future, it will be possible to diagnose diabetes from the eye using automatic digital retinal screening, without the assistance of an ophthalmologist‘: these were the words used by Ursula Schmidt-Erfurth, Head of MedUni Vienna‘s Department of Ophthalmology and Optometrics. The scientist has opened the press conference about the ART-2018 Specialist Meeting on new developments in retinal therapy. The automatic diabetes screening, has been recently implemented at MedUni Vienna.
Patients flock to the Department to undergo this retinal examination to detect any diabetic changes. It takes just a few minutes and is completely non-invasive
Essentially this technique can detect all stages of diabetic retinal disease – high-resolution digital retinal images with two million pixels are taken and analyzed within seconds – but Big Data offers even more potential: nowadays it is already possible to diagnose an additional 50 other diseases in this way. Diabetes is just the start. And MedUni Vienna is among the global leaders in this digital revolution.
The Division of Cardiology led by Christian Hengstenberg within the Department of Medicine II is working on how digital retinal analysis can also be used in future for the early diagnosis of cardiovascular diseases.
“This AI medicine is ‘super human’,” emphasizes Schmidt-Erfurth. “The algorithms are quicker and more accurate. They can analyze things that an expert cannot detect with the naked eye.” And yet the commitment to Big Data and Artificial Intelligence is not a plea for medicine without doctors, which some experts predict for the not-to-distant future. “What we want are ‘super doctors’, who are able to use the high-tech findings to make the correct, individualized therapeutic decision for their patients, in the spirit of precision medicine, rather than leaving patients on their own.”
However, it is not only in the diagnosis of diseases that Artificial Intelligence and Big Data, plus virtual reality, provide better results. “We are already performing digitized operations with support from Artificial Intelligence. This involves projecting a virtual and precise image of the area of the eye being operated on onto a huge screen – and the surgeon then performs the operation with a perfect view “on screen” as it were, while actually operating on the patient with a scalpel.”