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While recommended screenings beginning at age 45 have helped decrease colorectal cancer cases in older adults, cancer rates are continuing to increase in younger populations.

Since 2009, the rate of new colorectal cancer diagnoses in patients under age 50 has increased by 2% each year.

"When I started practice and residency around 2010, Id uncommonly see patients who were less than 50 years old," said Jordan Kharofa, MD, associate professor in the Department of Radiation Oncology in the University of Cincinnatis College of Medicine, a University of Cincinnati Cancer Center member and a UC Health physician. "But more and more were seeing these patients in our clinics now to the point where it doesnt strike us as an exception to the rule."

The research is still unclear exactly what is causing increased cancer rates in young people, but Kharofa said one hypothesis is that patients diets and the bacteria in their gut are contributing factors. This led he and his colleagues to research the relationship between bacteria in the fecal microorganisms, or microbiome, and rates of colorectal cancer in younger populations.

Kharofa delivered a poster presentation on his findings at the recent American Society of Clinical Oncology annual meeting in Chicago.

The microbiome is a term used for the collection of microbes, including microorganisms like bacteria, that live on or in the human body. Kharofa said advances in DNA sequencing have allowed researchers to better characterize what species of bacteria are present in the microbiome, leading to a boom in research over the past 10 years.

In the past, wed have to culture specific bacteria and isolate them, and thats really complicated, he said. But now with the genetics and the cost of sequencing going down, we can quickly characterize what species are where and try to understand if they have implications for normal health and disease.

Kharofa said previous studies have shown that certain bacteria species present in the gut are associated with colorectal cancer. The research team then asked the question if these cancer-causing bacteria were elevated specifically in younger colorectal cancer patients compared to older patients and to healthy patients.

Kharofa collaborated with a team including Nicholas J. Ollberding, PhD, a Cincinnati Childrens Hospital Medical Center bioinformatician and associate professor in the UC Department of Pediatrics. Using genetic data from 11 previous studies, the team analyzed microbiome data from 609 patients who were healthy and 692 patients with colorectal cancer.

The research found two species of bacteria most closely associated with causing colorectal cancer were not found in higher levels among young patients, meaning these bacteria are unlikely to be responsible for increased cancer rates in young people.

Five other bacteria were found in higher levels in young people, including one species that is associated with a sulfur microbial diet, or a diet that is both high in processed meats, low-calorie drinks and liquor and low in raw fruits, vegetables and legumes.

Other epidemiologic studies without access to stool have revealed connections between a sulfur microbial diet and a higher increased risk of cancer in younger people, and Kharofa said this study is consistent with these previous findings.

Although these patients arent obese, there may be dietary patterns that happen early in life that enrich for certain bacteria such as this one, Kharofa said. Its not that what youre eating has carcinogens in them, but the byproducts produced during bacteria metabolism may lead to carcinogenic chemicals. Its possible that interactions between diet and the microbiome may mediate the formation of colorectal cancer cells and heightened risk in younger populations over the last several decades.

While more research is needed, Kharofa said a tangible takeaway from the study is for young people to eat more raw fruits and vegetables and legumes and less processed meats in their diets.

Theres still a lot we dont understand about how the diet influences the microbiome and how that might influence cancer, but this is a small sneak peek at something that might be going on, he said. Theres a lot of reasons to eat less processed foods and diets rich in raw fruits, vegetables and legumes, and this might be one more.

Kharofa said further research will look to learn more about the bacteria species that were found in higher levels in younger patients and how these species contribute both to the development of cancer and to the cancers response to treatment.

As the role of bacteria becomes clearer, there is also the potential for more advanced and tailored screening for younger patients.

Its really difficult to just screen everybody because the rates are pretty low in the entire population of individuals less than 45 years old, he said. But if you are able to profile the microbiome and maybe do targeted screening in some patients who had higher risk based on their stool, that might be a worthwhile investigation.

Even if a person is younger, Kharofa said anyone with symptoms should be evaluated by a doctor. Signs and symptoms of colorectal cancer include rectal bleeding or blood in the stool; persistent abdominal discomfort, including gas, bloating, fullness or cramps; diarrhea, constipation or feeling that the bowel does not fully empty; unknown weight loss; fatigue and vomiting.

Screening is for asymptomatic people, and anyone with symptoms needs to be evaluated, Kharofa said. We unfortunately see these patients presenting later at diagnosis because their symptoms were ignored. If youre young and you have symptoms, you need to be evaluated.

Other contributing authors to the research were Senu Apewokin, MD, associate professor in the UC College of Medicine, and Theresa Alenghat, PhD, member of Cincinnati Childrens Hospital Medical Centers Division of Immunobiology and an associate professor in the UC Department of Pediatrics.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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How diet and the microbiome affect colorectal cancer - EurekAlert

Researchers have recently successfully treated Type 1 diabetes by transplanting insulin-producing pancreas cells into the patient.

University of Missouri scientists are partnering with Harvard and Georgia Tech to create a new diabetes treatment that involves transplanting insulin-producing pancreatic cells

Type 1 diabetes is estimated to affect around 1.8 million Americans. Although type 1 diabetes often develops in childhood or adolescence, it can occur in adulthood.

Despite active research, type 1 diabetes has no cure. Treatment methods include taking insulin, monitoring your diet, managing blood sugar levels, and exercising regularly. Scientists have also recently discovered a new treatment method that holds promise.

A group of researchers from the University of Missouri, Georgia Institute of Technology, and Harvard University has proved the successful use of a novel Type 1 diabetes treatment in a large animal model in a new study published in Science Advances on May 13th. Their method includes transferring insulin-producing pancreas cells, known as pancreatic islets, from a donor to a recipient without the need for long-term immunosuppressive medicines.

According to Haval Shirwan, a professor of child health and molecular microbiology and immunology at the MU School of Medicine and one of the studys primary authors, people with Type 1 diabetes immune system may malfunction, leading it to target itself.

The immune system is a tightly controlled defense mechanism that ensures the well-being of individuals in an environment full of infections, Shirwan said. Type 1 diabetes develops when the immune system misidentifies the insulin-producing cells in the pancreas as infections and destroys them. Normally, once a perceived danger or threat is eliminated, the immune systems command-and-control mechanism kicks in to eliminate any rogue cells. However, if this mechanism fails, diseases such as Type 1 diabetes can manifest.

Diabetes impairs the bodys ability to produce or utilize insulin, a hormone that aids in the regulation of blood sugar metabolism. People with Type 1 diabetes are unable to manage their blood sugar levels because they do not produce insulin. This lack of control may result in life-threatening problems including heart disease, kidney damage, and vision loss.

Shirwan and Esma Yolcu, a professor of child health and molecular microbiology and immunology at the MU School of Medicine, have spent the last two decades targeting an apoptosis mechanism that prevents rogue immune cells from causing diabetes or rejection of transplanted pancreatic islets by attaching a molecule called FasL to the islets surface.

A type of apoptosis occurs when a molecule called FasL interacts with another molecule called Fas on rogue immune cells, and it causes them to die, said Yolcu, one of the studys first authors. Therefore, our team pioneered a technology that enabled the production of a novel form of FasL and its presentation on transplanted pancreatic islet cells or microgels to prevent being rejected by rogue cells. Following insulin-producing pancreatic islet cell transplantation, rogue cells mobilize to the graft for destruction but are eliminated by FasL engaging Fas on their surface.

Haval Shirwan and Esma Yolcu work in their lab at the Roy Blunt NextGen Precision Health building. Credit: University of Missouri

One advantage of this new method is the opportunity to potentially forgo a lifetime of taking immunosuppressive drugs, which counteract the immune systems ability to seek and destroy a foreign object when introduced into the body, such as an organ, or in this case, cell, transplant.

The major problem with immunosuppressive drugs is that they are not specific, so they can have a lot of adverse effects, such as high instances of developing cancer, Shirwan said. So, using our technology, we found a way that we can modulate or train the immune system to accept, and not reject, these transplanted cells.

Their method utilizes technology included in a U.S. patent filed by the University of Louisville and Georgia Tech and has since been licensed by a commercial company with plans to pursue FDA approval for human testing. To develop the commercial product, the MU researchers collaborated with Andres Garca and the team at Georgia Tech to attach FasL to the surface of microgels with proof of efficacy in a small animal model. Then, they joined with Jim Markmann and Ji Lei from Harvard to assess the efficacy of the FasL-microgel technology in a large animal model, which is published in this study.

Haval Shirwan looks at a sample through a microscope in his lab at the Roy Blunt NextGen Precision Health building. Credit: University of Missouri

This study represents a significant milestone in the process of bench-to-bedside research, or how laboratory results are directly incorporated into use by patients in order to help treat different diseases and disorders, a hallmark of MUs most ambitious research initiative, the NextGen Precision Health initiative.

Highlighting the promise of personalized health care and the impact of large-scale interdisciplinary collaboration, the NextGen Precision Health initiative is bringing together innovators like Shirwan and Yolcu from across MU and the UM Systems three other research universities in pursuit of life-changing precision health advancements. Its a collaborative effort to leverage the research strengths of MU toward a better future for the health of Missourians and beyond. The Roy Blunt NextGen Precision Health building at MU anchors the overall initiative and expands collaboration between researchers, clinicians, and industry partners in the state-of-the-art research facility.

I think by being at the right institution with access to a great facility like the Roy Blunt NextGen Precision Health building, will allow us to build on our existing findings and take the necessary steps to further our research, and make the necessary improvements, faster, Yolcu said.

Haval Shirwan and Esma Yolcu. Credit: University of Missouri

Shirwan and Yolcu, who joined the faculty at MU in the spring of 2020, are part of the first group of researchers to begin working in the NextGen Precision Health building, and after working at MU for nearly two years they are now among the first researchers from NextGen to have a research paper accepted and published in a high-impact, peer-reviewed academic journal.

Reference: FasL microgels induce immune acceptance of islet allografts in nonhuman primates by Ji Lei, Mara M. Coronel, Esma S. Yolcu, Hongping Deng, Orlando Grimany-Nuno, Michael D. Hunckler, Vahap Ulker, Zhihong Yang, Kang M. Lee, Alexander Zhang, Hao Luo, Cole W. Peters, Zhongliang Zou, Tao Chen, Zhenjuan Wang, Colleen S. McCoy, Ivy A. Rosales, James F. Markmann, Haval Shirwan and Andrs J. Garca, 13 May 2022, Science Advances.DOI: 10.1126/sciadv.abm9881

Funding was provided by grants from the Juvenile Diabetes Research Foundation (2-SRA-2016-271-S-B) and the National Institutes of Health (U01 AI132817) as well as a Juvenile Diabetes Research Foundation Post-Doctoral Fellowship and a National Science Foundation Graduate Research Fellowship. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

The studys authors would also like to acknowledge Jessica Weaver, Lisa Kojima, Haley Tector, Kevin Deng, Rudy Matheson, and Nikolaos Serifis for their technical contributions.

Potential conflicts of interest are also noted. Three of the studys authors, Garca, Shirwan, and Yolcu, are inventors on a U.S. patent application filed by the University of Louisville and the Georgia Tech Research Corporation (16/492441, filed Feb. 13, 2020). In addition, Garca and Shirwan are co-founders of iTolerance, and Garca, Shirwan, and Markmann serve on the scientific advisory board for iTolerance.

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Harvard Scientists Have Developed a Revolutionary New Treatment for Diabetes - SciTechDaily

Upon receiving a diagnosis of type 1 diabetes (T1D), many people have the same reaction: But why me?

Some people have T1D that runs in their family, while others have no idea how or why they received a diagnosis. Often, to their frustration, those questions go unanswered.

But some people can seemingly link their T1D diagnosis to a previous virus they had endured directly before their onset of T1D.

This makes sense, as T1D is an autoimmune disease. This means your bodys own immune system mistakenly attacks its own insulin-producing beta cells. Although scientists dont know the exact causes or reasons why T1D develops, some researchers believe this haywire immune system reaction is the result of a virus triggering your bodys defense system to go into overdrive.

Viruses are now one main hypothesis of the cause of T1D. In particular, coxsackievirus is on the rise in those with newly diagnosed T1D. That has led some to wonder if theres a direct correlation between this virus, or any virus for that matter.

Read on for more about coxsackievirus, how it materializes in people, and what research has to say about its potential for causing T1D.

Coxsackievirus is a virus thats part of the enterovirus family, which lives in the human digestive tract. This enterovirus family also includes polioviruses, hand, foot, and mouth disease (HFMD), and hepatitis A virus.

This virus spreads easily from person to person, usually through human touch or on surfaces contaminated with feces. The virus can live for several days without a host, making it extremely easy to spread.

When theres a coxsackievirus outbreak, its most likely to affect babies and children younger than 5 years old, as its easily spreadable in places such as daycare centers, schools, and summer camps. Youre most contagious the first week that youre sick, and the best preventive mechanism is hand washing.

Usually, infection with this virus results in these mild flu-like symptoms initially:

Many people have no symptoms at all, and most people recover without treatment. But sometimes the virus can trigger more serious conditions or reactions, such as with HFMD, where a blister-like rash may appear on your hands or feet or in your mouth.

Theres no specific treatment for this virus, and antibiotics dont help with viral infections.

When a virus invades your body, your immune system produces antibodies to fight off that infection. T cells are in charge of developing antibodies as well as fighting off the virus.

But if the virus has some of the same antigens (or substances that cause your immune system to produce antibodies against them) as your bodys own pancreatic beta cells (in the case of T1D), the T cells sometimes start attacking your bodys own beta cells.

This miscommunication is common and results in autoimmune diseases like T1D. Once all the beta cells have been destroyed, T1D is developed and diagnosed. This is why people sometimes receive a diagnosis of T1D a few months after recovering from a bad virus.

But it can sometimes take more than a year for your bodys T cells to destroy the majority of your beta cells (sometimes people experience the honeymoon phase of diabetes, where their pancreas is still producing a minimal amount of insulin), but that original viral infection is hypothesized to be a trigger in the development of T1D.

Not every virus can trigger this reaction ending in T1D. The virus must have antigens that are similar enough to the antigens in pancreatic beta cells. Those viruses include:

Theres mounting evidence that the coronavirus disease 19 (severe acute respiratory syndrome coronavirus 2) pandemic is causing a tidal wave of new T1D diagnoses to be received by both children and adults. But the full repercussions of the pandemic are yet to be seen.

A 2018 study showed that kids exposed to enteroviruses are more likely to develop T1D.

The Environmental Determinants of Diabetes in the Young study found, through nearly 8,000 stool samples of children in the United States and Europe, an association between an exposure and infection with coxsackievirus. This study followed participants for 30 days or longer and focused on the development of an autoimmune reaction that can lead to a T1D diagnosis.

In a Finland-based study, researchers tested more than 1,600 stool samples from 129 children who had recently developed T1D. They also tested 282 children without diabetes for enterovirus RNA, a marker of previous exposure to infection.

Researchers also found 60 percent of the control group showed signs of prior infection (without diabetes), compared with 75 percent of the group with T1D.

They also found that children who developed T1D were exposed to the virus more than a year before their diabetes was diagnosed. Taking this lag time of viral infection to T1D diagnosis into account, the researchers believed that children with diabetes are exposed to three times more enteroviruses than children without diabetes.

Viral infections arent the only hypothesized cause of T1D, but research is homing in on viruses as a common trigger. Studies have shown that even if pregnant people are exposed to enteroviruses, such as coxsackievirus, theyre more likely to give birth to children who eventually develop T1D.

Researchers arent exactly sure what the precise cause of T1D is, and the virus hypothesis is just one theory. Many people believe that T1D is caused by a mix of genetic and environmental factors and that the disease may just be finally triggered by catching a virus such as coxsackievirus or another enterovirus.

While preventing viral spread is always important, even if all enteroviruses were prevented, T1D wouldnt be prevented in everyone, but it would probably make a big difference.

Researchers are hopeful with new trials showing vaccines against enteroviruses could potentially prevent many new diagnoses of T1D, but they wont prevent all people from receiving diagnoses of course.

While theres no vaccine to prevent T1D, Dr. Denise Faustman, Director of the Massachusetts General Hospital Immunobiology Laboratory, is working on that research front. Her work focuses on the bacillus Calmette-Gurin (BCG) vaccine, traditionally used to prevent tuberculosis, and how it can help people with T1D. Specifically, this century-old BCG vaccine may boost a substance called tumor necrosis factor, which eliminates T cells and helps develop more beneficial cells called regulatory T cells.

If you have diabetes, this could help improve your blood sugar and A1C levels while lowering your insulin requirements even years after your initial vaccination. That research is expected to continue for at least several more years beyond 2022.

The exact causes of T1D arent known. But research shows enteroviruses, and in particular coxsackievirus, may play a part in the development of this autoimmune condition. Most researchers believe it to be a mix of both environmental and genetic factors, with perhaps a viral infection trigger. Research remains ongoing, and the development of a coxsackievirus vaccine could go a long way in preventing people worldwide from receiving diagnoses of T1D in the future.

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Do Viruses and Coxsackievirus Cause Type 1 Diabetes? - Healthline

While managing diabetes can be challenging, you can still do the things you enjoy in life. (Getty Images)

This diabetes week, and every week, it's important that just because diabetes is a hidden condition, it doesn't get ignored.

One in 14 of us live with the condition, while even more care for a loved one who does, according to Diabetes UK.

So, whether you might suspect you have diabetes, support someone else with it, are recently diagnosed, or just want to learn more about the condition, here are the basics of what there is to know.

Read more: Kate Moss' daughter Lila proudly sports blood glucose monitor in Fendace campaign

If you're diagnosed with diabetes, a medical professional will explain all you need to know about managing it. (Getty Images)

Diabetes is a lifelong condition that causes a person's blood glucose levels (also called blood sugar) to become too high, according to the NHS. There are two main types, Type 1 and Type 2, though some can also get Gestational diabetes.

Pre-diabetes is when people have blood glucose levels above the normal range, but are not high enough to be diagnosed with the condition itself. But it's important to keep in mind that if your levels are higher than most, your risk of developing full-scale diabetes is increased.

Getting diabetes diagnosed early is key to prevent it from getting progressively worse, which can happen if left untreated.

The finger-prick test has long been used to manage diabetes, though there are now more advanced methods. (Getty Images)

Type 1 diabetes is where the body's immune system attacks and destroys the cells that produce insulin. You need to take insulin every day to keep your blood glucose levels under control. Type 1 is not linked with age, being overweight or lifestyle factors, whereas Type 2 is.

The NHS website says you should see a GP if you have symptoms of type 1, which include:

feeling very thirsty

peeing more than usual, particularly at night

feeling very tired

losing weight without trying

thrush that keeps coming back

blurred vision

cuts and grazes that are not healing

fruity-smelling breath

Type 1 signs and symptoms can come on quickly, particularly in children.

To get tested, your GP will do a urine test and might also check your blood glucose level. If they suspect you have diabetes, you'll be advised to go to hospital immediately for further assessments, where you will stay until you get results (usually the same day).

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If you are diagnosed, then a specialist diabetes nurse will explain everything you need to know about the condition, including how to manage it, test your own blood glucose and how to inject insulin.

Finger-prick tests have long been used to manage diabetes, though you can now check your glucose levels at any time with a continuous glucose monitor (CGM) or flash monitor.

This involves using a sensor, a small device you attach to your arm or tummy that senses how much glucose is in the 'interstitial' fluid under your skin, and a reader or receiver, which shows the results (you can also read them on your smartphone). Some types have optional alarms to alert you if your levels go too low or high.

Read more: What types of dementia are there? Signs and symptoms to see your GP about

While interstitial fluid readings have made many people living with diabetes' lives much easier, it's important to remember they're a few minutes behind your blood glucose levels. This means you'll still need to do finger-prick checks every now and then, particularly when you drive or have a hypoglycaemia (when your blood glucose level is too low), as this tells you what your level is at that moment.

Although being diagnosed with and managing diabetes can be difficult at times, you can still do the things you enjoy. This useful NHS guide on being newly diagnosed provides information to help, including how to recognise and treat a hypo, useful websites, online courses and more.

Do you have the symptoms of diabetes? (Getty Images)

Type 2 diabetes is where the body does not produce enough insulin, or the body's cells do not react to insulin. It is far more common than type 1, with around 90% of all adults in the UK with diabetes living with it.

It can be linked to being overweight or inactive, or having a family history of type 2 diabetes. You're also more at risk of this type of diabetes if you're over 40 (or 25 for south Asian people), have a close relative with diabetes, are overweight or obese, are of Asian, African-Caribbean or black African heritage.

Many people can have type 2 diabetes without realising, because symptoms don't always make you feel unwell.

The NHS website says you should see a GP if you have symptoms of type 2 (similar to type 1), which include:

peeing more than usual, particularly at night

feeling thirsty all the time

feeling very tired

losing weight without trying to

itching around your penis or vagina, or repeatedly getting thrush

cuts or wounds taking longer to heal

blurred vision

You should also see a GP if you're worried you may have a higher risk of getting type 2. You check your risk here.

Some people find checking blood glucose levels with a continuous glucose monitor (CGM) or flash monitor easier. (Getty Images)

Gestational diabetes can also occur during pregnancy, when some women have such high levels of blood glucose that their body is unable to produce enough insulin to absorb it all.

While it can happen at any stage of pregnancy, it is more common in the second or third trimester. It usually disappears after giving birth.

That said, it can cause problems for you and your baby during pregnancy and after birth, but the risks can be reduced if the condition is detected early and well managed.

Read more: How to stay safe in hot weather: Top tips to avoid heatstroke this summer

With the causes of Type 1 and Type 2 different, a doctor will explain how management differs. (Getty Images)

Elaborating on the above, the amount of sugar in the blood is controlled by a hormone called insulin, which is produced by the pancreas (a gland behind the stomach), the NHS explains.

Normally, when food is digested and enters your bloodstream, insulin moves glucose out of the blood and into cells, where it's broken down to produce energy.

However, if you have diabetes, your body is unable to break down glucose into energy because there's either not enough insulin to move it, or the insulin produced doesn't work properly.

While there are no lifestyle changes you can make to lower your risk of of type 1 diabetes, you can help manage type 2 diabetes through healthy eating, regular exercise and achieving a healthy body weight.

There's nothing you can't eat if you have type 2 diabetes, but the NHS suggests limiting certain foods. You should eat a wide range of food (fruit, veg and some starchy foods like pasta), keep sugar, fat and salt to a minimum, and make sure you eat breakfast, lunch and dinner every day do not skip meals.

If you need to change your diet, it might be easier to make small changes every week, it adds.

Altering your lifestyle in small ways can go a long way to reduce your risk of type 2 diabetes. (Getty Images)

Diet, exercise and a healthy lifestyle can also help to reduce the likelihood of getting type 2 diabetes, with more than 13.6 million people in the UK at an increased risk.

"Fortunately even in people with a strong family history of diabetes making positive lifestyle choices can help avoid diabetes altogether," says Dr Sundhya Raman, Medical Doctor and Lifestyle Medicine Physician, Plant Based Health Professionals.

In terms of diet, Ruman says we should try to avoid "processed foods, sugar-sweetened foods and drinks, saturated fats (found in animal source foods and tropical oils), and red and processed meats".

On exercise, she explains it is never too late to start, and build up gradually. "Most people think they need to be quite fit before they get a benefit from exercising, but in fact going from doing nothing to doing something is when the biggest gains are achieved."

It seems sleep is very important too. "We should all be aiming for 7-8 hours of sleep a night, and people who chronically sleep less than this amount raise their risk of diabetes by about 30%," she says.

"When we dont get enough sleep we also have dysregulated levels of our hunger and satiety hormones so are more likely to eat more, particularly foods that are not good for us and make us put on weight, so sleep should also be a priority."

Of all lifestyle factors, Raman says poor diet is the biggest risk. "In studies, the dietary group who have the lowest rates of diabetes are whole-food plant based. They are also the group that tend to have the lowest BMI compared with any other dietary group such as pescatarians or omnivores, and we know that a high BMI is one of the most significant risk factors [for having diabetes].

Some believe food is medicine when it comes to reducing your risk of diabetes, or even reversing it. (Getty Images)

Plant-based diets can reduce the risk of type 2 diabetes by up to 60%, according to Plant Based Health Professionals. But how does this work?

Soluble fibre, she explains helps us to feel full and maintain a healthy weight, release the carbohydrate from our food into our bloodstream slowly, and is the superfood for bugs that live in our colon, of which a healthy balance of can lower the risk of diabetes.

"Plant foods are also full of antioxidants that help reduce the damage that happens to our cells from everyday activities, as well as some of the more damaging things we do such as eating the wrong kinds of foods or sitting for prolonged periods," Ruman adds. "We also know that some of the compounds in plant foods switch on genes that optimise our metabolism.

She also says wholegrains are the food type that have been shown in studies to be particularly important in reducing diabetes and cardiovascular risk. However, in the UK we don't have specific guidelines on how many portions to eat, or any legislation on what can be termed a wholegrain, so people can eat processed foods with few wholegrains, thinking they are improving their health, or think they're bad for people with diabetes, as are often grouped under carbs.

Read more: Earth Day 2022: 7 ways to reduce your carbon 'foodprint' to save the planet

"I would recommend 3 portions of wholegrains per day, ideally as unprocessed as possible." She also reccomends a variety of fruit and vegetables, as well as variety in your nuts, seeds, wholegrains, lentils, legumes, herbs and spices, while prioritising plant sources of proteins over those from animal sources.

In some cases, plant-based are also effective at reversing Type 2 diabetes, effective at reversing insulin resistance, which is thought to happen fat gets stored in our muscle and liver, and damages cells."One of the ways in which a whole-food plant-based diet is incredibly beneficial is that people tend to lose weight when they follow this dietary pattern, and we know that weight loss can reverse diabetes."

Make sure you consult a doctor before making any big dietary changes.

For more information, visit the NHS' website on diabetes, or seek support from Diabetes UK on 0345123 2399.

Watch: Diabetes drug leads to significant weight loss in those with obesity, study finds

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Diabetes Week: Types 1 and 2 symptoms, causes and prevention - Yahoo Entertainment

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Great sex, anecdotally, is uninhibited and free of worry. Its a time to put aside the usual responsibilities that plague you and just enjoy the moment. But diabetes and sex have a slightly complicated relationship. For people with type 1 diabetes, fully detaching from responsibilities isnt an option in fact, it can be dangerous. Its no surprise then that a study conducted by Oxford University professors found that 62 percent of people with diabetes say their condition has negatively impacted their relationships with their partners.

Having to think about your type 1 diabetes during intimacy can be agitating and even disheartening. But its important to remember that many adults have to do some planning before sex. Some men have to take pills for erectile dysfunction. Tons of women need lubricant due to a hormonal imbalance. And lets not forget about all of the people who need a lumbar support pillow for missionary. Everyone deserves to enjoy sex. Heres what you need to know about having safe and enjoyable sex, when you have type 1 diabetes.

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There are several reasons that those with type 1 diabetes cant explore the Kama Sutra without some planning. First off, a lot of sex depending on how you go about it counts as a workout. It gets your blood pumping, it gets you sweating and, like any exercise, it impacts blood sugar levels. While people who dont have diabetes can handle these blood sugar fluctuations fairly well, people with diabetes need to be careful.

Next, theres the added factor of booze. Its common for people to enjoy a drink (or a few) before having sex. Alcohol helps loosen those inhibitions and make you feel relaxed. But, if you drink too much or dont stick to diabetic-friendly cocktails, your blood sugar levels can go on a roller coaster.

The ways sex plays on blood sugar levels dont stop there. Even if you stay sober for sex, the mere excitement of being with a partner can impact blood sugar levels. So, while its frustrating, the fact that sex affects blood sugar levels cannot be ignored.

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If you know that your night will likely end in sex, take steps to put your blood sugar levels in a healthy range by the time intimacy occurs. This means being careful about what you eat, using insulin when necessary and even monitoring other physical activity throughout the day. If your sessions in the sack are particularly active, then you might need to skip your afternoon workout. You dont want to put yourself at risk of low blood sugar mid-coitus due to over-exertion.

Source: NurPhoto / Getty

Even if you eat right and monitor your blood sugar levels, things can still go awry after a few rounds with your partner. Be sure to keep snacks on the nightstand so you can reach for them if you feel your blood sugar levels dropping. Better yet, incorporate sexy foods like strawberries or chocolate sauce (sugar-free if necessary) into sex so it doesnt feel like snack time is putting a pause on the fun.

Source: FG Trade / Getty

Sex is always better when you can communicate with your partner. That is true about every topic, from what positions work for you to managing your blood sugar levels. Notify your partner in advance that sex can impact your blood sugar, and that you might need to pause during the activities to have a snack or take insulin. Additionally, if you can tell tonight is just not a good night to do the deed, speak up. Pushing yourself through sex when your blood sugar levels are off can be dangerous.

Source: Andriy Onufriyenko / Getty

If you wear an insulin pump or a blood glucose monitor, you might be tempted to remove this during sex. Some diabetics struggle to feel sexy when wearing these devices (and nothing else) in front of a partner. First off, theres no shame in wearing a device that keeps you alive and enables you to live the way that you enjoy. However, there are some practicalities to consider, like the fact that these devices can get tangled or fall off during sex.

If you want to remove your device during sex, make sure to get your blood sugar levels in a healthy range right before the activities. And then put the device back on immediately after sex. If your blood sugar levels arent stable enough for device removal, get creative and choose positions that let you keep the device on. Again, communication is key here.

Source: Andreas Stamm / Getty

It is important to know that type 1 diabetes can impact sexual function in many ways. For women, high blood sugar can lead to vaginal dryness, according to the Journal of Natural Science, Biology and Medicine. For men, blood sugar issues can cause erectile dysfunction. And people of all genders can experience mood swings and a low libido in connection to type 1 diabetes.

While there are practical fixes for vaginal dryness like finding a lubricant you love the other symptoms can be more complicated to treat. If you are struggling with any of these issues, first off, know that its common for people with type 1 diabetes and is nothing to be embarrassed about. Then talk to your doctor about the best way to treat the problem.

Having type 1 diabetes doesnt have to mean the end of a fun, playful and even erotic sex life. It simply means you have to do a little extra planning. But when you have a partner with whom you can communicate openly, that planning wont feel like a burden. And when you know your body will be safe and taken care of, then you can let go and be in the moment.

RELATED CONTENT:7 Things Doctors Wish Black Women Knew About Diabetes

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Diabetes And Sex: Have Safe Sex While Managing Diabetes - MadameNoire

Wilmington, Delaware, United States: According to Transparency Market Researchs latest report on the global diabetes devices market for the historical period 20172018 and forecast period 20192027, increase in prevalence of diabetes, and increase in adoption of insulin pumps among type 1 diabetes patients are projected to drive the global diabetes devices market during the forecast period.

According to the report, the global diabetes devices market was valued at US$ 41.8 Bn in 2018 and is anticipated to expand at a CAGR of 6.4% from 2019 to 2027.

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Increase in Prevalence of Diabetes Expected to Drive Global Diabetes Devices Market: Key Drivers

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Increase in Adoption of Insulin Pump among Type 1 Diabetes Patients Boost Market Growth

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Global Diabetes Devices Market: Competitive Landscape

This report profiles major players in the global diabetes devices market based on various attributes such as company overview, financial overview, product portfolio, business strategies, and recent developments

The global diabetes devices market is highly fragmented, with the presence of a number of international as well as regional players

Leading players operating in the global diabetes devices market are

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Diabetes Devices Market to Expand at the CAGR of 6.4% from 2019 to 2027, Increase in Prevalence of Diabetes Expected to Drive Global Market - BioSpace

If you live with diabetes, you may be aware that having the condition and its complications may put you at greater risk of developing anemia. But how are the two conditions related and what does this mean for you?

This article will investigate the relationship between diabetes and anemia, and what you should know if you have diabetes-related complications impacting your life.

According to the National Heart, Lung, and Blood Institute, Anemia is a condition in which the blood doesnt have enough healthy red blood cells to function properly. This leads to reduced oxygen flow to the bodys organs.

There are more than 3 million cases of anemia diagnosed in the United States every year, making this a very common condition.

You may experience the following symptoms:

Its important to note that some anemia symptoms are similar to symptoms of high blood sugar, including dizziness, lightheadedness, extreme fatigue, rapid heart rate, and headache.

Check your blood sugar often to make sure youre not confusing high blood sugar for suspected anemia. If your symptoms continue for a few days or weeks without high blood sugar numbers or ketones, call a healthcare professional to get checked for anemia.

Diabetes doesnt cause anemia and anemia doesnt cause diabetes. The two conditions are related, though.

Up to 25 percent of Americans with type 2 diabetes also have anemia. So its relatively common for people with diabetes, and especially diabetes-related complications, to also develop anemia.

However, if you have one condition or the other, you wont automatically develop the other condition.

As seen in this 2004 study, Anemia is a common complication of people with diabetes who develop chronic kidney disease because damaged or failing kidneys dont produce a hormone called erythropoietin (EPO), which signals to the bone marrow that the body needs more red blood cells to function.

Early stages of kidney disease (nephropathy) may be asymptomatic, but if youre diagnosed with anemia and you have diabetes, it might be a sign that your kidneys arent working properly.

People with diabetes are also more likely to have inflamed blood vessels. This prevents the bone marrow from even receiving the EPO signal to create more red blood cells to begin with. That makes anemia a more likely result.

Additionally, if you have existing anemia and are then diagnosed with diabetes, it may make you more likely to develop diabetes-related complications, such as retinopathy and neuropathy (eye and nerve damage).

A lack of healthy red blood cells can additionally worsen kidney, heart, and artery health, systems that are already taxed with a life lived with diabetes.

Certain diabetes medications can decrease your levels of the protein hemoglobin, which is needed to carry oxygen through the blood. These diabetes medications can increase your risk of developing anemia:

Since blood loss is also a significant contributor to the development of anemia, if you have diabetes and are on kidney dialysis, you may want to talk with your healthcare team about your increased risk of anemia as well.

Anemia can affect blood sugar levels in several ways.

One 2010 study found that anemia produced false high blood sugar levels on glucose meters, leading to dangerous hypoglycemia events after people overtreat that false high blood sugar.

As shown in a 2014 study, theres a direct link between anemia caused by iron deficiency and higher amounts of glucose in the blood. A 2017 review of several studies found that in people both with and without diabetes, iron-deficiency anemia was correlated with increased A1C numbers.

This resulted from more glucose molecules sticking to fewer red blood cells. After iron-replacement therapy, HbA1c levels in the studies participants decreased.

If you receive an anemia diagnosis and you live with diabetes, there are many excellent treatment options.

Treatment will depend on the underlying cause of the condition, but may include supplementation with iron and/or vitamin B.

If your anemia is caused by blood loss, a blood transfusion may be necessary. If your bodys blood production is reduced, medications to improve blood formation may be prescribed.

Diabetes and anemia are closely related, though neither directly causes the other condition.

Diabetes-related complications such as kidney disease or failure and inflamed blood vessels may contribute to anemia. Certain diabetes medications can also increase the likelihood of developing anemia. Anemia may also make diabetes management more challenging, with higher A1C results, false high blood sugars, and a potential risk of worsening organ health leading to future diabetes complications.

Still, anemia is very treatable with supplementation, dietary or medication changes.

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Anemia and Diabetes: What You Should Know - Healthline

Patient education is a component of prevention of progression of kidney disease. Paul Flynn and colleagues at SUNY Downstate Health Science University, Brooklyn, New York, interviewed patients with end-stage kidney disease (ESKD) secondary to diabetic kidney disease to determine their knowledge of their disease and how it relates to chronic kidney disease (CKD).

Results of the interviews were reported during a poster session at the NKF 2022 Spring Clinical Meetings. The poster was titled Knowledge Gaps Regarding Chronic Kidney Disease and Diabetes in a Population of Inner-City Dialysis Patients.

The survey was administered to 15 randomly selected dialysis patients with diabetes. The survey included questions about patient knowledge about diabetes and kidney disease at the time of diagnosis. The researchers also collected demographic information.

Mean age of the respondents was 64.3 years, 53% (n=8) were male, 47% (n=7) had less than a college education, 89% (n=8/9) made less than $40,000 per year. Mean time with diabetes was 29.0 years. Eight of 13 patients saw an endocrinologist, and four reported most recent hemoglobin A1c (HbA1c) >10%. Twelve of 13 respondents reported they had no knowledge of what CKD was and 10 of 13 did not know at the time of their diabetes diagnosis that diabetes could cause kidney disease.

There was no correlation between knowledge and age, education, length of time with diabetes, income, or sex. Patients who were older were lesse likely to see an endocrinologist (r=0.64; P=.019), checked their glucose less frequently (r=0.71; P=.006), and did not check after eating (r=0.62; P=.023). Thirteen of 14 patients said they did know what HbA1c was, 11 of 14 knew that insulin decreases blood glucose levels, 12 of 14 knew that a person with type 2 diabetes had increased blood glucose, and ten of 14 patients knew that HbA1c should be checked every 3 months. Six of 13 patients did not know what a nephrologist is and nine of 13 did not know how kidney function is measured.

In summary, the authors said, In our population of inner-city dialysis patients with diabetes mellitus: (1) The majority were knowledgeable about diabetes, although older patients were less likely to see an endocrinologist and check their blood sugar frequently or after eating. (2) The majority of patients had no knowledge of kidney disease and did not know that diabetes could cause kidney disease at the time of their diagnosis. (3) Almost half of patients currently did not know what a nephrologist was and did not know how kidney function is measured. (4) An early education program for our underserved population regarding the relationship between kidney disease and diabetes should be designed in the hopes of delaying progression to ESKD.

Source: Flynn P, Sherman B, Wei L, et al. Knowledge gaps regarding chronic kidney disease and diabetes in a population of inner-city dialysis patients. Abstract of a poster presented at the National Kidney Foundation 2022 Spring Clinical Meetings (Abstract 273), Boston, Massachusetts, April 6-10, 2022.

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Patient Knowledge of Diabetes and CKD in an Inner-City Population - DocWire News

BASEL, Switzerland, June 16, 2022 /PRNewswire/ --Ascensia Diabetes Care, a global diabetes care company,maker of CONTOURblood glucose monitoring (BGM) system portfolio and distributor of Eversense Continuous Glucose Monitoring (CGM) Systems, announces that its partner Senseonics Holdings, Inc. has received CE Mark approval for the Eversense E3 Continuous Glucose Monitoring (CGM) System, clearing the way for its use in European Union (EU) member countries. Ascensia plans to make the next-generation system, which can be used for up to 6 months, available to patients in certain European markets from the third quarter of 2022.

The fully implantable, long-term Eversense E3 CGM System has been designed to deliver key improvements on the currently available Eversense XL CGM System, whilst building on the unique benefits that European users already experience. The next-generation system offers exceptional accuracy and long-term sensor wear, alongside reduced frequency of calibration and significantly enhanced sensor survivability. Unlike the XL System, the new E3 System has also been approved for non-adjunctive use, meaning that it can inform insulin treatment decisions without confirmation of glucose levels from fingerstick testing. Both Eversense XL and Eversense E3 are approved for use up to 6 months, making them the longest lasting CGM sensors available. This gives people with diabetes freedom from the burdens associated with other available CGM systems, such as weekly or bi-weekly self-insertions.

Eversense E3 is already available in the U.S. following FDA approval and launch earlier this year. Following the CE Mark approval in Europe the Eversense E3 System will be distributed in Germany, Italy, Spain (including Andorra), the Netherlands, Poland, Switzerland, Norway and Sweden.

Robert Schumm, President at Ascensia Diabetes Care, said, "This approval is an exciting milestone for us as we look forward to bringing Eversense E3 to people with diabetes across Europe. From this next-generation system you can expect the excellent features and benefits that European users currently experience with Eversense XL, but with design improvements that address requests we repeatedly hear from patients and healthcare providers. Our role is to make sure that as many people have access to this innovative product as possible, and efforts are already under way to launch this system in certain European countries in the coming months."

Developed by Senseonics and brought to people with diabetes by Ascensia, the newly approved Eversense E3 CGM System offers patients:

"The features and benefits of this improved system offer people with diabetes unparalleled flexibility, convenience and accuracy," said Elaine Anderson, Head of Eversense CGM Business Unit at Ascensia Diabetes Care. "Choice is key in managing diabetes and we are proud to work alongside our partner Senseonics to bring an outstanding and unique CGM option to patients and healthcare providers across Europe and in the U.S."

People in these markets who are interested in getting started with Eversense XL now can visit http://www.ascensia.com/eversense for more information, and will be among the first to know when Eversense E3 is commercially available.

* There is no glucose data generated when the transmitter is removed.

1 Garg S. et al. Evaluation of Accuracy and Safety of the Next-Generation Up to 180-Day Long-Term Implantable Eversense Continuous Glucose Monitoring System: The PROMISE Study. Diabetes Technology & Therapeutics 2021; 24(2): 1-9.DOI: 10.1089/dia.2021.0182

SOURCE Ascensia Diabetes Care

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ASCENSIA DIABETES CARE ANNOUNCES EUROPEAN APPROVAL OF THE NEXT-GENERATION EVERSENSE E3 CONTINUOUS GLUCOSE MONITORING SYSTEM - PR Newswire

What should diabetes health care professionals consider when treating patients who have sickle cell trait or disease?

World Sickle Cell Day is observed annually on June 19th to raise awareness of sickle cell disease, a group of inherited red blood cell disorders that affect more than 100,000 people in the United States and 20 million people worldwide. For people with sickle cell disease, red blood cells are crescent or sickle shaped and do not bend or move easily, which can block blood flow to the rest of the body and cause repeated infections and episodes of pain.

Hemoglobinopathies (also called hemoglobin variants) are inherited red blood cell conditions that affect hemoglobin, the protein that carries oxygen through the body. One of the most common hemoglobinopathies is hemoglobin S, the sickle cell gene. In a severe form of sickle cell disease, sickle cell anemia, a patient inherits two genes for hemoglobin S.

Patients can also inherit one sickle cell gene and have sickle cell trait, often with no signs or symptoms. This means that many patients are unaware they have sickle cell trait. It is also worth noting that certain populations are more likely to inherit sickle cell traitabout 1 in 13 African Americans and about 1 in 100 Hispanics/Latinos have sickle cell trait.

Sickle Cell Hemoglobinopathies and the A1C Test

For patients who have the sickle cell gene or other hemoglobinopathies, some A1C testing methods for blood glucose may produce unreliable results. An A1C test with falsely high outcomes could lead to the prescription of more aggressive treatments, resulting in increased episodes of hypoglycemia. Conversely, falsely low outcomes could lead to the undertreatment of diabetes.

Laboratories use many different assay methods to measure A1C. Health care professionals should suspect the presence of a hemoglobinopathy when

For more information about hemoglobinopathies and alternative tests to measure blood glucose levels, view NIDDKs health information on Sickle Cell Trait & Other Hemoglobinopathies & Diabetes.

And to learn more about NIDDK Director Dr. Griffin P. Rodgers career researching blood conditions, including sickle cell, watch the videos below.

Link:
Understanding the Link between Diabetes Care and Sickle Cell Disease | NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases...

The number of children being treated at paediatric diabetes units (PDUs) in England and Wales has increased by more than 50% amid a perfect storm of rising obesity levels and the cost of living crisis, health leaders have said.

Diabetes UK said alarming obesity levels among children had led to a concerning climb in the number diagnosed with type 2 diabetes, and predicted that the cost of living crisis could lead to further problems in the years to come.

Data from NHS Digital shows that almost one in seven children start primary school obese a rise of almost 50% in just a year. More than a quarter are obese by the time they finish primary school.

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The high levels of obesity combined with the squeeze on personal finances are creating a perfect storm which risks irreversible harm to the health of young people, Diabetes UK said. It accused the government of letting our children down as it called for concerted action to tackle obesity.

It comes after the governments decision to delay measures to reduce unhealthy eating, weakening its anti-obesity strategy by postponing for a year a ban on buy one, get one free deals for foods high in fat, salt and sugar.

Demand for care for children with type 2 diabetes at paediatric diabetes units across England and Wales has increased by more than 50% in the last five years, according to the Diabetes UK analysis. A total of 973 children with type 2 diabetes were treated in PDUs in 2020-21, up from 621 in 2015-16.

PDUs employ a team of specialists to care for children with type 2 diabetes that can include consultants, nurses and dieticians. The team usually work in a hospital setting, where a child may attend appointments as an outpatient rather than being seen at their GPs surgery. Previous statistics have shown that in England alone, about 1,600 children have been diagnosed with type 2 diabetes.

Diabetes UK said children in the most deprived parts of England and Wales were disproportionately affected by the disease, with four in 10 children and young people with type 2 diabetes living in the poorest areas, compared with only one in 19 from the richest. This is similar to data for childhood obesity prevalence, it said.

The charity said that in light of the additional burden of the cost of living crisis, the poorest children would bear the brunt for decades to come.

Chris Askew, the chief executive of Diabetes UK, said: We are very concerned that this spike in childhood obesity will translate into an even greater increase in children with type 2 diabetes in the coming years, a crisis fuelled by longstanding health inequalities and made worse still by impacts of the cost of living crisis.

Government needs to entirely rethink its commitment to child health. This must start with urgently reversing the decision to backtrack on their obesity strategy commitments and go further still, with bold steps to address childhood obesity and poorer outcomes for children living in poverty in the forthcoming health disparities white paper.

The UK government is letting our children down. With soaring numbers of children now living with obesity, and numbers diagnosed with type 2 diabetes on a very concerning climb, we are facing a perfect storm, which risks irreversible harm to the health of young people.

Continued here:
Child type 2 diabetes referrals in England and Wales jump 50% amid obesity crisis - The Guardian

LUBBOCK, Texas (PRESS RELEASE) The following is a press release from Covenant Health:

Covenant Childrens will host a free Diabetes Camp called New Beginnings for children ages 5-14 who have diabetes. The camp will be July 13-16, 2022, from 9 a.m. to 4 p.m., with each day at a different location in Lubbock. Locations will include the Science Spectrum, Main Event, YWCA and Spirit Ranch.

Due to the recent loss of the local American Diabetes Association chapter in the area, Covenant Childrens and Covenant Health Foundation recognized the need to replace the annual diabetes camp that used to be held by the organization.

We recognize the value and impact that a camp for children with diabetes holds. Kids with diabetes, and their families, need to know and see they are not alone, said Brittny Ayola, Covenant Childrens PICU nurse manager and diabetes education program coordinator.

The camp is free and open to all children in Lubbock and the surrounding area. Lunches, snacks, t-shirt and activities are covered; however, housing is not provided for attendees from out of town. Children will need to bring their own diabetes supplies.

As a diabetic herself, Ayola said when she was growing up, there were no camps in Lubbock, so she had to go out of town for similar experiences. Ayola said it can feel very isolating to have a chronic condition that takes daily management and being able to do normal activities with other children who also have diabetes can have a vast impact.

There will be medical professionals who have had diabetes training to oversee safety and give parents peace of mind while their child builds friendships and enjoys the camp. Through the day campers will do carb counts, take insulin and check blood sugar together.

On the last day of camp, there will be vendor booths for parents and families to learn more about diabetes technology, products and medications.

There are still spots available. The deadline to register is July 1, or when spots are full. Parents can sign up their child through the form at the following link: https://bit.ly/39tVGH5

If children with diabetes over the age of 15 are interested in participating, there are opportunities to help as a junior counselor or counselor. Contact Brittny Ayola at AYOLABS2@covhs.org or (806) 786-2968 for more information.

About Covenant Health:

Covenant Childrens is the only independently licensed, freestanding, childrens hospital in West Texas and eastern New Mexico and is one of only eight members of the Childrens Hospital Association of Texas and is the only one in our region.

As a faith-based health care system, it is Covenant Healths vision to create Health for a Better World. As the Best Hospital in the Panhandle Plains region as voted by U.S. News and World Report, Covenant Health has consistently provided exceptional health care to West Texas, and eastern New Mexico for more than 100 years. Our clinically integrated health network of eight hospitals, and more than 6,000 caregivers allows us to provide our patients with better access to care using more innovative technology and procedures, while focusing on new age approaches to health care like education and preventative medicine. To learn more about Covenant Health, please visit covenanthealth.org or our Facebook, LinkedIn, or Twitter, pages.

(Press release from Covenant Health)

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Covenant Childrens to host diabetes camp in July - KLBK | KAMC | EverythingLubbock.com

Sarki AM, Nduka CU, Stranges S, Kandala N-B, Uthman OA: Prevalence of hypertension in low-and middle-income countries: a systematic review and meta-analysis. Medicine 2015, 94(50).

Khan MN, Oldroyd JC, Chowdhury EK, Hossain MB, Rana J, Islam RM: Prevalence, awareness, treatment, and control of hypertension in Bangladesh: Findings from National Demographic and Health Survey, 201718. medRxiv 2021.

Islam R, Khan MN, Oldroyd JC, Rana J, Chowdhury EK, Karim MN, Hossain MB: Prevalence of diabetes and prediabetes among Bangladeshi adults and associated factors: Evidence from the Demographic and Health Survey, 201718. medRxiv 2021.

Patel SA, Ali MK, Alam D, Yan LL, Levitt NS, Bernabe-Ortiz A, Checkley W, Wu Y, Irazola V, Gutierrez L. Obesity and its relation with diabetes and hypertension: a cross-sectional study across 4 geographical regions. Global heart. 2016;11(1):719.

PubMed Article Google Scholar

Say L, Chou D, Gemmill A, Tunalp , Moller A-B, Daniels J, Glmezoglu AM, Temmerman M, Alkema L. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014;2(6):e32333.

PubMed Article Google Scholar

Mackin ST, Nelson SM, Wild SH, Colhoun HM, Wood R, Lindsay RS. Factors associated with stillbirth in women with diabetes. Diabetologia. 2019;62(10):193847.

CAS PubMed PubMed Central Article Google Scholar

Hedderson MM, Ferrara A. High blood pressure before and during early pregnancy is associated with an increased risk of gestational diabetes mellitus. Diabetes Care. 2008;31(12):23627.

PubMed PubMed Central Article Google Scholar

Pons RS, Rockett FC, de Almeida Rubin B, Oppermann MLR, Bosa VL: Risk factors for gestational diabetes mellitus in a sample of pregnant women diagnosed with the disease. In: Diabetology & metabolic syndrome: 2015: BioMed Central; 2015: 12.

Lu J, Zhang S, Li W, Leng J, Wang L, Liu H, Li W, Zhang C, Qi L, Tuomilehto J. Maternal gestational diabetes is associated with offsprings hypertension. Am J Hypertens. 2019;32(4):33542.

PubMed PubMed Central Article Google Scholar

Miranda JO, Cerqueira RJ, Barros H, Areias JC. Maternal diabetes mellitus as a risk factor for high blood pressure in late childhood: a prospective birth cohort study. Hypertension. 2019;73(1):e17.

CAS PubMed Article Google Scholar

Zhang S, Liu H, Zhang C, Wang L, Li N, Leng J, Li Y, Liu G, Fan X, Yu Z: Maternal glucose during pregnancy and after delivery in women with gestational diabetes mellitus on overweight status of their children. BioMed research international 2015, 2015.

Tam WH, Ma RCW, Ozaki R, Li AM, Chan MHM, Yuen LY, Lao TTH, Yang X, Ho CS, Tutino GE. In utero exposure to maternal hyperglycemia increases childhood cardiometabolic risk in offspring. Diabetes Care. 2017;40(5):67986.

CAS PubMed PubMed Central Article Google Scholar

Hillier TA, Pedula KL, Schmidt MM, Mullen JA, Charles M-A, Pettitt DJ. Childhood obesity and metabolic imprinting: the ongoing effects of maternal hyperglycemia. Diabetes Care. 2007;30(9):228792.

PubMed Article Google Scholar

Association AD. Management of diabetes in pregnancy: standards of medical care in diabetes2019. Diabetes Care. 2019;42(Supplement 1):S16572.

Article Google Scholar

Chuang CH, Chase GA, Bensyl DM, Weisman CS. Contraceptive use by diabetic and obese women. Womens Health Issues. 2005;15(4):16773.

PubMed Article Google Scholar

Perritt JB, Burke A, Jamshidli R, Wang J, Fox M. Contraception counseling, pregnancy intention and contraception use in women with medical problems: an analysis of data from the Maryland Pregnancy Risk Assessment Monitoring System (PRAMS). Contraception. 2013;88(2):2638.

PubMed Article Google Scholar

Vahratian A, Barber JS, Lawrence JM, Kim C. Family-planning practices among women with diabetes and overweight and obese women in the 2002 National Survey For Family Growth. Diabetes Care. 2009;32(6):102631.

PubMed PubMed Central Article Google Scholar

Harris M, Egan N, Forder PM, Bateson D, Sverdlov AL, Murphy VE, Loxton D: Patterns of contraceptive use among young Australian women with chronic disease: findings from a prospective cohort study. 2021.

Nojomi M, Morrovatdar N, Davoudi F, Hosseini S. Contraceptive use by Iranian women with hypertension, diabetes or obesity. EMHJ-Eastern Mediterranean Health J. 2013;19(7):63843.

CAS Article Google Scholar

Mekonnen TT, Woldeyohannes SM, Yigzaw T. Contraceptive use in women with hypertension and diabetes: cross-sectional study in northwest Ethiopia. Int J Womens Health. 2015;7:957.

Google Scholar

Afshari M, Alizadeh-Navaei R, Moosazadeh M. Oral contraceptives and hypertension in women: results of the enrolment phase of Tabari Cohort Study. BMC Womens Health. 2021;21(1):17.

Article Google Scholar

Robinson A, Nwolise C, Shawe J. Contraception for women with diabetes: challenges and solutions. Open Access J Contracept. 2016;7:11.

PubMed PubMed Central Article Google Scholar

KHAN MN: Effects of Unintended Pregnancy on Maternal Healthcare Services Use in Bangladesh. Faculty of Health and Medicine, School of Medicine and Public Health, The; 2020.

Khan MN, Harris M, Loxton D. Modern contraceptive use following an unplanned birth in Bangladesh: an analysis of national survey data. Int Perspect Sex Reprod Health. 2020;46:7787.

PubMed Article Google Scholar

Khan MN, Islam MM. Exploring rise of pregnancy in Bangladesh resulting from contraceptive failure. Sci Rep. 2022;12(1):110.

Article Google Scholar

Bishwajit G, Tang S, Yaya S, Feng Z. Unmet need for contraception and its association with unintended pregnancy in Bangladesh. BMC Pregnancy Childbirth. 2017;17(1):19.

Article Google Scholar

Huda FA, Chowdhuri S, Robertson Y, Islam N, Sarker BK, Azmi AJ, Reichenbach L: Understanding unintended pregnancy in Bangladesh: country profile report. 2013.

NIPORT MaA, ICF International, : Bangladesh Demographic and Health Survey, 2017/18. In. NIPORT, Mitra & Associates and ICF International, Dhaka, Bangladesh and Calverton, MD, USA2013.; 2020.

Greydanus DE, Omar HA, Tsitsika A: Obesity and contraception. 2009.

WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet (London, England). 2004;363(9403):15763.

Article Google Scholar

Barros AJ, Hirakata VN. Alternatives for logistic regression in cross-sectional studies: an empirical comparison of models that directly estimate the prevalence ratio. BMC Med Res Methodol. 2003;3(1):113.

Article Google Scholar

Tamhane AR, Westfall AO, Burkholder GA, Cutter GR. Prevalence odds ratio versus prevalence ratio: choice comes with consequences. Stat Med. 2016;35(30):57305.

PubMed PubMed Central Google Scholar

O'Connell AA, McCoach DB: Multilevel modeling of educational data: IAP; 2008.

Von Elm E, Altman DG, Egger M, Pocock SJ, Gtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Bull World Health Organ. 2007;85:86772.

Article Google Scholar

World Health Organization: Maternal mortality. In. Geneva, Switzarland The World Health Organization 2021.

Buchanan TA, Xiang AH, Page KA. Gestational diabetes mellitus: risks and management during and after pregnancy. Nat Rev Endocrinol. 2012;8(11):639.

CAS PubMed PubMed Central Article Google Scholar

Khan MN, Islam MM, Akter S: Availability and readiness of healthcare facilities and their effects on long-acting modern contraception use in Bangladesh: Analysis of linked data. medRxiv 2021.

Beaglehole R, Epping-Jordan J, Patel V, Chopra M, Ebrahim S, Kidd M, Haines A. Improving the prevention and management of chronic disease in low-income and middle-income countries: a priority for primary health care. The Lancet. 2008;372(9642):9409.

Article Google Scholar

National Institute of Population Research and Training (NIPORT) and ICF: Bangladesh Health Facility Survey 2017. In. Dhaka, Bangladesh: NIPORT, ACPR, and ICF.; 2019.

Ahmad A, Oparil S. Hypertension in women: recent advances and lingering questions. Hypertension. 2017;70(1):1926.

CAS PubMed Article Google Scholar

Schwarz EB, Postlethwaite D, Hung Y-Y, Lantzman E, Armstrong MA, Horberg MA. Provision of contraceptive services to women with diabetes mellitus. J Gen Intern Med. 2012;27(2):196201.

PubMed Article Google Scholar

Marshall CJ, Huma Z, Deardorff J, Britton LE. Prepregnancy counseling among US Women with diabetes and hypertension, 20162018. Am J Prev Med. 2021;61(4):52936.

PubMed Article Google Scholar

Pallardo L, Cano A, Cristobal I, Blanco M, Lozano M, Lete I: Hormonal contraception and diabetes. Clinical Medicine Insights: Women's Health 2012, 5:CMWH. S9934.

Endriyas M, Eshete A, Mekonnen E, Misganaw T, Shiferaw M. Where we should focus? Myths and misconceptions of long acting contraceptives in Southern Nations, Nationalities and Peoples Region, Ethiopia: qualitative study. BMC Pregnancy Childbirth. 2018;18(1):16.

Article Google Scholar

Medical News Today: Debunking common birth control myths. In.; 2020.

Ochako R, Mbondo M, Aloo S, Kaimenyi S, Thompson R, Temmerman M, Kays M. Barriers to modern contraceptive methods uptake among young women in Kenya: a qualitative study. BMC Public Health. 2015;15(1):19.

Article Google Scholar

Kersten I, Lange AE, Haas JP, Fusch C, Lode H, Hoffmann W, Thyrian JR. Chronic diseases in pregnant women: prevalence and birth outcomes based on the SNiP-study. BMC Pregnancy Childbirth. 2014;14(1):113.

Article Google Scholar

Lykens JE, Broecker JE. Contraceptive options for women with metabolic syndrome. Osteopathic Family Physician. 2011;3(3):8898.

Article Google Scholar

Lathrop E, Jatlaoui T. Contraception for women with chronic medical conditions: an evidence-based approach. Clin Obstet Gynecol. 2014;57(4):67481.

PubMed Article Google Scholar

Adongo PB. Tabong PT-N, Azongo TB, Phillips JF, Sheff MC, Stone AE, Tapsoba P: A comparative qualitative study of misconceptions associated with contraceptive use in southern and northern Ghana. Front Public Health. 2014;2:137.

PubMed PubMed Central Article Google Scholar

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Pattern of contraceptive use among reproductive-aged women with diabetes and/or hypertension: findings from Bangladesh Demographic and Health Survey -...

CASES of diabetes are on the up and it's estimated around 13.6million Brits are at risk.

While key symptoms usually include extreme thirst and an increased need to urinate, there could also be signs on your skin.

1

Diabetes is a serious condition in which the level of glucose in your body is too high.

There are two types, with the main difference being that type 1 diabetes is a genetic condition, with type 2 mainly being down to lifestyle choices.

But both are as serious as each other and can lead to serious health complications.

With that in mind, it's important to know how the illness could show up in your skin.

Chartered chemist, Bruce Green said that diabetic skin can be similar to skin that has prematurely aged.

"The skin changing process is Glycation. A process where proteins and sugars are cross-linked to advanced glycation end products (age) there is a negative impact on the elasticity of the skin, when collagen and elastin are stiffened," he said.

He explained skin problems are more likely amongst diabeticsbecause of reduced circulation and reduced sensitivity of nerves.

In addition, Bruce, who is the founder of diabetic skincare range, SOS Serum Skincare said there are six key warning signs you need to be aware of.

Signs to look out for on the skin are:

However, these aren't the only signs you need to be aware of.

The NHS recommends that you see a doctor if you're feeling very thirsty and you're peeing more frequently than usual - especially at night.

Other key signs of diabetes include feeling very tired, weight loss and a loss of muscle bulk and blurred vision.

When it comes to your skin, the NHS says that itching around the penis or vagina or experiencing cuts or wounds that heal slowly are also common signs - all of which you should seek medical attention for.

If you are diabetic - then it's key that you look after your skin.

Bruce said that when it comes to cleaning yourself, you should use a mild soap-free, alcohol free substance.

You need to make sure that you wipe it off and dry off properly - as damp skin can cause irritation.

When it comes to keeping your skin soft and supple, the skin guru said you should also use a high quality moisturiser with a minimum SPF of 30.

"Avoid perfumed products and petrochemical ingredients and look for a short ingredient list, he advised.

He also suggested that when you can, you should try and wear 100 per cent cotton.

"This allows a healthy through flow of air and helps to reduce localised perspiration," he added.

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Diabetes warning: The 6 signs on your SKIN that can be a sign of life-threatening disease... - The Sun

Stem cells have two features: the ability to differentiate along different lineages and the ability of self-renewal. Two major types of stem cells have been described, namely, embryonic stem cells and adult stem cells. Embryonic stem cells (ESC) are obtained from the inner cell mass of the blastocyst and are associated with tumorigenesis, and the use of human ESCs involves ethical and legal considerations. The use of adult mesenchymal stem cells is less problematic with regard to these issues. Mesenchymal stem cells (MSCs) are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as umbilical cord, endometrial polyps, menses blood, bone marrow, adipose tissue, etc. This is because the ease of harvest and quantity obtained make these sources most practical for experimental and possible clinical applications. Recently, MSCs have been found in new sources, such as menstrual blood and endometrium. There are likely more sources of MSCs waiting to be discovered, and MSCs may be a good candidate for future experimental or clinical applications. One of the major challenges is to elucidate the mechanisms of differentiation, mobilization, and homing of MSCs, which are highly complex. The multipotent properties of MSCs make them an attractive choice for possible development of clinical applications. Future studies should explore the role of MSCs in differentiation, transplantation, and immune response in various diseases.

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Mesenchymal stem cells - PubMed

Cells in the body have specific purposes, but stem cells are cells that do not yet have a specific role and can become almost any cell that is required.

Stem cells are undifferentiated cells that can turn into specific cells, as the body needs them.

Scientists and doctors are interested in stem cells as they help to explain how some functions of the body work, and how they sometimes go wrong.

Stem cells also show promise for treating some diseases that currently have no cure.

Stem cells originate from two main sources: adult body tissues and embryos. Scientists are also working on ways to develop stem cells from other cells, using genetic reprogramming techniques.

A persons body contains stem cells throughout their life. The body can use these stem cells whenever it needs them.

Also called tissue-specific or somatic stem cells, adult stem cells exist throughout the body from the time an embryo develops.

The cells are in a non-specific state, but they are more specialized than embryonic stem cells. They remain in this state until the body needs them for a specific purpose, say, as skin or muscle cells.

Day-to-day living means the body is constantly renewing its tissues. In some parts of the body, such as the gut and bone marrow, stem cells regularly divide to produce new body tissues for maintenance and repair.

Stem cells are present inside different types of tissue. Scientists have found stem cells in tissues, including:

However, stem cells can be difficult to find. They can stay non-dividing and non-specific for years until the body summons them to repair or grow new tissue.

Adult stem cells can divide or self-renew indefinitely. This means they can generate various cell types from the originating organ or even regenerate the original organ, entirely.

This division and regeneration are how a skin wound heals, or how an organ such as the liver, for example, can repair itself after damage.

In the past, scientists believed adult stem cells could only differentiate based on their tissue of origin. However, some evidence now suggests that they can differentiate to become other cell types, as well.

From the very earliest stage of pregnancy, after the sperm fertilizes the egg, an embryo forms.

Around 35 days after a sperm fertilizes an egg, the embryo takes the form of a blastocyst or ball of cells.

The blastocyst contains stem cells and will later implant in the womb. Embryonic stem cells come from a blastocyst that is 45 days old.

When scientists take stem cells from embryos, these are usually extra embryos that result from in vitro fertilization (IVF).

In IVF clinics, the doctors fertilize several eggs in a test tube, to ensure that at least one survives. They will then implant a limited number of eggs to start a pregnancy.

When a sperm fertilizes an egg, these cells combine to form a single cell called a zygote.

This single-celled zygote then starts to divide, forming 2, 4, 8, 16 cells, and so on. Now it is an embryo.

Soon, and before the embryo implants in the uterus, this mass of around 150200 cells is the blastocyst. The blastocyst consists of two parts:

The inner cell mass is where embryonic stem cells are found. Scientists call these totipotent cells. The term totipotent refer to the fact that they have total potential to develop into any cell in the body.

With the right stimulation, the cells can become blood cells, skin cells, and all the other cell types that a body needs.

In early pregnancy, the blastocyst stage continues for about 5 days before the embryo implants in the uterus, or womb. At this stage, stem cells begin to differentiate.

Embryonic stem cells can differentiate into more cell types than adult stem cells.

MSCs come from the connective tissue or stroma that surrounds the bodys organs and other tissues.

Scientists have used MSCs to create new body tissues, such as bone, cartilage, and fat cells. They may one day play a role in solving a wide range of health problems.

Scientists create these in a lab, using skin cells and other tissue-specific cells. These cells behave in a similar way to embryonic stem cells, so they could be useful for developing a range of therapies.

However, more research and development is necessary.

To grow stem cells, scientists first extract samples from adult tissue or an embryo. They then place these cells in a controlled culture where they will divide and reproduce but not specialize further.

Stem cells that are dividing and reproducing in a controlled culture are called a stem-cell line.

Researchers manage and share stem-cell lines for different purposes. They can stimulate the stem cells to specialize in a particular way. This process is known as directed differentiation.

Until now, it has been easier to grow large numbers of embryonic stem cells than adult stem cells. However, scientists are making progress with both cell types.

Researchers categorize stem cells, according to their potential to differentiate into other types of cells.

Embryonic stem cells are the most potent, as their job is to become every type of cell in the body.

The full classification includes:

Totipotent: These stem cells can differentiate into all possible cell types. The first few cells that appear as the zygote starts to divide are totipotent.

Pluripotent: These cells can turn into almost any cell. Cells from the early embryo are pluripotent.

Multipotent: These cells can differentiate into a closely related family of cells. Adult hematopoietic stem cells, for example, can become red and white blood cells or platelets.

Oligopotent: These can differentiate into a few different cell types. Adult lymphoid or myeloid stem cells can do this.

Unipotent: These can only produce cells of one kind, which is their own type. However, they are still stem cells because they can renew themselves. Examples include adult muscle stem cells.

Embryonic stem cells are considered pluripotent instead of totipotent because they cannot become part of the extra-embryonic membranes or the placenta.

Stem cells themselves do not serve any single purpose but are important for several reasons.

First, with the right stimulation, many stem cells can take on the role of any type of cell, and they can regenerate damaged tissue, under the right conditions.

This potential could save lives or repair wounds and tissue damage in people after an illness or injury. Scientists see many possible uses for stem cells.

Tissue regeneration is probably the most important use of stem cells.

Until now, a person who needed a new kidney, for example, had to wait for a donor and then undergo a transplant.

There is a shortage of donor organs but, by instructing stem cells to differentiate in a certain way, scientists could use them to grow a specific tissue type or organ.

As an example, doctors have already used stem cells from just beneath the skins surface to make new skin tissue. They can then repair a severe burn or another injury by grafting this tissue onto the damaged skin, and new skin will grow back.

In 2013, a team of researchers from Massachusetts General Hospital reported in PNAS Early Edition that they had created blood vessels in laboratory mice, using human stem cells.

Within 2 weeks of implanting the stem cells, networks of blood-perfused vessels had formed. The quality of these new blood vessels was as good as the nearby natural ones.

The authors hoped that this type of technique could eventually help to treat people with cardiovascular and vascular diseases.

Doctors may one day be able to use replacement cells and tissues to treat brain diseases, such as Parkinsons and Alzheimers.

In Parkinsons, for example, damage to brain cells leads to uncontrolled muscle movements. Scientists could use stem cells to replenish the damaged brain tissue. This could bring back the specialized brain cells that stop the uncontrolled muscle movements.

Researchers have already tried differentiating embryonic stem cells into these types of cells, so treatments are promising.

Scientists hope one day to be able to develop healthy heart cells in a laboratory that they can transplant into people with heart disease.

These new cells could repair heart damage by repopulating the heart with healthy tissue.

Similarly, people with type I diabetes could receive pancreatic cells to replace the insulin-producing cells that their own immune systems have lost or destroyed.

The only current therapy is a pancreatic transplant, and very few pancreases are available for transplant.

Doctors now routinely use adult hematopoietic stem cells to treat diseases, such as leukemia, sickle cell anemia, and other immunodeficiency problems.

Hematopoietic stem cells occur in blood and bone marrow and can produce all blood cell types, including red blood cells that carry oxygen and white blood cells that fight disease.

People can donate stem cells to help a loved one, or possibly for their own use in the future.

Donations can come from the following sources:

Bone marrow: These cells are taken under a general anesthetic, usually from the hip or pelvic bone. Technicians then isolate the stem cells from the bone marrow for storage or donation.

Peripheral stem cells: A person receives several injections that cause their bone marrow to release stem cells into the blood. Next, blood is removed from the body, a machine separates out the stem cells, and doctors return the blood to the body.

Umbilical cord blood: Stem cells can be harvested from the umbilical cord after delivery, with no harm to the baby. Some people donate the cord blood, and others store it.

This harvesting of stem cells can be expensive, but the advantages for future needs include:

Stem cells are useful not only as potential therapies but also for research purposes.

For example, scientists have found that switching a particular gene on or off can cause it to differentiate. Knowing this is helping them to investigate which genes and mutations cause which effects.

Armed with this knowledge, they may be able to discover what causes a wide range of illnesses and conditions, some of which do not yet have a cure.

Abnormal cell division and differentiation are responsible for conditions that include cancer and congenital disabilities that stem from birth. Knowing what causes the cells to divide in the wrong way could lead to a cure.

Stem cells can also help in the development of new drugs. Instead of testing drugs on human volunteers, scientists can assess how a drug affects normal, healthy tissue by testing it on tissue grown from stem cells.

Watch the video to find out more about stem cells.

There has been some controversy about stem cell research. This mainly relates to work on embryonic stem cells.

The argument against using embryonic stem cells is that it destroys a human blastocyst, and the fertilized egg cannot develop into a person.

Nowadays, researchers are looking for ways to create or use stem cells that do not involve embryos.

Stem cell research often involves inserting human cells into animals, such as mice or rats. Some people argue that this could create an organism that is part human.

In some countries, it is illegal to produce embryonic stem cell lines. In the United States, scientists can create or work with embryonic stem cell lines, but it is illegal to use federal funds to research stem cell lines that were created after August 2001.

Some people are already offering stem-cells therapies for a range of purposes, such as anti-aging treatments.

However, most of these uses do not have approval from the U.S. Food and Drug Administration (FDA). Some of them may be illegal, and some can be dangerous.

Anyone who is considering stem-cell treatment should check with the provider or with the FDA that the product has approval, and that it was made in a way that meets with FDA standards for safety and effectiveness.

See the original post here:
Stem cells: Sources, types, and uses - Medical News Today

Fat cells are the basic building blocks of fat tissue. Fat (or adipose) tissue is found throughout the human body and is concentrated beneath the skin, between the muscles, and around the internal organs.

The primary functions of fat cells are to store lipids for energy, to produce and secret hormones, and to release heat energy from lipids.

Fat cells (AKA adipocytes or adipose cells) are the cells that make up the adipose tissue. Their main functions are to store energy in the form of lipids and to create an insulating layer beneath the skin for the conservation of body heat. Adipose tissue also insulates, cushions, and protects the internal organs.

Fat cells are primarily located beneath the skin, between the muscles, and around the internal organs. Adipose tissue under the skin is known as subcutaneous fat, and it mainly functions as an insulating layer and energy store. Fat tissue found between the muscles and internal organs is called visceral fat. Visceral fat also helps to insulate the body and prevent heat loss, whilst acting as a shock absorber to cushion and protect the organs.

There are three main types of adipocytes in vertebrates; there are white fat cells, brown fat cells, and beige fat cells. Different types of fat cells are found in different regions of the body and have different functions to one another.

Most fat in the human body is white fat tissue. White fat cells are highly specialized for fat storage and contain large lipid droplets. For this reason, they function as the bodys main energy reserve.

White adipose tissue also makes up the bulk of the insulating layer that lies beneath the skin and surrounds the internal organs. This layer is important for the conservation of body heat and, therefore, regulation of body temperature.

Brown adipose tissue also stores energy but, unlike white fat cells, brown fat cells are specialized to release energy in the form of heat. This process (known as thermogenesis) is switched on in response to low external temperatures, and helps to maintain body temperature in cold conditions.

Brown fat cells are typically smaller than white fat cells and may contain multiple, small lipid droplets (rather than the single large droplet found in white adipocytes). They are also equipped with abundant mitochondria, which is how these cells get their brown color. During thermogenesis, the mitochondria in brown fat cells convert the chemical energy stored in lipids into heat energy. The heat is released from the fat cell and dissipates through the tissues of the body to maintain or raise its overall temperature.

Brown fat tissue is found in specific regions of the body, including between the neck muscles and shoulder blades, along the spinal cord, above the collarbone, and, sometimes, surrounding the internal organs.

Beige adipocytes are halfway between white and brown fat cells and have characteristics of both. They are found in similar areas to white fat cells and behave like white adipocytes until they are activated by low temperatures. When this happens, they go through a process called browning and begin to behave like brown adipocytes (i.e., they start to burn lipids for energy).

Adipocytes are specialized to store fat and mainly function as a fuel reserve for the body. However, fat cells also have two other key functions, and these are the release of hormones and the production of heat.

White fat cells function as a long-term energy store and are specialized to store lipids in the form of triglycerides. They are the bodys safety net against starvation and, in times of fasting, will release fatty acids and glycerol as fuel for the rest of the body.

When we consume excess calories, our bodies store more fats, and the size of the lipid droplets inside the fat cells increases. This gradually causes an increase in the mass of adipose tissue and can contribute to obesity.

The storage and release of fatty acids by white blood cells is controlled by hormones, such as insulin. The release of pancreatic insulin stimulates fat cells to take up and store triglycerides, while a drop in insulin levels causes fat cells to release their fatty acids.

Adipose tissue is more than just an energy-storing mass. It also functions as an endocrine organ, meaning it synthesizes and releases hormones. These hormones influence a wide range of biological processes in the body, including the regulation of food intake and control of sensitivity to insulin.

Like white adipocytes, brown fat cells store lipids for energy. However, they also have their own unique function, and this is thermogenesis: the use of lipids to produce heat.

Brown adipose tissue protects vertebrates from the cold and is switched on by exposure to low temperatures. When this happens, the abundant mitochondria in brown fat cells are triggered to increase their oxidation of fatty acids, a process that wastes chemical energy as heat. The heat produced by thermogenesis dissipates through the tissues surrounding the brown fat cells, helping to maintain the body temperature of the organism.

Whether brown or white, all adipose cells consist of a large lipid droplet surrounded by a thin layer of cytoplasm and a plasma membrane. Each cell also contains organelles including a nucleus, Golgi apparatus, endoplasmic reticulum, ribosomes, and mitochondria. Brown fat cells contain lots more mitochondria than white fat cells do, which is what gives their lipid droplets their darker color.

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Fat Cells - The Definitive Guide | Biology Dictionary

Degenerative Disc Disease (DDD), Herniated Discs & Sciatica Causing Lumbar Back Pain

What is degenerative disc disease and what are the symptoms?

Spinal disc degeneration and disc herniations are two of the most common causes of back pain, affecting in particular the lumbar spine (low back). Spinal discs are soft, compressible structures that separate the vertebrae of the spine. The discs act as shock absorbers, allowing the spine to flex, bend, and twist.

Sciatica is the name for the horrible leg pain that is caused when a bulging lumbar disc irritates a lumbar nerve root. The discomfort can be a combination of burning pain and numbness that responds poorly to pain medication.

There is a normal amount of expected wear and tear of our spinal discs as we age. On the other hand, arthritis, injury, and extreme wear and tear of sports can accelerate the degeneration. On a cellular level, there is continual loss of healthy cells inside the disc that is responsible for the discs structure. Over time, normal cells are damaged and hydration is lost, leading to tears in the internal structure of the discs.

When discs degenerate, mobility is affected and function is limited, resulting in symptoms that include stiffness, weakness, and ultimately, unrelenting pain.

What is spinal facet disease and what are the symptoms?

Spinal facet disease is one of the most common causes of neck and back pain and can cause pain at any level of the spine. The spinal facets joints are located on both sides of the back of each spinal segment. They connect each spinal level and are responsible for stabilizing the vertebral bodies and counterbalancing the intervertebral discs. The facets can be injured during acute trauma often seen in flexion extension injuries such as a whiplash event or sports accident. The surfaces of the facet joints are covered by articular cartilage and are also prone to chronic degenerative arthritis much like the larger joints such as knees and hips.

Pain that is caused by facet dysfunction is typically isolated to the back of the lumbar spine, thoracic region and neck. The discomfort can be isolated to one side or may affect both sides of the spine at once. The pain may radiate into the muscles but does not extend into the extremities like sciatic pain that is caused from a disc herniation. Typically the pain is worsened with extension and or rotation of the neck or back. Diagnosis of facet pain begins with a physical exam and imaging studies, but often requires diagnostic injection with local anesthetic and or steroid to confirm the diagnosis.

When the facet joints are injured mobility is affected and function is limited, resulting in symptoms that can mimic disc disease such as stiffness, weakness, and ultimately, unrelenting pain.

Read more here:
Stem Cells For Back Pain | Stem Cells For Herniated Discs

-- First Site Will Enroll First Patient in the Clinical Study--

MELVILLE, NY., June 13, 2022 (GLOBE NEWSWIRE) -- BioRestorative Therapies, Inc. (the Company” or BioRestorative”) (NASDAQ: BRTX), a clinical stage company focused on stem cell-based therapies, today announced site initiation for its Phase 2 clinical trial targeting chronic lumbar disc disease (cLDD). The Denver Spine and Pain Institute is the first clinical site to be initiated. Additional selected sites are expected to be initiated in 2022.

BioRestorative’s Phase 2 trial is a double-blind controlled, randomized study to evaluate the safety and preliminary efficacy of a single dose intradiscal injection of the Company’s autologous investigational stem cell-based therapeutic, BRTX-100. A total of up to 99 eligible patients will be randomized at up to 15 centers in the United States to receive either the investigational drug (BRTX-100) or control in a 2:1 fashion.

Currently there are no approved, cell-based therapies for cLDD. While there is encouraging data that suggests that patients with cLDD could benefit from autologous stem cell transplants, the low oxygen micro-environment of the disc makes cell-based therapies challenging. BRTX-100 is manufactured under low oxygen conditions and engineered to survive this environment,” said Scott Bainbridge, M.D., Principal Investigator for the BRTX-100 trial at The Denver Spine and Pain Institute. Positive proof-of-concept data in this trial could be disruptive and support the potential applicability of BRTX-100 to other spine and musculoskeletal disorders where low oxygen micro-environments are found.”

We are pleased to initiate the first of several sites across the United States that will be enrolling for the trial,” said Lance Alstodt, Chief Executive Officer of BioRestorative Therapies. Our sites have been carefully reviewed and selected and have clinical expertise in treating patients who could potentially benefit from BRTX-100. We look forward to working with the principal investigators and their clinical trial teams.”

About BioRestorative Therapies, Inc.

BioRestorative Therapies, Inc. (www.biorestorative.com) develops therapeutic products using cell and tissue protocols, primarily involving adult stem cells. Our two core programs, as described below, relate to the treatment of disc/spine disease and metabolic disorders:

Forward-Looking Statements

This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause future circumstances, events or results to differ materially from those projected in the forward-looking statements as a result of various factors and other risks, including, without limitation, those set forth in the Company's latest Form 10-K filed with the Securities and Exchange Commission and other public filings. You should consider these factors in evaluating the forward-looking statements included herein, and not place undue reliance on such statements. The forward-looking statements in this release are made as of the date hereof and the Company undertakes no obligation to update such statements.

CONTACT: Email: ir@biorestorative.com

Excerpt from:
2022-06-13 | OTCPK:BRTXD | Press Release | BioRestorative Therapies - Stockhouse

Introduction to DPP-4 Enzyme

In 1966, Hopsu-Havu and Glenner found dipeptidyl peptidase-4 (DPP-4) in rat liver during the processing of the cells and commercially enzymatic preparations as an activity that liberates naphthylamine from GlyPro-2-naphthylamide, and it was originally called glycylproline naphthylamidase.1 Meanwhile, the protein characteristics and distribution were intensively investigated, and it was rediscovered numerous times as a binding protein and a cellular marker.2 DPP-4 is the enzyme for the immune response which is known as antigen CD26 co-stimulator of T- cell, having a multiuse protein that serves as a binding protein and a ligand for a range of extracellular molecules in addition to its catalytic activity.3 It is a membrane protein that is expressed on cells all over the body, but it is also detached from the membrane and comes into circulation in the plasma as a soluble protein.4,5 Lymphocytes, fibroblasts, endothelial cells, and apical portions of acinar and epithelial cells express DPP-4, which is also found in plasma as in soluble circulating form.6,7

All membrane-bound molecules like proline or alanine-specific exopeptidases have been proposed to have a biological function in the degradation of bioactive peptides,8 but the DPP-4 role has been explored and reported most. In comparison to other peptidase enzymes, like aminopeptidase and carboxypeptidase, which have a limited distribution, DPP-4 is found in almost all vertebrate tissues, but its activity varies greatly.9

The enzyme is found largely in the cortical region and in the brush-border and microvillus portions of the kidney and hepatocytes at the cytoplasmic membrane surrounding bile canaliculi and on epithelial of the bile duct in the liver. It can also be detected on pancreatic duct epithelial cells.10 DPP-4 is thus present in body compartments/fluids engaged in nutrition and excretion (bile, pancreatic fluid, intestinal lumen, urine). As a result, DPP-4 plays a digestive role in the final breakdown of peptides produced by other endo and exo-peptidases from nutritious proteins and their absorption in these tissues.11 In both rats and humans, DPP-4 is a ubiquitous enzyme, including the exocrine pancreas, biliary tract, spleen, small intestine, and brain.12,13 DPP-4 possesses differentially expressed biological functions, as evidenced by its extensive organ distribution. The liver is among the organs with the highest levels of DPP-4 expression.14 DPP-4 marking is high in hepatic acinar zones 2 and 3, but never in zone 1, in a normal healthy liver.15 DPP-4 may be implicated in the control of hepatic metabolism, based on the uneven lobular distribution.16

DPP-4, on the other hand, is in direct touch with hormones flowing in the blood, as it is present on blood vessels endothelial cells17 and as a mobile enzyme in plasma. DPP-4 is expressed on excited T-helper lymphocytes18 as well as fractions of macrophages19 among immune system cells.20 DPP-4 is highly expressed in the endocrine organs, but occasionally in parenchymal cells, such as thyroid follicular epithelial cells and luteal cells.21 DPP-4 is expressed in specialized fibroblasts in a variety of tissues, including the skin, mammary gland, and synovia.22 The concentration and activity of DPP-4 in different organs/tissues/cells are shown in Figure 1.

Figure 1 Graphical representation of the concentration and activity of DPP-4 in different organs/tissues/cells.

DPP-4 includes membrane-bound peptidases like fibroblast activation protein (FAP)/seprase, resident cytoplasmic enzymes, and nonenzymatic members, which are found in neuronal membranes, as well as prolyl endopeptidase. Despite other major changes in sequence, the position and identity of the residues are crucial for catalytic activity within the C-terminal region of these related enzymes and are highly conserved in prokaryotes and eukaryotes.23 DPP-4 interacts with other membrane proteins and sends signals across cell membranes. The molecular structure of DPP-4 is shown in Figure 2.

Figure 2 Molecular structure of DPP-4.

Notably, the majority of the protein is extracellular, including the catalytic domain at the C-terminus, a cysteine-rich region, and a large glycosylated region connected to the transmembrane portion by a flexible stalk. Only six amino acids at the N-terminus are expected to reach into the cytoplasm. DPP-4 can form tetramers between two soluble proteins or two membrane-bound proteins, which could alter the efficiency of substrate entrance and cleavage by the catalytic active site or facilitate cellcell communication, as reported in a study of the protein crystal structure.23

The intracellular signalling of membrane-bound DPP-4 is initiated by the interactions with T-cell antigen CD-45, Adenosine deaminase (ADA), caveolin-1, and the caspase recruitment domain-containing protein 11.24,25 DPP-4 binds to the extracellular matrix proteins, collagen, and fibronectin, as well as ADA, binding to these proteins and ADA, is mediated by amino acid residues that are not part of the substrate-binding site26,27 (Figure 2). DPP-4 which is catalytically active is released from the plasma membrane, resulting in DPP-4 (727 aa), a soluble circulating form that lacks the intracellular tail and transmembrane portions (cytoplasmic domain, flexible stalk)28,29 and accounts for a significant amount of DPP-4 activity in human blood.30 Moreover, both membrane-bound and circulating soluble DPP-4 share some domains such as ADA binding domain, glycosylated region, cytosine-rich domain, catalytic domain, fibronectin domain, and the disulfide bonds.25 Here are some examples of target peptides of DPP-4 as shown in Table 1.

Table 1 Various Target Peptide of DPP-4

DPP-4 is a kind of enzyme that cleaves alanine or proline-containing peptides such as incretin, chemokines, and appetite-suppressing hormones (neuropeptide) at their N-terminal dipeptides. GLP-1, peptide YY, GLP-2, chemokine ligand 12/stromal-derived factor-1 (CXCL12/SDF-1), and substance P are examples of potential targets. Consequently, DPP-4 peptidase activity has different modes of action on glucose metabolism, hunger regulation, gastrointestinal motility, immune system function, inflammation, and pain regulation. Figure 3 shows that DPP-4 has different modes of action on chemokine production and metabolism through its peptidase activity. DPP-4 is also implicated in immunological stimulation, anti-cancer drug resistance, and ECM (Extracellular Matrix) binding and breakdown. DPP-4 also has an impact on lipid build-up.

Figure 3 Physiological properties of DPP-4 in various regions.

The functions and abundance of DPP-4 in the body have already been discussed in the above section. But the major focus is on the cleavage of alanine or proline-containing peptides such as incretins by the DPP-4 and its resulting consequences.

Incretins are hormones with an important role in the homeostasis of glucose, type 2 diabetes pathophysiology, and other metabolic disorders.54 These incretin hormones help in lowering the blood glucose level by stimulating the release of insulin and insulin opens the GLUT4 channel so that glucose can enter the cell and is utilized by the cells for energy production.55 There is an interesting fact that oral administration of glucose stimulates more insulin release than the intravenous administration of glucose while the concentration of glucose reaches circulation remains the same.56 This situation is known as the incretin effect and it is credited to specialized cells enteroendocrine present in the gut and coupled with glucose absorption. When glucose is administered orally, it reaches the enteroendocrine cells during absorption, and incretin hormones like glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (GLP-1) are released from enteroendocrine cells, which stimulate pancreatic -cells to release insulin.57 On the other hand, in the intravenous administration of glucose, the enteroendocrine cells are bypassed and thus less availability of incretins leads to less stimulation of pancreatic -cells as compared to oral administration of glucose at the same concentration.56,58 When blood glucose concentrations rise beyond a threshold of roughly 66 mg dL1, gut hormones including incretins generated in response to dietary absorption of glucose which provides the endocrine signal to the pancreatic -cells, boosting insulin production and modifying glucagon secretion.59 Incretin hormones stimulate insulin secretion physiologically, whereas physiological degrees of hyperglycemia constitute to provide a stimulus accordingly for the release of insulin.56,60,61 An isoglycemic intravenous glucose administration induces an identical increase in arterial blood glucose level just as an oral glucose load leads to a rise in insulin secretion that is around one-third of the stimulation responses induced by oral glucose, which is the combined action of hyperglycemia and incretin hormones.62 The contribution of incretin hormones in the secretion of insulin responses following oral glucose administration is estimated to be in the range of 25% and 75%, depending on the dosage of glucose used. Undoubtedly, this measurable contribution supports incretin hormones physiological role in the maintenance of normal glucose homeostasis.56 The endocrine pancreas receives three signals from the gut, which is possible due to three substrates viz. incretin hormones, glucose, and neural signals by the autonomic nervous system.62,63

After the utilization of glucose by the cells throughout the body, insulin release is reduced accordingly and extra available incretins are degraded by the enzyme DPP-4 as a part of homeostasis. However, excess availability of enzyme DPP-4 leads to a condition by unnecessarily inhibiting the activity of incretins, which leads to a reduction in the secretion of insulin, and reduced insulin is not able to open the sufficient amount of glucose channels GLUT4 leads to cause glucose intolerance or hyperglycemia. As the intestinal hormone, glucagon-like peptide-1 (GLP-1) was discovered to be a DPP-4 substrate, the relationship between DPP-4 and glucose homeostasis was discovered.64,65 GLP-1 role in managing glycemia was discovered in 198666 when this unknown peptide was discovered to have dramatic effects on the endocrine pancreas. Denmark and the United States researchers described potent insulinotropic67 and glucagonostatic effects.68 Whenever the level of glucose increases then incretins stimulate the release of insulin which lowers the blood glucose, but when the DPP-4 level increases due to any cause, it metabolizes the GLP-1 and reduces the availability of the incretin hormones. The level of glucose continuously increases but incretin hormones are unable to stimulate insulin release which can result in hyperglycemia or glucose intolerance due to the high availability of DPP-432 (Figure 4). It is observed that the level of DPP-4 is increased in various liver conditions. The pathological role of DPP-4 in liver diseases and associated glucose intolerance with their therapeutic management are discussed below in detail.

Figure 4 Role of Incretins and DPP-4 in glucose regulation.

As per research, as the DPP-4 level increases in individuals with liver conditions6971 and up-regulation of hepatic DPP-4 expression is likely to be the cause of glucose intolerance or insulin resistance.72,73 The effects of DPP-4 on each liver disease with pathology are described below.

HCV is a serious public health concern around the world. Consequently, HCV has a high proclivity for causing severe infection, and chronic hepatitis C affects 58 million people worldwide, with about 1.5 million new infections occurring per year as per reports by WHO. This can progress to severe hepatic fibrosis, cirrhosis, and hepatic cancer in the long run. As a result, in developed countries, HCV is a very common reason for liver transplantation.74 Interferon has always been the cornerstone of HCV treatment for almost two decades. In 1998, ribavirin was added to the medication, and subsequently, in 20012002, the interferon (INF) molecule was linked to polyethylene glycol (PEG) to enhance treatment responses.75,76 IP-10 (interferon-inducible protein of 10 kDa), commonly known as chemokine ligand 10 (CXCL10), is a CXC chemokine that binds to chemokine receptor 3 (CXCR3) and plays a vital role in selecting candidates for T lymphocytes and natural killer cells. IP-10 and other chemokines are secreted by hepatocytes infected with the hepatitis C virus to boost the adaptive and innate immune response.20 Surprisingly, elevated blood levels of IP-10, a powerful chemoattractant, have been linked to PEG-IFN and ribavirin therapy failure. IP-10 is usually changed by DPP-4, which produces the antagonist version of IP-10 by cleaving two amino acids from the amino terminal portion of IP-10. Antagonist version of IP-10 has the ability to bind to the IP-10 receptor but does not cause signalling. CD8+ T-cells, which express DPP-4, have also been seen in the portal and periportal areas of patients with HCV infection. In hepatocytes, DPP-4 expression is enhanced in patients with HCV infection.69,77 In patients with HCV infection, a high baseline blood soluble DPP-4 concentration is linked to poor treatment results. The IP-10 and DPP-4 proteins expression and binding capabilities are affected by genetic differences in the IP-10 and DPP-4 genes.78,79

According to lymphocyte subset analysis, HCV attacks CD8+ T-cells; hence, HCV-infected T-cells could be blamed for the elevated blood DPP-4 activation in HCV patients. DPP-4 alters the immune response by cleaving two amino acids from the amino-terminal portion of IP-10 which suppress the immune responses toward the HCV which may lead to more severe hepatic infection.80,81 Furthermore, Hepatitis-C is related to hyperglycemia and insulin sensitivity, which is linked to the progression of the disease and prognosis because of elevation in DPP-4 level.8289 HCV is engaged in the development of insulin resistance by the disruption of signaling pathway substrate,90 in addition to hepatic inflammation and steatosis. Furthermore, Hepatitis-C has been linked to higher DPP-4 expression in the intestinal lumen, hepatic portion, and blood.77,91 Transfection of hepatocyte cell lines with cDNA expressing a portion of the Hepatitis viral non-structural genomic region 4B/5A increases DPP-4 expression.92 HCV infection may directly upregulate DPP-4 activity, resulting in glucose metabolism impairment.16,77 Inhibition of DPP-4 is significant in HCV infection as well as in glucose intolerance as successfully shown in Figure 5.

Figure 5 Schematic representation of HCV infected hepatocytes releases IP-10 responsible for an immune response towards HCV infection but DPP-4 level elevated due to CD8+ cells attacked by HCV. Increased DPP-4 converted the IP-10 into an inactive form which suppresses the immune response and on the other hand DPP-4 results in glucose intolerance by degrading incretins. Interferon and DPP-4 inhibitors are found to be significant in both HCV resulting conditions.

Hence, interferon therapy for HCV eradication lowers serum DPP-4 levels and helps in treating the HCV,90,9396 and Sitagliptin treatment dramatically improves HCV-related glucose intolerance.97,98

NAFLD is the most prevalent cause of chronic liver disease.99102 It is a hepatic expression of metabolic syndrome. Whereas many factors contribute to the formation of NAFLD, elevated blood glucose has been observed, stimulated by DPP-4 expression in hepatoma cells (HepG2), and the amount of liver DPP-4 mRNA activity in the liver is much higher in NAFLD patients than in healthy subjects.103 Cui et al 2016 conducted a randomized controlled trial for NAFLD by DPP-4 inhibitor (sitagliptin) versus placebo. Researchers randomized, double-blind, placebo-controlled clinical study to compare the effectiveness of sitagliptin (100 mg/day orally) versus an identical placebo for 24 weeks to improve hepatic steatosis as measured by MRI-PDFF (Magnetic Resonance Imaging Proton Density Fat Fraction), which is a proven, precise, and quantifiable biomarker for hepatic steatosis. Fifty patients of NAFLD were randomised to receive sitagliptin and placebo from January 2014 to March 2015. The research included 84 patients in total. The primary outcomes of their study towards the liver fat which is measured by MRI-PDFF, when compared to the placebo group, was not substantially lowered in the sitagliptin group. Sitagliptin was not really substantially superior than placebo for lowering liver fat as evaluated by MRI-PDFF in this randomised, double-blind, placebo-controlled clinical study. Sitagliptin did not outperform placebo in terms of improving supplementary targets such as LDL, AST, ALT, and HOMA IR. Sitagliptin did not markedly reduce fibrosis as determined by MRE, despite the fact that participants in the placebo group had more fibrosis. In the conclusion, it is reported that sitagliptin was shown to be safe but ineffective in lowering liver fat in persons with NAFLD who were pre-diabetic or diabetic, and this trial was observed for 24 weeks only.104 On the other hand, Alam et al105 conducted a randomized controlled trial for the impact of sitagliptin on nonalcoholic steatohepatitis patients hepatic histological activity and fibrosis which was observed for 12 months in a randomized control study. That randomized controlled research found that using sitagliptin (100 mg daily) for one year, a DPP-4 inhibitor reduces steatosis and swelling in NASH patients. The NAS (score for NASH) in coupled biopsy samples was considerably reduced as a result of these two adjustments. This intervention did not affect fibrosis. The control groups NAS was likewise reduced by steatosis reduction, although hepatocyte ballooning remained the same. The sitagliptin group was shown to have a much larger reduction in steatosis and NAS than the control group. Regardless of diabetes condition, sitagliptin (100 mg once daily) for a year reduces NAS through alleviating steatosis and hepatocyte enlargement. Sitagliptin has a more powerful effect than weight loss. Sitagliptin has identical safety profile to the control. To validate and solidify these findings, future major, double-blind, randomised control clinical studies are recommended. In a study of fructose-fed rats with metabolic syndrome, sitagliptin shown to be reduced liver steatosis, -cell apoptosis, and insulin sensitivity.106 Another animal research in Japan found that sitagliptin helps to reduce hepatic steatosis in mice fed a high-fructose diet and prevents the growth of NAFLD by suppressing inflammatory cytokines and the expression levels of genes involved in lipid production in the liver.107 The studys most important conclusion was that sitagliptin reduced the severity of hepatocyte ballooning hepatic histopathology. Ballooning degradation, which was identified as a characteristic of steatohepatitis, is connected to cytoskeletal damage in NASH and is associated with cell swelling.108,109 As a result, it is tempting to say that DPP-4 inhibitors may improve histology activity by lowering steatosis and swelling. Another uncontrolled experimental trial from Turkey found a similar histologically verified advantage.110

Apart from DPP-4 inhibitors, Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a kind of glucose-lowering medication that has been authorized to treat Type 2 diabetes.111 Large randomized controlled trials on GLP-1 RAs have also consistently shown that these medicines reduce the risk of adverse cardiovascular events, all-cause morbidity, and nephropathy worsening in T2DM patients112,113 GLP-1 RAs reduce body weight and insulin sensitivity while improving glycemic management.111 A number of RCTs have recently investigated the putative positive hepatic effects of liraglutide and other long-acting injectable GLP-1 RAs among individuals with NAFLD, regardless of diabetes status. GLP-1 RAs were studied for their effectiveness and safety in treating NAFLD or NASH in people either with or without pre-existing T2DM. Mantovani et al114 compared and conducted the largest and most up-to-date systematic review and meta-analysis of RCTs that used different GLP-1 RAs (including two new long-acting injectable GLP-1 RAs, such as dulaglutide and semaglutide) for the treatment of NAFLD or NASH, regardless of T2DM status. Treatment given with GLP-1RAs was observed to be related to a substantial improvement in the absolute percentage of liver fat content, as measured by magnetic resonance-based methods, as well as blood liver enzymes (particularly serum ALT and GGT levels), as compared to control or standard therapy. The current meta analysis does not include a detailed examination of the hypothesized molecular pathways via which GLP-1 RAs may help people with NAFLD. However, it is plausible to infer that liraglutides and other GLP-1 RAs good effects on individual NASH histologic scores are multidimensional and a result of their combined effects on hyperglycemia or insulin resistance, weight loss, and a direct positive impact on the liver (beyond the reduction in body weight and hyperglycemia). In reality, GLP-1 RAs are effective in the treatment of T2DM and can also help people lose weight (on mean 45 kg).115 GLP-1 RAs are also able to alleviate hepatic steatosis through lowering de novo lipogenesis, boosting fatty acid oxidation, and improving several aspects of the insulin signaling pathways, according to experimental findings based on both human hepatocytes and animal models.116120 Furthermore, preclinical NASH investigations have revealed that GLP-1 RAs may lower hepatic inflammation via independent pathways, at least in part, of body weight loss.121 Obesity could be a reason for NAFLD and for that cause GLP-1 RAs could be a choice, as recent clinical studies have been shown to successfully promote weight loss in diabetic individuals. The existing evidence suggests that weight loss caused by GLP-1R agonism in humans is mostly due to reduced food consumption. GLP-1 (glucagon-like peptide-1) is known as an endogenous peptide produced in the gastrointestinal tract by enteroendocrine specifically by L cells. GLP-1RAs can help with glucoregulation by promoting satiety, delaying stomach emptying, and lowering calorie intake. The only GLP-1RA licensed for the treatment of obesity is liraglutide. Semaglutides first Phase III clinical trial has finished, and the results indicated a considerable weight loss benefit. GLP-1RAs have been shown in clinical studies to be effective and safe, and they are regarded as potential anti-obesity medications.122 On the other side, according to Velija-Asimi et al 2013, it is found that DP-4 inhibitors DPP-4 inhibitors in combination with metformin were related to improved glycaemic control and a decrease in body weight in obese adults with type 2 diabetes.123

The increase of intrahepatic triglycerides (TGs) is the major symptom of NAFLD, which affects 7590% of people with type 2 diabetes.124,125 NAFLD can proceed to NASH, which is marked by extensive histologic transformation, such as hepatocellular ballooning, lobular inflammation, fibrosis, and an increased risk of hepatocellular carcinoma. Various pharmacotherapies are being explored since insulin resistance, oxidative stress, lipotoxicity, immunology, mitochondrial damage, the cytokine system, and apoptosis are all implicated in the pathophysiology of NASH. Although no medicine is available for the evidence-based therapy of NASH, antidiabetic therapies may be beneficial in individuals who also have diabetes mellitus. Several investigations have found a relationship between DPP-4 and hepatic insulin sensitivity. Upregulation of DPP-4 in hepatocytes is linked to hepatic insulin resistance and liver steatosis as observed in rats,73 whereas knocking down DPP-4 optimizes insulin sensitivity and lowers lipid buildup in cultured hepatocytes.126 DPP-4 has also been linked to the occurrence of insulin sensitivity and glucose intolerance in the liver and adipose tissue, according to other research. Obesity and accompanying visceral adipose tissue inflammation cause insulin sensitivity in mice, a process that appears to be driven by increased hepatic DPP-4 production and release, since abolishing hepatocyte DPP-4 expression reduces inflammation and improves insulin sensitivity. DPP-4 is thought to be a new adipokine that affects insulin sensitivity in both autocrine and paracrine ways. DPP-4 release is closely correlated with adipocyte size, suggesting that adipocytes may be a major source of DPP-4.127 The more fat in the liver, the higher the activation of hepatokine DPP-4, which might lead to NAFLD and subsequently, NASH in a paracrine and autocrine manner. Thus, omarigliptin may inhibit the activity of DPP-4, which is abundantly released from the liver in NAFLD/NASH, preventing the stimulation of adipose inflammation and insulin resistance in the liver.128 According to Wang et al 2021, study findings show that the major cause of hepatic inflammation like NFB pathway activation, oxidative stress, and cell apoptosis inhibition reduces hepatic inflammation. In the study, sitagliptin was found to be restricting the DPP-4 activity in hepatocytes reducing NFB pathway activation and oxidative stress, as well as cell apoptosis, in diabetic conditions, and sitagliptins ROS cleaning function promotes NFB pathway deactivation; additionally, sitagliptin can reduce Streptozotocin chronic hepatotoxicity and oxidative stress. Under diabetes circumstances, sitagliptin inhibits DPP4 activity in hepatocytes, resulting in reduced NFB pathway activation, oxidative stress, and cell death.122 The inactivation of the NFB pathway is promoted by sitagliptins ROS cleansing action and DPP-4 inhibitors are also known for the reduction in body weight in obese adults with type 2 diabetes.122 But there is vildagliptin, which is also a strong and selective DPP-4 inhibitor that is weight neutral in type 2 diabetic patients in several solotherapy and combined studies. Because of its glucose-dependent mode of action, vildagliptin has a reduced risk of hypoglycemia, which eliminates the defensive eating that can emerge with insulin injections or independent glucose-insulin secretagogues. More data show that vildagliptin may affect postprandial lipid and lipoprotein metabolism by decreasing the absorption of triglyceride from the gut and boosting sympathetically triggered lipid mobilization and catabolism in the postabsorptive phase. Additional research into these pathways might offer a molecular foundation for understanding the weight-loss benefits of vildagliptin medication.129 Vildagliptin is an important DPP-4 inhibitor that may be used for lowering the risk or decreasing hepatic inflammation without body weight reduction.

In reality, hepatic DPP-4 expression and serum DPP-4 activity are linked to hepatic steatosis and fatty liver grading.130,131 Furthermore, as compared to wild-type rats, DPP-4 deficient animals have lower levels of liver pro-inflammatory and pro-fibrotic cytokines, as well as less hepatic steatosis. These beneficial alterations in lipid metabolism are not caused by changes in glucose metabolism.132 In individuals with NAFLD, DPP-4 activity in serum and liver specimens correlates with indicators of hepatic injury like blood gamma-glutamyl transferase (GGT) and alanine aminotransferase amounts, but not with fasting blood glucose levels or glycosylated hemoglobin (HbA1c) values, similar to the findings in animal studies. As a result, hepatic DPP-4 expression in NAFLD could be linked to hepatic lipogenesis and liver damage.133,134 In humans and rodents, a DPP-4 inhibitor has been shown to ameliorate hepatic steatosis.135 The activity of DPP-4 inhibitors is successfully shown in Figure 6.

Figure 6 Non-alcoholic fatty liver disease results in an increased level of DPP-4 expression leads to hepatic insulin sensitivity and liver steatosis but sitagliptin and omarigliptin improve the conditions.

A case of refractory fatty liver that was successfully treated with sitagliptin, a DPP-4 inhibitor.136 In addition, omarigliptin and sitagliptin have been shown to reduce liver enzymes and hepatocyte ballooning in patients with NASH.110,128 These data suggest that DPP-4 inhibitors may help patients with NAFLD with hepatic damage and glucose intolerance.

The cirrhotic liver has been shown to have increased hepatic DPP-4 expression.128,137 Although the consequence of increased DPP-4 expression is unknown, recently showed that human liver stem cells express DPP-4 but not CD34 or CD45, which are markers of hematopoietic stem and endothelial progenitor cells.138 If we understand the concept of Cell-released chemokines, cytokines, and other growth-modulating substances that elicit their effects through particular receptor-mediated intracellular signaling modulate hematopoietic progenitor cell (HPC) and hematopoietic stem cell (HSC) functions in a paracrine manner.139 Other progenitor and stem cell types are regulated by these proteins, and also impact the more mature cells function. On HPCs expressing CD26, inhibiting DPP4 enzymatic activity with short peptides such diprotin A (ILE-PRO-ILE) or VAL-PYR improves chemotaxis to the chemokine stromal cell-derived factor-1 (SDF-1/CXCL12)140 as well as homing and engraftment of HSCs.141143 CXCL12 with a DPP4 truncation lacked chemotactic efficacy but prevented chemotaxis triggered by full-length SDF-1.140 A pilot clinical trial evaluated the effects of sitagliptin (inhibitor of DPP4 used to treat type 2 diabetes)144 administration to patients with high-risk hematologic malignancies receiving single-unit cord blood transplants. With the findings that DPP4 has a detrimental effect on CSFs6, which nourish immature cell types in the bone marrow, attempts are being made to change the dosing schedule of sitagliptin to improve the time to engraftment of cord blood.145 Chemokines are important for degranulation, angiogenesis, and leukocyte trafficking in the immune system,146 and DPP4 may have a major impact on the activity of chemokine. DPP4 induces negative feedback by lowering CCL22/MDC activity, similar to its actions on CXCL.140,147,148 CCL22 purportedly possesses antiHIV-1 action and attracts activated lymphocytes, dendritic cells, natural killer cells, and monocytes. In CCR4-transfected cells, DPP4-truncated CCL22 fails to desensitize calcium mobilization by full-length CCL22 or thymus and activation-regulated chemokine.149 HUT-78 T-cell chemotactic activity is reduced by truncated CCL22, which is 100 times less effective than full-length CCL22. As a result, DPP4s N-terminal truncation of CCL22 has various effects on its multiple immunologic roles. Eosinophils are drawn to allergic inflammation and parasite infections by the CCL11 (eotaxin) and, CC chemokine. When DPP4 truncates it, its chemotactic potency for signaling capability and blood eosinophils through CCR3 are lowered 30-fold.44 These examples show the importance of DPP4 in infectious processes and inflammatory, as well as in steady-state hematopoiesis. It has been documented that the DPP4-truncated versions of the chemokines studied (CCL2, CCL3, CXCL8/IL-8, and CXCL9) lost their suppressive effect and blocked myelosuppression in vitro and in vivo when compared to their full-length counterparts. The shortened molecule functions as a dominant-negative or competitive inhibitor form of the full-length molecule in both circumstances. This could lead to feedback regulation of their full-length molecules actions. Its also possible that DPP4 truncation enhances a molecules stimulatory or inhibitory activity beyond that of the full-length version.145 Its critical to double-check protein sequences in databases containing potential DPP4 truncation domains on a regular basis to make sure they have not been altered. TGF-, for example, once had a DPP4 truncation site; however, the sequence has since been changed and no longer possesses a DPP4 site. Finally, biochemical and biological (in vitro and in vivo) studies are needed to confirm whether the putative DPP4 truncation sites are true truncation sites for each protein, especially when different alanine, proline, serine, or other potential DPP4 truncation sites are present at the N-terminus of every molecule. If that is the case, it is crucial to figure out whether the abbreviated forms activity differs from that of its full-length counterpart, and if so, how. Overall understanding of the in vitro and in vivo control of various stem, progenitor, and more mature hematopoietic and other kinds of cells might result from such studies. This data might have therapeutic implications.145

Through activation of insulin resistance (IR), obesity-related inflammation raises the risk of type 2 diabetes mellitus (T2DM), obstructive sleep apnea syndrome (OSAS), and polycystic ovary syndrome (PCOS).150 In obesity-related NAFLD, IR is nearly universally found, leading to the development of the metabolic syndrome and hepatocarcinoma.151 Stem cell growth factor-beta (SCGF-) has been shown to have activity on macrophage/granulocyte progenitor cells.152,153 C-reactive protein (CRP) levels were found to be elevated only in one-third of obese patients in the investigation, indicating a link with SCGF. The study characterizes itself by the prediction of homeostatic metabolic assessment (HOMA) values by SCGF levels, possibly mediated by indicators of inflammation, offering some insight on processes inducing/worsening IR in male patients with obesity-related NAFLD. M-CSF, TNF-, IL-12p40, and IL-6, among other pro-inflammatory cytokines, were not linked with HOMA values, with the exception of IL-6, which predicted a reduced chronic inflammation state. The small rise in CRP levels supports this notion. According to the study of Tarantino et al 2020, suggest that barely raised CRP levels might make IL-10 more accessible in an attempt to partially decrease inflammation, the major cause of IR, in line with data that CRP affects the anti-inflammatory or pro-inflammatory balance, exacerbating inflammation. In this regard, we would like to call attention to our results, which include the presence of IR in almost half of the obese individuals, increased levels of IL-10, and IL-12p40s defensive response. SCGF- serum concentrations might also be due to hematopoietic stem or progenitor cells limited autocrine/paracrine activity. It is thought that by switching M1 to M2, inflammation could be reversed and IR reduced. Even though our median HOMA values overlapped according to gender, individuals with a more prominent HOMA had a greater frequency of moderate-to-severe steatosis than those with a HOMA below the median. The finding that SCGF levels solely predicted the severity of hepatic steatosis in men might indicate that these patients obesity influences their inflammatory state and/or immune system. As a result, only males CRP and IL-6 levels predicted SCGF-concentrations. These findings support the observation that SCGF levels solely predict IR, as measured by HOMA, in males. CRPs mediating involvement is conceivable when we consider its functional role in inflammation. In summary, this study is characterized by the estimation of HOMA values by SCGF levels, which is likely mediated by inflammation, providing insights on processes worsening IR in male patients having obesity-related NAFLD.154 As a result, DPP-4 is a particular marker of adult hepatic stem and progenitor cells, suggesting that it may play a role in liver regeneration in chronically inflamed patients. CXCL12/SDF-1 is a chemokine that promotes the homing of hematopoietic stem cells (HSCs) and is critical for hepatic regeneration.155,156 CXCL12/SDF-1 is a DPP-4 target peptide, and inhibiting cell-surface DPP-4 activity promotes CXCL12/SDF-1 directed chemotaxis, homing, and engraftment in HSC/hematopoietic progenitor cell populations. As a result, inhibiting DPP-4 might be a good way to improve the efficacy and success of HSC/hematopoietic progenitor cell transplantation.157 DPP-4 suppression also increases the number of progenitor cells, and DPP-4 inhibition can stabilize endogenous CXCL12/SDF-1, which could be a promising technique for increasing the sequestration of regenerative stem cells.158

Breast cancer,159,160 malignant mesothelioma,161 lung cancer,162 and squamous cell laryngeal carcinoma163 are all known to have increased DPP-4 expression. Increased DPP-4 expression is also found in liver tissues and serum from rats164 and humans with hepatocellular carcinoma (HCC).165

Higurashi et al (2016) conducted a multicentre double-blind, placebo-controlled, randomized Phase 3 trial for the chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes and it is observed that non-diabetic patients were given a small dose of metformin for a year with no side effects. After polypectomy, a small dose of metformin decreased the prevalence and quantity of metachronous adenomas or polyps. Metformin shows the potential to prevent colorectal cancer through chemoprevention. However, further large-scale, long-term studies are required to draw definitive results.166

Kawakita et al (2021) observed the potential influence of DPP-4 inhibitors and DPP-4 on cancer with diabetes and states that there is currently no obvious link between DPP-4 inhibitors and cancer incidence or prognosis in diabetic individuals, according to available clinical evidence. However, the safety profile of a DPP-4 inhibitor (which is the same as different anti-diabetic medications) on cancer development or recurrence has yet to be shown. The results suggested for further mechanistic studies into the relationship between DPP-4 inhibitors and cancer biology, particularly in diabetic situations, are an important study subject in both diabetes and oncology.167 Zhao et al 2017 worked on a meta-analysis of randomized clinical trials on DPP-4 inhibitors and cancer risk in patients with type 2 diabetes and there were 72 studies in all, with 35,768 and 33,319 patients recruited in the DPP-4 inhibitors and comparator medicine trials, respectively. In comparison to the usage of other active medicines or placebo, no significant connections between DPP-4 inhibitor use and cancer development were found. The findings were similar in pre-defined subgroups stratified by DPP-4 inhibitor type, cancer kind, comparative medication, trial duration, or baseline characteristics. The findings of this meta-analysis reveal that people with type 2 diabetes who take DPP-4 inhibitors have no increased risk of cancer than people who take a placebo or other medicines. Wilson et al 2021 provide clear evidence data that the currently authorized medication sitagliptin (DPP-4 inhibitors) can boost antitumor immunity in a syngeneic ovarian cancer mouse model, lowering metastatic burden and lengthening longevity. Our findings suggest a method for improving immune responses in ovarian cancer patients, as well as a justification for using DPP4 inhibitors as a fast translatable 2nd line therapy for this illness.168

According to Hsu et al 2021, DPP-4 inhibitors can lower the incidence of hepatocellular carcinoma in individuals with chronic hepatitis C infection with type 2 diabetes. In this study, individuals with type 2 diabetes and persistent HCV infection who used DPP-4 inhibitors had a decreased risk of HCC. DPP-4 inhibitors were associated with a greater incidence of HCC-free patients. This suggests that DPP-4 inhibitors may help people with type 2 diabetes and persistent HCV infection avoid developing HCC. DPP-4 inhibitors may be used as a second-line treatment after metformin for individuals with type 2 diabetes with persistent HCV infection.69

DPP-4 inhibition suppresses tyrosine kinase in human hepatoma cells, resulting in anti-apoptotic effects.165 Recently, a case has been discussed in which a patient with HCV-related chronic hepatitis experienced remarkable HCC reduction following four weeks of treatment with a DPP-4 inhibitor (Figure 7). Although it is unclear whether the DPP-4 inhibitor is directly involved in the regression of HCC, a significant invasion of CD8+ T-cells around the HCC tissue was observed, suggesting that the DPP-4 inhibitor may have improved the immune response, which has been compromised by chronic HCV infection.169 Whereas treatment with exogenous insulin or sulfonylureas raises the risk of HCC,85 treatment with a DPP-4 inhibitor had no tumor-promoting effects in mice.170 As a result, a DPP-4 inhibitor may have a safe effect on HCV-related HCC through modulating immunity.

Figure 7 Liver diseases cause an increase in DPP-4, which causes glucose intolerance and DPP-4 inhibitors lead to relief in glucose intolerance as well as in liver conditions.

This review discussed the various liver conditions and glucose intolerance management with DPP-4 inhibitors. The summarizing table with the mechanism of action and treatment of liver conditions associated with DPP-4 is given in Table 2.

Table 2 Various Mechanisms of Action and Management of Some DPP-4-Associated Liver Diseases

DPP-4 elevation could be considered a biomarker for diabetes and is a very interesting molecule in understanding the relationship between diabetes and liver or other organs, and inhibition of DPP-4 could help to reduce the risk of its associated diseases but, on the other hand, DPP-4 inhibitors have some negative aspects. DPP-4 inhibitors have been linked to an increase in gastrointestinal side effects in 24-week research, 1091 T2DM patients were randomly assigned to different combinations of sitagliptin and metformin.173 There have been a number of instances of allergic responses occurring spontaneously in people using sitagliptin and angioedema has also been documented with DPP-4 inhibitors, usually commonly within the first three months of therapy, with some responses occurring even before the first dosage.174176 As per the study design of saxagliptin (2.5mg/day v/s 5mg/day v/s 10mg/day) with placebo on metformin for 24 weeks revealed that skin disorders, nasopharyngitis, headache, sinusitis, urinary tract infection, and arthralgia are the adverse effects produced by saxagliptin which are in high proportion than the placebo.176 Alogliptin versus placebo (Population 5380 and duration is 18 months) study showed the adverse effects of alogliptin at more proportion than placebo such as acute and chronic pancreatitis, angioedema, malignancy, renal dialysis, and hypoglycemia but without a comparison of proportions of alogliptin and placebo showed non-fatal myocardial infarction or non-fatal stroke.177 Similarly, other DPP-4 inhibitors also showed some side effects such as musculoskeletal disorders, infections (immune-related disorders such as irritable bowel syndrome, arthritis, and multiple sclerosis because of their potential influence on immunological function), nervous system (Headache and dizziness), Fertility (A 39-year-old physician started on sitagliptin, he had issues with spermatogenesis, according to a case study), and Blood effects (increase in white blood cell count).178

In glucose regulation, the role of incretins (GIP & GLP-1) is very important. They are released from the GIT lumen in response to the increased level of glucose during absorption and then stimulate pancreatic beta-cells to release insulin which lowers the blood glucose level by enhancing the entry of glucose in the cell through the GLUT4 channel and the cell utilizes the glucose to form energy. But there is an enzyme that inhibits this process by degrading the incretins and creating low availability of incretins which leads to reduced signaling towards pancreatic -cells to release insulin resulting in an increased level of blood glucose as glucose remains in the blood, unable to enter in the cell through GLUT4. Apart from that, it is commonly observed that in various liver disorders such as hepatitis C, Non-alcoholic fatty liver, hepatocellular carcinoma, hepatic regeneration, and stem cell the serum level of DPP-4 is increased and leads to glucose intolerance. It is observed and reported that DPP-4 inhibitors are commonly used as a reliever in glucose intolerance and diabetes and have potential activities to improve liver conditions also. Hence, DPP-4 inhibitors like Sitagliptin could be a choice of drug in DPP-4-associated glucose intolerance because of various liver conditions and also in the therapy of liver conditions.

GIP, Glucose-dependent insulinotropic peptide; GLP, Glucagon-like peptide; VIP, Vasoactive intestinal peptide; PACAP-38, Pituitary adenylate cyclase-activating polypeptide-38; GRP, Gastrin-releasing peptide; NPY, Neuropeptide Y; RANTES, Regulated upon activation; CCL, Chemokine (C-C motif) ligand; CXCL, Chemokine (C-X-C motif) ligand; SDF-1, Stromal-derived factor-1; MDC, Macrophage-derived chemokine; MIg, Monokine induced by gamma interferon; IP-10, Protein 10 from interferon ()-induced cell line; GHRH, Growth hormone-releasing hormone; I-TAC, Interferon-inducible T-cell chemoattractant; LH, Leutinizing hormone chain; IGF-1, Insulin-like growth factor-1; CGRP, Calcitonin-related peptide; hCG, Human chorionic gonadotropin subunit.

The authors declare no conflicts of interest in relation to this work.

1. Hopsu-Havu VK, Glenner GG. A new dipeptide naphthylamidase hydrolyzing glycylprolyl-b-naphthylamide. Histochemie. 1966;201:197201.

2. Heymann E, Mentlein R. Liver dipeptidyl aminopeptidase IV hydrolyzes substance P. FEBS Lett. 1978;91(2):360364. doi:10.1016/0014-5793(78)81210-1

3. Nicotera R, Casarella A, Longhitano E, et al. Antiproteinuric effect of DPP-IV inhibitors in diabetic and non-diabetic kidney diseases. Pharmacol Res. 2020;159:105019. doi:10.1016/j.phrs.2020.105019

4. Anderluh M, Kocic G, Tomovic K, Kocic H, Smelcerovic A. DPP-4 inhibition: a novel therapeutic approach to the treatment of pulmonary hypertension? Pharmacol Ther. 2019;201:17. doi:10.1016/j.pharmthera.2019.05.007

5. Yu DMT, Yao T, Chowdhury S, et al. The dipeptidyl peptidase IV family in cancer and cell biology. FEBS J. 2010;277:11261144. doi:10.1111/j.1742-4658.2009.07526.x

6. Holst JJ. Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture, 2005. Diabetologia. 2006;49:253260. doi:10.1007/s00125-005-0107-1

7. Iwanaga T, Nio-Kobayashi J. Cellular expression of CD26/dipeptidyl peptidase IV. Biomed Res. 2021;42(6):229237. doi:10.2220/BIOMEDRES.42.229

8. Vanhoof G, Goossens F, Meester D, Hendriks D, Scharp S. Proline motifs in peptides and their biological processing. FEBS J. 1995;9:736744.

9. Singh AK, Yadav D, Sharma N, Jin JO. Dipeptidyl peptidase (Dpp)iv inhibitors with antioxidant potential isolated from natural sources: a novel approach for the management of diabetes. Pharmaceuticals. 2021;14(6):586. doi:10.3390/ph14060586

10. Gupta S, Sen U. More than just an enzyme: dipeptidyl peptidase-4 (DPP-4) and its association with diabetic kidney remodelling. Methods Mol Biol. 2019;176(5):139148. doi:10.1016/j.phrs.2019.104391.More

11. Koh JA, Ong JH, Manan FA, Ee KY, Wong FC, Chai TT. Discovery of bifunctional anti-dpp-iv and anti-ace peptides from housefly larval proteins after in silico gastrointestinal digestion. Biointerface Res Appl Chem. 2022;12(4):49294944. doi:10.33263/BRIAC124.49294944

12. Heike M, Mobius U, Knuth A, Meuer S, Zum KM, Medizinische BI. Tissue distribution of the T cell activation antigen Tal. Serological, immunohistochemical and biochemical investigations. Clin Exp Immunol. 1988;1640:431434.

13. Mentzel S, Dijkman HB, Van Son JP, Koene RA, Assmann KJ. Organ distribution of aminopeptidase A and dipeptidyl peptidase IV in normal mice. Journal Histochem Cytochem. 1996;44(5):445461. doi:10.1177/44.5.8627002

14. Deacon CF. Physiology and pharmacology of DPP-4 in glucose homeostasis and the treatment of type 2 diabetes. Front Endocrinol. 2019;10:114. doi:10.3389/fendo.2019.00080

15. Rhrborn D, Wronkowitz N, Eckel J. DPP4 in diabetes. Front Immunol. 2015;6:120. doi:10.3389/fimmu.2015.00386

16. Itou M, Kawaguchi T, Taniguchi E, Sata M. Dipeptidyl peptidase-4: a key player in chronic liver disease. World J Gastroenterol. 2013;19(15):22982306. doi:10.3748/wjg.v19.i15.2298

17. Avogaro A, Kreutzenberg S, Fadini G. Dipeptidyl-peptidase 4 inhibition: linking metabolic control to cardiovascular protection. Curr Pharm Des. 2014;20(14):23872394. doi:10.2174/13816128113199990474

18. Casrouge A, Sauer AV, Barreira da Silva R, et al. Lymphocytes are a major source of circulating soluble dipeptidyl peptidase 4. Clin Exp Immunol. 2018;194(2):166179. doi:10.1111/cei.13163

19. Jackman HL, Tan F, Schraufnagel D, et al. Plasma membrane-bound and lysosomal peptidases in human alveolar macrophages. Am J Respir Cell Mol Biol. 1995;13(2):196204. doi:10.1165/ajrcmb.13.2.7626287

20. Shao S, Xu Q, Yu X, Pan R, Chen Y. Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions. Pharmacol Ther. 2020;209:107503. doi:10.1016/j.pharmthera.2020.107503

21. Trzaskalski NA, Fadzeyeva E, Mulvihill EE. Dipeptidyl peptidase-4 at the interface between inflammation and metabolism. Clin Med Insights Endocrinol Diabetes. 2020;13:110. doi:10.1177/1179551420912972

22. Lee SY, Wu ST, Liang YJ, et al. Soluble dipeptidyl peptidase-4 induces fibroblast activation through proteinase-activated receptor-2. Front Pharmacol. 2020;11:113. doi:10.3389/fphar.2020.552818

23. Engel M, Hoffmann T, Wagner L, et al. The crystal structure of dipeptidyl peptidase IV (CD26) reveals its functional regulation and enzymatic mechanism. Proc Natl Acad Sci U S A. 2003;100(9):50635068. doi:10.1073/pnas.0230620100

24. Ohnuma K, Uchiyama M, Yamochi T, et al. Caveolin-1 triggers T-cell activation via CD26 in association with CARMA1. J Biol Chem. 2007;282(13):1011710131. doi:10.1074/jbc.M609157200

25. Mulvihill EE, Drucker DJ. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocr Rev. 2014;35(6):9921019. doi:10.1210/er.2014-1035

26. Stulc T, Sedo A. Inhibition of multifunctional dipeptidyl peptidase-IV: is there a risk of oncological and immunological adverse effects? Diabetes Res Clin Pract. 2010;88(2):125131. doi:10.1016/j.diabres.2010.02.017

27. Zhong J, Kankanala S, Rajagopalan S. DPP4 inhibition: insights from the bench and recent clinical studies. Curr Opin Lipidol. 2017;176(5):139148. doi:10.1097/MOL.0000000000000340.DPP4

28. Shi S, Koya D, Kanasaki K. Dipeptidyl peptidase-4 and kidney fibrosis in diabetes. Fibrogenes Tissue Repair. 2016;9(1):110. doi:10.1186/s13069-016-0038-0

29. Durinx C, Lambeir AM, Bosmans E, et al. Molecular characterization of dipeptidyl peptidase activity in serum soluble CD26/dipeptidyl peptidase IV is responsible for the release of X-pro dipeptides. Eur J Biochem. 2000;267(17):56085613. doi:10.1046/j.1432-1327.2000.01634.x

30. Cordero OJ, Salgado FJ, Nogueira M. On the origin of serum CD26 and its altered concentration in cancer patients. Cancer Immunol Immunother. 2009;58(11):17251749. doi:10.1007/s00262-009-0728-1

31. Mentlein R, Gallwitz B, Schmidt WE. Dipeptidylpeptidase IV hydrolyses gastric inhibitory polypeptide, glucagonlike peptide 1(736)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem. 1993;214(3):829835. doi:10.1111/j.1432-1033.1993.tb17986.x

32. Deacon CF, Nauck MA, Toft-Nielsen M, Pridal L, Willms B, Holst JJ. Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes. 1995;44(9):11261131. doi:10.2337/diab.44.9.1126

33. Brubaker PL, Drucker DJ. Structure-function of the glucagon receptor family of G protein-coupled receptors: the glucagon, GIP, GLP-1, and GLP-2 receptors. Recept Channels. 2002;8(34):179188. doi:10.3109/10606820213687

34. Ballantyne GH. Peptide YY(1-36) and peptide YY(3-36): part II. Changes after gastrointestinal surgery and bariatric surgery. Obes Surg. 2006;16(6):795803. doi:10.1381/096089206777346619

35. Byrd JB, Touzin K, Sile S, et al. Dipeptidyl peptidase IV in angiotensin-converting enzyme inhibitor-associated angioedema. Hypertension. 2008;51(1):141147. doi:10.1161/HYPERTENSIONAHA.107.096552

36. Mentlein R. Dipeptidyl-peptidase IV (CD26) -role in the inactivation of regulatory peptides. Regul Pept. 1999;85:924. doi:10.1016/S0167-0115(99)00089-0

37. Liu X, Murali SG, Holst JJ, Ney DM. Enteral nutrients potentiate the intestinotrophic action of glucagon-like peptide-2 in association with increased insulin-like growth factor-I responses in rats. Am J Physiol. 2008;295(6):17941802. doi:10.1152/ajpregu.90616.2008

38. Walsh NA, Yusta B, Dacambra MP, Anini Y, Drucker DJ, Brubaker PL. Glucagon-like peptide-2 receptor activation in the rat intestinal mucosa. Endocrinology. 2003;144(10):43854392. doi:10.1210/en.2003-0309

39. Mentlein R, Roos T. Proteases involved in the metabolism of angiotensin II, bradykinin, calcitonin gene-related peptide (CGRP), and neuropeptide Y by vascular smooth muscle cells. Peptides. 1996;17(4):709720. doi:10.1016/0196-9781(96)00066-6

40. Ahrn B, Hughes TE. Inhibition of dipeptidyl peptidase-4 augments insulin secretion in response to exogenously administered glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, pituitary adenylate cyclase-activating polypeptide, and gastrin-releasing peptide in mice. Endocrinology. 2005;146(4):20552059. doi:10.1210/en.2004-1174

41. Lun SWM, Wong CK, Ko FWS, Hui DSC, Lam CWK. Increased expression of plasma and CD4+ T lymphocyte costimulatory molecule CD26 in adult patients with allergic asthma. J Clin Immunol. 2007;27(4):430437. doi:10.1007/s10875-007-9093-z

42. Liu Z, Christensson M, Forslw A, De Meester I, Sundqvist K-G. A CD26-controlled cell surface cascade for regulation of T cell motility and chemokine signals. J Immunol. 2009;183(6):36163624. doi:10.4049/jimmunol.0804336

43. Rai AK, Thakur CP, Kumar P, Mitra DK. Impaired expression of CD26 compromises T-cell recruitment in human visceral leishmaniasis. Eur J Immunol. 2012;42(10):27822791. doi:10.1002/eji.201141912

44. Struyf S, Proost P, Schols D, et al. CD26/dipeptidyl-peptidase IV down-regulates the eosinophil chemotactic potency, but not the anti-HIV activity of human eotaxin by affecting its interaction with CC chemokine receptor 3. J Immunol. 1999;162:49034909.

45. Lambeir AM, Proost P, Durinx C, et al. Kinetic investigation of chemokine truncation by CD26/dipeptidyl peptidase iv reveals a striking selectivity within the chemokine family. J Biol Chem. 2001;276(32):2983929845. doi:10.1074/jbc.M103106200

46. Wong PTY, Wong CK, Tam LS, Li EK, Chen DP, Lam CWK. Decreased expression of T lymphocyte co-stimulatory molecule cd26 on invariant natural killer t cells in systemic lupus erythematosus. Immunol Invest. 2009;38(5):350364. doi:10.1080/08820130902770003

47. Crane M, Oliver B, Matthews G, et al. Immunopathogenesis of hepatic flare in HIV/hepatitis B virus (HBV)-coinfected individuals after the initiation of HBV-active antiretroviral therapy. J Infect Dis. 2009;199(7):974981. doi:10.1086/597276

48. Faidley TD, Leiting B, Pryor KD, Lyons K, Hickey GJ, Thompson DR. Inhibition of dipeptidyl-peptidase IV does not increase circulating IGF-1 concentrations in growing pigs. Exp Biol Med. 2006;231:13731378. doi:10.1177/153537020623100811

49. Sakurada C, Sakurada S, Hayashi T, Katsuyama S, Tan-No K, Sakurada T. Degradation of endomorphin-2 at the supraspinal level in mice is initiated by dipeptidyl peptidase IV: an in vitro and in vivo study. Biochem Pharmacol. 2003;66(4):653661. doi:10.1016/S0006-2952(03)00391-5

50. Kirly K, Szalay B, Szalai J, et al. Intrathecally injected Ile-Pro-Ile, an inhibitor of membrane ectoenzyme dipeptidyl peptidase IV, is antihyperalgesic in rats by switching the enzyme from hydrolase to synthase functional mode to generate endomorphin 2. Eur J Pharmacol. 2009;620(13):2126. doi:10.1016/j.ejphar.2009.08.018

51. Guieu R, Fenouillet E, Devaux C, et al. CD26 modulates nociception in mice via its dipeptidyl-peptidase IV activity. Behav Brain Res. 2006;166(2):230235. doi:10.1016/j.bbr.2005.08.003

52. Tian L, Gao J, Hao J, et al. Reversal of new-onset diabetes through modulating inflammation and stimulating -cell replication in nonobese diabetic mice by a dipeptidyl peptidase IV inhibitor. Endocrinology. 2010;151(7):30493060. doi:10.1210/en.2010-0068

53. Zhang XY, De Meester I, Lambeir AM, et al. Study of the enzymatic degradation of vasostatin I and II and their precursor chromogranin A by dipeptidyl peptidase IV using high-performance liquid chromatography/electrospray mass spectrometry. J Mass Spectrom. 1999;34(4):255263. doi:10.1002/(SICI)1096-9888(199904)34:4<255::AID-JMS752>3.0.CO;2-7

54. Radbakhsh S, Atkin SL, Simental-Mendia LE, Sahebkar A. The role of incretins and incretin-based drugs in autoimmune diseases. Int Immunopharmacol. 2021;98:107845. doi:10.1016/j.intimp.2021.107845

55. Gallwitz B. Emerging DPP-4 inhibitors: focus on linagliptin for type 2 diabetes. Diabetes Metab Syndr Obes Targets Ther. 2013;6:19. doi:10.2147/dmso.s23166

56. Nauck MA, Meier JJ. The incretin effect in healthy individuals and those with type 2 diabetes: physiology, pathophysiology, and response to therapeutic interventions. Lancet Diabetes Endocrinol. 2016;4(6):525536. doi:10.1016/S2213-8587(15)00482-9

57. Andukuri R, Drincic A, Rendell M. Alogliptin: a new addition to the class of DPP-4 inhibitors. Diabetes Metab Syndr Obes Targets Ther. 2009;2:117126. doi:10.2147/dmsott.s4312

58. Holst JJ. The incretin system in healthy humans: the role of GIP and GLP-1. Metabolism. 2019;96:4655. doi:10.1016/j.metabol.2019.04.014

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