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Towards a New Drug Class in the Treatment of Type 2 Diabetes

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Towards a New Drug Class in the Treatment of Type 2 Diabetes 

Type 2 diabetes is a major public health problem that affects millions of people worldwide. Developing new drugs to help better treat its underlying causes is therefore a research priority.

In a new study coordinated by Inserm researcher Vincent Marion in collaboration with Monash University, the University of Birmingham (UK), and Alexander Fleming, former senior endocrinologist at the US Food and Drug Administration (FDA), the scientists have developed PATAS, a peptide that is part of a new class of antidiabetic drugs. PATAS can correct the metabolic abnormalities leading to type 2 diabetes and its associated comorbidities which include insulin resistance(1).

PATAS works by specifically targeting the adipocytes (fat cells) (2), restoring glucose entry and thus correcting and re-establishing the metabolic physiology of the adipose tissue. The teams hope to set up a clinical trial soon to test this new therapy. Their study has been published in the journal Diabetes.

Diabetes mellitus is a chronic condition that affects 537 million people worldwide, with the majority affected by type 2 diabetes. The prevalence of type 2 diabetes, which is characterized by high levels of glucose in the blood (see box), has been increasing for decades due to population aging, inactivity, and poor diet. The age of onset is also decreasing, and although the disease is considered to be an “adult disease”, it is now seen frequently in adolescents and children.

Available drugs treat the consequences of type 2 diabetes by focusing mainly on lowering blood glucose; they do not target the underlying biological mechanism that causes the disease. Despite the urgency for developing new and more effective treatments, there have been no disruptive therapeutic innovations to reach market in over a decade.

And this is precisely the objective of the research led by Inserm researcher Vincent Marion and his team at the Medical Genetics Laboratory (Inserm/Université de Strasbourg). In a recent study in collaboration with the University of Birmingham and Monash University, the scientists have developed a product called PATAS in a new class of diabetes drugs called “Adipeutics” (for therapies that specifically target the adipocytes).

Their study, conducted on animal models, shows that this new therapy specifically restores glucose uptake in the adipocytes, resulting in the treatment of insulin resistance with beneficial effects on the whole body. This is made all the more promising by the fact that treating insulin resistance has the potential to address not only type 2 diabetes but a large array of serious medical conditions that result from this resistance.

 

Type 2 diabetes in brief 

Diabetes mellitus is characterized by excessive blood glucose levels over a prolonged period of time: this is known as hyperglycemia.

Hyperglycemia is caused by a reduced sensitivity of the cells, particularly those in the liver, muscle, and adipose tissue, to insulin. This is known as “insulin resistance.”

Insulin is a hormone produced by the pancreas whose role is to facilitate the entry of glucose into the body cells as their main source of energy.  To meet the increased demand for insulin caused by the cells’ resistance to this hormone, the pancreas produces even more insulin, depleting the body requirements. Insulin production then becomes insufficient and the blood glucose levels rise as a result.

The role of adipocytes 

This study follows on from years of rigorous, in depth work carried out in the lab. In previous research, published in Diabetes in 2020, the scientists had identified a new therapeutic target for type 2 diabetes when investigating at an ultra-rare monogenic disease known as Alström syndrome.

The scientists had shown that adipose tissue abnormalities (3) caused by a dysfunctional protein called ALMS1 led to extremely severe insulin resistance associated with early-onset type 2 diabetes in people with Alström syndrome. In animal models, restoring the function of this protein within the adipocytes re-established blood glucose balance.

The teams then went on to focus more closely on ALMS1 and how it interacts with other proteins within the adipocytes. In particular, they have shown that in the absence of insulin, ALMS1 binds to another protein called PKC alpha. The activation of insulin in the adipocytes induces the separation of these two proteins ALMS1 and PKC alpha, resulting in glucose entry into cells. In people with diabetes, who are insulin-resistant, this link between the two proteins is maintained.

Drawing on this knowledge, the scientists have developed the peptide PATAS, which works by breaking the interaction between ALMS1 and PKC alpha – thus restoring insulin signaling in the adipocytes.

In mouse models of diabetes, PATAS has been able to re-establish the normal physiology of the adipocytes by restoring glucose uptake. “Thanks to PATAS, the adipocytes that could no longer access glucose were once again able to absorb it and then metabolize it in order to synthesize and secrete lipids which are beneficial to the entire body. These positive effects are visible in our animal models, with a marked improvement in insulin resistance. Other parameters and comorbidities are also improved, including better blood glucose control and decreased liver fibrosis and steatosis,” explains Vincent Marion.

These promising results in animals have paved the way for the researchers to organise a clinical trial as soon as possible, in order to test PATAS in humans. The successful development of a new class of antidiabetic drugs could have significant implications for public health, not only to treat type 2 diabetes but also many other cardio-metabolic disorders in which dysfunctional adipocytes and insulin resistance are very problematic.

In order to create value from these findings and facilitate the organization of such a trial, Vincent Marion has founded the start-up AdipoPharma SAS.

 

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Whooping Cough and Pneumonia Cases Surge in NSW, Posing Significant Risk to Children

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Whooping Cough and Pneumonia

Whooping Cough and Pneumonia Cases Surge in NSW, Posing Significant Risk to Children

 

Whooping cough rates have surged to their highest levels in nearly a decade in New South Wales (NSW), and the number of young children hospitalised with pneumonia has more than doubled compared to the same period last year, according to state health data.

Pertussis Cases Reach Alarming Levels

The latest NSW Health respiratory surveillance report reveals that there have been 103.1 notifications of pertussis, commonly known as whooping cough, per 100,000 people in the state so far this year. The last time figures were this high was in 2016, with a rate of 139.6 per 100,000.

Professor Robert Booy, an infectious diseases paediatrician at the University of Sydney, attributes the rise to several viruses and bacteria, including pertussis and mycoplasma, actively spreading, particularly among primary school-aged children.

“Both [pertussis and mycoplasma] are causing pneumonia, leading to hospital admissions, emergency department presentations, and the need for antibiotic treatment,” said Professor Booy.

Public Health Advisory

NSW Health advises individuals to stay home if unwell and to wear a mask if going out is necessary, in an effort to reduce the spread of these respiratory illnesses.

Young People Particularly at Risk

Health data indicates that pneumonia rates among children aged zero to 16 are “unseasonably high” and exceed levels recorded in the past five years. In early June this year, nearly 140 children under the age of four presented to emergency departments with pneumonia, compared to fewer than 60 at the same time last year. For children aged five to 16, the number was 400, up from fewer than 50 last year.

The increase is attributed to a specific strain of pneumonia, commonly referred to as “walking pneumonia.” The report states that Mycoplasma pneumoniae is a frequent cause of pneumonia in school-aged children, with epidemics occurring every three to five years. The last epidemic in NSW occurred before the COVID-19 pandemic.

Expert Insights

Dr. Rebekah Hoffman, chair of the NSW and ACT branch of the Royal Australian College of General Practitioners, noted that while most individuals contracting Mycoplasma pneumoniae would remain “quite well,” they might suffer from a persistent cough for several weeks or months. “For some kids, especially if they are immunocompromised or have other respiratory problems, they might get really sick and need hospitalization,” Dr. Hoffman said.

Both Dr. Hoffman and Professor Booy highlighted that social distancing during the COVID-19 pandemic, particularly in 2020 and 2021, resulted in children not being exposed to other respiratory illnesses, such as whooping cough and pneumonia. Professor Booy explained that the absence of exposure created a group of susceptible young children who are now developing and spreading whooping cough in school and other settings.

Resurgence Patterns

Whooping cough typically surges every three to six years, but due to the pandemic, this interval has now stretched to six to eight years. Dr. Hoffman noted that the spike in respiratory illnesses reflects young people “catching up” on infections they missed in previous years. She expressed surprise at the significant increase in whooping cough rates.

Professor Booy emphasized the seriousness of whooping cough for certain groups, particularly newborn babies. “The children at most risk are the very young… they need protection from their mother being vaccinated during pregnancy to develop antibodies which pass to the baby before it’s even born,” he said.

The health department data also indicated that COVID-19 cases remain “high” in the state.

Conclusion

The surge in whooping cough and pneumonia cases in NSW is a significant public health concern, particularly for young children. Continued vigilance, vaccination, and adherence to public health guidelines are essential to manage and mitigate the spread of these illnesses.

 

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Mental Well-Being Crucial for Healthy Aging, New Study Reveals

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Mental Well-Being HEALTHY AGING

Mental Well-Being Crucial for Healthy Aging, New Study Reveals

 

A recent study published in the journal Nature Human Behaviour has established the significant impact of mental well-being on healthy aging. The research evaluated the causal effects of mental well-being on genetically independent aging phenotypes (aging GIP), providing new insights into the relationship between mental health and aging.

Key Findings:

  • Human Longevity and Challenges: While human life expectancy has increased over time, the aging population poses challenges for both individuals and society. Mental well-being is known to correlate with lifestyle behaviours and morbidity and is linked to physical health and increased survival.
  • Socioeconomic Status (SES) Connection: Socioeconomic status (SES) is interlinked with both aging and mental well-being, but a direct causal relationship between mental well-being and healthy aging had yet to be established until now.

Study Overview:

Researchers utilised Mendelian randomisation (MR) to assess the effects of mental well-being on aging phenotypes. Summary-level genome-wide association study (GWAS) data from people of European descent were used. The exposures included various well-being traits such as life satisfaction, neuroticism, depressive symptoms, and positive affect. SES indicators—education, occupation, and income—were also considered.

A total of 106 candidate mediators were screened, including lifestyle factors, physical function traits, diseases, and behaviours. These mediators were selected based on their causal association with aging GIP and the well-being spectrum.

Methodology:

  • Linkage Disequilibrium Score Regression: This was used to examine genetic correlations between mental well-being traits, aging phenotypes, and SES indicators.
  • Univariable and Multivariable MR Analyses: These analyses were performed to assess the causal effects of mediators and mental well-being traits on aging phenotypes and to investigate the impact of SES indicators on mental well-being traits.
  • Two-Step MR Analysis: This tested the mediating effects between the well-being spectrum and aging GIP.

Results:

  • Genetic Correlations: Positive genetic correlations were observed between all mental well-being traits and aging GIP components (except for longevity). The well-being spectrum was linked to increased aging GIP, resilience, health span, parental lifespan, and self-rated health.
  • Positive and Negative Associations: Positive affect and life satisfaction were positively associated with aging phenotypes, while depressive symptoms and neuroticism were inversely associated.
  • SES and Well-Being: Higher income, education, and occupation were causally linked to improved mental well-being. The well-being spectrum independently correlated with higher aging GIP, even after adjusting for SES indicators.

Mediators:

Out of 106 candidate mediators, 33 met the criteria for inclusion. Key findings included:

  • Unhealthier Lifestyle Factors: These were associated with lower aging GIP.
  • Positive Influences: Factors such as later smoking initiation age, higher cheese consumption, appendicular lean mass (ALM), cognitive performance, high-density lipoprotein cholesterol (HDL-C), and fresh fruit intake were associated with higher aging GIP.
  • Significant Diseases: Heart failure, hypertension, stroke, and coronary heart disease had the highest effect sizes on aging GIP.

Several factors, including antihypertensive medication, smoking initiation age, and television watching time, mediated at least 7% of the effect of the well-being spectrum on aging GIP. Other mediators, such as non-steroidal anti-inflammatory drugs, waist-to-hip ratio, and fresh fruit intake, also played significant roles.

Conclusion

The study illustrated the causal effects of mental well-being on aging phenotypes independent of SES. Better mental well-being was linked to improved aging GIP, with the causal effect partly explained by various mediators, including lifestyle factors, physical functions, diseases, and behaviours. These findings underscore the importance of prioritising mental well-being to promote healthy aging.

 

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Beyond Blue champions peer support for men’s mental health

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men's mental health Beyond Blue

Beyond Blue champions peer support for men’s mental health

 

Beyond Blue is encouraging men to check-in with peers online for early mental health support as part of Men’s Health Week.

The annual week’s theme for 2024 is ‘men’s health checks’, with a focus on encouraging men to adopt new, healthier habits to improve physical and mental wellbeing.

Beyond Blue Clinical Spokesperson Dr Luke Martin said men are less likely than women to seek support for mental health issues and there remains a stigma which can stop them seeking support.

“Many men like to be self-reliant and often try to handle problems on their own and can be reluctant to confide in friends and family about how they are feeling,” Dr Martin said.

“Unfortunately, this can lead to unhealthy coping behaviours, which can result in problems snowballing. Taking steps to get support early on can really help people feel better sooner and anonymous online forums can provide that safe and less confronting option that some men need to open up.”

Research reports the effectiveness of digital peer support models, which provide people with a safe and supportive environment to discuss their issues.

In the digital age, online forums, like Beyond Blue’s Forums are a valuable platform, providing people with a free, accessible, anonymous, welcoming place to discuss their mental wellbeing with those who understand because they have had or are having similar experiences.

Beyond Blue Forums are moderated by trained professionals, together with experienced volunteers known as Community Champions, who ensure the Beyond Blue Forums remain a safe and supportive place, and that everyone who posts a question is heard and responded to.

Now in his mid-70s, Community Champion Mark Davis volunteers approximately 20 hours a week to support others through the Forums.

“In Australia, we’ve been brought up in a culture where men don’t complain, they have traditionally needed to be the strong, stoic ones; and they just want to fix the problems,” Mr Davis said.

“The forums offer anonymity and discretion, allowing men in particular to express themselves openly without fear of judgment or stigma.”

Mr Davis often helps young men to navigate relationship break ups and study stress, and supports mature-age men experiencing depression, relationship problems, are single parents, or worried about family member’s mental health.

“I have Post Traumatic Stress Disorder (PTSD), depression, anxiety and was suicidal, and about 10 years ago, I wanted to see how other people handled the same thing,” he said.

“I had medical support, but I was battling my issues in isolation, so I joined the Beyond Blue Forums, to just look at them; I had no intention of writing anything – and I had no intention of ever using my real name; I simply wanted to see how others were coping with similar mental health issues.”

Dr Martin says getting support early, means you get well sooner and stay well.

“Latest research shows that 40 per cent of users of the service are men; but we encourage more men to reach out to our Forums; whether it’s to take that first step to ask for help, or to complement existing treatment, our team is available whenever you need them.

“By destigmatising mental health conversations and promoting peer support initiatives, we can create a culture where men feel comfortable seeking the support they need to get back on track – no problem is too big or too small to ask for help,” Dr Martin said.

Beyond Blue’s Peer Support Forums average 150,000 visits to the forums every month.

The content is monitored by moderators 24 hours/7 days a week.

Men can also check-up on their mental health using Beyond Blue’s online checklist, and receive recommendations tailored to their need. Beyond Blue Forums. For people who need more immediate support, the Beyond Blue Support Service provides 24/7 free counselling, advice and referrals via phone 1300 22 4636, webchat or email.

 

 

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