Category: Metabolic Disorders

Categories : Metabolic DisordersTags :

Liraglutide Results in Increased Insulin Sensitivity Independent of Weight Loss

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A new Vanderbilt University study published in the journal Diabetes demonstrates that a glucagon-like peptide-1 receptor (GLP-1R) agonist, a member of a class of medication used to treat Type 2 diabetes and obesity, can lead to a rapid improvement in insulin sensitivity.

Insulin sensitivity is how responsive cells are to insulin; reduced insulin sensitivity or insulin resistance is a feature of Type 2 diabetes, so improving it can reduce the risk of developing the disease or improve its treatment.

GLP-1R agonists are medications that influence metabolism, such as decreasing blood sugar levels by promoting insulin secretion. Dipeptidyl peptidase 4 (DPP-4) inhibitors block the degradation of the body’s own endogenous GLP-1, as well as other peptide hormones such as glucose-dependent insulinotropic peptide (GIP).

“We know that GLP-1R agonists promote weight loss, but we were surprised to find that the GLP-1R agonist liraglutide also has rapid effects on insulin sensitivity, independent from weight loss,” said Mona Mashayekhi MD, PhD, assistant professor of Medicine in the Division of Diabetes, Endocrinology and Metabolism.

“This effect requires activation of the GLP-1 receptor, but increasing the body’s own endogenous GLP-1 through the use of the DPP4 inhibitor sitagliptin does not achieve similar effects.”

“Our research suggests that liraglutide, and presumably other GLP-1R agonists, are having important metabolic effects in a way that’s different from increasing endogenous GLP-1 levels, even though they’re using the same receptor. Future research will focus on potential mechanisms of how GLP-1R agonists are improving insulin sensitivity independent of weight loss.”

Eighty-eight individuals with obesity and pre-diabetes were randomized for 14 weeks to receive the GLP-1R agonist liraglutide, the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin, or weight loss without drug using a low-calorie diet.

To further investigate the GLP-1R-dependent effects of the treatments, the GLP-1R antagonist exendin and a placebo were given in a two-by-two crossover study during mixed meal tests.

Crossover studies allow the response of a subject to treatment A to be compared with the same subject’s response to treatment B.

Liraglutide was shown to rapidly improve insulin sensitivity as well as decrease blood glucose within two weeks of beginning treatment and before any weight loss.

“GLP-1R agonists are an exciting class of medications, given their strong glucose-lowering effects combined with tremendous weight-loss benefits, and they have transformed how we manage diabetes and obesity in the clinic,” Mashayekhi said.

“Since the number of medications in this class is rapidly expanding, a deeper understanding of the mechanisms of benefit is crucial so we can design the right drugs for the desired effects in the right patients.”

The investigators’ prior research demonstrated that liraglutide, but not sitagliptin or diet, improves measures of heart disease and inflammation.

This matches the clinical findings of reduced cardiovascular disease with GLP-1R agonist treatment.

Future studies will continue to explore both receptor- and weight loss-dependent effects of GLP-1R agonists in humans.

Source: Vanderbilt University Medical Center

Categories : Mental Health Metabolic DisordersTags :

Feeling Depressed Linked to Short-term Increase in Bodyweight

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Increases in symptoms of depression are associated with a subsequent increase in bodyweight when measured one month later, new research from the University of Cambridge has found.

The study, published in PLOS ONE, found that the increase was only seen among people with overweight or obesity, but found no link between generally having greater symptoms of depression and higher bodyweight.

Research has suggested a connection between weight and mental health – with each potentially influencing the other – but the relationship is complex and remains poorly understood, particularly in relation to how changes in an individual’s mental health influence their bodyweight over time.

To help answer this question, researchers at Cambridge’s Medical Research Council (MRC) Epidemiology Unit examined data from over 2,000 adults living in Cambridgeshire, UK, who had been recruited to the Fenland COVID-19 Study.

Participants completed digital questionnaires on mental wellbeing and bodyweight every month for up to nine months during the COVID-19 pandemic (August 2020 – April 2021) using a mobile app developed by Huma Therapeutics Limited.

Questions assessed an individual’s symptoms of depression, anxiety and perceived stress.

A higher score indicated greater severity, with the maximum possible scores being 24 for depression, 21 for anxiety and 40 for stress.

The team then used statistical modelling to explore whether having poorer mental wellbeing than usual was related to changes in bodyweight one month later.

The researchers found that for every increment increase in an individual’s usual score for depressive symptoms, their subsequent weight one month later increased by 45g.

This may seem small but would mean, for example, that in an individual whose depressive symptoms score rose from five to 10 (equal to an increase from ‘mild’ to ‘moderate’ depressive symptoms) it would relate to an average weight gain of 225g (0.225kg).

This effect was only observed in those individuals with overweight (defined as BMI 25-29.9kg/m2) or with obesity (BMI of over 30kg/m2). Individuals with overweight had on average an increase of 52g for each increment point increase from their usual depressive symptoms score and for those with obesity the comparable weight gain was 71g.

The effect was not seen in those individuals with a healthy weight.

First author Dr Julia Mueller from the MRC Epidemiology Unit said: “Overall, this suggests that individuals with overweight or obesity are more vulnerable to weight gain in response to feeling more depressed. Although the weight gain was relatively small, even small weight changes occurring over short periods of time can lead to larger weight changes in the long-term, particularly among those with overweight and obesity.

“People with a high BMI are already at greater risk from other health conditions, so this could potentially lead to a further deterioration in their health. Monitoring and addressing depressive symptoms in individuals with overweight or obesity could help prevent further weight gain and be beneficial to both their mental and physical health.”

The researchers found no evidence that perceived stress or anxiety were related to changes in weight.

Senior author Dr Kirsten Rennie from the MRC Epidemiology Unit said: “Apps on our phones make it possible for people to answer short questions at home more frequently and over extended periods of time, which provides much more information about their wellbeing. This technology could help us understand how changes in mental health influence behaviour among people with overweight or obesity and offer ways to develop timely interventions when needed.”

Although previous studies have suggested that poor mental health is both a cause and consequence of obesity, the research team found no evidence that weight predicted subsequent symptoms of depression.

The research was supported by the Medical Research Council.

The original text of this story is licensed under Creative Commons CC BY-SA 4.0.

Source: University of Cambridge.  Note: Content may be edited for style and length.

Journal Reference:

  1. Julia Mueller, Amy L. Ahern, Rebecca A. Jones, Stephen J. Sharp, Alan Davies, Arabella Zuckerman, Benjamin I. Perry, Golam M. Khandaker, Emanuella De Lucia Rolfe, Nick J. Wareham, Kirsten L. Rennie. The relationship of within-individual and between-individual variation in mental health with bodyweight: An exploratory longitudinal study. PLOS ONE, 2024; 19 (1): e0295117 DOI: 10.1371/journal.pone.0295117
Categories : Metabolic Disorders Respiratory DiseasesTags :

Why People with Diabetes are More Vulnerable to Respiratory Infection

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Credit: Scientific Animations CC4.0

It has long been known that people with diabetes are at a substantially increased risk of developing severe lung disease if they become infected with viruses such as influenza, as well as other pathogens. When the COVID-19 pandemic started in early 2020, it became even more important to understand this mysterious phenomenon. It became clear that people with diabetes were at a significantly higher risk of coming down with severe, even fatal, lung disease after developing severe COVID, but no one understood why. In fact, some 35% of the pandemic’s COVID mortalities had diabetes.

Now, research conducted at the Weizmann Institute of Science and published in Nature has revealed how, in diabetics, high levels of blood sugar disrupt the function of key cell subsets in the lungs that regulate the immune response. It also identifies a potential strategy for reversing this susceptibility and saving lives.

Prof. Eran Elinav‘s team in his lab at Weizmann, headed by Drs. Samuel Nobs, Aleksandra Kolodziejczyk and Suhaib K. Abdeen, subjected multiple mouse models of types 1 and 2 diabetes to a variety of viral lung infections. Just as in diabetic humans, in all these models the diabetic mice developed a severe, fatal lung infection following exposure to lung pathogens such as influenza. The immune reaction, which in nondiabetics eliminates the infection and drives tissue healing, was severely impaired in the diabetic mice, leading to uncontrolled infection, lung damage and eventual death.

Next, to decode the basis of this heightened risk, the team performed an evaluation of gene expression on the level of individual cells, in more than 150 000 single lung cells of infected diabetic and nondiabetic mice. The researchers also performed an extensive array of experiments involving immune and metabolic mechanisms, as well as an in-depth assessment of immune cell gene expression in infected diabetic mice. In the diabetic mice they identified a dysfunction of certain lung dendritic cells, the immune cells that orchestrate a targeted immune response against pathogenic infection. “High blood sugar levels severely disrupt certain subsets of dendritic cells in the lung, preventing these gatekeepers from sending the molecular messages that activate the critically important immune response,” says Nobs, postdoctoral fellow and study first author. “As a result, the infection rages on, uncontrolled.”

Next, they explored ways to prevent the harmful effects of hyperglycaemia in lung dendritic cells, as a means of lowering the infection’s risk in diabetic animals. Indeed, tight control of glycaemic levels by insulin supplementation prompted the dendritic cells to regain their capacity to generate a protective immune response that could prevent the cascade of events leading to a severe, life-threatening viral lung infection. Alternatively, administration of small molecules reversing the sugar-induced regulatory impairment corrected the dendritic cells’ dysfunction and enabled them to generate a protective immune response despite the presence of hyperglycaemia.

“Correcting blood sugar levels, or using drugs to reverse the gene regulatory impairment induced by high sugar, enabled our team to get the dendritic cells’ function back to normal,” says Abdeen, a senior intern who co-supervised the study. “This was very exciting because it means that it might be possible to block diabetes-induced susceptibility to viral lung infections and their devastating consequences.”

Lung tissue of a diabetic mouse (right) contains fewer immune cells (small purple dots) than that of a non-diabetic animal (left)

With over 500 million people around the world affected by diabetes, and with diabetes incidence expected to rise over the next decades, the new research has significant, promising clinical implications.

“Our findings provide, for the first time, an explanation as to why diabetics are more susceptible to respiratory infection,” Elinav says. “Controlling sugar levels may make it possible to reduce this pronounced diabetes-associated risk. In diabetic patients whose sugar levels are not easily normalized, small molecule drugs may correct the gene alterations caused by high sugar levels, potentially alleviating or even preventing severe lung infection. Local administration of such treatments by inhalation may minimize adverse effects while enhancing effectiveness, and merits future human clinical testing.”

Source: Weizmann Institute of Science

Categories : Metabolic Disorders Obstetrics & GynaecologyTags :

Newer Diabetes Drugs don’t Increase Risk to Foetus

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Newer diabetes medicines do not appear to increase the risk of birth defects. The largest comparative study to date found no increased risk compared to treatment with insulin, which is considered safe during pregnancy. The study was published in JAMA Internal Medicine.

Newer diabetes drugs such as sulfonylureas, DPP-4 inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors are being increasingly used, both in the treatment of diabetes, but also extended indications for several of the preparations. 

However, knowledge of the foetal effects of these drugs is still low, so women with type 2 diabetes are often advised to switch to insulin before a planned pregnancy because it is considered safe. However, not all pregnancies are planned and more and more people are becoming pregnant while being treated with these drugs.

An international research team has now investigated whether the use of these drugs during pregnancy increases the risk of birth defects. The researchers used health data from 3.5 million pregnancies in six different countries (Sweden, Norway, Finland, Iceland, USA and Israel) between 2009 and 2021. Among these 3.5 million women, nearly 52 000 were diagnosed with type 2 diabetes and more than 8000 took one of the newer diabetes drugs in the three months before or after their last menstrual period.

Diabetes itself poses a risk of birth defects. High blood sugar levels in early pregnancy, which are more common in people with diabetes, increase the risk of foetal malformations. Therefore, the researchers were not surprised to see a slightly elevated risk in this group.

Among women diagnosed with type 2 diabetes before pregnancy, 5.3% of babies were born with severe birth defects, including 2.2% with heart defects, compared to the overall group where 3.8% had severe birth defects and 1.3% with heart defects. 

No increased risk of birth defects

However, the researchers found that the women with diabetes treated with the newer diabetes drugs did not have a higher risk of giving birth to children with birth defects than the women with diabetes treated with insulin.

“It has already been shown that insulin is safe to use during pregnancy and that it does not cross the placenta. The increased risk of birth defects in the children of women with type 2 diabetes using the newer diabetes drugs is therefore very likely caused by the disease,” says first author Carolyn Cesta, Associate Professor at the Center for Drug Epidemiology at Karolinska Institutet.

Despite being the largest study in this field to date, covering more than 3.5 million pregnancies, relatively few women used the new diabetes drugs, and the researchers stress that further studies are needed to confirm the results. However, they note that the study still shows that these drugs do not pose a major risk of birth defects.

As type 2 diabetes becomes more common among women of childbearing age and as GLP-1 receptor agonists such as semaglutide (Wegovy, Ozempic) are approved to treat obesity, the number of exposed pregnancies is likely to increase. 

“Our findings provide a first indication of the safety of infants exposed to these medications during pregnancy,” says Carolyn Cesta.

Source: Karolinska Institutet

Categories : Metabolic DisordersTags :

Public Urged To Use Registered Ozempic Products

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Photos supplied by Novo Nordisk

The South African Health Products Regulatory Authority (SAHPRA) is aware of the falsified Ozempic products currently being sold on the market and online.

SAHPRA has been informed of advertisements regarding unauthorised Ozempic/semaglutide-containing products that are being disseminated through radio stations and social media platforms.

The Regulator is warning the public to be wary of products claiming to be Ozempic (semaglutide) which are not approved by SAHPRA.  

Ozempic is a Schedule 4, prescription-only medicine, authorised by SAHPRA only for the treatment of type 2 diabetes mellitus in adults. SAHPRA has not authorised/registered Ozempic for weight-loss, therefore, use in that regard would be off-label. It must be noted that only a healthcare practitioner can make a Schedule 4 product available off-label as they would provide the requisite guidance and support to the patient/individual.

Novo Nordisk South Africa, who is the Holder of Certificate of Registration (HCR) has confirmed a national shortage of Ozempic stock; this resulted in limited access to treatment for diabetic patients. This may have created an opportunity for falsified/counterfeit products flooding the market claiming to be Ozempic and being used off-label for weight loss. Consumers should be wary of online offers for products claiming to be Ozempic or semaglutide.

Currently, there are no generic versions of this medicine being lawfully manufactured. Therefore, any product not manufactured by Novo Nordisk claiming to contain semaglutide is likely to be fake or counterfeit. The public is being exposed to many different types of unregistered/unauthorised products that are either substandard or falsified thereby putting their health at risk. See examples of registered vs counterfeit products.

Registered products safe to use
Ozempic solution for injection is a registered product by SAHPRA belonging to the HCR, Novo Nordisk South Africa.

There are only two (2) registered presentations of the pre-filled pen for Ozempic available in South Africa namely, Ozempic 0,25 mg and 0,5 mg/dose pen and Ozempic 1 mg/dose pen.

What the public should know

  • Using unregistered semaglutide products claiming to have the effects of Ozempic bought from unverified/illegally trading suppliers could be detrimental to your health as these have not been evaluated by SAHPRA for safety, quality, and efficacy.
  • These falsified/fake Ozempic products may contain certain active ingredients found in the registered Ozempic products; however, the formulations or manufacturing processes may be different. These formulations have not been evaluated by SAHPRA.
  • SAHPRA urges the public to first consult their medical professionals for their health treatment and prescriptions, and only purchase or use SAHPRA registered/authorised products sold at registered pharmacies.
  • Any medicines that are bought outside of the legal supply chain:
    • May not contain any active ingredient.
    • May contain dangerous levels of the active ingredient.
    • May contain another active ingredient such as insulin instead of semaglutide.
    • May contain harmful inactive ingredients.
    • May be nonsterile and contaminated with microbes, therefore not suitable for injection.

“Protecting the health of South Africans is top of mind for the regulator. The scourge of unregistered, substandard, and falsified medicines on the market is a serious health risk for the public. SAHPRA is listening to the public concerns, and we have an ongoing investigation into these falsified Ozempic and unregistered semaglutide-containing products”, indicates SAHPRA CEO, Dr Boitumelo Semete-Makokotlela.

Public are urged to report any suspected products that are falsely claiming to work like Ozempic. You can report through these whistle blower platforms, SAHPRA’s 24-hour hotline (0800 204 307) or via our web reporting facility: .

Categories : Metabolic DisordersTags :

Scientists Identify New Cause of Diabetes – and Potential Treatment Target

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Researchers have identified an enzyme that blocks insulin produced in the body – a discovery that could provide a new target to treat diabetes. Their study, published the journal Cell, focuses on nitric oxide, which dilates blood vessels, improves memory, fights infection and stimulates the release of hormones, among other functions.

How nitric oxide performs these activities had long been a mystery.

The researchers at Case Western Reserve University and University Hospitals discovered a novel “carrier” enzyme (called SNO-CoA-assisted nitrosylase, or SCAN) that attaches nitric oxide to proteins, including the receptor for insulin action.

They found that the SCAN enzyme was essential for normal insulin action, but also discovered heightened SCAN activity in diabetic patients and mice with diabetes.

Mouse models without the SCAN enzyme appeared to be shielded from diabetes, suggesting that too much nitric oxide on proteins may be a cause of such diseases.

“We show that blocking this enzyme protects from diabetes, but the implications extend to many diseases likely caused by novel enzymes that add nitric oxide,” said the study’s lead researcher Jonathan Stamler, professor at the Case Western Reserve School of Medicine.

“Blocking this enzyme may offer a new treatment.”

Given the discovery, next steps could be to develop medications against the enzyme, he said.

Many human diseases, including Alzheimer’s, cancer, heart failure and diabetes, are thought to be caused or accelerated by nitric oxide binding excessively to key proteins.

With this discovery, Stamler said, enzymes that attach the nitric oxide become a focus.

With diabetes, the body often stops responding normally to insulin.

The resulting increased blood sugar stays in the bloodstream and, over time, can cause serious health problems.

Individuals with diabetes, the Centers for Disease Control reports, are more likely to suffer such conditions as heart disease, vision loss and kidney disease.

But the reason that insulin stops working isn’t well understood.

Excessive nitric oxide has been implicated in many diseases, but the ability to treat has been limited because the molecule is reactive and can’t be targeted specifically, Stamler said.

“This paper shows that dedicated enzymes mediate the many effects of nitric oxide,” he said. “Here, we discover an enzyme that puts nitric oxide on the insulin receptor to control insulin. Too much enzyme activity causes diabetes. But a case is made for many enzymes putting nitric oxide on many proteins, and, thus, new treatments for many diseases.”

Source: Case Western Reserve University

Categories : Cancer Metabolic DisordersTags :

GLP-1 Agonists may Reduce Colorectal Cancer Risk

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By HualinXMN – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=133759262

A groundbreaking study by researchers at Case Western Reserve University suggests that glucagon-like peptide-1 receptor agonists (GLP-1 RAs), normally used to treat diabees, may also reduce the risk of colorectal cancer (CRC). The findings, published in the journal JAMA Oncology, support the need for clinical trials to determine whether these medications could prevent one of the deadliest types of cancers.

Eventually, the medications may also show promise in warding off other types of cancer associated with obesity and diabetes.

“Our results clearly demonstrate that GLP-1 RAs are significantly more effective than popular anti-diabetic drugs, such as Metformin or insulin, at preventing the development of CRC,” said Nathan Berger, the Hanna-Payne Professor of Experimental Medicine at the Case Western Reserve School of Medicine and the study’s co-lead researcher.

Glucagon-like peptide-1 receptor agonists, or GLP-1 RAs can lower blood-sugar levels, improve insulin sensitivity and help manage weight. They’ve also been shown to reduce the rates of major cardiovascular ailments. Importantly the protective effect of GLP-1 RAs are noted in patients with or without overweight/obesity.

“To our knowledge,” said co-lead researcher Rong Xu, a professor at the School of Medicine, “this is the first indication this popular weight-loss and anti-diabetic class of drugs reduces incidence of CRC, relative to other anti-diabetic agents.”

Berger and Xu are members of the Case Comprehensive Cancer Center.

In the US, the American Cancer Society estimates CRC is the third-leading type of cancer in both sexes, with 153 000 new cases per year. It is also the second-leading cause of cancer mortality with 52 550 deaths per year.

Since GLP-1 RAs have been shown to be effective anti-diabetic and weight-loss agents, the researchers hypothesized they might reduce incidence of CRC.

Using a national database of more than 100 million electronic health records, the researchers conducted a population-based study of more than 1.2 million patients.

These individuals had been treated with anti-diabetic agents from 2005-19; the CWRU team examined the effects of GLP-1 RAs on their incidence of CRC, as compared to those prescribed other anti-diabetic drugs.

Population-based research means matching as many people as possible with the same characteristics, such as sex, race, age, socio-economic determinants of health and other medical conditions, to accurately compare the drug’s effects.

Among 22 572 patients with diabetes treated with insulin, there were 167 cases of CRC. Another 22 572 matched patients treated with GLP-1 RAs saw 94 cases of CRC. Those treated with GLP-1 RAs had a 44% reduction in incidence of CRC.

In a similar comparison of 18 518 patients with diabetes treated with Metformin, compared to 18 518 patients with diabetes treated with GLP-1 RAs, had a 25% reduction in CRC.

“The research is critically important for reducing incidence of CRC in patients with diabetes, with or without overweight and obesity,” Berger said.

Source: Case Western Reserve University

Categories : Metabolic DisordersTags :

Can Weight Loss Drugs Reduce Mortality Risk in Knee or Hip Osteoarthritis?

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Besides its significant impact on disability, symptomatic OA is associated with an increased risk of all-cause mortality. Current guidelines advise weight loss to improve function and reduce pain but there is little data on whether it also reduces mortality risk.

New research published in Arthritis & Rheumatology suggests that for people overweight or with obesity and also knee or hip osteoarthritis, a slow-to-moderate – but not fast – rate of weight loss caused by anti-obesity medications may lower their risk of premature death.

Researchers enrolled 6524 participants with knee or hip osteoarthritis who were taking orlistat, sibutramine, or rimonabant to the study. The five-year death rate was 5.3%, 4.0%, and 5.4% for the “weight gain/stable”, “slow-to-moderate weight loss,” and “fast weight loss” groups, respectively. Compared with the “weight gain/stable” group,” the risk of death was 28% lower for the “slow-to-moderate weight loss” group and only 1% lower for the “fast weight loss” arm.

“A slow-to-moderate rate of weight loss induced by anti-obesity medications may lower the risk of death in overweight/obese people with knee/hip osteoarthritis”, said first author Jie Wei, PhD, of Xiangya Hospital, Central South University, in China.

Source: Wiley

Categories : Metabolic Disorders Obstetrics & GynaecologyTags :

Macrophages ‘Eat’ Pancreatic β Cells to Regulate Insulin Post Partum

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A 3D map of the islet density routes throughout the healthy human pancreas. Source: Wikimedia CC0

Scientists have long known that pancreatic β cells increase during pregnancy and promptly return to their original number following birth. But the underlying mechanisms that cause the cells to go back to their original number are still not well understood.

In a significant breakthrough, a research group using mouse models, has discovered that macrophages ‘eat’ (phagocytose) the pancreatic β cells, thereby revealing the process behind their return to previous levels after pregnancy.

The research group, which was led by Associate Professor Junta Imai, Assistant Professor Akira Endo, and Professor Hideki Katagiri from Tohoku University’s Graduate School of Medicine, published the results in the journal Development Cell.

Initially, the group examined the number of pancreatic β cells in the islets of Langerhans in a mouse model of pregnancy.

They confirmed the cell number was double at the end of the pregnancy when compared to non-pregnant mice, but that it then gradually decreased, returning to the original amount after delivery.

“After we observed the islets of Langerhans before and after delivery, we noticed an increase in macrophages, which protect the body from infections by engulfing bacteria, foreign substances and dead cells, after delivery,” says Imai.

“When we applied treatment to inhibit this process, the blood glucose levels became too low (hypoglycaemia).”

Additional microscopic observation of the islets of Langerhans after birth revealed β cells to be phagocytosed by macrophages.

This mechanism appeared to keep the mother’s blood glucose levels from decreasing excessively after delivery by rapidly reducing pancreatic β cells to their normal pre-pregnancy number.

Next, the group identified the protein responsible for attracting the macrophages into the islets of Langerhans: cytokine CXCL10.

Accordingly, the inhibition of CXCL10 function suppressed the decrease in pancreatic β cells after birth.

“We hope our results will contribute to clarifying the means by which normal blood glucose levels are maintained as well as the development of methods to prevent and treat diabetes,” adds Imai.

Source: Tohoku University

Categories : Metabolic Disorders Neurodegenerative DiseasesTags :

Abnormally High Levels of HDL-C Linked to Dementia in Older Adults

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Abnormally high levels of high density lipoprotein cholesterol (HDL-C), are associated with an increased risk of dementia in older adults, according to study led by Monash University. Researchers said very high levels of the ‘good cholesterol’ HDL-C linked to dementia risk in this study were uncommon and not diet related, but more likely to reflect a metabolic disorder. The findings may help doctors to recognise a group of older patients potentially at risk of dementia, particularly in those aged 75 and older.

Published in The Lancet Regional Health – Western Pacific, this is one of the largest studies of elevated HDL-C levels and dementia in initially healthy older people aged mostly over 70, enrolled in the ASPREE* study.

Over an average 6.3 years, participants with very high HDL-C (> 80mg/dL or > 2.07mmol/L) at study entry were observed to have a 27% higher risk of dementia compared to participants with optimal HDL-C levels, while those aged 75 years and older also showed a 42% increased risk compared to those with optimal levels.

Very high HDL-C levels were categorised as 80mg/dL (> 2.07mmol/L) or above.

The optimal level of HDL-C of 40 to 60mg/dL (1.03–1.55mmol/L) for men and 50 to 60mg/dL (1.55–2.07mmol/L) for women was generally beneficial for heart health.

Among 18 668 participants included in this analysis, 2709 had very high HDL-C at study entry, with 38 incidents of dementia in those aged less than 75 years with very high levels, and 101 in those aged 75 and more with very high levels.

First author and Monash University School of Public Health and Preventive Medicine senior research fellow Dr Monira Hussain said that further research was needed to explain why a very high HDL cholesterol level appeared to affect the risk of dementia.

Dr Hussain said these study findings could help improve our understanding of the mechanisms behind dementia, but more research was required.

“While we know HDL cholesterol is important for cardiovascular health, this study suggests that we need further research to understand the role of very high HDL cholesterol in the context of brain health,” she said.

“It may be beneficial to consider very high HDL cholesterol levels in prediction algorithms for dementia risk.”

*The Aspirin in Reducing Events in the Elderly (ASPREE) trial is a double-blind, randomised, placebo-controlled trial of daily aspirin in healthy older people. 

Source: Monash University