Category: Metabolic Disorders

Categories : Metabolic DisordersTags :

Oestrogen’s Protection against Fatty Liver Points to New Drug Treatment

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New research from Karolinska Institutet shows how oestrogen protects against MASLD, a fatty liver disease on the increase in the obesity epidemic. The study, published in Molecular Systems Biology, shows how a new drug under development could become a future treatment for fatty liver disease and liver cancer.

The global obesity epidemic has resulted in a dramatic increase in fatty liver, a disease in which fat that does not fit into fat cells is stored in liver cells instead.

Since last year, fatty liver due to obesity (and not excessive alcohol consumption) is known as MASLD (metabolic dysfunction-associated steatotic liver disease). According to previous research, as many as one in three adults are affected by some degree of MASLD, which in the worst cases can develop into cirrhosis and liver cancer.

Protection until menopause

However, the disease is very unevenly distributed between the sexes, with a large majority of affected individuals being men.

“Women have a natural protection until menopause due to the female sex hormone oestrogen,” explains study leader Claudia Kutter, senior researcher at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.

Although women’s protection has been known for some time, the mechanism behind the protective effect has been less clear. Now Claudia Kutter’s research team may have found the answer.

Through genetic analyses of mice of both sexes fed a high-fat diet, with some of the male mice also receiving oestrogen, the researchers were able to identify a key protein in the development of fatty liver. 

The protein, called TEAD1, was found to play an overall role in regulating how liver cells absorb fat. Blocking TEAD1 protected liver cells from the harmful accumulation of fat. Mice receiving oestrogen treatment had lower TEAD1 activity and less fat accumulation in the liver.

New drug under development

In the next step, the researchers tested blocking TEAD1 in human liver cells with the same result. The fact that this was possible at all, however, was a bit of luck.

“It turned out that a pharmaceutical company is developing an anti-cancer drug that blocks TEAD1, which allowed us to test our hypothesis,” says Claudia Kutter.

The fact that TEAD1 is also involved in cancer does not worry her, quite the contrary.

“Since the activity of TEAD proteins is elevated in cancer, blocking TEAD at an early stage can also be positive from a cancer point of view,” she says. “Patients suffering from liver cancer are currently diagnosed very late. If the patient is given this drug early in the process to protect against fatty liver, it can hopefully also prevent the development of liver cancer.”

The pharmaceutical company will now start clinical trials of the drug as a protection against fatty liver disease, while Claudia Kutter’s research team will continue researching further ways to tackle the disease.

“We want to focus on how to find the disease earlier and identifying new treatment targets,” she says. “Different approaches may be needed for different patients depending on their gender and hormonal status.”

Source: Karolinska Institutet

Categories : Mental Health Metabolic DisordersTags :

Mental Health and Diabetes Complications are Strongly Interlinked, New Study Finds

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Photo by Sydney Sims on Unsplash

Myocardial infarction, stroke, neuropathy: when a person has any of these chronic diabetes complications, they are more likely to have a mental health disorder, and vice versa, according to a University of Michigan-led study. 

“We wanted to see if chronic diabetes complications led to mental health disorders or if mental health disorders led to those diabetes complications – but we found that both relationships are true,” said Brian Callaghan, MD, MS, senior author of the study published in Diabetes Care. 

“The findings highlight a need for clinicians to actively screen for mental health disorders in patients with diabetes in addition to screening for chronic complications, which is the recommended standard of care in diabetes.”

Three-times greater risk

The research team, led by Michigan Medicine and the Department of Biostatistics at the U-M School of Public Health, examined insurance claims data from over 500 000 individuals with type 1 or type 2 diabetes and 350 000 people without diabetes. 

The results reveal that people with chronic diabetes complications had up to a three-times greater risk of having a mental health condition, such as anxiety or depression. This effect increased as adults got older. 

Those with mental health disorders were up to 2.5 times more likely to experience sustained diabetes complications. 

In adults younger than 60 years old, having type 1 diabetes was more associated with chronic complications. People with the more common type 2 diabetes were more likely to experience mental health difficulties. 

A possible reason for this bi-directional relationship, researchers say, may be that having a diabetes complication or mental health condition has direct effects on developing the other complication.

“For instance, a stroke causes detrimental effects on the brain, which may directly lead to depression,” Callaghan said. 

“And having a mental health condition and diabetes may affect a person’s self-management of their condition – like poor glycaemic control or not taking medications – which, in turn, may increase their risk of diabetes complications.”

Common risk factors

The relationship may also be less direct. Diabetes complications and mental health conditions share common risk factors; obesity, issues with glycaemic control and social determinants of health can all increase the likelihood of developing both comorbidities. 

“Most likely, a combination of direct and indirect effects and shared risk factors drive the association we are seeing,” said first author Maya Watanabe, MS, a biostatistician at the Harvard T.H. Chan School of Public Health and former graduate student research assistant at U-M.  

“Diabetes care providers may be able to simultaneously prevent the risk of multiple complications by providing interventions to treat these shared risk factors.” 

Source: University of Michigan

Categories : Ageing Metabolic DisordersTags :

Reconsidering Dialysis for Chronic Kidney Failure in the Elderly

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Chronic kidney disease (CKD). Credit: Scientific Animations CC4.0

Whether dialysis is the best option for kidney failure and, if so, when to start, may deserve more careful consideration, according to a new study published in Annals of Internal Medicine.

For older adults who were not healthy enough for a kidney transplant, starting dialysis when their kidney function fell below a certain threshold, rather than waiting, afforded them roughly one more week of life, Stanford Medicine researchers and their colleagues found.

More critically, perhaps, they spent an average of two more weeks in hospitals or care facilities, in addition to the time spent undergoing dialysis.

“Is that really what a 75- or 80-year-old patient wants to be doing?” asked lead author Maria Montez Rath, PhD, a senior research engineer. Manjula Tamura, MD, a professor of nephrology, is the senior author.

“For all patients, but particularly for older adults, understanding the trade-offs is really essential,” Tamura said. “They and their physicians should carefully consider whether and when to proceed with dialysis.”

Patients with kidney failure who are healthy enough for transplantation may receive a donated kidney, which will rid their blood of toxins and excess fluid. But that option is unavailable to many older adults who have additional health conditions such as heart or lung disease or cancer.

For those patients, physicians often recommend dialysis when patients progress to kidney failure – when estimated glomerular filtration rate (eGFR), a measure of renal function, falls below 15.

Patients and their family members sometimes assume that dialysis is their only option, or that it will prolong life significantly, Montez Rath said. “They often say yes to dialysis, without really understanding what that means.”

But patients can take medications in lieu of dialysis to manage symptoms of kidney failure such as fluid retention, itchiness and nausea, Tamura said. She added that dialysis has side effects, such as cramping and fatigue, and typically requires a three- to four-hour visit to a clinic three times a week.

“It’s a pretty intensive therapy that entails a major lifestyle change,” she said.

Lifespan and time at home

The researchers conducted the study to quantify what dialysis entails for older adults who are ineligible for a transplant: whether and how much it prolongs life, along with the relative number of days spent in an inpatient facility such as a hospital, nursing home or rehabilitation center.

The team evaluated the health records, from 2010 to 2018, of 20 440 patients (98% of them men) from the U.S. Department of Veterans Affairs. The patients were 65 and older, had chronic kidney failure, were not undergoing evaluation for transplant and had an eGFR below 12.

Simulating a randomised clinical trial with electronic health records, they divided patients into groups: those who started dialysis immediately, and those who waited at least a month. Over three years, about half of the patients in the group who waited never started dialysis.

Patients who started dialysis immediately lived on average nine days longer than those who waited, but they spent 13 more in an inpatient facility. Age made a difference: Patients 65 to 79 who started dialysis immediately on average lived 17 fewer days while spending 14 more days in an inpatient facility; patients 80 and older who started dialysis immediately on average lived 60 more days but spent 13 more days in an inpatient facility.

Patients who never underwent dialysis on average died 77 days earlier than those who started dialysis immediately, but they spent 14 more days at home.

“The study shows us that if you start dialysis right away, you might survive longer, but you’re going to be spending a lot of time on dialysis, and you’re more likely to need hospitalization,” Montez Rath said.

Tamura noted that physicians sometimes recommend dialysis because they want to offer patients hope or because the downsides of the treatment haven’t always been clear. But the study indicates physicians and patients may want to wait until the eGFR drops further, Tamura said, and should consider symptoms along with personal preferences before starting dialysis.

“Different patients will have different goals,” she said. “For some it’s a blessing to have this option of dialysis, and for others it might be a burden.”

It may be helpful, she added, if clinicians portray dialysis for frail, older adults as a palliative treatment – primarily intended to alleviate symptoms.

“Currently, dialysis is often framed to patients as a choice between life and death,” she said. “When it’s presented in this way, patients don’t have room to consider whether the treatment aligns with their goals, and they tend to overestimate the benefits and well-being they might experience. But when treatment is framed as symptom-alleviating, patients can more readily understand that there are trade-offs.”

Source: Stanford Medicine

Categories : Medical Industry Metabolic DisordersTags :

Sanofi Commits to Affordable Insulin Pens for Diabetic Patients

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Novolog insulin pen. Photo by Dennis Klicker on Unsplash

Over the past few years, there has been a notable shift towards the use of insulin pens in the public sector, replacing traditional vials. This transition has been driven by the advantages insulin pens offer, including improved dosing accuracy, ease of use for patients, greater convenience, and better adherence to treatment.1

The move to basal insulin is in line with the National Strategic Plan for the Prevention and Control of Non-Communicable Diseases 2022-2027, which outlines specific targets for managing diabetes. This plan aims to improve early detection and treatment of diabetes by ensuring that 90% of people over 18 know their blood pressure and blood sugar levels. It also aims for 60% of those with high levels to receive treatment, and 50% of those treated to have their levels under control. These measures are designed to improve the management and outcomes of diabetes in the population.2

Since May 2023, the Department of Health has faced insulin pen rationing as the previous sole supplier opted not to tender. Nearly 50% of the insulin required for patients was expected to come in pen sets. To mitigate the impact, the health department has sourced a limited supply of insulin pens and analogues for vulnerable groups like the elderly, young children, and visually impaired individuals, despite the higher cost of insulin analogues, which offer more convenient and effective blood sugar management.3

In 2021, long-acting analogue insulins were added to the WHO Model List of Essential Medicines (EML) and have significantly reduced aligning with those of human insulin.3 Recognising this need, Sanofi has adjusted the price of its basal insulin to the cost of human insulin in South Africa.

Sanofi has been engaging with the National Department of Health to meet the needs of vulnerable patient groups,” says Dr Asafika Mbangata, Medical Advisor for Diabetes and Established Products, Sanofi. “A circular has been released by the department, identifying patient groups that would benefit from analogue insulins. This includes vulnerable groups like the elderly, young children, and visually impaired individuals. Sanofi is committed to ensuring that patients have access to treatment which will help control the disease by achieving adequate glycaemic control and eventually, prevention of complications in South Africa.”

Long-acting insulin analogues offer significant clinical benefits over human insulin, including prolonged duration of action,4 more stable glucose control with less hypoglycaemia, and reduced need for multiple daily doses.5 These benefits are particularly crucial for patients experiencing dangerously low blood glucose levels with human insulin.5 In addition, reductions in HbA1c (a key blood sugar indicator) are greater with all basal insulin analogues compared to human basal insulins.6

Diabetes Type 1

It’s estimated that more than 31 000 people in South Africa live with Type 1 diabetes and require full insulin replacement therapy, with multiple daily injections. Among them, 5000 are children.7

“Insulin pens, which are more accurate, user-friendly, and associated with less pain when used with short and fine needles, significantly enhance their quality of life,” says Dr. Mbangata. “This is particularly important for children, who are more likely to adhere to their treatment schedules with the easier-to-use and less painful pens.”

Diabetes Type 2

According to the International Diabetes Federation (IDF), 4.2 million South African adults are living with diabetes, primarily type 2.7 Of these, 84% access diabetes care in the public sector. Diabetes is the second leading cause of death in South Africa, following tuberculosis, and the leading cause of death among females.8

More than 9% of the South African population is 60 or older.9 Around 600 000 elderly individuals are living with diabetes, with approximately 500 000 of them accessing public sector healthcare.10

Treating diabetes in the elderly often requires a multidrug regimen, including insulin therapy. However, due to comorbidities such as dementia, vision loss, neuropathies, poor mobility, and manual dexterity issues, elderly patients are at increased risk of hypoglycaemia and dosing errors associated with insulin administration. Insulin pen devices have been shown to provide more reliable, accurate, and simplified dosing, making them a safer and more acceptable method of insulin delivery for the elderly population.11

Impaired vision

Diabetic retinopathy (impaired vision) is the third most common cause of blindness in South Africa, following cataracts and glaucoma​​.12 A pilot project screening for diabetic retinopathy in primary care at three Cape Town community healthcare centres assessed 400 patients living with diabetes. Over 80% had significantly reduced visual acuity, and 63% had retinopathy.12 These visually impaired patients would greatly benefit from using insulin pens, which make a clicking sound when the dial is turned, indicating the dose.

“Against the backdrop of these statistics, Sanofi continues in its efforts to make insulin pens more affordable and accessible, and our aim is to improve the quality of life and healthcare outcomes for South Africa’s diabetic population,” says Prudence Selani, External Affairs Head, Sanofi.

References

  1. Diabetes Spectr 2012;25(2):117–122
  2. Health Policy Watch. New WHO Essential Medicines List Includes Controversial Insulin Analogues. Available from: https://healthpolicy-watch.news/who-essential-medicines-insulin-analogues/
  3. Brunetti VC et al. Diabetes ObesMetab. 2022;1–13
  4. Sims EK et al. Nat Med. 2021;27:1154-64
  5. MannucciE et al. Endocrine. 2021;74:508-17
  6. IDF Diabetes Atlas 10th edition 2021
  7. Report-03-08-012018 (www.statssa.gov.za)
  8. StatsSA report: Marginalised Groups Series VI: The Social Profile of Older Persons, 2017–2021
  9. Werfalli M, Kassanjee R, Kalula S, Kowal P, Phaswana-Mafuya N, Levitt NS. Diabetes in South African older adults: prevalence and impact on quality of life and functional disability – as assessed using SAGE Wave 1 data. Glob Health Action. 2018;11(1):1449924. doi: 10.1080/16549716.2018.1449924. PMID: 29699475; PMCID: PMC5933282.
  10. Wright BM, Bellone JM, McCoy EK. A review of insulin pen devices and use in the elderly diabetic population. Clin Med Insights Endocrinol Diabetes. 2010;3:53-63. doi: 10.4137/CMED.S5534. Epub 2010 Nov 22. PMID: 22879787; PMCID: PMC3411523.
  11. Bertram MY, Jaswal AV, Van Wyk VP, Levitt NS, Hofman KJ. The non-fatal disease burden caused by type 2 diabetes in South Africa, 2009. Glob Health Action 2013;6:12944. [http://dx.doi.org/10.3402/gha.v6i0.19244]
  12. Cairncross JP, Steinberg WJ, Labuschagne MJ. Prevalence of eye pathology in a group of diabetic patients at National District Hospital Outpatient Department in Bloemfontein, South Africa. Afr J Prim Health Care Fam Med. 2017 Sep 27;9(1):e1-e7. doi: 10.4102/phcfm.v9i1.1440. PMID: 29041796; PMCID: PMC5645559.
Categories : Metabolic DisordersTags :

Strong Link Between Haem Iron in Red Meat and Type 2 Diabetes Risk

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Higher intake of haem iron, the type found in red meat and other animal products – as opposed to non-haem iron, found mostly in plant-based foods – was associated with a higher risk of developing type 2 diabetes (T2D) in a new study published in Nature Metabolism. While the link between haem iron and T2D has been reported previously, the findings from this study, which was led by Harvard T.H. Chan School of Public Health, more clearly establish and explain the link.

“Compared to prior studies that relied solely on epidemiological data, we integrated multiple layers of information, including epidemiological data, conventional metabolic biomarkers, and cutting-edge metabolomics,” said lead author Fenglei Wang, research associate in the Department of Nutrition. “This allowed us to achieve a more comprehensive understanding of the association between iron intake and T2D risk, as well as potential metabolic pathways underlying this association.”

The researchers assessed the link between iron and T2D using 36 years of dietary reports from 206 615 adults (79% female) enrolled in the Nurses’ Health Studies I and II and the Health Professionals Follow-up Study. They examined participants’ intake of various forms of iron – total, haem, non-haem, dietary (from foods), and supplemental (from supplements) – and their T2D status, controlling for other health and lifestyle factors.

The researchers also analysed the biological mechanisms underpinning haem iron’s relationship to T2D among smaller subsets of the participants. They looked at 37 544 participants’ plasma metabolic biomarkers, including those related to insulin levels, blood sugar, blood lipids, inflammation, and two biomarkers of iron metabolism. They then looked at 9024 participants’ metabolomic profiles – plasma levels of small-molecule metabolites.

The study found a significant association between higher haem iron intake and T2D risk. Participants in the highest intake group had a 26% higher risk of developing T2D than those in the lowest intake group. In addition, the researchers found that haem iron accounted for more than half of the T2D risk associated with unprocessed red meat and a moderate proportion of the risk for several T2D-related dietary patterns. In line with previous studies, the researchers found no significant associations between intakes of non-haem iron from diet or supplements and risk of T2D.

The study also found that higher haem iron intake was associated with blood metabolic biomarkers associated with T2D. A higher haem iron intake was associated with higher levels of biomarkers such as C-peptide, triglycerides, C-reactive protein, leptin, and markers of iron overload, as well as lower levels of beneficial biomarkers like HDL cholesterol and adiponectin.

The researchers also identified a dozen blood metabolites – including L-valine, L-lysine, uric acid, and several lipid metabolites – that may play a role in the link between haem iron intake and TD2 risk. These metabolites have been previously associated with risk of T2D.

On a population level, the study findings carry important implications for dietary guidelines and public health strategies to reduce rates of diabetes, according to the researchers. In particular, the findings raise concerns about the addition of heme to plant-based meat alternatives to enhance their meaty flavor and appearance. These products are gaining in popularity, but health effects warrant further investigation.

“This study underscores the importance of healthy dietary choices in diabetes prevention,” said corresponding author Frank Hu, Fredrick J. Stare Professor of Nutrition and Epidemiology. “Reducing haem iron intake, particularly from red meat, and adopting a more plant-based diet can be effective strategies in lowering diabetes risk.”

The researchers noted that the study had several limitations, including the potential for incomplete accounting for confounders and measurement errors in the epidemiological data. In addition, the findings – based on a study population that was mostly white – need to be replicated in other racial and ethnic groups.

Source: Harvard T.H. Chan School of Public Health

Categories : Metabolic DisordersTags :

Do Dietitians have Weight Bases Towards Themselves and Others?

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In a survey-based study, UK dietitians exhibited significant weight stigma, both towards themselves and towards others.

The study in the Journal of Human Nutrition and Dietetics involved an online survey completed in 2022 by 402 registered dietitians aged 20–70 years old. Most respondents reported personally experiencing weight stigma prior to (51%) and after becoming (59.7%) registered dieticians, and nearly a quarter (21.1%) felt that their weight influenced their own ability to perform as a dietitian.

Weight stigma was experienced across the weight spectrum. Participants reported explicit (or conscious) weight bias attitudes, moderate beliefs that obesity is controllable, and implicit (or unconscious) anti-fat bias.

“The study highlights the need to address weight stigma and its implications within the dietetic profession,” the authors wrote.

Source: Wiley

Categories : Metabolic Disorders New Compounds and TreatmentsTags :

Controlling Lipid Levels with Less Side Effects Possible with New Drug

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Image Credit: Institute of Transformative Bio-Molecules (ITbM), Nagoya University

Researchers at Nagoya University in Japan have developed a new compound, ZTA-261, that binds to thyroid hormone receptor beta (THRβ). THRβ plays an important role in the regulation of lipid metabolism, which affects lipid levels in the blood. Mice administered the drug showed decreased lipid levels in the liver and blood, with fewer side effects in the liver, heart, and bones compared to existing compounds.  These findings, published in Communications Medicine, suggest that ZTA-261 is an effective treatment for lipid disorders such as dyslipidaemia.

Approximately one in ten people is classified as obese or overweight, often due to abnormalities in lipid metabolism. Abnormal levels of lipids in the blood, known as dyslipidaemia, lead to an increased risk of chest pain, heart attack, and stroke.

There is growing interest in developing treatments for dyslipidaemia that leverage the properties of thyroid hormones. Thyroid hormones increase overall metabolism through binding to two types of receptors: alpha (THRα) and beta (THRβ). The brain, heart, and muscle contain the α-subtype, whereas the liver and pituitary gland primarily express the β-subtype.

Treatments that rely on THR activation face challenges due to the side effects of thyroid hormones. Although THRα regulates cardiovascular functions, excess levels of thyroid hormone lead to adverse effects in nearby organs such as heart enlargement and muscle and bone wasting. On the other hand, activation of THRβ influences lipid metabolism without these severe side effects.

As a result, THRβ has become a desirable target for treating metabolic disorders such as dyslipidaemia. However, common treatments, such as the natural thyroid hormone T3, show almost no selectivity between the α and β receptors, making it difficult to avoid the severe side effects caused by binding to THRα.

To address this problem, a research team, including Masakazu Nambo, Taeko Ohkawa, Ayato Sato, Cathleen Crudden, and Takashi Yoshimura from Nagoya University’s WPI-ITbM, developed ZTA-261, a thyroid hormone derivative drug with a similar structure. To test its efficacy, they compared it with GC-1, another thyroid hormone derivative, and the natural thyroid hormone T3 in a mouse model.

They found that ZTA-261 had almost 100 times higher selectivity for THRβ than THRα. In comparison, GC-1 showed only a 20-fold difference in affinity, showing ZTA-261’s superior selectivity. This was confirmed by the significant increase in heart weight and bone damage indicators in T3-treated mice but not in those treated with ZTA-261.

“Our findings suggest that ZTA-261 is much less toxic than T3 and even less toxic than GC-1, which is known as a THRβ-selective compound,” Ohkawa said. “I find it amazing that the difference in THR beta-selectivity between ZTA-261 and GC-1 – 100 times selectivity versus 20 times selectivity – truly has this big an impact on heart and bone toxicity.”

As many drugs have been discontinued in preclinical trials because of their toxicity in the liver, the researchers checked for potential liver toxicity by measuring alanine aminotransferase (ALT) levels in the blood. Their findings confirmed the safety of the drug, finding no significant differences in ALT levels between mice treated with ZTA-261 and those treated with saline. Although these results are promising, more studies, including human trials, will be necessary before considering ZTA-261 for clinical use. However, this breakthrough represents a significant step forward in the development of safer treatments for lipid disorders.

“ZTA-261 has extremely high affinity and selectivity for THRβ among the thyroid hormone derivatives developed to date,” Nambo explained. “In the process of synthesising a variety of derivatives, we have found that precise molecular design is crucial for both selectivity and affinity. We believe that this study will provide new and important insights into drug discovery.”

Source: Institute of Transformative Bio-Molecules (ITbM), Nagoya Universityy

Categories : Metabolic DisordersTags :

Body Appreciation Varies Across Cultures

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Body appreciation levels are associated with internalisation of thin ideals and with sociocultural pressure, which vary by culture and age

Photo by I Yunmai on Unsplash

People from different cultures show both similarities and differences in how body appreciation, sociocultural pressure, and internalisation of thin ideals vary, according to a study published July 31, 2024 in the open-access journal PLOS ONE by Louise Hanson from Durham University, UK, and colleagues.

Body image is a multifaceted and complex phenomenon encapsulating how we think, behave, and feel about our body. To date, most body image research has focused on young, White, Western women, and has focused on negative rather than positive body image.

By contrast, Hanson and colleagues examined body appreciation, encapsulating positive thoughts and feelings regarding one’s own body. They also included participants not only from Western countries (ie, Australia, Canada, United Kingdom, United States of America), but also China and Nigeria. A final sample of 1186 women completed the questionnaires and were included in the analysis.

The results did not reveal significant difference in body satisfaction between women of different ages, but there was significant variation between cultures. Black Nigerian women had the highest body appreciation, followed by Eastern Asian Chinese women, with White Western women reporting lowest body appreciation. The findings suggest that ethnicity and culture are important influences on body appreciation and might act as protective factors that promote positive body image.

High internalisation of the thin ideal, and high perceived pressure about appearance from family, peers, and the media, were associated with lower body appreciation. Internalisation varied by age in some cultures: older White Western and Black Nigerian women reported lower thin-ideal internalisation than younger women, but Chinese women experienced the same thin-ideal internalisation across the lifespan.

For women from all cultures, older women reported lower perceived sociocultural pressure than younger women. White Western women experienced more perceived pressure from the media than Black Nigerian and Chinese women, but Chinese women reported the most pressure from peers. The results also showed that Black Nigerian women reported the lowest sociocultural pressure overall, and that Chinese women reported the most pressure.

The authors suggest that future studies should include more women in older age groups to obtain a fully representative picture of women’s body appreciation across the lifespan. In addition, further development of measurement tools is necessary for future research in cross-cultural contexts. According to the authors, the results of the current study could be used to target positive body image interventions to each culture. Further research may be required to develop effective interventions for each group.

The authors add: “We found that body appreciation was relatively stable across all ages and sociocultural pressure was evident in all cultures. However, the extent to which this pressure was experienced and where it came from differed across cultures.”

Provided by PLOS

Categories : Metabolic DisordersTags :

Recent Steps in Treatment and Management Show Promise in Stemming the Rise of Diabetes

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A new paper surveying advances in diabetes pathogenesis and treatment explores the complex factors contributing to the onset and progression of the disease, suggesting that an understanding of these dynamics is key to developing targeted interventions to reduce the risk of developing diabetes and managing its complications.

In a paper in a special 50th anniversary issue of the peer-reviewed journal Cell, the authors surveyed hundreds of studies that have emerged over the years looking at the causes underpinning types 1 (T1D) and 2 (T2D) diabetes and new treatments for the disease. They examine the role that genes, environmental factors, and social determinants of health play and diabetes’ effect on cardiovascular and kidney disease.

What they found shows there are many advances in treatments that could stem the tide of a disease that has struck millions of people around the globe and continues to grow. In addition, some of these advances could be used to treat other disorders. But there are still challenges ahead.

“As the prevalence of diabetes continues to grow around the world, it is important to understand the latest advancements in research so that clinicians can provide the best care to their patients, and patients can make informed choices that support improved health outcomes,” said lead author Dr E. Dale Abel, chair of the UCLA Department of Medicine. “This is an educational resource that integrates the latest research and trends in diabetes management, which may have implications for clinical practice as the diabetic patient population continues to grow.

“This review will be the go-to reference for physicians and researchers, providing a state-of-the-art update of where the field is currently, and where it is headed,” Abel added.

Most people are affected by type 2 diabetes, for which inadequate diet and obesity are important underlying causes. Type 1 diabetes accounts for fewer than 5% of all cases. As of 2021 about 529 million people around the world were diagnosed with diabetes, representing about 6.1% of the global population, or about one in 16 people. Prevalence in some regions is as high as 12.3%. Type 2 diabetes comprises about 96% of cases, with more than half due to obesity. Some 1.31 billion people are projected to have the disease by 2050, with prevalence rising as high as 16.8% in North Africa and the Middle East and 11.3% in Latin America and the Caribbean, the researchers write.

Genetics, the central nervous system, and the interplay between various organs as well as social and environmental factors such as food insecurity and air pollution play a role in development of diabetes.

But some recent discoveries represent significant strides toward managing and perhaps even reversing the disease. For instance, a 2019 study found that a 14-day course of the antibody teplizumab delayed the progression of type 1 diabetes from stage 1 to stage 3 by 24 months. A follow-up analysis in 2021 showed that the delay could be up to 32.5 months.

Based on these results, the U.S. Food and Drug Administration approved teplizumab as the first disease-modifying therapy for type 1 diabetes, the researchers write.

Advances in insulins with optimised pharmacokinetics, algorithm-driven subcutaneous insulin pumps, continuous glucose monitoring, and improved tools for self-management have significantly improved the quality of life and outcomes for people with stage 3 type 1 diabetes.

In addition, stem cells could replace insulin-producing cells that are lost in type 1 diabetes, Abel said.

For type 2 diabetes, three classes of glucose-lowering medicines that were introduced in the last 20 years – GLP1RAs (glucagon like peptide-1 receptor agonists), DPP-4 inhibitors, and SGLT-2 inhibitors – have enabled people to control their glucose levels without gaining weight and with a low risk of developing hypoglycaemia. Personalised and precision medicine approaches are being explored to target the molecular mechanisms behind diabetes. However, they must demonstrate that benefits are clinically superior to standard care and are cost-effective. Also, it remains to be seen if precision approaches can be implemented in all settings worldwide, including those with few resources.

Combinations of GLP1Ras and with molecules that target other receptors such as GIP have shown even greater efficacy in treating diabetes. Recent trials have also shown that they are very effective in treating obesity, certain types of heart failure and even sleep apnoea, in part because of their potency to induce weight loss and reduce inflammation. Clinical trials are now underway to test their efficacy in treating other disorders such as Alzheimer’s disease, Abel said.

“Advances in therapy now raise the hope of preventing or curing T1D and treating T2D in ways that not only improve metabolic homeostasis, but also concretely reduce the risk and progression of cardio-renal disease,” the researchers write. “Finally, as we understand and develop tools for discerning the underlying heterogeneity leading to diabetes and its complications, the stage will be set for targeting therapies and prevention strategies to optimize their impact, in ways that will be broadly applicable across diverse populations and availability of health care resources.”

Source: UCLA Health

Categories : Gastrointestinal Metabolic DisordersTags :

Targeting Inflammation may Not Help Reduce Liver Fibrosis in MAFLD

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Source: CC0

Researchers at UCLA Health uncovered new information about the role inflammation plays in mitigating liver fibrosis, which is associated with metabolic-associated fatty liver disease (MAFLD).  While inflammation in the liver has long been considered a prerequisite to developing liver fibrosis, the scarring and thickening of tissue that can impair the liver’s ability to function, this new research, published in the Journal of Clinical Investigation, suggests that reducing inflammation may not influence the extent of fibrosis. 

“Liver fibrosis is the critical feature that creates chronic liver disease and liver cancer. If we can keep fibrosis in check then we can meaningfully impact liver disease,” said Tamer Sallam, MD, corresponding author of the study and vice chair and associate professor in the department of medicine at the David Geffen School of Medicine at UCLA. 

“For decades we have believed that targeting inflammation is one of the most important ways to reduce MAFLD. But this new research indicates that inflammation, while still important, may not be the main driver of fibrosis.”

The study looked specifically at a protein called lipopolysaccharide binding protein (LBP), which is involved in the body’s immune response, and how LBP functions in mice. Findings showed that mice without LBP in their liver cells had lower levels of liver inflammation and better liver function but no change in fibrosis. 

In addition to mouse models, the researchers also studied genetic analyses from large human datasets and human tissue samples from MAFLD patients at different stages in the disease, to examine the consequence of loss of LBP function. The evidence combined showed that the LBP does not alter scar tissue markers. 

Sallam indicated a need to further explore how LBP influences inflammation and whether other factors can offer a more potent reduction in inflammation and have an impact on reducing fibrosis. 

“Reducing scar burden is one of the holy grails in the treatment of advanced liver diseases,” Sallam said. “These results suggest that certain ways of targeting inflammation may not be a viable option and that more directed therapies against other pathways could help us better target fibrosis and improve outcomes for patients.”

Source: UCLA Health