In an analysis of information on adults with colorectal cancer, patients who also had diabetes, particularly those with diabetic complications, faced a higher risk of early death. The results are published in CANCER, a peer-reviewed journal of the American Cancer Society.
For the study, Kuo‐Liong Chien, MD, PhD, of National Taiwan University, and his colleagues examined data registered between 2007 and 2015 in the Taiwan Cancer Registry Database, which is linked to health insurance and death records. Their analysis included 59 202 individuals with stage I–III colorectal cancer who underwent potentially curative surgery to remove their tumours. Among these patients, 9448 experienced a cancer recurrence and 21 031 died from any cause during the study period.
Compared with individuals without diabetes, those with uncomplicated diabetes were at a minimally or insignificantly higher risk of all‐cause and cancer‐specific death, whereas those with complicated diabetes had 85% higher odds of death from any cause and 41% higher odds of death from cancer. These associations were more pronounced in women and in patients with early‐stage colorectal cancer.
Also, compared to patients without diabetes, patients with uncomplicated or complicated diabetes had a 10–11% higher risk of colorectal cancer recurrence.
The mechanisms behind the relationship between diabetic severity and poor colorectal cancer prognosis could involve various pathways and responses triggered by high insulin and glucose levels in the blood, as well as elevated inflammatory states, which are characteristic of type 2 diabetes.
“While a higher diabetes prevalence was noted in patients with colorectal cancer, the study suggests that coordinated medical care involving multiple specialists can help prevent diabetes complications, potentially improving long-term colorectal cancer oncological outcomes, particularly in women and patients with early-stage cancer,” said Dr Chien.
To reduce the risk of complications, it is important to measure antibodies those with adult onset diabetes, while also considering the levels of these antibodies.
In a study published in the journal Diabetes Care, researchers demonstrate that individuals with Latent Autoimmune Diabetes in Adults (LADA) have an equally high risk of developing cardiovascular disease as people with type 2 diabetes, but a higher risk of developing retinopathy and poorer glucose control. Many also lack adequate treatment.
LADA is a common but relatively unknown form of diabetes. Similar to type 1 diabetes, it is an autoimmune disease characterised by antibodies against insulin-producing cells. It develops in adulthood, and the autoimmune process progresses more slowly than in type 1 diabetes. LADA also shares features with type 2 diabetes, which means those affected risk getting the wrong diagnosis if antibodies are not measured. Incorrect diagnosis can result in inadequate treatment. Previous studies suggest that between five and ten percent of all individuals initially diagnosed with type 2 diabetes actually have LADA. Researchers at Karolinska Institutet, and the Universities of Lund and Helsinki set out to examine the risk of complications in LADA.
Our results emphasise the importance of diagnosing LADA correctly and careful monitoring of glucose control in these individuals, so that treatment can be intensified if needed, thereby reducing the risk of complications.
Yuxia Wei, PhD-student and Sofia Carlsson, senior lecturer, Institute of Environmental Medicine, Karolinska Institutet
According to the study LADA was characterised by fewer metabolic risk factors than type 2 diabetes, such as high blood pressure and high blood lipids. However, a lower proportion of individuals with LADA achieved good glucose control. The lack of glucose control was most evident in LADA patients with high levels of the antibody GADA (glutamic acid decarboxylase antibody). A significant portion of individuals with LADA lacked any glucose-lowering treatment.
The results of the new study are based on the ESTRID study, where researchers followed over 4000 individuals with diabetes, of whom 550 had LADA, for up to 12 years after diagnosis. According to the researchers, it is the most comprehensive study to date regarding the risk of complications in LADA.
Freddie Mercury performing with Queen in 1977. Source: Wikimedia Commons
Music has often been touted as a soothing treatment to aid healing. Now, researchers at ETH Zurich in Basel have come up with another medical approach. They have developed a novel method to get music to make specially designed cells secrete insulin. They found that this works especially well with the bass rhythm “We Will Rock You,” a global hit by British rock band, Queen.
Diabetics depend on an external supply of insulin via injection or pump. Researchers led by Martin Fussenegger from the Department of Biosystems Science and Engineering at ETH Zurich in Basel want to make the lives of these people easier and are looking for solutions to produce and administer insulin directly in the body. Any alternatives must be able to release insulin in controlled quantities on command.
One such solution the scientists are pursuing is enclosing insulin-producing designer cells in capsules that can be implanted in the body. To be able to control from the outside when and how much insulin the cells release into the blood, researchers have studied and applied different triggers in recent years: light, temperature and electric fields.
Equipping cells to receive sound waves
To make the insulin-producing cells receptive to sound waves, the researchers used a protein from the bacterium E. coli. Such proteins respond to mechanical stimuli and are common in animals and bacteria. The protein is located in the membrane of the bacterium and regulates the influx of calcium ions into the cell interior. The researchers incorporated the blueprint of this bacterial ion channel into human insulin-producing cells, letting these cells create the ion channel themselves and embed it in their membrane.
As the scientists have been able to show, the channel in these cells opens in response to sound, allowing positively charged calcium ions to flow into the cell. This leads to a charge reversal in the cell membrane, which in turn causes the tiny insulin-filled vesicles inside the cell to fuse with the cell membrane and release the insulin to the outside.
Turn up the bass
In cell cultures, the researchers first determined which frequencies and volume levels activated the ion channels most strongly. They found that volume levels around 60 decibels (dB) and bass frequencies of 50 hertz were the most effective in triggering the ion channels. To trigger maximum insulin release, the sound or the music had to continue for a minimum of three seconds and pause for a maximum of five seconds. If the intervals were too far apart, substantially less insulin was released.
Finally, the researchers looked into which music genres caused the strongest insulin response at a volume of 85dB. Rock music with booming bass like the song “We Will Rock You,” from Queen, came out on top, followed by the soundtrack to the action movie The Avengers. The insulin response to classical music and guitar music was rather weak by comparison.
“We Will Rock You” triggered roughly 70% of the insulin response within five minutes, and all of it within 15 minutes. This is comparable to the natural glucose-induced insulin response of healthy individuals, Fussenegger says.
Sound source must be directly above the implant
To test the system as a whole, the researchers implanted the insulin-producing cells into mice and placed the animals so that their bellies were directly on the loudspeaker. This was the only way the researchers could observe an insulin response. If, however, the animals were able to move freely in a “mouse disco,” the music failed to trigger insulin release.
“Our designer cells release insulin only when the sound source with the right sound is played directly on the skin above the implant,” Fussenegger explains. The release of the hormone was not triggered by ambient noise such as aircraft noise, lawnmowers, fire brigade sirens or conversations.
Ambient noise won’t do
As far as he can tell from tests on cell cultures and mice, Fussenegger sees little risk that the implanted cells in humans would release insulin constantly and at the slightest noise.
Another safety buffer is that insulin depots need four hours to fully replenish after they have been depleted. So even if the cells were exposed to sound at hourly intervals, they would not be able to release a full load of insulin each time and thereby cause life-threatening hypoglycaemia. “It could, however, cover the typical needs of a diabetes patient who eats three meals a day,” Fussenegger says. He explains that insulin remains in the vesicles for a long time, even if a person doesn’t eat for more than four hours. “There’s no depletion or unintentional discharge taking place.”
As a proof of concept only, clinical application is a long way off, but it shows that genetic networks can be controlled by mechanical stimuli such as sound waves. Whether this principle will ever be put to practical use depends on whether a pharmaceutical company is interested in doing so. It could, after all, be applied broadly: the system works not only with insulin, but with any protein that lends itself to therapeutic use.
Diabetes and muscle function might seem like they don’t have much to do with each other. But University of Utah Health researchers have discovered that metformin can also prevent muscle atrophy and muscular fibrosis – which can help the elderly bounce back faster from injury or illness. Their findings were published in the journal Aging Cell.
Metformin, the researchers found, actually has surprising applications on a cellular level. It can target senescent cells which impact muscle function. Senescent cells secrete factors associated with inflammation that may underlie fibrotic tissue, a hardening or scarring of tissues. They also discovered that metformin also reduces muscle atrophy.
“We’re interested in clinical application of this research,” says Micah Drummond, PhD, senior author of the study and professor of physical therapy and athletic training at the College of Health. “For example, knee surgeries in the elderly are notoriously hard to recover from. If we give a metformin-type agent during the recovery period, could we help the muscles get back to normal faster?”
Reinvigorating muscle recovery
Ageing comes with the risks of falls, hospitalisation, or developing chronic disease, which are more likely with muscle disuse. The research team wanted to find a therapeutic solution that could properly target both disuse atrophy and muscle recovery.
There’s an optimal level of senescent cells that are beneficial, no matter your age. In younger, healthier people, short-term senescence is required for a proper recovery from injury, and completely blocking the senescent effect impedes the body’s efforts to heal. Typically, a younger person can bounce back more easily after muscle disuse without the use of an intervention such as Metformin.
“In the case of aging, we know that there’s immune dysfunction,” says Drummond. “As you get older, it becomes harder for your body to clear senescent cells and they accumulate. That’s one reason recovery is much slower for the elderly after periods of disuse.”
Metformin’s anti-senescent properties have been demonstrated through pre-clinical studies. To test the intervention in humans, the team recruited 20 healthy male and female older adults for a multi-week study. They had participants undergo a muscle biopsy and MRI before the intervention, which involved five days of bed rest. One group of 10 received metformin and the other 10 received placebo pills during a two-week run-in period, then each group continued the placebo or metformin treatment during bed rest.
After the bed rest, participants received another muscle biopsy and MRI, then ceased treatments. All patients completed a seven-day re-ambulation period followed by a final muscle biopsy.
“We saw two things in our study,” Drummond says. “When participants took Metformin during a bed rest, they had less muscle atrophy. During the recovery period, their muscles also had less fibrosis or excessive collagen. That build-up can make it harder for the muscle to properly function.”
Tying these results to senescence, the research team examined muscle biopsies from study participants. They found that the participants who took Metformin had fewer markers of cellular senescence.
“This is the first paper that has made the direct connection between a therapy targeting cellular senescence and improved muscle recovery following disuse in aging,” says lead author Jonathan Petrocelli, PhD He explains that metformin helps muscle cells better remodel and repair tissue during periods of recovery after inactivity.
“Our real goal is to have patients maintain their muscle mass and function as they age, because atrophy and weakness are some of the strongest predictors of disease development and death,” he says.
Drummond’s team is following up on these findings by examining combining the drug with leucine, an amino acid that promotes growth and could accelerate recovery even further. They’ve already demonstrated the potency of this combination in preclinical animal studies.
“Metformin is cheap, effective and quite safe, so it’s exciting to see that we can use it to accelerate recovery for older individuals,” adds Drummond.
Research team led by Joshua Pearce has developed a new 3-D printed, completely open-source autoinjector for a tenth of the cost of a commercially purchased product. (Photo by Anjutha Selvaraj)
A new study published in PLOS One describes the development of a spring-driven autoinjector for the delivery of insulin and other medications. This device, made from a combination of 3D-printed and commercially available parts, could cost less than $7 to make while a store-bought version is closer to $70.
Sir Frederick Banting was an inspiration for a new open source self-administering drug delivery device. Long before open source was an option or even a concept, the now-celebrated former University of Western Ontario lecturer refused to patent insulin because he wanted it to be inexpensive and widely available for the betterment of all.
A century after Banting won the Nobel Prize for his discovery, Western researchers led by engineering and Ivey Business School professor Joshua Pearce has developed a new 3D printed, completely open-source autoinjector – a device designed to deliver a single dose of medicine – for a tenth of the cost of a commercially purchased product.
“I think of this device, like so much of what we’re doing here at Western, very much as following the golden rule: do unto others as you would have them do unto you,” said Pearce. “It makes the world slightly better to have an open-source version of an autoinjector, especially for people who don’t have access or the financial means to purchase a proprietary one.”
Autoinjectors are used all over the world by health care practitioners, patients and parents (for children under 12) to inject insulin into people with diabetes. Other chronic conditions such as psoriasis, multiple sclerosis and rheumatoid arthritis can also be treated using an autoinjector. The device is also essential during emergency conditions for migraine, anaphylaxis and status epilepticus patients, as well.
Pearce, along with research assistant Anjutha Selvaraj and post-doctoral associate Apoorv Kulkarni, have created the new open-source autoinjector to make the device – considered more reliable and easier to operate than a simple syringe for self-administering medications into the body – an equitable alternative to the more expensive options.
Studies show self-administration of medications by patients improves compliance and comfort and empowers patients as they are actively involved in their personal care. It also allows patients to avoid time-consuming and costly visits to the hospital, which is a bonus for overburdened health care systems.
And, as with all open-source hardware, there is money to be made as the digitally replicable device enables low-cost distributed manufacturing. All materials, designs and assembly instructions are also detailed in the new study, and the effectiveness of the autoinjector is tested against the current standard (ISO 11608-1:2022) for needle-based injection systems. It is released with an open source hardware license. Companies wishing to commercialise the device will still need to meet their own local regulatory requirements.
“Does this design make it possible for other people to commercialise it anywhere in the world? Yes, it does,” said Pearce. “But more importantly, it means we can really target isolated communities, whether they’re in northern Canada, Africa or anywhere in else in the world, and improve health care access for everyone.”
Having only one or two alcoholic drinks per day does not protect against endocrine conditions such as obesity and type 2 diabetes, according to a new study published in the Journal of Clinical Endocrinology & Metabolism.
It is widely accepted that excessive alcohol consumption causes a wide range of health issues and is thus a major public health concern. Whether modest alcohol consumption has beneficial health effects remains controversial, however, due to the limited power of observational studies.
The researchers used mendelian randomisation (MR), which can help to mitigate biases due to confounding and reverse causation in observational studies, and evaluate the potential causal role of alcohol consumption.
“Some research has indicated that moderate drinkers may be less likely to develop obesity or diabetes compared to non-drinkers and heavy drinkers. However, our study shows that even light-to-moderate alcohol consumption (no more than one standard drink per day) does not protect against obesity and type 2 diabetes in the general population,” said Tianyuan Lu, PhD, from McGill University in Québec, Canada. “We confirmed that heavy drinking could lead to increased measures of obesity (body mass index, waist-to-hip ratio, fat mass, etc) as well as increased risk of type 2 diabetes.”
The researchers assessed self-reported alcohol intake data from 408 540 participants in the U.K. Biobank and found people who had more than 14 drinks per week had higher fat mass and a higher risk of obesity and type 2 diabetes. An extra drink per week was associated with an increased of 8% for diabetes risk and 10% for obesity risk.
These associations were stronger in women than in men. No data supported the association between moderate drinking and improved health outcomes in people drinking less than or equal to seven alcoholic beverages per week.
Studies have shown that children with autism spectrum disorder (ASD) have an increased risk of obesity. In turn, obesity has been linked to increased risks for diabetes, dyslipidaemia and other cardiometabolic disorders. However, the question of whether or not there is an association between autism, cardiometabolic disorders and obesity remains largely unanswered.
To help provide an insight into the possible link between ASD and cardiometabolic diseases, Texas Tech University researchers conducted a systematic review and meta-analysis. Their findings were published in JAMA Pediatrics.
In this latest meta-analysis, the researchers evaluated 34 studies that included 276 173 participants who were diagnosed with ASD and 7 733 306 who were not. The results indicated that ASD was associated with greater risks of developing diabetes overall, including both type 1 and type 2 diabetes.
The meta-analysis also determined that autism is associated with increased risks of dyslipidaemia and heart disease, though there was no significant increased risk of hypertension and stroke associated with autism. However, meta-regression analyses revealed that children with autism were at a greater associated risk of developing diabetes and hypertension when compared with adults.
Study leader Chanaka N. Kahathuduwa, MD, PhD, said the overall results demonstrate the associated increased risk of cardiometabolic diseases in ASD patients, which should prompt clinicians to more closely monitor these patients for potential contributors, including signs of cardiometabolic disease and their complications.
“We have established the associations between autism and obesity, as well as autism and cardiometabolic disease, including diabetes and dyslipidaemia,” Kahathuduwa said. “We don’t have data to support a conclusion that autism is causing these metabolic derangements, but since we know that a child with autism is more likely to develop these metabolic complications and derangements down the road, I believe physicians should evaluate children with autism more vigilantly and maybe start screening them earlier than the usual.”
Kahathuduwa also believes the study shows that physicians should think twice before prescribing medications such as olanzapine that are well known to have metabolic adverse effects to children with autism.
“Our findings should also be an eye opener for patients with autism and parents of kids with autism to simply be mindful about the higher risk of developing obesity and metabolic complications,” Kahathuduwa added. “Then they can talk with their physicians about strategies to prevent obesity and metabolic disease.”
Kahathuduwa said the next logical step for the collaborative team would be to generate evidence that either supports or rejects causality with regard to the observed associations.
Hypertension and diabetes are known risk factors for stroke, but now a new study shows that the amount of risk may decrease as people age. The study is published in Neurology.
“High blood pressure and diabetes are two important risk factors for stroke that can be managed by medication, decreasing a person’s risk,” said study author George Howard, DrPH, of the University of Alabama at Birmingham School of Public Health. “Our findings show that their association with stroke risk may be substantially less at older ages, yet other risk factors do not change with age. These differences in risk factors imply that determining whether a person is at high risk for stroke may differ depending on their age.”
The study involved 28 235 people who had never had a stroke and were followed for 11 years. Risk factors included hypertension, diabetes, smoking, atrial fibrillation, heart disease and left ventricular hypertrophy. Because of the well-known higher stroke risk in Black people (comprising 41% of participants), race was also considered as part of the assessed risk factors, Howard added.
Researchers followed up with participants every six months, confirming strokes by reviewing medical records.
During the study, there were 1405 strokes over 276 074 person-years. Participants were divided into three age groups. The age ranges for those groups varied slightly depending on the data being analysed by researchers. In general, the younger group included participants ages 45–69, the middle group included people in their late 60s to 70s and the older group included people 74 and older.
Researchers found that people with diabetes in the younger age group were approximately twice as likely to have a stroke as people of similar age who did not have diabetes, while people with diabetes in the older age group had an approximately 30% higher risk of having a stroke than people of similar older age who did not have diabetes.
Researchers also found that people with high blood pressure in the younger age group had an 80% higher risk of having stroke than people of similar age without high blood pressure while that risk went down to 50% for people with high blood pressure in the older age group compared to people of similar age without high blood pressure.
With race/ethnicity as a risk factor, Black participants in the younger age group compared to White participants in that group, a difference which decreased in the older age group. For stroke risk factors such as smoking, atrial fibrillation and left ventricular hypertrophy, researchers did not find an age-related change in risk.
“It is important to note that our results do not suggest that treatment of high blood pressure and diabetes becomes unimportant in older age,” said Howard. “Such treatments are still very important for a person’s health. But it also may be wise for doctors to focus on managing risk factors such as atrial fibrillation, smoking and left ventricular hypertrophy as people age.”
Howard also noted that even where the impact of risk factors decreases with age, the total number of people with strokes at older ages may still be larger since overall risk of stroke increases with age. For example, in the younger age group for hypertension, researchers estimate that about 2.0% of normotensive people had a stroke, compared to 3.6% of hypertensive people. In the older age group, about 6.2% of normotensive people had a stroke, compared to 9.3% of hypertensive people.
A limitation of the research was that participants’ risk factors were assessed only once at the start of the study, and it’s possible they may have changed over time.
The year 2022 finally saw the COVID pandemic petering out, largely through the less-lethal but still highly contagious Omicron variant. Significant strides were made in cancer and Alzheimer’s research, although not without controversy. Amid growing public healthcare challenges in South Africa, the NHI Bill advanced closer to reality.
As Omicron displayed greatly reduced severity compared to prior strains, South African medical experts were some of the first to justify no longer being at ‘code red’. This brought an end to the cycles of lockdowns and travel restrictions characterised by the two previous years.
A number of key medical advances were made during the year for a variety of conditions. Studies showed that administering steroids after COVID hospitalisation with severe inflammation reduced mortality up to one year post-infection.
COVID was found to be linked to a spate of new-onset Type 1 diabetes, but this may just have been due to medical checkups as a result of developing COVID. The rheumatoid arthritis drug auranofin was found to relieve diabetes symptoms. And research suggested a possible way to deliver insulin and cancer drugs orally, by adding a ‘tag’ that lets them enter the bloodstream through the intestines.
The fields of cancer and Alzheimer’s research was rocked by findings of numerous red flags. This controversy did not stop real progress: the first new drug that had any real effectiveness against Alzheimer’s disease was confirmed in a historic trial. Fortunately, the flu jab also seems to protect against developing the disease. Indeed, serious infections appear to increase the risk of both Alzheimer’s and Parkinson’s.
In advanced ER-positive, HER-2 negative breast cancers, the new drug capivasertib halved the rate of progression.
Despite lessons learned in the COVID pandemic, South Africa saw the progression of systemic problems in healthcare such as a critical shortage of nurses. Dr Tim de Maayer’s open letter on appalling conditions at Rahima Moosa exposed deep-seated problems in Gauteng’s public healthcare system. This was followed by the shock resignation of top cancer surgeon Professor Carol-Ann Benn. The appointment of Nomantu Nkomo-Ralehoko as Gauteng Health MEC should hopefully change the province’s situation.
A new study using mouse models describes an orally administered small-molecule drug that reduces lowers cholesterol by 70% by preventing the degradation of low-density lipoprotein (LDL) receptors. Published in Cell Reports, the findings point to a previously unrecognised strategy for managing cholesterol – one which may also impact cancer treatments.
“Cholesterol lowering is one of the most important therapies we have to prolong life and protect people from heart disease, which is still the number one cause of morbidity and mortality in the Western world,” said senior author Jonathan S. Stamler, MD, professor at Case Western Reserve School of Medicine.
“Statins only lower cholesterol so far. This is a drug class that we think would represent a new way to lower cholesterol, a new way to hit PCSK9.”
Study Findings
Central to cholesterol regulation are LDL receptors, which sit at the surface of liver cells and remove cholesterol from the blood, thereby lowering serum levels. PCSK9 in the bloodstream controls the number of LDL receptors by marking them for degradation. Therefore, agents that inhibit PCSK9 increase the number of LDL receptors that remove cholesterol.
Nitric oxide is a molecule that is known to prevent heart attacks by dilating blood vessels. In the new study, Stamler and colleagues show that nitric oxide can also target and inhibit PCSK9, thus lowering cholesterol. They identify a small molecule drug that functions to increase nitric oxide inactivation of PCSK9. Mice treated with the drug display a 70% reduction in LDL cholesterol.
Beyond Cholesterol to Cancer
In addition to impacting the field of cholesterol metabolism, the findings may impact patients with cancer, as emerging evidence suggests targeting PCSK9 can improve the efficacy of cancer immunotherapies.
“PCSK9 not only targets LDL receptors for degradation, it also mediates the degradation of MHC 1 on lymphocytes, which is used for recognition of cancer cells” said Stamler. “PCSK9 is effectively preventing your lymphocytes from recognising cancer cells. So, if you inhibit PCSK9, you can boost the body’s cancer surveillance. There may be an opportunity one day to apply these new drugs to that need.”
