Tag: diabetes

Categories : Ageing Metabolic DisordersTags :

Metformin Also Seems to Protect Against Muscle Atrophy and Fibrosis

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Diabetes and muscle function might seem like they don’t have much to do with each other. But University of Utah Health researchers have discovered that metformin can also prevent muscle atrophy and muscular fibrosis – which can help the elderly bounce back faster from injury or illness. Their findings were published in the journal Aging Cell.

Metformin, the researchers found, actually has surprising applications on a cellular level. It can target senescent cells which impact muscle function. Senescent cells secrete factors associated with inflammation that may underlie fibrotic tissue, a hardening or scarring of tissues. They also discovered that metformin also reduces muscle atrophy.

“We’re interested in clinical application of this research,” says Micah Drummond, PhD, senior author of the study and professor of physical therapy and athletic training at the College of Health. “For example, knee surgeries in the elderly are notoriously hard to recover from. If we give a metformin-type agent during the recovery period, could we help the muscles get back to normal faster?”

Reinvigorating muscle recovery

Ageing comes with the risks of falls, hospitalisation, or developing chronic disease, which are more likely with muscle disuse. The research team wanted to find a therapeutic solution that could properly target both disuse atrophy and muscle recovery.

There’s an optimal level of senescent cells that are beneficial, no matter your age. In younger, healthier people, short-term senescence is required for a proper recovery from injury, and completely blocking the senescent effect impedes the body’s efforts to heal. Typically, a younger person can bounce back more easily after muscle disuse without the use of an intervention such as Metformin.

“In the case of aging, we know that there’s immune dysfunction,” says Drummond. “As you get older, it becomes harder for your body to clear senescent cells and they accumulate. That’s one reason recovery is much slower for the elderly after periods of disuse.”

Metformin’s anti-senescent properties have been demonstrated through pre-clinical studies. To test the intervention in humans, the team recruited 20 healthy male and female older adults for a multi-week study. They had participants undergo a muscle biopsy and MRI before the intervention, which involved five days of bed rest. One group of 10 received metformin and the other 10 received placebo pills during a two-week run-in period, then each group continued the placebo or metformin treatment during bed rest.

After the bed rest, participants received another muscle biopsy and MRI, then ceased treatments. All patients completed a seven-day re-ambulation period followed by a final muscle biopsy.

“We saw two things in our study,” Drummond says. “When participants took Metformin during a bed rest, they had less muscle atrophy. During the recovery period, their muscles also had less fibrosis or excessive collagen. That build-up can make it harder for the muscle to properly function.”

Tying these results to senescence, the research team examined muscle biopsies from study participants. They found that the participants who took Metformin had fewer markers of cellular senescence.

“This is the first paper that has made the direct connection between a therapy targeting cellular senescence and improved muscle recovery following disuse in aging,” says lead author Jonathan Petrocelli, PhD He explains that metformin helps muscle cells better remodel and repair tissue during periods of recovery after inactivity.

“Our real goal is to have patients maintain their muscle mass and function as they age, because atrophy and weakness are some of the strongest predictors of disease development and death,” he says.

Drummond’s team is following up on these findings by examining combining the drug with leucine, an amino acid that promotes growth and could accelerate recovery even further. They’ve already demonstrated the potency of this combination in preclinical animal studies.

“Metformin is cheap, effective and quite safe, so it’s exciting to see that we can use it to accelerate recovery for older individuals,” adds Drummond.

Source: University of Utah Health

Categories : Medical Research & Technology Metabolic DisordersTags :

This Open-source Autoinjector Could Be Made for a Tenth of the Price of Commercial Ones

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Research team led by Joshua Pearce has developed a new 3-D printed, completely open-source autoinjector for a tenth of the cost of a commercially purchased product. (Photo by Anjutha Selvaraj)

A new study published in PLOS One describes the development of a spring-driven autoinjector for the delivery of insulin and other medications. This device, made from a combination of 3D-printed and commercially available parts, could cost less than $7 to make while a store-bought version is closer to $70.

Sir Frederick Banting was an inspiration for a new open source self-administering drug delivery device. Long before open source was an option or even a concept, the now-celebrated former University of Western Ontario lecturer refused to patent insulin because he wanted it to be inexpensive and widely available for the betterment of all.

A century after Banting won the Nobel Prize for his discovery, Western researchers led by engineering and Ivey Business School professor Joshua Pearce has developed a new 3D printed, completely open-source autoinjector – a device designed to deliver a single dose of medicine – for a tenth of the cost of a commercially purchased product.

“I think of this device, like so much of what we’re doing here at Western, very much as following the golden rule: do unto others as you would have them do unto you,” said Pearce. “It makes the world slightly better to have an open-source version of an autoinjector, especially for people who don’t have access or the financial means to purchase a proprietary one.”

Autoinjectors are used all over the world by health care practitioners, patients and parents (for children under 12) to inject insulin into people with diabetes. Other chronic conditions such as psoriasis, multiple sclerosis and rheumatoid arthritis can also be treated using an autoinjector. The device is also essential during emergency conditions for migraine, anaphylaxis and status epilepticus patients, as well.

Pearce, along with research assistant Anjutha Selvaraj and post-doctoral associate Apoorv Kulkarni, have created the new open-source autoinjector to make the device – considered more reliable and easier to operate than a simple syringe for self-administering medications into the body – an equitable alternative to the more expensive options.

Studies show self-administration of medications by patients improves compliance and comfort and empowers patients as they are actively involved in their personal care. It also allows patients to avoid time-consuming and costly visits to the hospital, which is a bonus for overburdened health care systems.

And, as with all open-source hardware, there is money to be made as the digitally replicable device enables low-cost distributed manufacturing. All materials, designs and assembly instructions are also detailed in the new study, and the effectiveness of the autoinjector is tested against the current standard (ISO 11608-1:2022) for needle-based injection systems. It is released with an open source hardware license. Companies wishing to commercialise the device will still need to meet their own local regulatory requirements.

“Does this design make it possible for other people to commercialise it anywhere in the world? Yes, it does,” said Pearce. “But more importantly, it means we can really target isolated communities, whether they’re in northern Canada, Africa or anywhere in else in the world, and improve health care access for everyone.”

Source: University of Western Ontario

Categories : Metabolic DisordersTags :

Even Modest Alcohol Intake Does not Reduce Diabetes, Obesity Risk

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Having only one or two alcoholic drinks per day does not protect against endocrine conditions such as obesity and type 2 diabetes, according to a new study published in the Journal of Clinical Endocrinology & Metabolism.

It is widely accepted that excessive alcohol consumption causes a wide range of health issues and is thus a major public health concern. Whether modest alcohol consumption has beneficial health effects remains controversial, however, due to the limited power of observational studies.

The researchers used mendelian randomisation (MR), which can help to mitigate biases due to confounding and reverse causation in observational studies, and evaluate the potential causal role of alcohol consumption.

“Some research has indicated that moderate drinkers may be less likely to develop obesity or diabetes compared to non-drinkers and heavy drinkers. However, our study shows that even light-to-moderate alcohol consumption (no more than one standard drink per day) does not protect against obesity and type 2 diabetes in the general population,” said Tianyuan Lu, PhD, from McGill University in Québec, Canada. “We confirmed that heavy drinking could lead to increased measures of obesity (body mass index, waist-to-hip ratio, fat mass, etc) as well as increased risk of type 2 diabetes.”

The researchers assessed self-reported alcohol intake data from 408 540 participants in the U.K. Biobank and found people who had more than 14 drinks per week had higher fat mass and a higher risk of obesity and type 2 diabetes. An extra drink per week was associated with an increased of 8% for diabetes risk and 10% for obesity risk.

These associations were stronger in women than in men. No data supported the association between moderate drinking and improved health outcomes in people drinking less than or equal to seven alcoholic beverages per week.

Source: The Endocrine Society

Categories : Metabolic Disorders PaediatricsTags :

Autism in Children Linked to Diabetes, Dyslipidaemia

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Studies have shown that children with autism spectrum disorder (ASD) have an increased risk of obesity. In turn, obesity has been linked to increased risks for diabetes, dyslipidaemia and other cardiometabolic disorders. However, the question of whether or not there is an association between autism, cardiometabolic disorders and obesity remains largely unanswered.

To help provide an insight into the possible link between ASD and cardiometabolic diseases, Texas Tech University researchers conducted a systematic review and meta-analysis. Their findings were published in JAMA Pediatrics.

In this latest meta-analysis, the researchers evaluated 34 studies that included 276 173 participants who were diagnosed with ASD and 7 733 306 who were not. The results indicated that ASD was associated with greater risks of developing diabetes overall, including both type 1 and type 2 diabetes.

The meta-analysis also determined that autism is associated with increased risks of dyslipidaemia and heart disease, though there was no significant increased risk of hypertension and stroke associated with autism. However, meta-regression analyses revealed that children with autism were at a greater associated risk of developing diabetes and hypertension when compared with adults.

Study leader Chanaka N. Kahathuduwa, MD, PhD, said the overall results demonstrate the associated increased risk of cardiometabolic diseases in ASD patients, which should prompt clinicians to more closely monitor these patients for potential contributors, including signs of cardiometabolic disease and their complications.

“We have established the associations between autism and obesity, as well as autism and cardiometabolic disease, including diabetes and dyslipidaemia,” Kahathuduwa said. “We don’t have data to support a conclusion that autism is causing these metabolic derangements, but since we know that a child with autism is more likely to develop these metabolic complications and derangements down the road, I believe physicians should evaluate children with autism more vigilantly and maybe start screening them earlier than the usual.”

Kahathuduwa also believes the study shows that physicians should think twice before prescribing medications such as olanzapine that are well known to have metabolic adverse effects to children with autism.

“Our findings should also be an eye opener for patients with autism and parents of kids with autism to simply be mindful about the higher risk of developing obesity and metabolic complications,” Kahathuduwa added. “Then they can talk with their physicians about strategies to prevent obesity and metabolic disease.”

Kahathuduwa said the next logical step for the collaborative team would be to generate evidence that either supports or rejects causality with regard to the observed associations.

Source: Texas Tech University Health Sciences Center

Categories : Ageing Cardiovascular DiseaseTags :

Increasing Age Blunts the Strength of Certain Stroke Risk Factors

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Hypertension and diabetes are known risk factors for stroke, but now a new study shows that the amount of risk may decrease as people age. The study is published in Neurology.

“High blood pressure and diabetes are two important risk factors for stroke that can be managed by medication, decreasing a person’s risk,” said study author George Howard, DrPH, of the University of Alabama at Birmingham School of Public Health. “Our findings show that their association with stroke risk may be substantially less at older ages, yet other risk factors do not change with age. These differences in risk factors imply that determining whether a person is at high risk for stroke may differ depending on their age.”

The study involved 28 235 people who had never had a stroke and were followed for 11 years. Risk factors included hypertension, diabetes, smoking, atrial fibrillation, heart disease and left ventricular hypertrophy. Because of the well-known higher stroke risk in Black people (comprising 41% of participants), race was also considered as part of the assessed risk factors, Howard added.

Researchers followed up with participants every six months, confirming strokes by reviewing medical records.

During the study, there were 1405 strokes over 276 074 person-years. Participants were divided into three age groups. The age ranges for those groups varied slightly depending on the data being analysed by researchers. In general, the younger group included participants ages 45–69, the middle group included people in their late 60s to 70s and the older group included people 74 and older.

Researchers found that people with diabetes in the younger age group were approximately twice as likely to have a stroke as people of similar age who did not have diabetes, while people with diabetes in the older age group had an approximately 30% higher risk of having a stroke than people of similar older age who did not have diabetes.

Researchers also found that people with high blood pressure in the younger age group had an 80% higher risk of having stroke than people of similar age without high blood pressure while that risk went down to 50% for people with high blood pressure in the older age group compared to people of similar age without high blood pressure.

With race/ethnicity as a risk factor, Black participants in the younger age group compared to White participants in that group, a difference which decreased in the older age group. For stroke risk factors such as smoking, atrial fibrillation and left ventricular hypertrophy, researchers did not find an age-related change in risk.

“It is important to note that our results do not suggest that treatment of high blood pressure and diabetes becomes unimportant in older age,” said Howard. “Such treatments are still very important for a person’s health. But it also may be wise for doctors to focus on managing risk factors such as atrial fibrillation, smoking and left ventricular hypertrophy as people age.”

Howard also noted that even where the impact of risk factors decreases with age, the total number of people with strokes at older ages may still be larger since overall risk of stroke increases with age. For example, in the younger age group for hypertension, researchers estimate that about 2.0% of normotensive people had a stroke, compared to 3.6% of hypertensive people. In the older age group, about 6.2% of normotensive people had a stroke, compared to 9.3% of hypertensive people.

A limitation of the research was that participants’ risk factors were assessed only once at the start of the study, and it’s possible they may have changed over time.

Source: American Academy of Neurology 

Categories : General InterestTags :

Looking Back at 2022: Pandemic Fades but Other Challenges Remain

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The year 2022 finally saw the COVID pandemic petering out, largely through the less-lethal but still highly contagious Omicron variant. Significant strides were made in cancer and Alzheimer’s research, although not without controversy. Amid growing public healthcare challenges in South Africa, the NHI Bill advanced closer to reality.

As Omicron displayed greatly reduced severity compared to prior strains, South African medical experts were some of the first to justify no longer being at ‘code red’. This brought an end to the cycles of lockdowns and travel restrictions characterised by the two previous years.

It even saw the lifting of some aspects of China’s ultra-strict ‘zero-COVID’ policy, with citizens paying online tribute to the memory of the heroic doctor who defied government censorship to warn the world. However, the pandemic’s true cost became apparent as the World Health Organization put global excess deaths for the pandemic at almost 15 million.

A number of key medical advances were made during the year for a variety of conditions. Studies showed that administering steroids after COVID hospitalisation with severe inflammation reduced mortality up to one year post-infection.

COVID was found to be linked to a spate of new-onset Type 1 diabetes, but this may just have been due to medical checkups as a result of developing COVID. The rheumatoid arthritis drug auranofin was found to relieve diabetes symptoms. And research suggested a possible way to deliver insulin and cancer drugs orally, by adding a ‘tag’ that lets them enter the bloodstream through the intestines.

The fields of cancer and Alzheimer’s research was rocked by findings of numerous red flags. This controversy did not stop real progress: the first new drug that had any real effectiveness against Alzheimer’s disease was confirmed in a historic trial. Fortunately, the flu jab also seems to protect against developing the disease. Indeed, serious infections appear to increase the risk of both Alzheimer’s and Parkinson’s.

In advanced ER-positive, HER-2 negative breast cancers, the new drug capivasertib halved the rate of progression.

It was also revealed that humans are paying through the nose for common medications compared to those that animals receive. Antimicrobial resistance also remains a growing problem, causing an estimated 1.2 million deaths in 2019.

A major South African Medical Research Council (SMARC) study told a familiar story: unsafe sex, interpersonal violence, obesity, hypertension, and alcohol consumption are the top risk factors for disease and death in South Africa.

Despite lessons learned in the COVID pandemic, South Africa saw the progression of systemic problems in healthcare such as a critical shortage of nurses. Dr Tim de Maayer’s open letter on appalling conditions at Rahima Moosa exposed deep-seated problems in Gauteng’s public healthcare system. This was followed by the shock resignation of top cancer surgeon Professor Carol-Ann Benn. The appointment of Nomantu Nkomo-Ralehoko as Gauteng Health MEC should hopefully change the province’s situation.

As for the National Health Insurance (NHI) Bill, medical aids have aimed to reposition themselves in the new uncertain paradigm while the threat of a mass exodus of healthcare professionals from the country still hangs in the air. A slew of legal challenges now await the Bill, which still has no details on how it will be financed.

Categories : New Compounds and TreatmentsTags :

A New Drug Class Lowers Cholesterol by 70%

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A new study using mouse models describes an orally administered small-molecule drug that reduces lowers cholesterol by 70% by preventing the degradation of low-density lipoprotein (LDL) receptors. Published in Cell Reports, the findings point to a previously unrecognised strategy for managing cholesterol – one which may also impact cancer treatments.

“Cholesterol lowering is one of the most important therapies we have to prolong life and protect people from heart disease, which is still the number one cause of morbidity and mortality in the Western world,” said senior author Jonathan S. Stamler, MD, professor at Case Western Reserve School of Medicine.

“Statins only lower cholesterol so far. This is a drug class that we think would represent a new way to lower cholesterol, a new way to hit PCSK9.”

Study Findings

Central to cholesterol regulation are LDL receptors, which sit at the surface of liver cells and remove cholesterol from the blood, thereby lowering serum levels. PCSK9 in the bloodstream controls the number of LDL receptors by marking them for degradation. Therefore, agents that inhibit PCSK9 increase the number of LDL receptors that remove cholesterol.

Nitric oxide is a molecule that is known to prevent heart attacks by dilating blood vessels. In the new study, Stamler and colleagues show that nitric oxide can also target and inhibit PCSK9, thus lowering cholesterol. They identify a small molecule drug that functions to increase nitric oxide inactivation of PCSK9. Mice treated with the drug display a 70% reduction in LDL cholesterol.

Beyond Cholesterol to Cancer

In addition to impacting the field of cholesterol metabolism, the findings may impact patients with cancer, as emerging evidence suggests targeting PCSK9 can improve the efficacy of cancer immunotherapies.

“PCSK9 not only targets LDL receptors for degradation, it also mediates the degradation of MHC 1 on lymphocytes, which is used for recognition of cancer cells” said Stamler. “PCSK9 is effectively preventing your lymphocytes from recognising cancer cells. So, if you inhibit PCSK9, you can boost the body’s cancer surveillance. There may be an opportunity one day to apply these new drugs to that need.”

Categories : Medical Research & TechnologyTags : 1 Comment

Delivering Cancer and Diabetes Drugs in Pills Instead of Injections

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In a new Journal of the American Chemical Society paper, researchers describe how they are developing a new way for diabetes and cancer patients to manage their conditions by enabling drugs to be delivered in pill form instead of through injections.

Some drugs for these diseases are water soluble, so transporting them through the intestines, is not feasible and makes them impossible to administer orally. However, UCR scientists have created a chemical “tag” that can be added to these drugs, allowing them to enter blood circulation via the intestines.

This tag is composed of a small peptide. “Because they are relatively small molecules, you can chemically attach them to drugs, or other molecules of interest, and use them to deliver those drugs orally,” said research leader Min Xue, UC Riverside chemistry professor.

Xue’s laboratory was testing something unrelated when the researchers observed these peptides making their way into cells.

“We did not expect to find this peptide making its way into cells. It took us by surprise,” Xue said. “We always wanted to find this kind of chemical tag, and it finally happened serendipitously.”

This observation was unexpected, Xue said, because previously, the researchers believed that this type of delivery tag needed to carry positive charges to be accepted into the negatively charged cells. Their work with this neutral peptide tag, called EPP6, shows that belief was not accurate.

Testing the peptide’s ability to move through a body, the Xue group teamed up with Kai Chen’s group in the Keck School of Medicine at the University of Southern California and fed the peptide to mice. With PET scans, the team observed the peptide accumulating in the intestines, and documented its ultimate transfer into the animals’ organs via the blood.

Having proven the tag successfully navigated the circulatory systems through oral administration, the team now plans to demonstrate that the tag can do the same thing when attached to a selection of drugs. “Quite compelling preliminary results make us think we can push this further,” Xue said.

Many drugs, including insulin, must be injected. The researchers are hopeful their next set of experiments will change that, allowing them to add this tag to a wide variety of drugs and chemicals, changing the way those molecules move through the body.

“This discovery could lift a burden on people who are already burdened with illness,” Xue said.

Source: University of California – Riverside

Categories : Metabolic DisordersTags :

Strengthening the Case for the ‘Trigger Finger’ and Diabetes Link

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Diabetes - person measures blood glucose
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Locked fingers, known as ‘trigger finger’, are more common among people with diabetes than in the general population, finds a study published in Diabetes Care. A study led by Lund University in Sweden shows that the risk of being affected increases with hyperglycaemia.

Trigger finger means that one or more fingers, often the ring finger or thumb, ends up in a bent position that is difficult to straighten out. It is due to the thickening of tendons, which bend the finger, and their connective tissue sheath, which means that the finger becomes fixed in a bent position towards the palm. It is a painful condition that can often be treated with cortisone injections, but sometimes requires surgery.

“At the hand surgery clinic, we have noted for a long time that people with diabetes, both type 1 and type 2, are more often affected by trigger finger. Over 20 percent of those who require surgery for this condition are patients who have, or will develop, diabetes,” says Mattias Rydberg, doctoral student at Lund University, resident physician at Skåne University Hospital and first author of the study.

To study whether blood sugar dysregulation increases the risk of trigger finger, the researchers examined two registers. The prevalence of trigger finger in the general population 1–1.5%, but is 10-15% among those who have diabetes, particularly in type 1 diabetes.

The study added to the evidence for a link between blood sugar and trigger finger. Hyperglycaemia increased the risk of being affected by trigger finger among both men and women in the groups with type 1 diabetes and type 2 diabetes. The group of men with the worst regulated blood sugar (HbA1c > 64) had up to 5 times as high a risk of being affected than men with well-regulated (HbA1c < 48) blood sugar.

“However, we can’t know for certain if any of the groups seek healthcare more often than others which could be a factor that affects the results,” said Mattias Rydberg.

The mechanism, or mechanisms, behind the increased risk are unknown, but there are theories that high blood sugar makes both the flexor tendons and their connective tissue sheaths thicker, thus causing them to lock more easily. It was previously known that those with unregulated blood sugar are more prone to nerve entrapments in the hand.

“It is important to draw attention to the complications from diabetes and how they can arise in order to discover them early, which enables faster treatment and thus a better outcome. In addition to nerve compressions and trigger finger, there may also be a link with thickening of the connective tissue in the palm (Dupuytren’s contracture), impairment of joint movement and the risk of arthritis at the base of the thumb. The mechanisms behind these complications probably differ in the case of diabetes. The results of this study are interesting, as we can show that blood sugar dysregulation has a connection with the development of trigger finger,” said Lars B. Dahlin, professor at Lund University and consultant in hand surgery at Skåne University Hospital.

Future research will measure the effectiveness of operating on patients with diabetes who are affected by trigger finger.

“From our experience at the clinic, surgery goes well and there are few complications, but it takes a little longer for patients with type 1 and type 2 diabetes to regain full movement and function. We want to investigate this hypothesis further. Another interesting idea is to see if trigger finger could be a warning signal for type 2 diabetes. It is far from all who are affected by trigger finger that have diabetes, but it would be interesting to see if by using modern registers we can discover those who are in the risk zone for developing diabetes,” concluded Mattias Rydberg.

Source: Lund University

Categories : Metabolic DisordersTags : 1 Comment

Arthritis Drug Auranofin may Improve Diabetes Symptoms

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Researchers have found that rheumatoid arthritis drug auranofin can potentially be repurposed to improve diabetes-associated symptoms. The study, which used a mouse model, appeared in the journal Cell Metabolism.

Although clear links have been identified between inflammation in white adipose tissue and insulin resistance in humans and rodents, broad anti-inflammatory treatments lack durable clinical efficacy on diabetes. In the current study, the researchers delved deeper into this association between inflammation and diabetes by looking for existing drugs that might affect both conditions.

“We computationally screened a small-molecule dataset and identified auranofin, an FDA-approved drug that has been used to treat rheumatoid arthritis, a condition involving inflammation,” said first and co-corresponding author Dr Aaron R. Cox, instructor of medicine-endocrinology, diabetes and metabolism at Baylor. “Auranofin exerts anti-inflammatory properties, which many people suspected would be beneficial in obesity and diabetes; however, nothing was really known about how it might affect metabolism.”

The team evaluated the metabolic effects of auranofin in a mouse model of diabetes in which the animals consume a high-fat diet.

“We discovered that auranofin has anti-inflammatory and anti-diabetic effects that are independent from each other,” said co-corresponding author Dr Sean Hartig, associate professor at Baylor. “Auranofin improved insulin sensitivity, or the body’s ability to respond to insulin to keep blood sugar at healthy levels. The drug also normalised obesity-associated changes such as hyperinsulinaemia in the mouse model. In addition, we found that auranofin accumulation in white adipose tissue reduced inflammatory responses without altering body composition in obese mice.”

Looking into the mechanism of these metabolic changes, the team discovered that auranofin’s anti-diabetic effects involved reduction of leptin levels. Leptin is a hormone whose levels markedly increase in obesity, contributing to insulin resistance and diabetes. In addition, auranofin restored white adipose tissue’s ability to respond to catecholamines, which are signals that increase metabolic activities in adipose tissue, triggering the burning of lipids at a higher rate.

“These changes coupled together contribute to the overall improvement in insulin sensitivity of the mice, leading to blood glucose control, which is the ultimate goal of diabetes treatments,” Dr Cox said. “High levels of glucose in the blood are detrimental to many tissues in the body. Uncontrolled, diabetes can lead to organ failure.”

Source: Baylor College of Medicine