Tag Archives: diabetes

Newly discovered “insulin-like” molecule could change how we treat diabetes

Credit: Salk Institute.

Scientists at the prestigious Salk Institute have discovered a second insulin-like molecule produced by fat tissue that, like insulin, quickly regulates blood glucose. In a new study, they found that although the hormone has almost identical effects on the human body as insulin, it uses a different molecular pathway, thereby potentially circumventing insulin resistance. The remarkable findings could lead to novel treatments for diabetes and may even open the doors to new areas of metabolic research.

Before insulin was discovered in the 1920s at the University of Toronto, patients with type 1 diabetes rarely lived for more than a year or two. But after the hormone was successfully isolated it quickly saved lives, going on to become one of the most important medical breakthroughs of the 20th century. Today, millions of people across the world are diagnosed with type 1 or type 2 diabetes and benefit from insulin treatments. However, these treatments aren’t perfect due to problems arising from insulin resistance.

Insulin is released by your pancreas to lower blood sugar and keep it in the normal range. It achieves this goal by inhibiting the breakdown of fat cells into free fatty acids, a process known as lipolysis. In people with insulin resistance, glucose is not removed properly from the blood because the liver, fat, and muscles don’t respond well to insulin signaling. Furthermore, lipolysis occurs in excess, leading to increases in fatty acid levels, which prompt the liver to produce more glucose, compounding the already high blood sugar levels. This positive feedback loop can exacerbate insulin resistance, which characterizes diabetes and obesity.

The pancreas compensates by producing more insulin to help glucose from the food enter your cells. But if excess glucose in the blood remains high, the patient is at risk of developing prediabetes and, eventually, type 2 diabetes.

But insulin isn’t alone in regulating blood sugar in the body. In a new study published in the journal Cell Metabolism, Salk scientists showed that a hormone called FGF1 also regulates blood glucose through inhibiting lipolysis — a behavior that remarkably mirrors that of insulin.

“Finding a second hormone that suppresses lipolysis and lowers glucose is a scientific breakthrough,” says Professor Ronald Evans, co-senior author of the new study and Director of the Gene Expression Laboratory at Salk. “We have identified a new player in regulating fat lipolysis that will help us understand how energy stores are managed in the body.”

Previously, researchers injected FGF1 into mice with insulin resistance, resulting in dramatically lower blood sugar levels. However, why exactly this happens remained a mystery until Evans and colleagues showed that FGF1 suppresses lipolysis and regulates the production of glucose in the liver. That’s exactly what insulin does, which begs the question: do these molecules also share the same pathways to regulate blood sugar?

Turns out that they don’t and that’s actually fantastic news. Insulin suppresses lipolysis through PDE3B, an enzyme that initiates the signaling pathway, whereas the FGF1 hormone works through the PDE4 pathway.

“This mechanism is basically a second loop, with all the advantages of a parallel pathway. In insulin resistance, insulin signaling is impaired. However, with a different signaling cascade, if one is not working, the other can. That way you still have the control of lipolysis and blood glucose regulation,” says first author Gencer Sancar, a postdoctoral researcher in the Evans lab.

Since FGF1 uses a different pathway, the authors hope that the hormone will prove to be a new promising therapeutic route for diabetic patients.

Insulin injection.

Stem-cell implant prototypes pave the way towards life-long treatment for type 1 diabetes

New research is paving the way towards reliable, long-term treatments for type 1 diabetes. The work focused on developing implants based on stem cells that can deliver insulin directly into the bloodstream of diabetes patients.

Insulin injection.
Image credits Peter Stanic.

While the implants are not yet ready for use in a clinical role, the research does prove the viability of such systems for use in the future. The implants consist of pancreatic endoderm cells derived from human pluripotent stem cells (PSCs) and were tested with 26 patients. After more research and development, once such implants become able to secrete levels of insulin that will have a clinical effect on their recipients, they could become a viable alternative to current insulin-delivery systems and islet replacement therapies (pancreatic transplants).

Promising first steps

“The device is band-aid sized and designed to contain the lab grown islet cells for subcutaneous implant. It allows the cells within to become vascularized to permit delivery of oxygen and nutrients and release of insulin into the bloodstream. It is also readily retrievable”, said Dr. Timothy J. Kieffer of the University of British Columbia, corresponding author of the study, for ZME Science.

The team aims to provide an unlimited supply of insulin-producing cells for patients with type 1 diabetes, to mediate continuous, long-term treatment options while minimizing the invasiveness of the procedure.

Insulin is a hormone that keeps the levels of glucose (sugar) in our blood under control, and is produced by pancreatic β-cells. Type 1 diabetes is characterized by the destruction of these cells and leads to dangerously high levels of glucose building up in patients’ bloodstreams. Current treatments for this condition involve the administration of insulin directly into the bloodstream, either via manual injection or through automated systems that a patient can wear, which deliver the hormone periodically. Another possibility — although seen much more rarely in the grand scheme of things — is to treat the condition through islet transplant from donor organs.

Each of these treatment options comes with its own drawbacks. Direct injections require users to monitor their own state, remember to perform the procedure, and also carry the risk that they administer the shots imperfectly. Automated devices can be very burdensome to wear for long periods of time, are associated with long-term complications, and can malfunction. Transplants are very intrusive procedures and the supply of donor organs is very limited compared to the demand.

As such, an alternative is required, the team argues.

The current study reports on a phase I/II clinical trial involving the use of pancreatic endoderm cells as one such alternative. The team’s devices contain such cells in special capsules that allow for direct vascularization of the cells; these were implanted under the skin of the patients. The procedure did, however, run the risk of the participants’ bodies rejecting the implants, and thus involved an immunosuppressive treatment regimen that is commonly used in donor islet transplantation procedures. Possible side-effects of such treatments is an increased risk of cancer and infections in patients, as a direct consequence of their immune systems being suppressed.

That being said, the authors report that the devices worked as intended, and the cells within them started secreting insulin and delivering it directly into the participants’ bloodstreams in response to the glucose levels in their blood. Insulin expression (secretion) was recorded in 63% of the devices after they were explanted at time periods between 3 and 12 months after implantation. Insulin-secreting cells started accumulating progressively in these devices over a period of between 6 and 9 months after implantation.

Although not yet able to cover their full requirements for insulin, over a one-year study period, they reduced the amount of insulin participants needed to be administered by 20%. They also spent 13% more time in the target blood glucose range compared to pre-study periods.

“We found the implants were able to produce insulin in a meal regulated manner like normal healthy pancreatic islets, albeit at low levels,” Dr. Kieffer adds for ZME Science. “The sponsor company ViaCyte recently reported achieving clinically meaningful levels of insulin when more of these devices were implanted (8) that resulted in a dramatic reduction in the insulin injection requirements accompanied by vastly improved control of blood sugar.”

Overall, these devices were well-tolerated by their bodies and there were no severe adverse effects caused by the grafts. Two participants did experience serious adverse effects related to the immunosuppression treatment. Most of the adverse effects reported by participants, however, were related to the actual implantation/explantation surgeries, or to side-effects of the immunosuppressive treatment. All things considered, the team explains, the risk of local infection posed by the devices was very low, suggesting that the devices themselves are well-tolerated even in participants with a poor immune or healing response.

This does raise questions regarding the use of such devices over a patient’s whole life. An ideal solution to this would be an option to perform stem cell-based islet replacement therapy without the devices themselves, as this would bypass the need for immunosuppressive treatments altogether.

Still work to be done

One of the major limitations of the study was the lack of a control group, so the findings should not be used to draw any conclusion on how effective such devices would be at treating type 1 diabetes. However, the study does show that they are relatively safe to use and validate the working principle behind their design. More research will be needed to determine the quantity of cells such implants should contain in order to produce clinically-relevant benefits for patients.

“It was very exciting to see clear meal regulated insulin production in patients following the implants and also see islet cells in the retrieved devices that looked like normal healthy pancreatic islet cells. We now have clear proof of principle data that this stem cell-based approach can work,” Dr. Kieffer adds for ZME Science.

Currently, the cells survive an average of 59 weeks after implantation. The total percentage of insulin-positive cells they contained at maturation was below the team’s ideal target, however. The researchers are now working on solutions to promote vascularization between the grafts and the patients’ bodies, and on measures to improve the survival of the cells they contain.

“Our ultimate goal is to entirely free patients from the burden of glucose monitoring and insulin injections, and without the use of any immunosuppression,” Dr. Kieffer concluded in his email for ZME Science. “We are thus very excited by the recent ViaCyte / CRISPR Therapeutics announcement that Health Canada has approved clinical testing of genetically modified cells that have been engineered to evade detection by the immune system.”

“With protocol refinements and immune-evasive cells, we hope to reach this goal.

The paper “Implanted pluripotent stem-cell-derived pancreatic endoderm cells secrete glucose-responsive C-peptide in patients with type 1 diabetes” has been published in the journal Cell Stem Cell.

Those suffering from migraines could be at lesser risk for diabetes

Those people who suffer migraines are also least likely to get diabetes. (Photo: Pixabay)

Migraines really suck, but to sufferers, maybe a lack of diabetes could be a consolation. A new study by the American Chemical Society has found that those who get the pleasure of getting skull-crushing headaches are also less likely to develop type 2 diabetes.

If the relationship between the two afflictions sounds odd, it’s because it kind of is.

“Migraines happen in the brain, while diabetes is associated with the pancreas, and these organs are far from each other,” says Thanh Do, Ph.D., the project’s principal investigator. His group became interested in the subject after a number of papers described an inverse relationship between the conditions.

The rapport between the two breaks down to how the peptides that cause migraine pain can also influence the production of insulin. Researchers believe the production comes down to the number of pancreatic cells which produce insulin.

The scientists already knew that two peptides in the nervous system — calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) — played a major role in causing the pain of migraines. These same peptides, along with the related peptide amylin, can also be found in the pancreas. There, they influence the release of insulin from beta cells.

Insulin is produced by the beta cells of the pancreatic islets. It is released when you have just eaten and the level of glucose in your bloodstream is high. Insulin then stimulates the uptake of glucose into cells, lowering your blood sugar level. Your muscles and liver can use glucose either for immediate energy or to be put in storage as glycogen until it’s needed.

In type 2 diabetes, those other cells become resistant to insulin and less capable of absorbing glucose, leading to high blood sugar levels. The beta cells initially compensate by ramping up insulin production but eventually wear themselves out and die, exacerbating the issue.

Due to their role in migraine and diabetes, CGRP and PACAP both offer targets for therapies that could treat either of the two illnesses. Migraine drugs that interfere with CGRP and its cellular receptors recently went on the market and other treatments are being studied. However, more research is needed to clarify the peptides’ effects. Do and his team from the University of Tennessee are trying to clear up contradictory discoveries about the peptides’ bearing on insulin.

Do’s team devised a method to glean data from just a few hundred beta cells. Using this technique, they reported showed that CGRP lowered levels of insulin in mice. That, in turn, could counter the insulin resistance which develops in type 2 diabetes. However, CGRP was less successful when it came to lowering insulin levels in humans.

Diabetes is also associated with the aggregation of amylin. These aggregates could contribute to the beta cell damage that helps cause type 2 diabetes. Because amylin and insulin are co-secreted by beta cells, using CGRP to limit insulin production could also limit amylin production, Do says. That could protect the cells and help normalize their function.

PACAP, too, is thought to play a protective role against type 2 diabetes. That can be somewhat confusing since PACAP has also been shown to stimulate insulin release, which leads to insulin resistance.

Do’s group’s initial findings in trying to figure out the conundrum show that PACAP’s actions could depend on glucose levels. The researchers found preliminary evidence that PACAP regulates insulin in a glucose-dependent manner and promotes beta cell proliferation, rather than prodding existing beta cells to work harder — thus preventing the risk of tiring out the existing cells. They are developing analytical procedures to test this.

“Despite these positive results, you can’t inject CGRP and PACAP into the body as therapeutic strategies for diabetes because these peptides cause migraine pain,” Do says. “But once we understand how they exert their effects on insulin secretion, we can design peptide analogs that would control insulin but would not bind to the pain receptor.”

However, Do and other researchers are afraid that current migraine medications currently on the market could actually up the risk of diabetes since some are anti-CGRP and anti-PACAP treatments. In addition, these peptides are involved in numerous other beneficial functions in the body, such as blood vessel dilation. Because of this, Do and other scientists are also investigating the possible hazards of altering the peptides’ activity.

So the next time you have a headache coming on, just know that at least there is a bright side.

Why is insulin so outrageously expensive?

As any diabetic patient is painfully aware, insulin can be incredibly expensive — and that’s particularly true for Americans. But why is a drug that was discovered a century ago so costly?

Insulin is the definite poster child of drug price gouging. If people wonder why ‘Big Pharma’ is so hated across the world, look no further than the ridiculous pricing for insulin and the suspicious policies of the handful of companies that manufacture it.

Over the past decade, the cost of insulin had tripled in the United States, and the out-of-pocket prescription costs that patients have to pay have doubled just in the last five years.

How much is a bottle of insulin?

The cost of a single vial of insulin varies depending on the type of insulin and whether or not it is covered by insurance. Each insurance plan can cover insulin products differently.

In 2012, the average cost of insulin per diabetes patient was $2,864 per year. By 2016, just four years later, it had risen to $5,705.

Today, one vial of insulin can cost $250 and a pack of pens ranges from $375 to $500. Most patients require two vials of insulin per month or 1-2 packs of insulin pens, but some people need up to six vials per month.

Besides insulin, diabetic patients need other types of medication, which also tend to be high priced. According to a 2016 study, the total average out-of-pocket pharmacy and medical costs for patients with diabetes reached $18,500 in 2016 — a surge of $6,000 from 2012 costs, half of which are accounted for by spending on insulin.

As a result of these exorbitant prices, one in four patients say that they ration their insulin because they can’t afford full proper doses. In some cases, this practice can cost lives. For patients with type 1 diabetes, just a single day without insulin is enough to send them to the emergency room.

There are nearly 30 million people suffering from diabetes in the United States, 5% of whom — or about 1.5 million — suffer from type 1 diabetes, hence they require insulin to literally survive. Although people with type 2 diabetes can control their blood sugar with diet and exercising, many still need insulin shots, especially as their condition deteriorates.

The market is dominated by only a few manufacturers

Only three pharmaceutical giants — Novo Nordisk, Sanofi-Aventis, and Eli Lilly — produce 90% of the global insulin supply. Basically, these big three control the market. They also tend to mirror each other’s prices.

Here’s the thing though: insulin was invented in 1923 by Frederick Banting who immediately gave away the patent after it was clear that the drug would save millions of lives each year. Along with co-inventors James Collip and Charles Best, the patent was sold to the University of Toronto for a symbolic $1. Soon after, insulin from pigs and cattle was being produced and sold on a massive scale around the world.

“Insulin does not belong to me, it belongs to the world,” Banting once said.

Now, nearly 100 years later, insulin is inaccessible to thousands of Americans because of its high cost. Usually, when a drug has been on the market for decades, its patent expires, which means any manufacturer can produce a generic version that should drive the prices down by a high margin. But this expectation falls apart in the case of insulin — if anything, the reverse is true.

Part of the reason for this is something called ‘evergreening’, the practice involving various techniques to extend the protection on a drug and block competition that might lead to price reductions.

Early insulin was not ideal, requiring multiple injections for some patients. Some even developed potentially dangerous allergic reactions. Over the decades, manufacturers have introduced all sorts of new processes and technologies that vastly improved insulin, making the drug purer and safer.

In the 1970s, manufacturers stopped making insulin from animals. Instead, everyone now uses a technique based on recombinant DNA technology that basically produces human insulin from genetically modified bacteria.

That was great news for animals, but kinda bad news for patients. Although there’s no clear reason why a company would stop producing the animal-version of insulin, this cheap, older alternative has disappeared from the market — at least in the U.S. (you can still find animal-derived insulin in other countries, such as in Canada).

And by making minor modifications to their manufacturing process or packaging, manufacturers were also able to extend patent protections, thereby discouraging competitors and promoting a cartel-like business environment. This strategy is a win-win for big business but a lose-lose for patients who require life-saving therapy.

Unlike aspirin or adderall, which are chemical drugs which contain the same ingredients every time, insulin is a biologic drug. This means that the manufacturing is a lot more complicated since you have to work with live cells. It also means that the rules for generic drug patents don’t apply. For instance, the generic equivalent of a biologic drug is called a ‘biosimilar’.

In the US, there are only 17 FDA approved biosimilars for insulin. Many of these biosimilars are manufactured by one of the ‘big three’ manufacturers, which doesn’t help to bring the price down.

When asked how they explain the high price of insulin, manufacturers often cite the “complexity of the supply chain” as a reason high up their list. That may be true, but that doesn’t explain why cheaper, easy to manufacture animal-derived insulin isn’t offered as an alternative.

There is some progress but prices are still ‘too damn high’

Due to public outrage surrounding the prices of insulin and pressure from some members of Congress to keep prices under control, some insurance and pharmaceutical companies have taken measures to lower the monthly cost.

According to Singlecare, some of these measures include:

  • Cigna and Express Scripts capped the monthly out-of-pocket cost at $25/month, with an estimated 700,000 people with diabetes being eligible. However, employers must opt into this program. Cigna covers less than 1% of the millions of people with diabetes in the US.
  • Sanofi has a program for cash payers that costs $99/month and provides either 10 vials, 10 boxes of pens, or a combination of the two. People with Medicare, Medicaid, or other federal and state programs are not eligible for this program, however.
  • Eli Lilly developed a generic version of Humalog that is priced at half the normal rate, at $137.35/vial. They also launched their Insulin Value Program in April, which offers a $35 copay card for the uninsured or those with commercial insurance.
  • In April 2020, Novo Nordisk announced that it would offer a free 90-day supply of insulin to patients who had lost their health insurance as a result of the pandemic.
  • The state of Colorado has taken the unusual route of capping the price of the drug. People with diabetes in Colorado don’t have to pay more than $100/month copay for their insulin.

Such programs, although welcomed, don’t help every patient. For instance, you can’t use these discounts if you have Medicare and most often than not they’re capped at $100-$150.

The bottom line is that insulin is expensive because manufacturers control its price and since competition (or the competitive spirit) is almost non-existent. In other words, insulin is expensive because it can be.

Electromagnetic fields treat type 2 diabetes in mice

Credit: Pxfuel.

The only options available to patients for managing their type 2 diabetes are pills and injections. These can have unpleasant side effects and can sometimes be cumbersome to perform. In the future, perhaps a third option may be available, centered around electromagnetic fields that can regulate blood sugar. According to a new study, this non-invasive type of treatment was successful in mice with diabetes.

A remote control for managing diabetes

Calvin Carter, a postdoc at the University of Iowa, was working with mice for a totally unrelated study of the effects of electromagnetic fields (EMF) on the brain and behavior of animals. His colleague Sunny Huang asked Carter to borrow some mice for his Ph.D. project, which required him to practice drawing blood and measuring blood sugar levels.

The mice that Carter used in his experiments all had type 2 diabetes, so they should have high blood sugar. But Huang was shocked to find the mice had normal blood sugar levels.

“That’s what sparked this project,” Carter said. “Early on, we recognized that if the findings held up, they could have a major impact on diabetes care.”

Although they’re invisible, electromagnetic fields are all around us all the time, whether it’s artificial EMFs generated by mobile devices or natural ones generated by electric charges in the atmosphere.

Sometimes these EMFs can influence biological mechanisms. You’ve probably heard all sorts of rumors and conspiracies about 5G and the wireless network’s potential harms to our health. Some have gone as far as saying the current coronavirus pandemic has been triggered by 5G networks. That’s just ridiculous and false, as we previously showed.

But that doesn’t mean other types of EMFs don’t have a biological effect. Birds, turtles, whales, and many other migratory animals can sense the Earth’s electromagnetic field in order to orient themselves for navigation.

While reviewing scientific literature published during the 1970s, Carter stumbled upon some studies that pointed to quantum biological phenomena whereby EMFs may interact with certain molecules.

“There are molecules in our bodies that are thought to act like tiny magnetic antenna, enabling a biological response to EMFs,” Carter says. “Some of these molecules are oxidants, which are studied in redox biology, an area of research that deals with the behavior of electrons and reactive molecules that govern cellular metabolism.”

Carter and colleagues at the University of Ohio and Brigham Young University probed the action of an oxidant molecule known as superoxide, which was previously identified as playing a role in type 2 diabetes.

When superoxide molecules were removed by researchers from the livers of mice, the effects of EMFs on blood sugar and the insulin response were blocked. What’s more, experiments suggest that EMFs alter the signaling of superoxide molecules, prolonging the activation of an antioxidant response and rebalancing the response to insulin.

“Exposure to electromagnetic fields (EMFs) for relatively short periods reduces blood sugar and normalizes the body’s response to insulin. The effects are long-lasting, opening the possibility of an EMF therapy that can be applied during sleep to manage diabetes all day.”

These findings are quite fantastic, but can they be translated to humans? After all, animal studies are often poor predictors of responses in humans. However, experiments performed on human liver cells that were treated with EMFs for six hours also showed that a surrogate marker for insulin sensitivity improved drastically. This lends some hope that it may be indeed possible to translate this therapy to humans.

According to the World Health Organization, low-energy EMFs are considered safe for human health, and Carter and colleagues found no evidence of any adverse effects in the mice used in the study. Nevertheless, the researchers plan to repeat these experiments on pigs, whose hearts and cardiovascular system more closely resemble those of humans. If all goes well, they plan to commence clinical trials that may show that magnetic fields can treat type 2 diabetes in humans.

“This project is so out there and so unique. It’s not really something you see, even in science these days,” Huang said. “I think being grounded in evidence and also having the backing of these reputable institutions is a testament to the fact that this is real and there are really interesting things going on here.”

The findings appeared in the journal Cell.

Leading experts warn that COVID-19 might trigger diabetes in previously healthy patients

By now, it’s an established fact that coronavirus patients who also suffer from diabetes are at a higher risk of death. But what’s perhaps even more worrisome is that COVID-19 might actually trigger the onset of diabetes in previously healthy people, according to new research.

Credit: Pixabay.

Diabetes is a disease that occurs when your blood glucose, also called blood sugar, is too high. There are two types of diabetes that can lead to this outcome.

Type 1 is triggered when the body’s own immune cells attack the islet cells in the pancreas responsible for producing insulin. This merciless attack is continuously carried out until there are no more islets left, halting the production of the insulin that controls blood glucose levels. As such, Type 1 diabetes is considered an autoimmune disease.

In Type 2 diabetes, insulin is still produced normally by the pancreas, however, the body is still unable to shuttle glucose into cells for fuel. This is due to growing insulin resistance in the body’s organs and tissue, such as in the liver, muscle, or fat. Because the body doesn’t respond to insulin messaging, the islet cells start producing too much insulin, exhausting the islet cells. Eventually, the islet cells start dying, decreasing insulin production while resistance increases.

Although both forms of diabetes have been studied for decades, there are still many unknowns as to how the two diseases are triggered. One possible avenue of disease onset may be viral infection.

For instance, the incidence of Type 1 diabetes often co-occurs with seasonal viral infections, and some claim that viruses can trigger the destruction of the islet cells, triggering a chronic autoimmune response.

In a recent article, Julian Hamilton-Shield, a professor in Diabetes and Metabolic Endocrinology at the University of Bristol, draws attention to a worrisome trend, stating that COVID-19 may trigger diabetes in some patients.

Hamilton-Shield points to the case of a Chinese young man of previous good health who developed severe diabetes after contracting COVID-19. He also mentions how during the SARS outbreak in 2002-2004, many people with SARS pneumonia went on to develop acute diabetes, something which wasn’t seen in patients with other types of pneumonia. SARS is another coronavirus closely related to SARS-CoV-2, the virus responsible for COVID-19. Although diabetes resolved within three years for most patients, it persisted in 10% of cases.

This sentiment is shared by leading experts who recently wrote an open letter published in The New England Journal of Medicine, in which they claim there may be “a bidirectional relationship between Covid-19 and diabetes.”

How COVID-19 might cause diabetes

SARS-CoV-2 infects susceptible cells by binding to angiotensin-converting enzyme 2 (ACE2) receptors. These receptors are expressed in some metabolic organs and tissue, including pancreatic beta cells and the kidneys. This may explain why patients with preexisting diabetes are at greater risk, while also pointing to new mechanisms of disease onset.

However, there are still many unknowns.

“How frequent is the phenomenon of new-onset diabetes, and is it classic type 1 or type 2 diabetes or a new type of diabetes? Do these patients remain at higher risk for diabetes or diabetic ketoacidosis? In patients with preexisting diabetes, does Covid-19 change the underlying pathophysiology and the natural history of the disease? Answering these questions in order to inform the immediate clinical care, follow-up, and monitoring of affected patients is a priority,” wrote the authors of the letter published in The New England Journal of Medicine.

To clear things up, diabetes researchers have launched the CoviDIAB Project, which aims to compile a global registry of COVID-19 patients with new-onset diabetes.

“Given the very short history of human infection with SARS-CoV-2, an understanding of how Covid-19–related diabetes develops, the natural history of this disease, and appropriate management will be helpful,” the authors of the letter concluded.

Modified immune cells could be a long-term treatment for type 1 diabetes

New research at the Seattle Children’s Research Institute’s Center for Immunity and Immunotherapies could result in a treatment against type 1 diabetes that has long-term efficacy and removes the need for insulin injection.

A patient has their blood sugar levels checked at the Wilford Hall Ambulatory Surgical Center, Joint Base San Antonio-Lackland.
Image credits U.S. Air Force / Staff Sgt. Chelsea Browning.

The authors plan to carry out a clinical trial with human patients at Seattle Children’s to test the treatment’s merits.

No more friendly fire

“What started as a dream is now within reach,” said Dr. David Rawlings, director of the center and corresponding author of the paper.

“My hope is that our research will lead to a new treatment that turns off the destructive immune response leading to the development of type 1 diabetes in children.”

Insulin production is handled by islet cells in the pancreas. Malfunctions in our bodies’ regulatory T cells (Treg) can cause the immune system to see them as threats, and attack. Treg cells work to organize and control effector T cells, which are the ones who actually carry out the attacks.

If enough of these cells are damaged, the pancreas becomes unable to regulate glucose levels in the blood, causing the early symptoms of type 1 diabetes such as frequent urination, unquenched thirst, insatiable hunger, and extreme fatigue. Current treatments require daily insulin injections, without which the disease can become fatal.

In a bid to find a treatment that doesn’t require the logistics of insulin production and supply, the team details how Treg cells of patients can be genetically engineered to function like their normal counterparts. Their approach targets the FOXP3 gene, which governs the process by which T cells can mutate into Treg cells.

In theory, once injected back into a patient, these cells (‘edited regulatory-like T cells’, or ‘edTreg’) should enter the pancreas and help keep the immune system in check.

The team notes that these edTreg cells look very similar to natural Treg ones, and that they behaved like them during tests in tissue samples and on animal models. They are currently working to start a phase 1 clinical trial of their therapy.

“This data offers the first proof that engineering by way of turning on FOXP3 is sufficient to make a functional Treg-like cell product,” said Dr Rawlings. “Not only is it a landmark research finding, but it’s directly translatable to clinical use.”

While all of this is going on, the authors are further refining the efficiency of their treatment and to devise a way to make edTreg cells target the pancreas directly.

The paper “Gene editing to induce FOXP3 expression in human CD4+ T cells leads to a stable regulatory phenotype and function” has been published in the journal Science Translational Medicine.

Diabetes rising worldwide: one in 11 adults affected

Diabetes is one of the world’s fastest growing chronic diseases with over 463 million adults (that’s 1 in 11 adults) around the world living with this chronic medical condition according to new data published in the 9th Edition of the International Diabetes Federation (IDF) Diabetes Atlas. The latest Atlas also reports that the global prevalence of diabetes has reached 9.3%, with more than half (50.1%) of adults undiagnosed. A further 1.1 million children and adolescents under the age of 20, live with type 1 diabetes.

A decade ago, in 2010, the global projection for diabetes in 2025 was 438 million. With over five years still to go, that prediction has already been surpassed by 25 million. IDF estimates that there will be 578 million adults with diabetes by 2030, and 700 million by 2045.

Diabetes itself is not a major problem unless the blood glucose is uncontrolled and either rises too high or drops too low. If diabetes is not managed correctly (meaning blood glucose is not properly regulated), sufferers are likely to become progressively sick and debilitated.

Over time, diabetes can damage the heart, blood vessels, kidneys, eyes and nerves. For diabetics, maintaining blood sugar levels in a normal range — not too high or too low — is a lifelong challenge. Half of the people with diabetes die of cardiovascular disease (primarily heart disease and stroke), and 10–20 percent of people with diabetes die of kidney failure. Diabetes is also a major cause of blindness and lower limb amputation.

IDF estimates that approximately 4.2 million adults will die as a result of diabetes and its complications in 2019. This is equivalent to one death every eight seconds.

Flu season is quickly approaching and patients with diabetes are particularly at high risk of serious flu-related complications that can result in hospitalization or even death. Diabetics are twice as likely to die from heart disease or stroke as people without diabetes and six times more likely to be hospitalized. 

Flu infection can cause changes in blood sugar and prevent people with diabetes from eating properly, which further affects blood glucose. Moreover, diabetes can make the immune system less able to fight infections. Diabetes patients with flu face very serious health risks such as ketoacidosis (a condition when the body cannot use sugar as a fuel source because there is no insulin or not enough insulin) and Hyperosmolar Hyperglycaemic State (HHS).

It is important for people with diabetes to follow the sick day guidelines if they become ill. Flu vaccination is especially important for people with diabetes because they are at high risk of developing serious flu complications. Flu vaccination has also been associated with reduced hospitalizations among people with diabetes (79%). Diabetics who get the flu should ask their doctors about prescription antiviral medications that can ease symptoms and shorten the duration of the illness. For best results, antivirals should be taken within 48 hours of the onset of flu symptoms.

Facebook posts can be used to predict anxiety, depression, and even diabetes

A new study finds that Facebook posts are better than demographic information when it comes to predicting a number of mental health conditions, as well as diabetes. This suggests that one day, our social media history might play an important role in the doctor’s office.

You can tell a lot of things by a person’s social media history, but medical information isn’t exactly one of them, but this is exactly what was presented in a new study. In the research, the team analyzed the entire Facebook post history of around 1,000 patients (who had given their consent for this study), building three analysis models: one that looked at post language, one that looked at demographics, and one that combined the two.

They then looked at 21 different medical conditions, assessing whether the Facebook history could be used to predict these conditions — all 21 were. Actually, 10 of them were predictable from post history alone, without even looking at the demographic information. It’s still early, but the results were impressive.

“This work is early, but our hope is that the insights gleaned from these posts could be used to better inform patients and providers about their health,” said lead author Raina Merchant, MD, MS, the director of Penn Medicine’s Center for Digital Health and an associate professor of Emergency Medicine. “As social media posts are often about someone’s lifestyle choices and experiences or how they’re feeling, this information could provide additional information about disease management and exacerbation.”

The language we use carries many unconscious biases which can be linked to our behaviors and habits. In turn, these behaviors can also be indicative of other underlying problems. Some connections were clear: people who tended to use words like “bottle” or “drink” more often were more likely to suffer from alcohol abuse. Others, however, were much less intuitive.

For instance, the people that most often used religious language (with words such as “God” or “pray”) were 15 times more likely to have diabetes than those who used these terms the least. When fed into the models, this information could be used and extrapolated to predict serious conditions.

“Our digital language captures powerful aspects of our lives that are likely quite different from what is captured through traditional medical data,” said study author Andrew Schwartz, PhD, visiting assistant professor at Penn in Computer and Information Science, and an assistant professor of Computer Science at Stony Brook University. “Many studies have now shown a link between language patterns and specific disease, such as language predictive of depression or language that gives insights into whether someone is living with cancer. However, by looking across many medical conditions, we get a view of how conditions relate to each other, which can enable new applications of AI for medicine.”

The thing is, because the content we publish on Facebook is not in a medical context, it can contain information that’s usually not mentioned in a medical or clinical context, including potential markers for specific diseases. For depression, words like “pain,” “crying,” or “tears” were good indicators, but also less obvious words such as “stomach,” “head,” or “hurt”.

It’s not the first time this idea was suggested. Previous research has found that Facebook history can be indicative of mental health conditions such as depression. The fact that this approach can be further extended to conditions such as diabetes is even more encouraging.

Now, the team is carrying a larger trial where they will ask participants to share social media history with their doctor to see how this data can be best used in a practical setting. This is the one big caveat to this study: the sample size. Not only was it fairly small, but it was also largely female (76%) and African American (71%) — not representative for the entire population.

Journal Reference: Merchant et al. Evaluating the predictability of medical conditions from social media posts. PLOS ONE. DOI:10.1371/journal.pone.0215476

Credit: Pixabay.

Could a combination of drug therapy and stem cells reverse type 2 diabetes?

Credit: Pixabay.

Credit: Pixabay.

Stem cells have opened a new range of possible treatments and recent studies suggest they could also deal with type 1 diabetes. This early-onset, less-common type of diabetes occurs when your body’s defense mechanisms harm insulin-producing cells in the pancreatic state, usually while preventing infections elsewhere in your body. With the help of stem cells, physicians have previously generated new insulin-producing cells in order to replace the ones that the pancreas has eliminated.

According to GenFollower, stem cells are also being used to tackle infertility and improve the reproductive system. 

On the other hand, type 2 diabetes — which makes up 90 % of diabetic issues globally — is more challenging to treat. It usually occurs in older people as a result of extra weight or hormonal instability.

Although people with type two diabetes do lose a few of their insulin-producing cells, their major issue is elsewhere. Their cells became immune to blood insulin. Although blood insulin is present in the entire body, the cells can’t use blood insulin to keep glucose levels under control.

Basically, restoring the lost insulin-producing cells isn’t enough to eliminate the problem.

But now, in a new study released in the journal Stem Cell Reports, researchers may have discovered a way.

A Bilateral Approach

In order to model type 2 diabetes, researchers at the University of British Colombia put mice on a high-carb, high-fat diet. The outward symptoms of type two diabetes quickly followed. The mouse became obese, intolerant to blood sugar (blood glucose), and immune to blood insulin. Their glucose levels increased.

Next followed the attempt to change the elicited diabetic state. The team of researchers cultured human embryonic stem cells and organized them to be properly implanted into the diabetic mouse.

As soon as they were transplanted, the stem cells slowly and gradually grew into insulin-producing cells during the period of a couple of months.

After three months, the rodents’ symptoms began to improve. Among various other changes, the mice recuperated some of their ability to regulate blood sugar levels. After six months, the improvements were considerable.

However, stem cells were not enough to reverse the diabetic state which is why the researchers also turned to antidiabetic medicines.

The authors used metformin (Glucophage), which decreases the rate at which the renal system produces blood sugar, and sitagliptin (Januvia), which reinforces blood insulin production and manages blood glucose.

The combination of antidiabetic medicines and stem cell transplants significantly boosted the mouse’s ability to process blood sugar.

The sitagliptin showed the best outcomes. Diabetic mice treated with sitagliptin and stem cells showed the same reactions after consuming carbohydrates as the non-diabetic mouse on the low-fat diet.

A New Pandemic

Diabetes mellitus affects about 385 million people around the world and at least 20 million people in the USA.

In the United States, diabetes mellitus treatment costs the healthcare industry about $612 billion, or 14 % of all healthcare budget for adults.

Without proper treatment and management, diabetes can lead to blindness, kidney failure, and gangrene resulting in arm or leg amputation. The WHO (World Health Organization) says that diabetes could be the 7th major cause of death by 2030.


Benefits of quitting smoking offset weight gain in people with diabetes


Credit: Pixabay.

It’s normal for people who’ve just quit smoking to gain weight. Being overweight or obese can lead to diabetes, and both smoking and diabetes are risk factors for heart attacks and strokes. So, it seems like there are also health risks to quitting smoking. But according to a new study, the health benefits of quitting smoking far outweigh the risks that come with gaining a few extra pounds.

Smoking tobacco suppresses appetite and increases your metabolism. When you quit smoking, your appetite and metabolism return to normal, which may lead you to eat more and burn fewer calories. Taste and smell also improve so food might become more appealing once you quit smoking.

A 2015 study found that the amount of weight gain following smoking cessation depends on the number of cigarettes a person puts off. Heavy smokers and those who were obese before taking on smoking are especially vulnerable, gaining up to 10kg (22 pounds) on average after quitting.

Researchers at the Harvard T. H. Chan School of Public Health in Boston wanted to see which is worse for people with diabetes: the weight gain from quitting smoking or all the cardiovascular problems arising from smoking itself? They analyzed data from two previous studies, including 10,895 men and women with diabetes.

Compared to individuals with diabetes who continued smoking, those who quit experienced a significantly lower risk for heart attacks, stroke, and other cardiovascular diseases. The risk for cardiovascular disease was 34% lower among recent quitters (six or fewer years since quitting) without weight gain, 25% lower among long-term quitters (more than six years since smoking cessation), and 41% lower among never-smoking adults with diabetes. Those who gained up to 5kg (11 pounds) after quitting smoking saw no increase in the risk of developing cardiovascular disease.

“Weight gain concerns should not stop people from being encouraged to quit smoking after they’re diagnosed with diabetes. And for those who do quit, preventing excessive weight gain would further maximize the health benefits of smoking cessation,” said Gang Liu, lead author of the study.

People who have just quit smoking are advised to exercise often, make wiser food choices (smaller portions and limiting sweets and alcohol), and work with a dietitian for personalized weight management support.

The findings were presented this week at the American Heart Association’s Epidemiology and Prevention: Lifestyle and Cardiometabolic Health Scientific Sessions 2019. A second study presented at this conference investigated the link between cognitive decline and smoking. Researchers at the Bloomberg School of Public Health at Johns Hopkins in Baltimore found that compared to individuals who never smoked, those who smoked a pack of cigarettes a day for 25 years or more had twice as severe signs of cognitive impairment — such as poorer performance of memory, reasoning, and other mental functions.

7 popular medical myths that need to go away

Despite the remarkable advancements in medical science, a large number of myths still plague the world of medical science. Here, we’ll have a look at some of the most common ones and see where the reality really stands

Supplements are always healthy

It is often assumed that if there is a deficit in the nutritive value of the food that is being consumed, then an artificial supplement can compensate and ensure normal functionality in the body. However, recent studies have shown that in most cases, the most popular medical supplements offer no benefits.

Furthermore, exaggerated reliance on these supplements can cause unpleasant long-term side effects. Other than being expensive, they make the body dependent and alter the normal functionalities of the body. Instead of consuming supplements, a person should aim at altering their diet and lifestyle to overcome the deficit of essential nutrients.

You need to drink 8 glasses of water a day

The human body is made up of 60% water and staying well hydrated is essential. However, the 8 glasses myth comes from a fundamental misunderstanding of some basic physiology. There is no real advantage to drinking more water than you need, and different bodies need different quantities of water (also depending on external factors such as temperature, sweating, etc). It also depends a lot on other liquids you might be consuming (such as soups or juices). So while 8 glasses might be a good ballpark figure, it’s by no means a strict limit.

Our body is good at signaling when it requires water. So essentially, you should “listen” to your body. The National Academies of Sciences, Engineering, and Medicine determined that an adequate daily fluid intake is about 15.5 cups (3.7 liters) of fluids for men and about 11.5 cups (2.7 liters) of fluids a day for women.

Cracking knuckles may lead to arthritis in old age

A liquid known as synovial fluid is present in the joints to lubricate them. When we crack our knuckles, the bubbles pop in the synovial fluid. This mechanism bears no relation or has no contribution to the inflammation in the joints due to arthritis.

Be advised, however, that while there’s no evidence that cracking your knuckles will cause arthritis, it can be quite annoying to the people around you.

Physical exercise is only good to build muscles

A rigorous exercise routine doesn’t only affect the muscles growth and strength but also helps the bones in becoming sturdier, improve your blood circulation, and has a myriad other beneficial effects on your body.

Strenuous exercises such as brisk walking, rock climbing, running, swimming, and trekking also work to build strength in the bones and exercising regularly also delays the onset of loss of bone density in old age.

All painkillers are not addictive

Chronic pain affects over one-third of all Americans and many manage that pain through prescription medication. In the US, the FDA mandated potentially addictive substances to be labeled, and many other countries have similar labeling systems — in India, for instance, all medicines that are addictive in nature are classified under the category of Schedule H.

This classification is mentioned on the medicine packaging. Almost all painkillers such as Ultracet have elements that have addictive aptitudes. It is quintessential to consult a doctor before taking any such medicine.

Eating a lot of sugar causes diabetes

Sugar doesn’t cause diabetes — though the two are correlated. Eating a lot of sugar is one of the main contributors to being overweight or obese. Diabetes is caused mainly by lifestyle disorders such as being overweight. So while there is no direct relation between consuming a lot of sugar and having diabetes, there could very well be an indirect one.

Managing weight and maintaining a good and healthy lifestyle ensures that a person does not have increased risks of acquiring diabetes.

Credit: Pixabay.

Insulin shortage to affect 40 million people by 2030

The rate at which people are developing diabetes has experts worried that we will not be able to keep up with the demand for insulin. According to a new study performed at Stanford University, 40 million people with type 2 diabetes won’t have access to the life-saving hormone by 2030.

Credit: Pixabay.

Credit: Pixabay.

In 1980, around 5% of adults around the globe had diabetes. Today, that figure almost doubled at roughly 9% — and global population has also swollen by another three billion individuals.

Sanjay Basu, Stanford Assistant Professor of Medicine, and colleagues, modeled the prevalence of type 2 diabetes in 221 countries between 2018 and 2030. The historical data that they used for their projections come from 14 studies that involved 60% of all people with type 2 diabetes around the world.

People with type 1 diabetes require supplemental insulin. Those with type 2 diabetes may eventually need insulin, but not necessarily. Type 2 diabetes is associated with obesity, poor diet, and physical inactivity.

The findings suggest that the total number of type 2 diabetes sufferers will increase by 20%, from 406 million in 2018 to 551 million in 2030. Half of these people would come from China (130 million), India (98 million), and the USA (32 million).

The researchers conclude in the journal The Lancet that of all these diabetes patients, 79 million would actually be in need of insulin to manage their diabetes. However, half of them won’t have access to an adequate supply of insulin, considering current trends.

“These estimates suggest that current levels of insulin access are highly inadequate compared to projected need, particularly in Africa and Asia, and more efforts should be devoted to overcoming this looming health challenge,” Basu said in a statement.

“Despite the UN’s commitment to treat non-communicable diseases and ensure universal access to drugs for diabetes, across much of the world insulin is scarce and unnecessarily difficult for patients to access. The number of adults with type 2 diabetes is expected to rise over the next 12 years due to ageing, urbanization, and associated changes in diet and physical activity. Unless governments begin initiatives to make insulin available and affordable, then its use is always going to be far from optimal.”

Having an accurate projection for insulin demand is important in order to mitigate healthcare risks. The issue is amplified by the fact that the treatment for diabetes is also highly costly — something that may be driven by business interests rather than free market forces. Only three manufacturers control most of the insulin supply of the world, all of which were accused of conspiring to hike prices intentionally. Between 2002 and 2013, the price of insulin tripled although there were only minimal increases in costs associated with the development of the treatment. The authors caution that unless governments intervene to make insulin more accessible and affordable, a huge number of people could risk not having access to life-saving treatment in the future.

“These comprehensive analyses explicitly accounted for a variety of circumstances. Nevertheless, they are based on mathematical models that are in turn based on other mathematical models. They are also based on a variety of assumptions… Such considerations suggest that predictions about the future need to be viewed cautiously. Regardless of these uncertainties, insulin is likely to maintain its place as a crucial therapy for type 2 diabetes, and as such a sufficient global supply needs to be estimated and ensured… Ongoing updates to models such as these that incorporate new data and trends as they accrue, may be the most reliable way of assuring their reliability and relevance to evidence-based care,” Dr. Hertzel Gerstein from McMaster University, who was not involved in the study, commented.

Diabetes drugs may have protective effects against Alzheimer’s

Researchers analyzed brain tissue sourced from people who had both diabetes and Alzheimer’s. The findings suggest that some anti-diabetes drugs that these people used offered protection that kept the neurodegenerative disease from progressing as rapidly as it would have otherwise.

Credit: Pixabay.

Many elderly people with diabetes have brain changes that are hallmarks of Alzheimer’s. Previous studies have suggested that there is a link between the risk of cognitive impairment, dementia, and type 2 diabetes, and there is evidence that an insulin receptor pathway in the brain is associated with Alzheimer’s pathologies, though the mechanism remains unknown.

A while ago, researchers at the Icahn School of Medicine at Mount Sinai in New York led by Vahram Haroutunian — a professor of psychiatry and neuroscience — found that the brains of people with Alzheimer’s who had also undergone treatment for diabetes (insulin or medicine) had reduced brain pathologies.

This time, Haroutunian and colleagues wanted to dive deeper, at the molecular level, to identify the specific pathways that may explain the association between diabetes and Alzheimer’s.

Using a technique that they designed, the team isolated brain capillaries from the brain tissues of 34 individuals who had both Alzheimer’s and type 2 diabetes, and who were treated for both. The researchers specifically focused on endothelial cells that line the inside of blood vessels and form an interface between circulating blood and the rest of the vessel wall.

The team compared the tissues to those of 30 people who had had Alzheimer’s but not diabetes, as well as 19 control subjects that had neither of the two diseases.

The findings suggest that individuals who were treated for both diseases had half as many markers for Alzheimer’s-related molecular changes in the brain’s capillary cells compared to those that only had Alzheimer’s. What’s more, the majority of molecular changes in RNA markers present in Alzheimer’s disease were not encountered in the study group that took medication for diabetes.

“The results of this study are important because they give us new insights for the treatment of Alzheimer’s disease,” said the study’s senior author, Vahram Haroutunian.

“Most modern Alzheimer’s treatments target amyloid plaques and haven’t succeeded in effectively treating the disease,” said Dr. Haroutunian. “Insulin and diabetes medications such as metformin are FDA approved and safely administered to millions of people and appear to have a beneficial effect on people with Alzheimer’s. This opens opportunities to conduct research trials on people using similar drugs or on drugs that have similar effects on the brains’ biological pathways and cell types identified in this study.”

The findings appeared in the journal PLOS One.

Pancreatic cells islets.

Pancreatic cells can naturally morph to combat diabetes, pointing to new avenues of treatment

An old cell can learn new tricks!

Pancreatic cells islets.

Dyed cells in a pancreatic islet.
Image credits Xiaojun Wang et al., (2013) PLOS One.

New research reveals a surprising level of plasticity in pancreatic cells, which morph to maintain proper hormone levels in the blood. The findings suggest that many other specialised cells could hold this ability, pointing the way to new treatment options for conditions that involve massive cellular death.

Class reroll

“What we are showing here is that the state of differentiation of a given cell is not carved in stone. Cell identity, at all stages of life, is modulated by the immediate cellular environment, particularly by inhibitory signals,” says lead author Professor Pedro Herrera from the Université de Genève (UNIGE) Faculty of Medicine. “Cell identity maintenance is therefore an active process of inhibition throughout the life of the cell, and not an intrinsic or passive state of differentiation.”

“This ability of specialized cells to change their function could prove crucial for treating other pathologies that are due to massive or inappropriate cell death, such as Alzheimer’s disease or myocardial infarction”.

The research was born of the team’s interest in diabetes, a disease that involves damage or destruction (through various means) of insulin-producing cells in the pancreas. This dismantles our bodies’ ability to regulate blood-sugar levels, leaving an excess in the blood over long periods of time, which leads to all sorts of complications: blindness, kidney failure, heart attacks, stroke, to name a few. Onset of diabetes is strongly linked to lifestyle. According to the WHO, over 8.5% of adults worldwide suffered from diabetes (both types combined, figures for 2014) and roughly 1.6 million deaths were directly caused by diabetes in 2015. Needless to say, it’s a wide-reaching condition with a severe quality of life impact — so there is a lot of interest in finding a cure.

Pancreatic cells involved in blood-sugar regulation come in three flavors: α (alpha) cells which produce glucagon, β (beta) cells which produce insulin, and δ (delta) cells which produce somatostatin. These cells bunch together in small clusters known as pancreatic islets. Glucagon raises sugar levels in the blood, insulin works to reduce it, and somatostatin is the hormonal equivalent of a manager’s email, governing activity in the pancreas. Diabetes is characterised by the absence of functional β cells, taking away the pancreas’ ability of reining in blood sugar.

In a study published back in 2014, however, Herrera and his colleagues showed that some pancreatic cells can switch their role to supplement the production of insulin if push comes to shove. In mice without β cells, they reported at the time, new insulin-producing cells appear spontaneously. However, it’s not a huge number — only “1 to 2% of α and δ cells”, Herrera explains, —  way too few to fix diabetes.

“Why do some cells do this conversion and others not? And above all, would it be possible to encourage it? These are the questions that are at the heart of our work,” Herrera adds.

To get to the bottom of things, the team analysed gene expression in pancreatic cells before and after the disappearance of β cells in pancreatic tissue. The first finding was that α cells suffer two key modifications: they start over-expressing some genes typically seen in β cells, and some that are characteristic for glucagon-producing α cells. Herrera’s team reports that insulin receptors on the surface of α cells suggests that their functions hinge on this hormone being present as well — hence, their activity is disrupted when β cells are destroyed.

Next, the team transplanted pancreatic islets into healthy mice to see what could coax these cells into morphing. Their hypothesis was that, when faced with hyperglycemia (high blood-sugar), α cells would change roles to address the lack of insulin.

In non-diabetic mice with functional β cells, and without hyperglycemia, some of the transplanted α cells started producing insulin when the β cells died in the grafted islets. This pretty much invalidated the team’s hypothesis, as a conversion was observed without hyperglycemia to act as a cue. The pancreatic environment itself was ruled out as a cause, too, as the grafts were placed in the renal capsule (i.e. outside of the pancreas). The only explanation, the team adds, is that the reprogramming capacity is intrinsic to the very pancreatic islet where these cells are located.

“Thus, in the same graft, only islets without β cells displayed reprogramming. No cell conversion occurred in neighbouring islets containing all their β cells,” says Herrera.

When the team blocked the insulin receptors of α cells in healthy mice, some of them started to produce insulin themselves — suggesting the hormone acts as a sort of ‘business as usual’ signal for α cells, preventing them from changing roles.

“By administering an insulin antagonist drug, we were able to increase the number of α cells that started producing insulin by 1 to 5%. In doing so, these cells became hybrids: they partially, but not fully changed their identity, and the phenomenon was reversible depending on the circumstances influencing the cells. Now that we are beginning to understand the mechanisms of this cellular plasticity, we believe that these adaptive cell identity changes could be exploited in future new treatments,” Herrera concludes.

While the work focused on pancreatic cells, there’s no reason why other specialised cells in the body couldn’t employ similar processes, the team says. More work will be needed to determine which cells can morph this way, and what would encourage them to do so — but, should we succeed, it could lead to new and very powerful treatments against conditions that involve cellular damage and death.

The paper has been published in the journal Nature Cell Biology.

Titanium dioxide nanoparticles.

White paint might be causing a lot of Type 2 diabetes, preliminary research finds

A pilot study from The University of Texas at Austin suggests white paint and Type 2 diabetes might be linked.

Titanium dioxide nanoparticles.

Titanium dioxide nanoparticles.
Image credits University of Turin.

In the mid-20th century, titanium dioxide (TiO2) overthrew lead-based compounds (which were really toxic) as the go-to white pigment. Today, it’s the most widely used white pigment, mixed into everything from food and medication to plastic and paper. We rely on this substance a lot, as we’re producing in excess of 9 million metric tons of the stuff per year.

However, the pigment may not be as harmless as we’ve believed. Preliminary research has found TiO2 crystals embedded in pancreas tissue afflicted with Type 2 diabetes (T2D).

The white tint of diabetes

The team worked with 11 pancreas specimens, 8 from donors with T2D and 3 from donors who didn’t have the condition. The specimens were provided by the Juvenile Diabetes Research Foundation nPOD at the University of Florida at Gainesville.

The last three samples didn’t contain any detectable levels of TiO2 crystals. The 8 specimens with T2D, however, all had TiO2 crystals embedded in their tissues. The researchers report finding over 200 million TiO2 crystallites per gram of TiO2 particles in the specimens of donors with diabetes.

It’s particularly suspicious to find TiO2 crystals in all of the T2D specimens since titanium dioxide doesn’t have any known role in human biology. Furthermore, while plenty of different salts and other metallic compounds have a role to play in our bodies, there is no known role for titanium salt or another type of titanium compound in our biochemistry.

“Our initial findings raise the possibility that Type 2 diabetes could be a chronic crystal-associated inflammatory disease of the pancreas, similar to chronic crystal-caused inflammatory diseases of the lung such as silicosis and asbestosis,” said Adam Heller, the study’s lead author.

Heller is a professor in the McKetta Department of Chemical Engineering in the Cockrell School of Engineering. He has had a life-long career of diabetes research, for which he received the National Medal of Technology and Innovation in 2007.

Statistics from the World Health Organization show that the number of diabetes patients has quadrupled over the past four decades, reaching some 425 million known cases today. T2D represents the majority of these cases.

Although rising obesity rates and higher average life expectancy (which means more people reach old age) are considered the main factors driving this increase in T2D, the team isn’t convinced. Heller suggests that the increased use of titanium dioxide during these past few decades may be a key, if overlooked, driver of the condition.

“The increased use of titanium dioxide over the last five decades could be a factor in the Type 2 diabetes epidemic,” he said.

“The dominant T2D-associated pancreatic particles consist of TiO2 crystals, which are used as a colorant in foods, medications and indoor wall paint, and they are transported to the pancreas in the bloodstream. The study raises the possibility that humanity’s increasing use of TiO2 pigment accounts for part of the global increase in the incidence of T2D.”

The findings, right now, are far from convincing — but they are, potentially, very far-reaching. This was only a pilot study, with a very limited sample; Heller will repeat the study using a larger sample.

The paper “Association of Type 2 Diabetes with Submicron Titanium Dioxide Crystals in the Pancreas” has been published in the journal Chemical Research in Toxicology.

Eggs aren’t really bad for your heart, despite common misconceptions

There is a lot of conflicting evidence when it comes to the health effects of eggs, but a new study found that eating up to 12 eggs a week doesn’t raise cardiovascular risk.

Lead researcher Dr. Nick Fuller from the University of Sydney had participants aim to maintain their weight while embarking on a high-egg (12 eggs per week) or low-egg (less than two eggs per week) diet. The participants’ cardiovascular risk was monitored, and there was no difference between those who ate few or many eggs. Essentially,  at all stages of the research, both groups showed no adverse changes in cardiovascular risk markers

Researchers also report that replacing the “bad” fats with the “good” fats did make a really big difference in terms of cardiovascular risk.

“Despite differing advice around safe levels of egg consumption for people with pre-diabetes and type 2 diabetes, our research indicates people do not need to hold back from eating eggs if this is part of a healthy diet,” Dr Fuller said.

“A healthy diet as prescribed in this study emphasised replacing saturated fats (such as butter) with monounsaturated and polyunsaturated fats (such as avocado and olive oil),” he added.

For those worrying about the extra pounds, researchers also have good news: egg consumption had no impact on weight loss or gain. Since the participants suffered from pre-diabetes and type 2 diabetes, monitoring weight evolution was important for the study.

“Interestingly, people on both the high egg and low egg diets lost an equivalent amount of weight – and continued to lose weight after the three month intended weight loss phase had ended,” Fuller said.

Researchers also comment that because of the mixed opinions people have of eggs, they often tend to overlook the nutritional benefits of eggs.

“While eggs themselves are high in dietary cholesterol – and people with type 2 diabetes tend to have higher levels of the ‘bad’ low density lipoprotein (LDL) cholesterol – this study supports existing research that shows consumption of eggs has little effect on the levels of cholesterol in the blood of the people eating them,” Dr Fuller explained.

Studies have found conflicting results about a possible connection between egg consumption and type two diabetes. A 1999 prospective study of over 117,000 people by the Harvard School of Public Health concluded, in part, that “The apparent increased risk of CHD associated with higher egg consumption among diabetic participants warrants further research.” A 2008 study wrote that the “data suggest that high levels of egg consumption (daily) are associated with an increased risk of type 2 diabetes.” However, a further study from 2010 found no connection between eggs and diabetes. Two meta-analyses also reported conflicting results.

This latest study seems to suggest that eggs are indeed harmless if consumed in moderation, but that’s unlikely to quench this debate anytime soon.

The study was published in the American Journal of Clinical Nutrition.

Intensive weight management can put type 2 diabetes into remission

After the intensive program, patients lost 10 kg (22 pounds) on average and half of them reverted to a non-diabetic state without any diabetes treatment whatsoever.

Image credits: Tero Vesalainen.

Type 2 diabetes is a chronic, lifelong condition where the body doesn’t produce enough insulin or the cells stop responding to insulin, leading blood sugar to rise to dangerously high levels. Almost 90% percent of the people suffering from it are overweight or obese, and there’s a very tight connection between extra pounds and diabetes. Worldwide, type 2 diabetes incidence has quadrupled, rising from 108 million in 1980 to 422 million in 2014 and showing no sign of stopping. The world is eating unhealthily and it’s paying the price for it. Heavy medication can keep the disease under control, but Scottish researchers had a different idea: if the problem lies in the diet, the solution might also be there. So they implemented an aggressive diet to 298 adults aged 20-65 years who had been diagnosed with type 2 diabetes. Results were encouraging to say the least.

“Our findings suggest that even if you have had type 2 diabetes for 6 years, putting the disease into remission is feasible”, says Professor Michael Lean from the University of Glasgow who co-led the study. “In contrast to other approaches, we focus on the need for long-term maintenance of weight loss through diet and exercise and encourage flexibility to optimise individual results.”

Rather surprisingly, diet and lifestyle are rarely discussed as a treatment for diabetes. Even when they are discussed, the focus is more on what you should and shouldn’t eat, not on how much you should eat. The root cause, unfortunately, is often ignored.

“Rather than addressing the root cause, management guidelines for type 2 diabetes focus on reducing blood sugar levels through drug treatments. Diet and lifestyle are touched upon but diabetes remission by cutting calories is rarely discussed”, explains Professor Roy Taylor from Newcastle University, UK, who co-led the study.

So researchers started by changing the diet of the patients. It wasn’t a simple diet to follow, as they were only allowed to consume 825-853 calories/day for 3 to 5 months — for comparison, sedentary men and women burn around 2,400 and 2,000 calories per day, respectively. After a period, patients were gradually reintroduced to a normal diet. They were also offered support for weight loss maintenance, including cognitive behavioral therapy combined with strategies to increase physical activity. For this entire period, all diabetes and blood pressure-lowering drops were completely stopped.

Image credits: Blue Diamond Gallery.

Interestingly, the program was considered acceptable by most participants. Dropout rate was 21%, but it was mostly caused by social reasons (i.e. moving to a different city or starting a new job). The results were truly impressive.

The average weight loss was 10 kg, but a quarter of participants dropped 15 kg (about 33 pounds) or more. The remission rate was also tightly connected to the weight loss rate. For instance, half of all participants were diabetes-free by the end of the study, but 9 out of 10 participants who lost 15 kg or more went into remission. Researchers note that the patients were white and British, so the same findings may or may not carry on to other types of people.

Even so, the results are truly encouraging, and there is a good chance they do pass on to other populations. The fact that simply losing weight (which also reduces your risk of cancer, cardiovascular diseases, and many other health issues) gives people a great chance of getting rid of diabetes, should give many people hope. Now, all we need to do is convince people to lose weight and not gain it back. Professor Taylor concludes:

“Our findings suggest that the very large weight losses targeted by bariatric surgery are not essential to reverse the underlying processes which cause type 2 diabetes. The weight loss goals provided by this programme are achievable for many people. The big challenge is long-term avoidance of weight re-gain. Follow-up of DiRECT will continue for 4 years and reveal whether weight loss and remission is achievable in the long-term.”

The study was published in The Lancet.


Broccoli-derived compound could become a new treatment for type 2 diabetes

A concentrated extract obtained from broccoli has been found to reduce blood sugar levels by up to 10% in patients with type 2 diabetes, and could provide an unexpected but indispensable treatment for the condition.


The real bro when fighting type 2 diabetes.
Image credits Engin Akyurt.

Patients suffering from type 2 diabetes see their body’s production of and response to insulin — the hormone that regulates glucose levels in the blood — severely limited or dropping down to almost zero. Needless to say, this does not make for good news, and the condition is associated with a host of symptoms you don’t want — from increased thirst, kidney problems, increased chances of heart attacks and wounds which don’t heal to blindness and loss of limbs.

The go-to drug prescribed to keep the condition in check is metformin, which works by lowering glucose production and so its concentration in the blood. The caveat, however, is that metformin goes really hard on your kidneys, preventing roughly 15% of patients from using this drug as they risk irrevocable damage to the organs.

Eat your greens

While a diet rich in plants has been shown to help prevent diabetes, broccoli seems to be especially good at it. Some time ago, a chemical found in the sprouts called sulforaphane was found to reduce glucose levels in diabetic rats. A team of researchers led by Anders Rosengren of the University of Gothenburg in Sweden, now found that its effect also carries over to human patients.

The team gave 97 people with type 2 diabetes either a high concentration dose of sulforaphane daily over a three-months period or a placebo. All but three of the participants had prescriptions for metformin and continued to take the drug during the trial. Those three could control their condition relatively well without metformin. The dose of sulforaphane the team used was about one hundred times more concentrated than that in broccoli.

“It was the same as eating around five kilograms [11 pounds] of broccoli daily,” says Rosengren.

The team found that on average, participants who received sulforaphane had 10% lower blood glucose levels those in the control group (who received placebos). The largest drop was reported for obese participants with “dysregulated” diabetes, whose baseline glucose levels were the highest. While 10% might not sound like much, it’s enough to reduce the chances of complications developing in the eyes or kidneys, the team reports.

They also found that sulforaphane lowers blood glucose levels in a completely different way from metformin. The latter makes cells more responsive to insulin, making them clear more of the surplus sugar from the blood. Sulforaphane, by contrast, lowers the quantity of the sugar injected into the bloodstream in the first place by suppressing the activity of liver enzymes which drive glucose production.

Because they work on different ‘ends’ of the problem, the team is confident that the two drugs could be used to complement each other. Alternatively, sulforaphane can be used as a substitute for metformin in patients who can’t take the drug fearing kidney complications. Finally, as it lowers glucose production, sulforaphane could help pre-diabetic patients avoid the condition altogether. Coupled with other emerging treatments, we may be close to overcoming type 2 diabetes.

The team is now working with the Swedish Farmers’ Association to seek approval for the broccoli powder to be used as a drug.

The full paper “Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes” has been published in the journal Science Translational Medicine.


To HEK with diabetes: new cell capsule could treat the condition with 0 insulin shots

A new cell-based treatment for type 1 and 2 diabetes could eliminate the need for constant insulin injections for patients. The method showed its effectiveness in mice trials, and the team hopes to test in on human patients within two years.

Insulin Syringe

Image credits Melissa Wiesse.

The method uses a capsule of genetically engineered cells which is grafted under the patient’s skin. They monitor blood glucose levels and automatically secret and release insulin when needed. This would lead to more reliable and more efficient treatment to the condition than the ones we use now — where patients administer their own insulin. But we’re still a way off from that. The ETG University team behind the new capsule hopes they will obtain a human clinical trial license for the technology in the next two years, with potential commercialization in the next decade.

A growing issue

In 2013, some 24.4 million American adults were estimated to suffer from one form or another of diabetes, and as a rough estimate 10% of them had type 1. This condition usually begins developing in childhood as the body’s immune system starts systematically destroying all the pancreatic beta cells. These cells are the body’s sugar’o’meter, and release insulin to regulate glucose levels in the blood. So without them, patients have to get regular insulin shots or face the risk of hyperglicemia. Type 2 diabetes by contrast, is also usually associated with low levels of insulin but is characterized by high resistance to the hormone. Some type 2 patients also require shots of insulin to keep blood levels in check.

But relying on insulin shots is already showing limitations, and the number of diabetes cases is expected to explode worldwide in the next few decades, according to the team. So a more efficient treatment is required.

“By 2040, every tenth human on the planet will suffer from some kind of diabetes, that’s dramatic. We should be able to do a lot better than people measuring their glucose,” said lead researcher Martin Fussenegger.

Fussengger added that if the technology is green-lighted for human use, diabetes patients could trade daily injections for the implant which would need to be replaced three times per year. It would do a much better job than than the shots which do not perfectly control blood glucose levels leading to complications such as eye, nerve, and heart damage associated with diabetes. Should it pass the trials, the capsule could do a lot of good by treating patients of type 1 diabetes as well as those with type 2 that require insulin shots.

Sweetening the deal

Previous efforts have tried to develop methods of artificially growing pancreatic cells from stem cells. Manufacturing these cells en masse has proven difficult, however, and the cells were prone to dying once introduced in the body.

“They are prima donnas in the cellular context,” he said.

Team thus looked at the more resilient kidney cells for a solution. A type known as HEK cells were grafted with two new genes allowing them to take on the role of pancreatic cells. One of them makes the cells sensitive to glucose levels and the other instructs them to release insulin into the blood after glucose levels rise get too high.

They were tested on mice (who were treated so that they lost all insulin-producing cells). The modified HEK cells were then implanted in porous capsules (think of a teabag) that protected the human cells from the mice’s immune response while allowing insulin to flow out.

The approach was found to be better at regulating blood-sugar levels than pancreatic cells and remained healthy three weeks after implantation.


Even the Daleks are excited at the idea.
Image modified after Radio Times.

“It’s hard to understand why ours should be better than something that evolved for millions of years,” said . “It shows that as engineers, thinking rationally, we can also do a very good job.”

In the study, mice were treated such that they lost all their insulin-producing pancreatic cells. The cells were then implanted into the mice, enclosed in a teabag-like porous capsule that protected the human cells from the mouse immune system, but allowed the hormone to diffuse out. One advantage of this approach is that the cells don’t have to be genetically matched to the patient. Capsules could be produced and frozen on an industrial scale, to be used whenever needed.

The full paper “β-cell–mimetic designer cells provide closed-loop glycemic control” has been published in the journal Science.