Category: Metabolic Disorders

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GLP-1 Agonists may Reduce Colorectal Cancer Risk

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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

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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

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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

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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

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Semaglutide Cuts CVD Events by 20% in People with Obesity or Overweight but not Diabetes

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In a large, international clinical trial, people with obesity or overweight but not diabetes taking semaglutide for more than three years had a 20% lower risk of cardiovascular disease outcomes and lost an average of 9.4% of their body weight.

Semaglutide, a GLP-1 medication primarily prescribed for people with Type 2 diabetes, is also FDA-approved for weight loss in people with obesity.

These results were shared in a late-breaking science presentation at the American Heart Association’s Scientific Sessions 2023 and the full manuscript was also published in The New England Journal of Medicine.

“This news is very encouraging for people with overweight or obesity because no treatment specifically directed at the management of obesity and overweight in people without Type 1 or Type 2 diabetes has been tested in a randomised trial and been shown to influence cardiovascular outcomes,” said lead study author A. Michael Lincoff, MD.

While prior research has confirmed the benefits of semaglutide in managing blood sugar, decreasing cardiovascular disease events and reducing weight in people with Type 2 diabetes, this study specifically investigated the potential impact of semaglutide on cardiovascular disease in people with overweight or obesity and cardiovascular disease who did not have either Type 1 or Type 2 diabetes.

In this randomised, controlled, double-blind trial, participants were assigned to take either 2.4mg of semaglutide (the FDA-approved semaglutide dose for weight management) or a placebo once a week, which is higher than the FDA-approved semaglutide dose limit for Type 2 diabetes of 2.0mg/week. Each person in the study used a ‘pen’ to inject the medicine or placebo into a skin fold in their stomach, thigh or upper arm each week on the same day, and the dose started at 0.24mg and gradually increased every four weeks up to 2.4mg, and mean follow-up for all participants was 40 months.

In addition to taking either semaglutide or placebo for the trial, all participants also received standard of care treatment for cardiovascular disease, such as cholesterol modifying medications, antiplatelet therapies, beta blockers or other treatments. The authors note that heart disease diagnoses varied among the participants, therefore, treatment was adjusted to meet each individual’s diagnosis and needs, as well as the treatment guidelines in their country of residence.

The study, which ran from October 2018 through June 2023, indicated the following:

  • There was a 20% reduction in the risk of heart attacks, strokes or death due to cardiovascular disease in the participants who took semaglutide, compared to the participants in the placebo group.
  • In the semaglutide group, the participants’ body weight was reduced, on average, by 9.4% compared to a reduction of 0.9% among the adults in the placebo group.
  • There were no new safety concerns found in the study, which researchers note is encouraging since the SELECT trial is the largest and longest (4.5 years) trial of semaglutide in adults without Type 1 or Type 2 diabetes.
  • The number of serious adverse events was lower in the semaglutide group. Previous studies of medications of the GLP-1 receptor agonist class have shown an association with gallbladder disorders, and in SELECT, there was a slightly higher rate of gallbladder disorders in the semaglutide vs placebo group (2.8% vs 2.3%, respectively).
  • Semaglutide was stopped more frequently than placebo for gastrointestinal intolerance, a known side effect of this class of medications; however, there was no higher rate of serious gastrointestinal events.
  • The researchers noted that this medication did not lead to an increased rate of pancreatitis, which has been a concern with prior medications of this type.
  • Of note, other weight-loss medications that are not GLP-1 receptor agonists have been associated with increased risks of psychiatric disorders or cancer; these risks were not elevated with semaglutide in the SELECT trial.

“It’s been estimated that within about ten years, over half of the world’s population will have overweight or obesity,” said Dr Lincoff. “And while GLP-1 medications are frequently prescribed for patients with vascular disease and Type 2 diabetes, there is a significant number of people who do not have Type 1 or Type 2 diabetes but do have vascular disease and overweight or obesity for whom these medications are often not available due to access to care issues, insurance coverage or other factors. This population may now potentially benefit from semaglutide, and importantly, our results indicate the magnitude of cardiovascular risk reduction with semaglutide among people without Type 1 or Type 2 diabetes is the same as what we have seen in people with Type 2 diabetes. Our findings expand the opportunity to treat patients who have overweight or obesity and existing heart disease without Type 1 or Type 2 diabetes, and we have a chance to significantly reduce their risk of a secondary cardiovascular event including death.”

Among the study limitations were including adults with prior cardiovascular disease, thereby not investigating primary prevention of cardiovascular disease (people with no history of a heart attack, stroke and/or peripheral artery disease). In addition, 28% of the study participants were female, which is not proportionate to the number of women with cardiovascular disease and overweight or obesity in the general population.

Additional analyses will include identifying the mediators of the cardiovascular benefit to determine to what extent the results were driven by reduction of metabolically unhealthy body fat, positive impacts on inflammation or blood sugar, direct effects of the medication itself on plaque build-up in the arteries, or a combination of one or more variables.

Source: American Heart Association

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Obesity Reduces the Rate at Which Energy is Burnt

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A new study published in the journal Obesity found that people at a healthy weight use more energy during the day, when most people are active and eat, while those who have obesity spend more energy during the night, when most people sleep. The study, from Oregon Health & Science University, also found that during the day, those with obesity have higher levels of insulin – a sign that the body is working harder to use glucose.

“It was surprising to learn how dramatically the timing of when our bodies burn energy differed in those with obesity,” said the study’s first author, Andrew McHill, PhD, an assistant professor in the OHSU School of Nursing and the Oregon Institute of Occupational Health Sciences at OHSU. “However, we’re not sure why. Burning less energy during the day could contribute to being obese, or it could be the result of obesity.”

Obesity is defined as having a Body Mass Index, or BMI, of 30 or more. Being overweight or obese increases the risk for health conditions such as high blood pressure and Type 2 diabetes.

Schedules and when people sleep, eat and exercise can also affect health, by either complementing or going against the body’s natural, daily rhythms. Every 24 hours, people experience numerous changes that are triggered by the human body’s internal clock. These changes normally occur at certain times of the day in order to best serve the body’s needs at any given hour.

McHill and the study’s senior author, Steven A. Shea, PhD, director of the Oregon Institute of Occupational Health Sciences at OHSU, focus their research on how circadian rhythms and sleep impact the human body. McHill leads the OHSU Sleep, Chronobiology and Health Laboratory.

While previous research has suggested circadian rhythm misalignment affects energy metabolism and glucose regulation, those studies have largely involved participants who have a healthy weight. To explore this further, McHill, Shea and colleagues organized a study that included people of different body sizes.

A total of 30 participants took part in the study, which involved them staying at a specially designed circadian research lab for six days. The study followed a rigorous circadian research protocol involving a schedule designed to have participants be awake and sleep at different times throughout each day.

After each period of sleep, volunteers were awakened to eat and participate in a variety of tests for the remaining time of each day. One test had participants exercise while wearing a mask that was connected to a machine called an indirect calorimeter, which measures exhaled carbon dioxide and helps estimate energy usage. Blood samples were also collected to measure glucose levels in response to an identical meal provided during each day.

Next, the research team plans to explore eating habits and hunger in people who are obese, as well as those who have a healthy weight. That new study will also follow up on a 2013 study, led by Shea, that found circadian clocks naturally increase food cravings at night.

Source: Oregon Health & Science University

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Collaboration Key to Address SA’s Fatal, Diabetes-linked Cardiovascular Disease Burden

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Only concerted multi-disciplinary collaboration and research will stem the tide of diabetes and diabetes-linked cardiovascular disease (CVD), the latter currently the leading cause of death locally and worldwide, claiming 17.9 million lives annually1.

This was the consensus among some of the world’s leading cardiologists and researchers gathered at the SA Heart Association’s annual congress aptly themed: ‘The Cardiac Collaboration,’ which took place at the Sandton Convention Centre in Johannesburg from 26-29 October this year.

Globally, CVD takes more lives than TB, HIV and malaria combined, while 215 South Africans are killed by CVD every day – with 80% of CVD and strokes being preventable.1,2 The prevalence of diabetes has also increased in South Africa, from 4.5% in 2010 to 12.7% in 2019. Of the 4.58 million people aged 20-79 years who were estimated to have diabetes in 2019, 52.4% were undiagnosed.3

With diabetes being a key driver of CVD – especially in Africa (with limited access to novel drugs and the prevalence of sugar-rich, poverty-driven lifestyles), the mutual consensus at this year’s congress was that collaboration is key.

Dr Zaheer Bayat, Chairperson of the Society for Endocrinology, Metabolism and Diabetes of South Africa (SEMDSA), told delegates that endocrinologists and cardiologists would have to work together to improve outcomes for diabetic patients, 30% of whom suffered cardiovascular events. He warned that a 134% increase of people living with diabetes was predicted over the next two decades, translating into a dramatic surge in chronic kidney disease, cardiovascular disease, blindness, and amputations.

Dr Bayat said he intends appealing for mass diabetes screening to find the 52% of people whom researchers estimate are undiagnosed. Ideally, this should be followed by access to cheaply acquired, effective new glucose-lowering drugs.

“The reality is that this country cannot afford all the new treatments for everyone – not private funders, not government. So, drugs are not really a solution – the best solution is to change lifestyle and prevent disease in the first place,” said Dr Bayat.

“We’re here to fight for our patients, not our pockets. Can we afford to have 52% of our patients not knowing they’re diabetic? People who should be contributing to our economy are living with diabetes and eventually dying,” he asserted.

Dr Bayat also said that globally, First World countries such as the USA and Sweden are reducing myocardial infarctions, strokes, and amputations, because they’re doing all the right things together. This included adopting a healthy lifestyle, effective management of sugar, blood pressure and cholesterol and smoking cessation.

“However, here in South Africa with private healthcare representing 15% of healthcare delivery but consuming 50% of the spend and the public sector representing 85% of the population and consuming the other half – we’re not doing nearly as well. With only 200 cardiologists in the country (one per 190 000 population), and even less nephrologists, we need to join together and change the trajectory of diabetes. We must work together to reduce morbidity and mortality,” said Dr Bayat.

According to the SA Heart Association, this graphically illustrates the importance of a multi-disciplinary approach, the very reason why the conference was called ‘The Cardiac Collaboration.’

The SA Heart Association has already begun forging formal ties with other academic societies and next year, it hopes to join and host joint sessions with collaborative meetings to connect a multidisciplinary team in order to achieve a well-rounded balance of care.

References:

  1. https://www.heartfoundation.co.za/wp-content/uploads/2017/10/CVD-Stats-Reference-Document-2016-FOR-MEDIA-1.pdf.
  2. https://world-heart-federation.org/what-we-do/prevention/#:~:text=An%20estimated%2080%25%20of%20cardiovascular,and%20%E2%80%9Cknowing%20your%20numbers%E2%80%9D.
  3. International Diabetes Federation. IDF Diabetes Atlas.10th ed. International Diabetes Federation; Brussels, Belgium: 2021. [Google Scholar] (primary). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218408/#:~:text=The%20prevalence%20of%20diabetes%20mellitus,%25%20were%20undiagnosed%20%5B5%5D. (secondary).
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Review Shows that Insulin can be Kept at Room Temperature for Longer

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Novolog insulin pen. Photo by Dennis Klicker on Unsplash

A new Cochrane review has found that insulin can be kept at room temperature for months without losing potency, offering hope to people living with diabetes in regions with limited access to healthcare or stable powered refrigeration. This affects millions of people living in low- and middle-income countries, particularly in rural areas, as well as people whose lives have been disrupted by conflict or natural disasters.

Insulin is an essential medicine for people with diabetes and current guidance states that before use it must be kept refrigerated to preserve its effectiveness. For millions of people with diabetes living in low- and middle-income countries, however, the harsh reality is that electricity and refrigeration are luxuries that are unavailable to them. Vulnerable populations in war-torn areas, disaster-prone regions, and climate crisis-affected areas, including those enduring extreme heat, also need solutions that don’t rely on powered fridges.

The new Cochrane review summarises results of different studies investigating what happens to insulin when stored outside of fridges, including previously unpublished data from manufacturers. The review found that it is possible to store unopened vials and cartridges of specific types of human insulin at temperatures of up to 25°C for a maximum of six months, and up to 37°C for a maximum of two months, without any clinically relevant loss of insulin activity. Data from one study showed no loss of insulin activity for specific insulin types when stored in oscillating ambient temperatures of between 25°C and 37°C for up to three months. This fluctuation resembles the day-night temperature cycles experienced in tropical countries.

The research team, led by Bernd Richter from the Institute of General Practice, Medical Faculty of the Heinrich-Heine-University in Düsseldorf, Germany, conducted comprehensive research to investigate insulin stability under various storage conditions. The review analysed a total of seventeen studies, including laboratory investigations of insulin vials, cartridges/pens, and prefilled syringes, demonstrating consistent insulin potency at temperatures ranging from 4°C to 37°C, with no clinically relevant loss of insulin activity.

Bernd stressed the significance of this research, particularly for people living with type 1 diabetes, where “insulin is a lifeline, as their very lives depend on it. While type 2 diabetes presents its challenges, type 1 diabetes necessitates insulin for survival. This underscores the critical need for clear guidance for people with diabetes in critical life situations, which many individuals lack from official sources.

“Our study opens up new possibilities for individuals living in challenging environments, where access to refrigeration is limited. By understanding the thermal stability of insulin and exploring innovative storage solutions, we can make a significant impact on the lives of those who depend on insulin for their well-being.”

These findings can help communities facing challenges in securing constant cold storage of insulin. They provide reassurance that alternatives to powered refrigeration of insulin are possible without compromising the stability of this essential medicine. It suggests that if reliable refrigeration is not possible, room temperature can be lowered using simple cooling devices such as clay pots for insulin storage.

The researchers have also identified uncertainties for future research to address. There remains a need to better understand insulin effectiveness following storage under varying conditions. Further research is also needed on mixed insulin, influence of motion for example when insulin pumps are used, contamination in opened vials and cartridges, and studies on cold environmental conditions.

Source: Cochrane Reviews

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Diabetes Worsens Colorectal Cancer Survival Odds by 41%

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In an analysis of information on adults with colorectal cancer, patients who also had diabetes, particularly those with diabetic complications, faced a higher risk of early death. The results are published in CANCER, a peer-reviewed journal of the American Cancer Society.

For the study, Kuo‐Liong Chien, MD, PhD, of National Taiwan University, and his colleagues examined data registered between 2007 and 2015 in the Taiwan Cancer Registry Database, which is linked to health insurance and death records. Their analysis included 59 202 individuals with stage I–III colorectal cancer who underwent potentially curative surgery to remove their tumours. Among these patients, 9448 experienced a cancer recurrence and 21 031 died from any cause during the study period.

Compared with individuals without diabetes, those with uncomplicated diabetes were at a minimally or insignificantly higher risk of all‐cause and cancer‐specific death, whereas those with complicated diabetes had 85% higher odds of death from any cause and 41% higher odds of death from cancer. These associations were more pronounced in women and in patients with early‐stage colorectal cancer.

Also, compared to patients without diabetes, patients with uncomplicated or complicated diabetes had a 10–11% higher risk of colorectal cancer recurrence.

The mechanisms behind the relationship between diabetic severity and poor colorectal cancer prognosis could involve various pathways and responses triggered by high insulin and glucose levels in the blood, as well as elevated inflammatory states, which are characteristic of type 2 diabetes.

“While a higher diabetes prevalence was noted in patients with colorectal cancer, the study suggests that coordinated medical care involving multiple specialists can help prevent diabetes complications, potentially improving long-term colorectal cancer oncological outcomes, particularly in women and patients with early-stage cancer,” said Dr Chien.

Source: Wiley

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Could an Existing Drug be Repurposed to Treat Type 1 Diabetes?

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A new study appearing in Cell Medicine Reports suggests that an existing drug could be repurposed to treat type 1 diabetes, potentially reducing dependence on insulin as the sole treatment.

Type 1 diabetes, an autoimmune disease which attacks insulin-producing beta cells in the pancreas, is traditionally managed by replacing the missing insulin with injections which, though effective, can be expensive and burdensome.

The research, led by researchers at the University of Chicago Medicine and Indiana University, focuses on α-difluoromethylornithine (DFMO), which inhibits an enzyme that plays a key role in cellular metabolism. The latest translational results are a culmination of years of research: In 2010, while corresponding author Raghu Mirmira, MD, PhD, was at Indiana University, he and his lab performed fundamental biochemistry experiments on beta cells in culture. They found that suppressing the metabolic pathway altered by DFMO helped protect the beta cells from environmental factors, hinting at the possibility of preserving and even restoring these vital cells in patients diagnosed with type 1 diabetes.

The researchers confirmed their observations preclinically in zebrafish and then in mice before senior author Linda DiMeglio, MD, MPH, Edwin Letzter Professor of Pediatrics at Indiana University School of Medicine and a pediatric endocrinologist at Riley Children’s Health, launched a clinical trial to evaluate the safety and tolerability of the drug in type 1 diabetes patients. The results of the trial, which was funded by the Juvenile Diabetes Research Foundation (JDRF) and used DMFO provided by Panbela Therapeutics, indicated that the drug is safe for type 1 diabetes patients and can help keep insulin levels stable by protecting beta cells.

“As a physician-scientist, this is the kind of thing we’ve always strived for – to discover something at a very basic, fundamental level in cells and find a way to bring it into the clinic,” said Mirmira, who is now Professor of Medicine and an endocrinologist at UChicago Medicine. “It definitely underscores the importance of supporting basic science research.”

“It’s been truly thrilling to witness the promising results in the pilot trial after this long journey, and we’re excited to continue our meaningful collaboration,” said DiMeglio.

Importantly, DFMO has already been FDA-approved as a high dose injection since 1990 for treating African Sleeping Sickness and received breakthrough therapy designation for neuroblastoma maintenance therapy after remission in 2020. Pre-existing regulatory approval could potentially facilitate its use in type 1 diabetes, saving effort and expense and getting the treatment to patients sooner.

“For a drug that’s already approved for other indications, the approval timeline can be a matter of years instead of decades once you have solid clinical evidence for safety and efficacy,” said Mirmira. “Using a new formulation of DFMO as a pill allows patients to take it by mouth instead of needing to undergo regular injections, and it has a very favorable side effect profile. It’s exciting to say we have a drug that works differently from every other treatment we have for this disease.”

To follow up on the recently published results, a multi-centre clinical trial was launched to gather even stronger data regarding the efficacy of DFMO as a type 1 diabetes treatment.

“With our promising early findings, we hold hope that DFMO, possibly as part of a combination therapy, could offer potential benefits to preserve insulin secretion in individuals with recent-onset type 1 diabetes and ultimately also be tested in those who are at risk of developing the condition,” said Sims.

“A new era is dawning where we’re thinking of novel ways to modify the disease using different types of drugs and targets that we didn’t classically think of in type 1 diabetes treatment,” said Mirmira.

Source: University of Chicago Medicine