Category: Metabolic Disorders

A Surprising Benefit of Dapagliflozin in Patients with Heart Failure

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Dapagliflozin, widely used to treat type 2 diabetes, was shown to improve symptoms and physical limitations in patients with heart failure with preserved ejection fraction, according to clinical trial results reported in Nature Medicine.

Heart failure with preserved ejection fraction (HFpEF) occurs when the heart’s lower left chamber is unable to fill with blood properly. The condition accounts for approximately half of all heart failure cases and disproportionally affects older individuals. Patients with HFpEF can experience a host of debilitating symptoms linked to cardiometabolic abnormalities, including physical limitations, impaired cognition and poor quality of life. Life expectancy is also reduced for patients with this diagnosis, with 50% of patients with the diagnosis not expected to survive more than five years.

Finding ways to improve patients’ health and developing or identifying therapeutic interventions that not only reduce hospitalisation but also improve patient survival is key, the researchers said, but at present there are no available treatments that improve patient survival for patients with HFpEF.

Previous studies have shown that sodium glucose cotransporter 2 (SGLT2) inhibitors – which inhibit SGLT2 receptor proteins produced by the kidneys and are used to treat type 2 diabetes – reduces risk of cardiovascular death and heart failure-related hospitalisation in patients with HFpEF.

For this trial, the researchers measured patient-reported symptoms, physical limitations and function in patients with HFpEF who were taking dapagliflozin, an SGLT2 inhibitor drug.

A total of 324 patients with HFpEF, 56.8% women, were randomised to receive either dapagliflozin or placebo for 12 weeks and at the end of the trial were evaluated using the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, a measure of heart failure-related health status.
“It’s important to note the percentage of women that were enrolled in this study because usually women are under-enrolled in clinical trials,” pointed out study co-author Professor Sadiya Khan.

Compared to the placebo group, an overall improvement in patient-reported symptoms, physical limitations and exercise function was seen in the dapagliflozin group. Adverse events were also similar between both groups, the authors reported.

“It was definitely surprising and very exciting to see such a stark difference between the treatment group and the placebo group, that there was this clear separation that happened even over a short period of time,” Prof Khan said, adding that next steps will be to investigate dapagliflozin’s precise molecular mechanisms that enable its effectiveness.

Source: Northwestern University

Gaps and Gender Differences in Diabetes Management

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A new study from the University of Eastern Finland revealed there are gaps and gender differences in diabetes management. Type 2 diabetes is often accompanied by elevated cholesterol levels, but many patients do not receive appropriate cholesterol-lowering treatment, according to the study, which appears in Scientific Reports.

Type 2 diabetes is a major risk factor of cardiovascular diseases, such as coronary artery disease and heart failure, as well as premature death. To prevent or at least delay complications, regular health care visits and good control of blood glucose, low-density lipoprotein cholesterol (LDL-C) and other risk factors are needed.

The present study shows that LDL-C control and statin prescriptions remain suboptimal in clinical practice – despite guidelines that consistently recommend treating elevated LDL-C with statins at moderate- to high-intensity. The study drew on electronic health records of 8592 type 2 diabetes patients between 2012 and 2017.

Analysing LDL-C values over time, researchers identified four groups with different trajectories. Most patients (86%) had relatively stable LDL-C values at moderate levels and only a few patients showed a significant increase (3%) or decrease (4%) during the follow-up. However, the second-largest group (8%) consisted of patients with alarmingly “high-stable” LDL-C levels at around 3.9 mmol/L.  

The “high-stable” LDL-C group had the lowest proportions of patients on moderate- and high-intensity treatment as well as any statin treatment. The proportion of patients receiving any statin treatment even decreased from 42% to 27% among men, and from 34% to 23% among women between 2012 and 2017.

“We observed significant gender differences in care processes and outcomes,” said Laura Inglin, Early Stage Researcher, University of Eastern Finland. “In all the trajectory groups, women had significantly higher average LDL-C levels and received any statin treatment and high-intensity treatment less frequently than men.”

Significant differences were seen in terms of longitudinal care processes, outcomes, and treatments, pointing out gaps in current diabetes management. Efforts to control LDL-C should be increased – especially in patients with continuously elevated levels – by initiating and intensifying statin treatment earlier and re-initiating the treatment after discontinuation if possible.

Source: University of Eastern Finland

Mirror, Mirror on the Wall…

Instead of being negatively impacted when looking in the mirror, it may in fact help positively alter behaviour in individuals with obesity, according to an analysis published in the Journal of Clinical Nursing.

The analysis examined the results of five studies that included 16 to 941 participants each. The results indicated that the mirror can be used to decrease anxiety and body dissatisfaction. Furthermore, investigators noted that when individuals spend a few minutes gazing at themselves in a therapeutic environment, they may attain self‐awareness that will elicit a positive change in their behaviour.

“Self-assessment and reflection are key to overall wellbeing. Our review hopes to introduce the mirror as a healthcare tool to combat obesity,” said lead author Harriet Omondi, MSN, FNP-C, of Texas Woman’s University.

Source: Wiley

DIY Artificial Pancreas Gets Expert Nod of Approval

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More than 40 healthcare professionals and legal experts have issued the first guidance of its kind to support people with type 1 diabetes using Do-it-Yourself (DIY) technology driven systems to manage their condition.

The paper sets out recommendations that allow health-care professionals to support DIY artificial pancreas systems as a safe and effective treatment option for type 1 diabetes.

Published in The Lancet Diabetes & Endocrinology and endorsed by nine professional diabetes organisations including the International Diabetes Federation. Patients say using the technology has been a “revolution and a revelation” which has had positive impacts on their wider health.

Study co-lead Dr Sufyan Hussain, a consultant diabetologist and honorary senior lecturer from King’s College London, who has lived with type 1 diabetes for over 30 years says: “The medical and legal position of do-it-yourself and citizen science approaches have been subject to a lot of debate and uncertainty. This paper not only clarifies the position for do-it-yourself artificial pancreas systems in diabetes as a safe and effective treatment but sets a precedent for achieving an international professional consensus for other treatments based on user-driven do-it-yourself technologies and innovations.”

Traditional monitoring of type 1 diabetes involves taking blood samples from the fingertips several times a day and calculating precise injections of insulin to maintain blood sugar levels. This can be a time-consuming and stressful method, but over 10 000 people worldwide are using DIY systems, also known as open-source Automated Insulin Delivery (AID) systems. These automatically adjust insulin dosing in response to continuous sensor glucose, insulin pump data and additional information using community generated algorithms. It means that the algorithm can calculate the dosage and administer the dose automatically through conventional insulin pumps.

The authors note that such systems aim to reduce both hypo- and hyperglycaemia, but can also improve glycaemic and long-term health outcomes, reducing diabetes distress and burden, and improving sleep quality.

A limited number of commercial versions of these systems have recently been approved by regulators, but they can be expensive and are accessible only in certain countries. Instead, DIY systems are a product of citizen science that have been co-created by people living with diabetes. These systems are not regulated. However, today’s landmark paper provides professional validation and clear recommendations for their use.

At least 20% of DIY system users are children or adolescents, although use in pregnancy and the elderly is also widely noted. For many families and users, use of an AID system improved quality of life for caregivers, allowing carers to remotely monitor their condition.

However, in common with other insulin-based treatments, these systems are not risk-free, the authors warn. Historically, people living with diabetes had to do their own research on how to build and set up these systems. The paper recommends that clinicians work with individuals living with diabetes or their caregivers to ensure safe and effective use of these systems, and provide guidance on how to achieve this.

At age 15, Dominic Nutt was diagnosed with type 1 diabetes. Now 54, he has a personalised algorithm that automatically controls his glucose monitor and insulin pump. He manages the process through a smartphone, putting in when he eats carbohydrates or exercises, as this affects his blood sugar.
“I’m not a techie at all,” he said, “but since I was diagnosed, I’ve always been excited to try the latest developments as soon as they’re available. A friend put me in touch with someone who could help me to personalise the algorithm to my diabetes and my insulin pump. I then worked with Dr Hussain who helped me to make it work for my diabetes and the technology I was already using.

“It’s been a revolution and a revelation. The swings in my blood sugar have gone. I used to have severe hypos needing emergency care about once every six months – my kids got used to having to talk to the paramedics. Now that never happens, my blood sugar is under control, which has wider health benefits as well, plus I’m feeling fitter and stronger, and I don’t have to eat as much sugar to control my blood sugar.

“The emotional weight that has been lifted is huge. I still have to think about my diabetes sometimes, but it’s not the daily grind it used to be. It’s exciting that now there’s more of an opportunity for others with diabetes to get the kind of personalised advice that I’ve had.”

Source: King’s College London

A Needle-free Way of Blood Glucose Monitoring

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In order to find an alternative to lancets for blood glucose monitoring, researchers applied needle-free jet injection, an emerging but well-developed technique in which a drug is delivered directly with a high-speed narrow jet of fluid.

The study, led by ABI researchers Jiali Xu and James McKeage, demonstrated for the first time that a jet injector could also be used to collect blood samples from humans – that is, release enough blood for glucose sampling, sans needles. The findings appear in the Journal of Diabetes Science and Technology.

Fingertips are the preferred site for blood sampling because they have a high density of blood vessels, they are also sensitive, and pain, skin damage, bruising and risk of infection from regular ‘pricking’ has spurred increasing efforts to develop needle-free methods of blood testing for people with diabetes.

Jet injection, which does not rely on a needle, is an appealing alternative. Jiali Xu of the Auckland Bionengineering Institute (ABI) and her team demonstrated that the technology, using electric motors rather than the standard mechanical spring, could also be used to pierce the skin with a small volume of harmless saline solution, releasing enough blood for glucose concentration measurement.

The study involved 20 healthy participants, each of which received a lancet prick and jet injection on four fingertips through three differently shaped and sized nozzles. “Which were designed to mimic the wound left from a lancet prick, in the anticipation that it might release blood in a way similar to a lancet prick,” said Ms Xu.

Some nozzle shapes performing better than others – a ‘slot’ shaped nozzle released more blood than a circle-shaped nozzle, for instance.

Most of the different jet injection nozzles were generally perceived by the participants, who were unable to see the injections, as no more painful than a standard lancet, and in some cases, less so. A questionnaire was given 24 hours later to assess pain, swelling and bleeding.

People with diabetes may find jet injection more acceptable than using a needle, but the researchers caution against jumping to conclusions. “When you know there’s not a device that is pricking your skin, you could speculate that people will find jet injection more acceptable,” says Professor Andrew Taberner, head of the Bioinstrumentation Lab at the ABI, and Ms Xu’s supervisor. “But we don’t have evidence to back that up. That wasn’t part of this study. We were first trying to find out if it worked, and it did.”

He was pleased, but not surprised. “Diesel mechanics have known for years that you should never put your finger in front of a fuel injector, because it will inject fuel into your finger. They found this out the hard way. But we’re taking advantage of what diesel mechanics discovered accidentally years ago, with a very small amount of harmless liquid, to deliberately release blood.”

The team is now trying to see if they can also extract blood with this technology, allowing for the design of an even smaller nozzle.

Moreover, “our technology has the capability to both deliver and withdraw fluid. No other jet projection technology has that capacity,” said Dr Taberner.

Development and commercialisation of the technology will take time but he believes Ms Xu’s research will contribute to the ultimate aim, of the development of a single lancet-free reversible technology that will allow for both blood sampling and insulin delivery based on the glucose measurement in one device.

“I hope that this research will contribute to that, and the improvement in human healthcare, especially in the management of diabetes,” said Ms Xu.

Source: University of Auckland

Dasatinib May Have Potential as an Antidiabetic Drug

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Dasatinib, a drug that often is used to treat certain types of leukaemia, may have significant potential as an antidiabetic drug, according to new research published in Mayo Clinic Proceedings.

Dasatinib is a tyrosine kinase inhibitor used to treat tumours and malignant tissue, as well as chronic myelogenous leukaemia. Dasatinib is a senolytic drug, which target senescent cells that accumulate in many ageing tissues and at sites of pathology in chronic diseases. Senolytic drugs appear to delay, prevent or alleviate age-related changes, chronic diseases and geriatric syndromes in animal studies.

“Our findings suggest that dasatinib or related senolytic drugs may become diabetic therapies,” said senior author Robert Pignolo, MD, PhD. “More study is needed to determine whether these findings also are observed in patients with type 2 diabetes mellitus but without underlying malignant disease.”

Researchers used records for a total of 9.3 million individuals from 1994 to 2019 who were screened for use of either dasatinib or imatinib, another tyrosine kinase inhibitor that was approved for treatment of a type of leukemia in 2001 but with weak senolytic activity. Of those patients, 279 were treated with imatinib and 118 with dasatinib, and after further screening, a total of 48 patients were included in the study.
The findings show that dasatinib lowers serum glucose in patients with pre-existing type 2 diabetes to a greater extent than imatinib and comparable to first-line diabetic medications such as metformin and sulfonylureas.

More work is needed to determine whether the antidiabetic effect of dasatinib is due largely to its senolytic properties, explained Dr Pignolo. If it is, the effectiveness of combining dasatinib with another senolytic drug such as quercetin may be greater than with dasatinib alone.

“This study was really the first proof-of-concept that a senolytic drug may have substantial long-term beneficial effects in humans,” Dr Pignolo says. “According to research in animal models, it is not necessary to give senolytic drugs continuously, and so patients may need only take a drug such as dasatinib every few weeks, reducing possible side effects.”

Source: EurekAlert!

1 in 20 People with Diabetes Achieve Remission on Their Own

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In Scotland. about one in 20 people  diagnosed with type 2 diabetes achieve remission from the disease, according to research appearing in PLOS Medicine. This suggests people are achieving remission outside of research trials and without bariatric surgery. Recognition of individuals in remission, following their progress, and understanding better the factors linked to remission could result in improved initiatives to help others.

In 2019 there were an estimated 463 million people with diabetes in the world, 90-95% of whom have type 2 diabetes. Ageing populations, growing obesity and sedentary lifestyles are increasing these numbers. The likelihood of achieving remission after 15% weight loss has been shown to be mainly determined by the duration of diabetes, with responders having better beta‐cell function at baseline.

Some people with type 2 diabetes have achieved remission after bariatric surgery, or after taking part in a research trial of a very low-calorie diet, but it is unknown how many people in the general population are in remission. Mireille Captieux at the University of Edinburgh and colleagues used a Scottish national register of people with type 2 diabetes to estimate the number of people in remission in 2019 and described the characteristics of those in remission and not in remission.

Of 162 316 patients aged > 30 who were eligible for the analysis, 7710 (5%) were in remission in 2019. Individuals in remission tend to have not previously taken glucose lowering medication; have lost weight since their diagnosis; be older; have lower blood sugar levels at diagnosis; or have had bariatric surgery. This finding helps to establish a baseline for future studies, and could also help clinicians identify patients with whom to discuss remission and weight loss.

Captieux added, “We have been able to show, for the first time, that 1 in 20 people in Scotland with type 2 diabetes achieve remission. This is higher than expected and indicates a need for updated guidelines to support clinicians in recognising and supporting these individuals.”

Source: EurekAlert!

Using The 5:2 Diet for Weight Loss in Gestational Diabetes

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In a welcome finding, researchers have found that women who have had gestational diabetes can use the popular 5:2 diet for weight loss to help prevent the onset of type 2 diabetes.   

It can be a challenge to lose weight and keep it off, especially for mothers with a new baby. The study by the University of South Australia suggests that the popular 5:2 or intermittent fasting diet is as effective as a conventional energy-restricting diet, giving women greater choice and flexibility for weight loss.

The 5:2 diet allows five days of normal eating each week while substantially restricting calories over two days a week, as opposed to a typical diet that requires moderate energy restrictions daily.

A fifth of pregnancies are affected by gestational diabetes, which carries a ten-fold risk of developing type 2 diabetes later in life, exacerbated even further by being overweight.

A welcome finding for a growing problem
The study’s lead researcher, Dr Kristy Gray, said women looking to lose weight will welcome the finding: “Gestational diabetes is the fastest growing type of diabetes in Australia, affecting 15% of pregnancies.

“Healthy eating and regular physical activity are recommended to manage gestational diabetes, with continuous energy restriction diets – or diets that cut calories by 25–30% being the most common strategy for weight loss and diabetes prevention.

“The trouble is, however, that new mums often put themselves last – they’re struggling with fatigue and juggling family responsibilities – so when it comes to weight loss, many find it hard to stick to a low-calorie diet.

“The 5:2 diet may provide a less overwhelming option. As it only cuts calories over two days, some women may find it easier to adopt and adhere to, as opposed to a consistently low-calorie diet requiring constant management.

“Our research shows that the 5:2 diet is just as effective at achieving weight loss as a continuous energy-restricted diet in women who have had gestational diabetes, which is great, because it provides women with greater choice and control,” she said, adding that women should seek advice from health professionals before starting the diet.

The research investigated the effects of both the 5:2 diet (five days eating normally and two days eating 500 calories) and a continuous energy-restricted diet (1500 calories per day) on weight loss and diabetes risk markers in women with a previous diagnosis of gestational diabetes. Both diets cut energy intake by about 25% a week.

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

Source: University of South Australia

A New, Lasting Diabetes Treatment

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Israeli researchers have come up with a novel approach to the treatment of type 2 diabetes, using an autograft of muscle cells engineered to take in sugar at increased rates.

The disease’s long-term complications include heart disease, strokes, retinal damage leading to blindness, kidney failure, and poor blood flow in the limbs that may result in amputations. Currently a combination of lifestyle changes, medication, and insulin injections are used to treat it, however it is still associated with a 10-year reduction in life expectancy.

Professor Shulamit Levenberg led the study alomg with PhD student Rita Beckerman from the Stem Cell and Tissue Engineering Laboratory in the Technion’s Faculty of Biomedical Engineering. An autograft of muscle cells engineered to take in sugar at increased rates were tested in mice, which displayed normal blood sugar levels for months after a single procedure. The study findings were published in Science Advances.

Muscle cells are among the main targets of insulin, and they are supposed to absorb sugar from the blood. In their study, Prof. Levenberg’s group isolated muscle cells from mice and engineered these cells to present more insulin-activated sugar transporters (GLUT4). These cells were then grown to form an engineered muscle tissue, and finally put back into diabetic mice. The engineered cells not only proceeded to absorb sugar correctly, improving blood sugar levels, but also induced improved absorption in the mice’s other muscle cells through intercellular signalling. After this one treatment, the mice remained cured of diabetes for four months – the entire observation period. Their blood sugar levels remained lower, and they had reduced levels of fatty liver normally seen in type 2 diabetes.

Prof. Levenberg explained how the process worked. “By taking cells from the patient and treating them, we eliminate the risk of rejection.” These cells can easily integrate back into being part of the body and respond to the body’s signaling activity.

An effective treatment, especially as a once-off, could significantly improve both quality of life and life expectancy of those who have diabetes. The same method could also be used to treat various enzyme deficiency disorders.

Source: Technion Israeli Institute of Technology

Sleep is Also Important in Avoiding Overweight in Babies

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While the importance has long been known, little research has examined the necessity of sufficient sleep during the first months of life. New research suggests that newborns who sleep longer and wake up less throughout the night are less likely to be overweight in infancy. Their results are published in Sleep.

“While an association between insufficient sleep and weight gain is well-established in adults and older children, this link has not been previously recognized in infants,” said study co-author Susan Redline, MD, MPH, senior physician in the Division of Sleep and Circadian Disorders at the Brigham. “In this study, we found that not only shorter nighttime sleep, but more sleep awakenings, were associated with a higher likelihood of infants becoming overweight in the first six months of life.”

To conduct this research, Dr Redline and colleagues observed 298 newborns born at Massachusetts General Hospital between 2016 and 2018. The infants’ sleep patterns were monitored using ankle actigraphy watches – devices that measure patterns of activity and rest over multiple days. Researchers obtained three nights’ worth of data at the one- and six-month marks while parents kept sleep diaries, recording their children’s sleep and wake episodes.

Scientists measured infant height and weight and determined their body mass index, classifying infants as overweight if they fell into or above the 95th percentile on the World Health Organization’s growth charts.

Notably, researchers found that just one extra hour of sleep was associated with a 26% decrease in overweight risk. Additionally, infants that woke up less during the night faced a lower risk of excess weight gain. Scientists speculate that having more sleep promotes routine feeding practices and self-regulation, factors that mitigate overeating.

Investigators noted an underrepresentation of African-American individuals and lower-income families in their dataset. Additionally, confounding variables, such as breastfeeding duration, could have impacted infant growth. In the future, the researchers aim to extend this study to evaluate how sleep patterns impact growth within the first two years of life and identify key factors that mediate the correlation between sleep and weight gain. They also aim to evaluate interventions for promoting healthy sleep habits.

“This study underscores the importance of healthy sleep at all ages,” said Dr Redline. “Parents should consult their pediatricians on the best practices to promote healthy sleep, like keeping consistent sleep schedules, providing a dark and quiet space for sleeping, and avoiding having bottles in bed.”

Source: EurekAlert!