Category: Metabolic Disorders

Categories : Genetics Metabolic DisordersTags :

Smart Moo-ve for Diabetes Treatment: Insulin Produced in Cow’s Milk

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An unassuming brown bovine from the south of Brazil has made history as the first transgenic cow capable of producing human insulin in her milk. The advancement, led by researchers from the University of Illinois Urbana-Champaign and the Universidade de São Paulo, could herald a new era in insulin production, one day eliminating drug scarcity and high costs for people living with diabetes.

“Mother Nature designed the mammary gland as a factory to make protein really, really efficiently. We can take advantage of that system to produce a protein that can help hundreds of millions of people worldwide,” said Matt Wheeler, professor in the Department of Animal Sciences, part of the College of Agricultural, Consumer and Environmental Sciences (ACES) at U. of I.

Wheeler is lead author on a new Biotechnology Journal study describing the development of the insulin-producing cow, a proof-of-concept achievement that could be scaled up after additional testing and FDA approval.

Precise insertion of DNA

Wheeler’s colleagues in Brazil inserted a segment of human DNA coding for proinsulin – the protein precursor of the active form of insulin – into cell nuclei of 10 cow embryos. These were implanted in the uteruses of normal cows in Brazil, and one transgenic calf was born. Thanks to updated genetic engineering technology, the human DNA was targeted for expression – the process whereby gene sequences are read and translated into protein products – in mammary tissue only.

“In the old days, we used to just slam DNA in and hope it got expressed where you wanted it to,” Wheeler said. “We can be much more strategic and targeted these days. Using a DNA construct specific to mammary tissue means there’s no human insulin circulating in the cow’s blood or other tissues. It also takes advantage of the mammary gland’s capabilities for producing large quantities of protein.”

When the cow reached maturity, the team unsuccessfully attempted to impregnate her using standard artificial insemination techniques. Instead, they stimulated her first lactation using hormones. The lactation yielded milk, but a smaller quantity than would occur after a successful pregnancy. Still, human proinsulin and, surprisingly, insulin were detectable in the milk.

“Our goal was to make proinsulin, purify it out to insulin, and go from there. But the cow basically processed it herself. She makes about three to one biologically active insulin to proinsulin,” Wheeler said. “The mammary gland is a magical thing.”

The insulin and proinsulin, which would need to be extracted and purified for use, were expressed at a few grams per liter in the milk. But because the lactation was induced hormonally and the milk volume was smaller than expected, the team can’t say exactly how much insulin would be made in a typical lactation.

Conservatively, Wheeler says if a cow could make 1 gram of insulin per liter and a typical Holstein makes 40 to 50 litres per day, that’s a lot of insulin. Especially since the typical unit of insulin equals 0.0347 milligrams.

“That means each gram is equivalent to 28,818 units of insulin,” Wheeler said. “And that’s just one liter; Holsteins can produce 50 liters per day. You can do the math.”

The team plans to re-clone the cow, and is optimistic they’ll achieve greater success with pregnancy and full lactation cycles in the next generation. Eventually, they hope to create transgenic bulls to mate with the females, creating transgenic offspring that can be used to establish a purpose-built herd. Wheeler says even a small herd could quickly outcompete existing methods – transgenic yeast and bacteria – for producing insulin, and could do so without having to create highly technical facilities or infrastructure.

“With regard to mass-producing insulin in milk, you’d need specialized, high-health-status facilities for the cattle, but it’s nothing too out of the ordinary for our well-established dairy industry,” Wheeler said. “We know what we’re doing with cows.”

An efficient system to collect and purify insulin products would be needed, as well as FDA approval, before transgenic cows could supply insulin for the world’s diabetics. But Wheeler is confident that day is coming.

“I could see a future where a 100-head herd, equivalent to a small Illinois or Wisconsin dairy, could produce all the insulin needed for the country,” he said. “And a larger herd? You could make the whole world’s supply in a year.

Source: University of Illinois College of Agricultural, Consumer and Environmental Sciences

Categories : Immunology Metabolic DisordersTags :

Liver Immune System Quickly ‘Eats up’ LDL Cholesterol

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Colourised electron micrograph image of a macrophage. Credit: NIH

A new study reveals that immune cells in the liver react to high cholesterol levels and eat up excess cholesterol that can otherwise cause damage to arteries. The findings, published in Nature Cardiovascular Research, suggest that the response to the onset of atherosclerosis begins in the liver.

Immediate response from the liver

In the current study, researchers from Karolinska Institutet wanted to understand how different tissues in the body react to high levels of LDL, commonly called ‘bad cholesterol’, in the blood.

To test this, they created a system where they could quickly increase the cholesterol in the blood of mice.

“Essentially, we wanted to detonate a cholesterol bomb and see what happened next,” says Stephen Malin, lead author of the study and principal researcher at the Department of Medicine, Solna, Karolinska Institutet.

“We found that the liver responded almost immediately and removed some of the excess cholesterol.”

However, it wasn’t the typical liver cells that responded, but a type of immune cell called Kupffer cells that are known for recognising foreign or harmful substances and eating them up. The discovery made in mice was also validated in human tissue samples.

“We were surprised to see that the liver seems to be the first line of defence against excess cholesterol and that the Kupffer cells were the ones doing the job,” says Stephen Malin.

“This shows that the liver immune system is an active player in regulating cholesterol levels, and suggests that atherosclerosis is a systemic disease that affects multiple organs and not just the arteries.”

Several organs could be involved

The researchers hope that by understanding how the liver and other tissues communicate with each other after being exposed to high cholesterol, they can find new ways to prevent or treat cardiovascular and liver diseases.

“Our next step is to look at how other organs respond to excess cholesterol, and how they interact with the liver and the blood vessels in atherosclerosis,” says Stephen Malin. “This could help us develop more holistic and effective strategies to combat this common and deadly disease.”

Source: Karolinska Institutet

Categories : Metabolic DisordersTags :

Worsening Metabolic Syndrome Exacerbates Cancer Risk

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Study reveals a significant link, suggesting that managing metabolic syndrome may help prevent cancer.

Source: Pixabay CC0

New research indicates that individuals with persistent and worsening metabolic syndrome – which encompasses conditions such as high blood pressure, elevated blood sugar, excess abdominal fat, and abnormal cholesterol – face an elevated risk of developing various types of cancer. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

In the study, 44 115 adults in China with an average age of 49 years were categorised into 4 different trajectories based on trends from 2006 (the time of the first physical exam) to 2010: 10.56% exhibited a low-stable pattern and maintained low metabolic syndrome scores; 40.84% exhibited a moderate-low pattern and maintained moderate to low metabolic syndrome scores; 41.46% exhibited a moderate-high pattern and consistently maintained moderate to high metabolic syndrome scores; and 7.14% exhibited an elevated-increasing pattern in which initially elevated metabolic syndrome scores increased over time.

During the follow-up period of 2010–2021, with a median follow-up of 9.4 years, there were 2271 cancer diagnoses among participants. Compared with participants with a low-stable trajectory pattern, those with an elevated-increasing trajectory pattern had 1.3-, 2.1-, 3.3-, 4.5-, 2.5-, and 1.6-times higher risks of developing any cancer, breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer, respectively.

Even when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined, the elevated-increasing trajectory pattern group had higher risks of developing all cancer types.

Also, participants with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of developing breast, endometrial, colon, and liver cancer, whereas the risk of kidney cancer was predominantly observed among participants with persistently high scores but without chronic inflammation.

“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” said senior author Han-Ping Shi, MD, PhD, of Capital Medical University, in Beijing. “Our study can guide future research into the biological mechanisms linking metabolic syndrome to cancer, potentially resulting in targeted treatments or preventive strategies. Formal evaluation of these interventions will be needed to determine if they are able to modulate cancer risk.” 

Source: Wiley

Categories : Metabolic Disorders PaediatricsTags :

Waist-to-height Ratio Superior to BMI for Detecting Fat Obesity in Children and Adolescents

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Photo by Andres Ayrton on Pexels

A simple measure of obesity in children and adolescents that could replace body mass index (BMI) has been identified in a new study as waist circumference-to-height ratio. This measure detected excess fat mass and distinguished fat mass from muscle mass in children and adolescents more accurately than BMI. The study was conducted in collaboration between the University of Bristol in the UK, the University of Exeter in the UK, and the University of Eastern Finland, and the results were published in Pediatric Research.

The prevalence of childhood and adolescent obesity has reached an epidemic proportion and is affecting nearly 1 in 4 children in the current decade.

Unfortunately, obesity in the young population has been associated with cardiovascular, metabolic, neurological, musculoskeletal diseases and premature death in adulthood.

Accurately detecting overweight and obesity in children is critical to initiating timely interventions.

For nearly a generation, weight-to-height ratio charts and BMI for age and sex have been used to diagnose children with obesity.

However, these surrogate assessment tools are inaccurate in childhood and adolescence since they do not distinguish fat mass from muscle mass.For instance, two children with similar BMI might have different proportions of fat and muscle mass which makes obesity diagnosis difficult.

Expensive tools such as the dual-energy Xray absorptiometry (DEXA) scan accurately measures fat and muscle content of the body, but this device is not readily available in primary health care centres.

Recently, the American Academy of Pediatrics (AAP) published a clinical guideline on childhood obesity and requested urgent research on inexpensive and accurate alternative measures of obesity.

Emerging studies in adults appear to suggest that waist circumference-to-height ratio predicts premature death better than BMI and could be a potential added tool to BMI measure in improving the diagnosis of obesity.

However, there has been no former evaluation of how much waist circumference-to-height ratio measurements agree with DEXA-measured fat mass and muscle mass during growth from childhood to young adulthood.

In addition, the threshold of waist circumference-to-height ratio needed to detect excess fat in children is not clear, hence this study.

The current study is the largest and the longest follow-up DEXA-measured fat mass and muscle mass study in the world using the University of Bristol’s Children of the 90s data (also known as the Avon Longitudinal Study of Parents and Children). The study included 7,237 children (51% females) aged 9 years who were followed-up until age 24 years.

Their BMI and waist circumference-to-height ratio were measured at ages 9, 11, 15, 17, and 24 years.

When different devices measure a variable with an exact resemblance, it is described as perfect agreement of the devices with a score of 100%. For example, two DEXA scans from different manufacturers would measure fat mass with a near-perfect agreement of 99 to 100%.

Waist circumference-to-height ratio had a very high agreement of 81 — 89% with DEXA-measured total body fat mass and trunk fat mass, but a low agreement with muscle mass (24 — 39%). BMI had a moderate agreement with total fat mass and trunk fat mass (65 — 72%) and muscle mass (52 — 58%). Since BMI had a moderate agreement with DEXA-measured muscle mass, it is difficult to specify whether BMI measures excess fat or muscle mass.

The optimal waist circumference-to-height ratio cut points that predicted the 95th percentile of total fat mass in males was 0.53 and 0.54 in females.

This cut point detected 8 out of 10 males and 7 out of 10 females who truly had excess DEXA-measured fat.

The cut point also identified 93 out of 100 males and 95 out of 100 females who truly do not have excess fat.

“This study provides novel information that would be useful in updating future childhood obesity guidelines and policy statements. The average waist circumference-to-height ratio in childhood, adolescence, and young adulthood is 0.45, it does not vary with age and among individuals like BMI. Waist circumference-to-height ratio might be preferable to BMI assessment in children and adolescent clinics as an inexpensive tool for detecting excess fat. Parents should not be discouraged by the BMI or weight of their children but can inexpensively confirm whether the weight is due to increase in excess fat by examining their kid’s waist circumference-to-height ratio,” says Andrew Agbaje, an award-winning physician and pediatric clinical epidemiologist at the University of Eastern Finland.

Source: University of Eastern Finland

Categories : Metabolic Disorders Skeletal SystemTags :

Type 2 Diabetes Alters the Behaviour of Discs in the Vertebral Column

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Type 2 diabetes alters the behaviour of discs in the vertebral column, making them stiffer, and also causes the discs to change shape earlier than normal. As a result, the disc’s ability to withstand pressure is compromised. This is one of the findings of a new rodent-based study published in PNAS Nexus.

Low back pain is a major cause of disability, often associated with intervertebral disc degeneration. People with type 2 diabetes face a higher risk of low back pain and disc-related issues. Yet the precise mechanisms of disc degeneration remain unclear.

Investigating the biomechanical properties of the intervertebral disc is crucial for understanding the disease and developing effective strategies for managing low back pain.

“These findings provide novel insight into the potential mechanisms underlying diabetes-related disc tissue damage and may inform the development of preventative and therapeutic strategies for this debilitating condition,” the research team wrote. The team consisted of engineers and physicians from the University of California San Diego, UC Davis, UCSF and the University of Utah.

The study emphasises that nanoscale deformation mechanisms of collagen fibrils accommodate compressive loading of the intervertebral disc.

In the context of type 2 diabetes, these mechanisms are compromised, resulting in collagen embrittlement.

These findings provide novel insight into the potential mechanisms underlying diabetes-related disc tissue damage and may inform the development of preventative and therapeutic strategies for this debilitating condition.

Researchers employed synchrotron small-angle x-ray scattering (SAXS), an experimental technique that looks at collagen fibril deformation and orientation at the nanoscale.

They wanted to explore how alterations in collagen behaviour contribute to changes in the disc’s ability to withstand compression.

They compared discs from healthy rats to those from rats with type 2 diabetes (UC Davis rat model). The healthy rats showed that collagen fibrils rotate and stretch when discs are compressed, allowing the disc to dissipate energy effectively.

“In diabetic rats, the way vertebral discs dissipate energy under compression is significantly impaired: diabetes reduces the rotation and stretching of collagen fibrils, indicating a compromised ability to handle pressure,” the researchers write.

Further analysis showed that the discs from diabetic rats exhibited a stiffening of collagen fibrils, with a higher concentration of non-enzymatic cross-links.

This increase in collagen cross-linking, induced by hyperglycaemia, limited plastic deformations via fibrillar sliding.

These findings highlight that fibril reorientation, straightening, stretching, and sliding are crucial mechanisms facilitating whole-disc compression.

Type 2 diabetes disrupts these efficient deformation mechanisms, leading to altered whole-disc biomechanics and a more brittle (low-energy) behaviour.

Source: University of California – San Diego

Categories : Lab Tests and Imaging Metabolic DisordersTags :

New, More Accurate Approach to Blood Tests for Determining Diabetes Risks

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Photo by National Cancer Institute on Unsplash

A new approach to blood tests could potentially be used to estimate a patient’s risk of type 2 diabetes, according to a new study appearing in BMC’s Journal of Translational Medicine. Currently, the most commonly used inflammatory biomarker currently used to predict the risk of type 2 diabetes is high-sensitivity C-reactive protein (CRP). But new research has suggested that jointly assessing of biomarkers, rather than assessing each individually, would improve the chances of predicting diabetes risk and diabetic complications.

A study by Edith Cowan University (ECU) researcher Dan Wu investigated the connection between systematic inflammation, assessed by joint cumulative high-sensitivity CRP and another biomarker called monocyte to high-density lipoprotein ratio (MHR), and incident type 2 diabetes.

The study followed more than 40 800 non-diabetic participants over a near ten-year period, with more than 4800 of the participants developing diabetes over this period.

Wu said that of those patients presenting with type 2 diabetes, significant interaction between MHR and CRP was observed.

“Specifically, increases in the MHR in each CRP stratum increased the risk of type 2 diabetes; concomitant increases in MHR and CRP presented significantly higher incidence rates and risks of diabetes.

“Furthermore, the association between chronic inflammation (reflected by the joint cumulative MHR and CRP exposure) and incident diabetes was highly age- and sex-specific and influenced by hypertension, high cholesterol, or prediabetes. The addition of the MHR and CRP to the clinical risk model significantly improved the prediction of incident diabetes,” said Wu.

Biological sex a risk factor

The study found that females had a greater risk of type 2 diabetes conferred by joint increases in CRP and MHR, with Wu stating that sex hormones could account for these differences.

Wu said that the research findings corroborated the involvement of chronic inflammation in causing early-onset diabetes and merited specific attention.

“Epidemiological evidence indicates a consistent increase in early-onset diabetes, especially in developing countries. Leveraging this age-specific association between chronic inflammation and type 2 diabetes may be a promising method for achieving early identification of at-risk young adults and developing personalised interventions,” she added.

Wu noted that the chronic progressive nature of diabetes and the enormous burden of subsequent comorbidities further highlighted the urgent need to address this critical health issue.

Although aging and genetics are non-modifiable risk factors, other risk factors could be modified through lifestyle changes.

Inflammation is strongly influenced by life activities and metabolic conditions such as diet, sleep disruptions, chronic stress, and glucose and cholesterol dysregulation, thereby indicating the potential benefits of monitoring risk-related metabolic conditions.

Wu said that the dual advantages of cost effectiveness and the wide availability of cumulative MHR and CRP in current clinical settings, potentiated the widespread use of these measures as a convenient tool for predicting the risk of diabetes.

Source: Edith Cowan University

Categories : Cardiovascular Disease Metabolic DisordersTags :

Long-term Blood Pressure Control from Bariatric Surgery is Most Effective

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Sleeve gastrectomy. Credit: Scientific Animations CC4.0

Compared to antihypertensives alone, bariatric surgery is more effective in controlling hypertension rates in people with obesity and uncontrolled hypertension, according to a study published in the Journal of the American College of Cardiology. People who underwent bariatric surgery had lower BMI and were on fewer medications after five years while maintaining normal blood pressure levels than those who only used antihypertensive medications.

“In clinical practice, obesity is an overlooked condition. As a consequence, there is a frequent failure in approaching obesity as a crucial step for mitigating the risk of important cardiovascular risk factors including hypertension,” said Carlos Aurelio Schiavon, MD, FACS, lead author of the study and a surgeon specialising in bariatric surgery at Heart Hospital (hcor) and BP Hospital in Sao Paulo.

Researchers in this study looked at the impact of treating obesity to lower hypertension. While new weight loss drugs exist, long-term adherence to medication can be challenging.

This study looks at bariatric surgery as a better long-term solution to control obesity and, as a result, hypertension.

The GATEWAY trial included 100 people (76% of whom were female) who had a body mass index (BMI) of around 36.9kg/m2. All participants had hypertension and were using at least two medications. People with previous cardiovascular events and poorly controlled Type 2 diabetes were excluded.

Subjects were assigned to either Roux-en-Y gastric bypass with medical therapy or medial therapy alone and the primary outcome was reduction of at least 30% antihypertensive medications while maintaining blood pressure levels less than 140/90mmHg at five years.

At five years, BMI was 28.01kg/m2 for those who received bariatric surgery and 36.40kg/m2 for those on medical therapy alone.

People who had bariatric surgery had an 80.7% reduction in the number of medications they were taking compared to a 13.7% reduction in those only using medical therapy.

Hypertension remission, defined as controlled blood pressure without medications, was 46.9% in those who underwent bariatric surgery compared to 2.4% in those on medical therapy alone.

“Our results underscore the importance of approaching obesity in reducing hypertension rates,” Schiavon said.

Limitations of the study include that it was a single-center, open-label study with a small sample size and there was loss of follow up in some patients.

In an accompanying editorial comment, Michael Hall, MD, MSc, professor and chair of the Department of Medicine at the University of Mississippi Medical Center, said the study provides important long-term data on the benefits of gastric bypass on weight loss and blood pressure control, but questions remain.

“Further studies assessing the threshold for bariatric surgery in people with obesity, optimal timing of bariatric surgery in obese people with cardiometabolic diseases, type of bariatric surgery and comparative studies of obesity pharmacotherapies and bariatric surgery are needed to clarify the optimal treatment pathways for this common and growing disease,” he said.

Source: American College of Cardiology

Categories : Metabolic DisordersTags :

A Single Gene Causes Mitochondria to ‘Fragment’ in Obesity

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These coloured streaks are mitochondrial networks within fat cells. Researchers from UC San Diego discovered that a high-fat diet dismantles mitochondria, resulting in weight gain. Credit: UC San Diego

While lifestyle factors like diet and exercise play a role in the development and progression of obesity, scientists have come to understand that obesity is also associated with intrinsic metabolic abnormalities. Now, researchers from University of California San Diego School of Medicine have shed new light on how obesity affects our mitochondria, the all-important energy-producing structures of our cells.

In a study published January 29, 2023 in Nature Metabolism, the researchers found that when mice were fed a high-fat diet, mitochondria within their fat cells broke apart into smaller mitochondria with reduced capacity for burning fat. Further, they discovered that this process is controlled by a single gene. By deleting this gene from the mice, they were able to protect them from excess weight gain, even when they ate the same high-fat diet as other mice.

“Caloric overload from overeating can lead to weight gain and also triggers a metabolic cascade that reduces energy burning, making obesity even worse,” said Alan Saltiel, PhD, professor in the Department of Medicine at UC San Diego School of Medicine. “The gene we identified is a critical part of that transition from healthy weight to obesity.”

Obesity occurs when the body accumulates too much fat, which is primarily stored in adipose tissue. Adipose tissue normally provides important mechanical benefits by cushioning vital organs and providing insulation. It also has important metabolic functions, such as releasing hormones and other cellular signaling molecules that instruct other tissues to burn or store energy.

In the case of caloric imbalances like obesity, the ability of fat cells to burn energy starts to fail, which is one reason why it can be difficult for people with obesity to lose weight. How these metabolic abnormalities start is among the biggest mysteries surrounding obesity.

To answer this question, the researchers fed mice a high-fat diet and measured the impact of this diet on their fat cells’ mitochondria, structures within cells that help burn fat. They discovered an unusual phenomenon. After consuming a high-fat diet, mitochondria in parts of the mice’s adipose tissue underwent fragmentation, splitting into many smaller, ineffective mitochondria that burned less fat.

In addition to discovering this metabolic effect, they also discovered that it is driven by the activity of single molecule, called RaIA. RaIA has many functions, including helping break down mitochondria when they malfunction. The new research suggests that when this molecule is overactive, it interferes with the normal functioning of mitochondria, triggering the metabolic issues associated with obesity.

“In essence, chronic activation of RaIA appears to play a critical role in suppressing energy expenditure in obese adipose tissue,” said Saltiel. “By understanding this mechanism, we’re one step closer to developing targeted therapies that could address weight gain and associated metabolic dysfunctions by increasing fat burning.”

By deleting the gene associated with RaIA, the researchers were able to protect the mice against diet-induced weight gain. Delving deeper into the biochemistry at play, the researchers found that some of the proteins affected by RaIA in mice are analogous to human proteins that are associated with obesity and insulin resistance, suggesting that similar mechanisms may be driving human obesity.

“The direct comparison between the fundamental biology we’ve discovered and real clinical outcomes underscores the relevance of the findings to humans and suggests we may be able to help treat or prevent obesity by targeting the RaIA pathway with new therapies,” said Saltiel “We’re only just beginning to understand the complex metabolism of this disease, but the future possibilities are exciting.”

Source: EurekAlert!

Categories : Diseases, Syndromes and Conditions Metabolic DisordersTags :

GLP-1 Agonists Associated with Reduced Risk of Liver Diseases

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

GLP1 agonists such as Ozempic (semaglutide) are associated with a reduced risk of developing cirrhosis and liver cancer in people with type 2 diabetes and chronic liver disease, according to a nationwide study from Karolinska Institutet published in the journal Gut.

GLP1 agonists reduce blood sugar levels and are mainly used to treat type 2 diabetes. Since the drug also reduces appetite, it is now increasingly used to treat obesity and has become a popular weight-loss drug.

Reduced risk of liver damage

Results from early clinical trials also suggest that GLP1 agonists may reduce the risk of liver damage. Therefore, researchers at Karolinska Institutet included all people in Sweden with chronic liver disease and type 2 diabetes in a register-based study. They then compared the risk of severe liver damage in those who were treated with GLP1 agonists and those who were not. The results show that those who took the drug for a long period of time had a lower risk of later developing more severe forms of liver disease such as cirrhosis and liver cancer.

According to the researchers, this suggests that GLP1 agonists could be an effective treatment to avoid severe liver disease in people with concurrent type 2 diabetes.

“Fatty liver disease is estimated to affect up to one in five people in Sweden, many of whom have type 2 diabetes, and about one in twenty develop severe liver disease,” says first author Axel Wester, assistant professor at the Department of Medicine, Huddinge, Karolinska Institutet. “Our findings are interesting because there are currently no approved drugs to reduce this risk.”

Many of the people in the study stopped taking GLP1 agonists, resulting in a lack of protective effect. However, those who continued taking their medication over a ten-year period were half as likely to develop severe liver disease.

Clinical trials needed for confirmation

“The results need to be confirmed in clinical trials, but it will take many years for these studies to be completed,” says Axel Wester. “Therefore, we use existing registry data to try to say something about the effect of the drugs before that.”

A limitation of the method is that it is not possible to control for factors for which there is no data, such as blood tests to describe the severity of liver disease in more detail. However, the researchers have recently built a new database called HERALD where they have access to blood samples from patients in Region Stockholm.

“As a next step, we will investigate the effect of GLP1 agonists in this database,” says the study’s last author Hannes Hagström, consultant in hepatology at the Karolinska University Hospital and adjunct professor at the Department of Medicine, Huddinge, Karolinska Institutet. “If we get similar results, it would further strengthen the hypothesis that GLP1 agonists can be used to reduce the risk of severe liver disease.”

The research was mainly funded by Region Stockholm (CIMED), the Swedish Research Council and the Swedish Cancer Society. Hannes Hagström’s research group has received funding from Astra Zeneca, EchoSens, Gilead, Intercept, MSD, Novo Nordisk and Pfizer, although no industry-supported funding was obtained for this specific study.

Source: Karolinska Institutet

Categories : Metabolic DisordersTags :

Few Patients Successfully Treat their Type 2 Diabetes Through Weight Loss

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People with the most weight loss in the first year were most likely to achieve sustained remission

Photo by Andres Ayrton on Pexels

A new study finds that very few patients diagnosed with type 2 diabetes are able to achieve normal blood glucose levels through weight loss alone. A team led by Andrea Luk of the Chinese University of Hong Kong, report these findings January 23rd in the open access journal PLOS Medicine.

Clinical trials suggest that people with type 2 diabetes can control their blood glucose levels without medication if they lose weight and keep it off. However, it is unknown how many patients can achieve remission through weight loss alone under real-world conditions. In the new study, researchers looked at 37 326 people in Hong Kong who were newly diagnosed with type 2 diabetes to see whether – and low long – patients could control the disease through weight loss.

The researchers discovered that only 6% of people achieved diabetes remission solely through weight loss by about eight years after diagnosis. For people who initially achieved remission, two-thirds had elevated blood glucose levels by three years after diagnosis. These rates are significantly lower than in clinical trials, where remission occurred in up to 73% of patients at one year post-diagnosis. People with the greatest weight loss in the first year were most likely to have sustained remission.

The study shows that controlling type 2 diabetes through sustained weight loss is possible in real-world settings, but that few patients will achieve normal blood glucose levels through weight management alone, especially over the long-term. One reason for the discrepancy with clinical trials is that trial participants receive intensive lifestyle interventions, including holistic support for dietary changes, physical exercise and mental health. The researchers conclude that patients should receive early weight management interventions as a way to increase the odds that they will achieve sustained remission. Furthermore, the data suggest that early weight management interventions increase the odds of sustained remission and that sustained lifestyle changes are likely to be paramount.

Luk adds, “Greater weight loss within the first year of diabetes diagnosis was associated with an increased likelihood of achieving diabetes remission. However, the incidence of diabetes remission was low with only 6% of people achieving remission over 8 years, and half of those with initial remission returned to hyperglycaemia within 3 years indicating poor sustainability of diabetes remission in real-world setting.”