Researchers from the University of Maryland School of Maryland report promising results from using adult stem cells from bone marrow in mice to help create tissue cells of other organs, such as the heart, brain and pancreas - a scientific step they hope may lead to potential new ways to replace cells lost in diseases such as diabetes, Parkinson's or Alzheimer's. The research in collaboration with the University of Paris Descartes is published online in Comptes Rendus Biologies, a publication of the French Academy of Sciences.
"Finding stem cells capable of restoring function to different damaged organs would be the Holy Grail of tissue engineering," says lead author David Trisler, PhD, assistant professor of neurology at the University of Maryland School of Medicine.
He adds, "This research takes us another step in that process by identifying the potential of these adult bone marrow cells, or a subset of them known as CD34+ bone marrow cells, to be 'multi-potent,' meaning they could transform and function as the normal cells in several different organs."
University of Maryland researchers previously developed a special culturing system to collect a select sample of these adult stem cells in bone marrow, which normally makes red and white blood cells and immune cells. In this project, the team followed a widely recognized study model, used to prove the multi-potency of embryonic stem cells, to prove that these bone marrow stem cells could make more than just blood cells. The investigators also found that the CD34+ cells had a limited lifespan and did not produce teratomas, tumors that sometimes form with the use of embryonic stem cells and adult stem cells cultivated from other methods that require some genetic manipulation.
"When taken at an early stage, we found that the CD34+ cells exhibited similar multi-potent capabilities as embryonic stem cells, which have been shown to be the most flexible and versatile. Because these CD34+ cells already exist in normal bone marrow, they offer a vast source for potential cell replacement therapy, particularly because they come from a person's own body, eliminating the need to suppress the immune system, which is sometimes required when using adults stem cells derived from other sources," explains Paul Fishman, MD, PhD, professor of neurology at the University of Maryland School of Medicine.
The researchers say that proving the potential of these adult bone marrow stem cells opens new possibilities for scientific exploration, but that more research will be needed to see how this science can be translated to humans.
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Adult Stem Cells From Bone Marrow
Marijuana Controls Diabetes
Marijuana Compound May Help Stop Diabetic Retinopathy
A compound found in marijuana won’t make you high but it may help keep your eyes healthy if you’re a diabetic, researchers say.
Early studies indicate cannabidiol works as a consummate multi-tasker to protect the eye from growing a plethora of leaky blood vessels, the hallmark of diabetic retinopathy, says Dr. Gregory I. Liou, molecular biologist at the Medical College of Georgia.
“We are studying the role of cannabinoid receptors in our body and trying to modulate them so we can defend against diabetic retinopathy,” Dr. Liou says. Diabetic retinopathy is the leading cause of blindness in working-age adults and affects nearly 16 million Americans.
High glucose levels resulting from unmanaged diabetes set in motion a cascade ultimately causing the oxygen-deprived retina to grow more blood vessels. Ironically, the leaky surplus of vessels can ultimately destroy vision.
Dr. Liou, who recently received a $300,000 grant from the American Diabetes Association, wants to intervene earlier in the process, as healthy relationships inside the retina first start to go bad.
Cannabinoid receptors are found throughout the body and endogenous cannabinoids are produced to act on them. “Their function is very different from organ to organ but in the central nervous system, cannabinoid receptors are responsible for the neutralization process that should occur after a nerve impulse is finished,” says Dr. Liou.
Nerves come together at a point of communication called a synapse. Glutamate is a neurotransmitter that excites these nerves to action at their point of communication. “There are also inhibitory neurotransmitters such as GABA,” Dr. Liou says. Endogenous cannabinoids help balance the excitation and inhibition, at least until oxygen gets scarce.
In the face of inadequate oxygen, or ischemia – another hallmark of diabetes – nerve endings start producing even more glutamate, setting in motion an unhealthy chain of events. Pumps that keep the right substances inside or outside of cells start to malfunction. Excess nitric oxide and superoxides are produced, which are toxic to the cells. Another irony is the heightened activity increases the retina’s need for oxygen. “We are talking about nerve cell death,” Dr. Liou says. “In the retina, if a lot of our nerve cells die, our vision is directly affected.”
And that’s not all that goes wrong in the nerve-packed retina. Nearby microglial cells, which can function as cell-eating scavengers in the body, sense something is going wrong with the nerve cells, become activated and start an inflammatory process that can be fatal to nerve cells.
Interestingly, the body starts producing more endogenous cannabinoids to stop glutamate release, then produces an enzyme to destroy the cannabinoids to keep them from continuing to accumulate. The same thing happens in the brain after a stroke.
That’s why cannabidiol, an antioxidant, may help save the retina. Test-tube studies by others, as well as Dr. Liou’s pilot studies in diabetic animal models show cannabidiol works to interrupt essentially all these destructive points of action.
“What we believe cannabidiol does is go in here as an antioxidant to neutralize the toxic superoxides. Number two, it inhibits the self-destructive system and allows the self-produced endogenous cannabinoids to stay there longer by inhibiting the enzyme that destroys them.” Cannabidiol also helps keep microglial cells from turning on nerve cells by inhibiting cannabinoid receptors on microglial cells that are at least partially responsible for their ability to destroy the cells.
“Cannabinoids are trying to ease the situation on both sides. They help save the neuron and, at the same time, make sure the microglial cells don’t become activated. How good do you want a drug to be?” Dr. Liou says.
“We are very pleased,” he says of studies in which cannabidiol is injected into diabetic rats and mice. He hopes the compound in marijuana may one day be given along with insulin to stop the early changes that set the stage for damaged or destroyed vision.
Does Psoriasis Increase Type 2 Diabetes Risk?
Two to four percent of adults suffer from psoriasis, a common chronic inflammatory disease, in which the irritated skin becomes red and flaky with silver-white scales. A new UK study, published Online First in JAMA's Archives of Dermatology, has now revealed that psoriasis could be a potential risk factor for developing type 2 diabetes mellitus (T2DM).
Rahat S. Azfar, M.D. from Philadelphia's University of Pennsylvania, and his team obtained data from The Health Improvement Network (THIN) to evaluate the risk of T2DM in 108,132 people with psoriasis, compared with 430,716 participants without psoriasis, aged between 18 to 90 years.
The researchers state:
"The adjusted attributable risk of developing T2DM among 1,000 patients with psoriasis per year is 0.9 extra cases overall, 0.7 cases in those with mild psoriasis, and 3.0 cases in those with severe psoriasis."
The population-based study also wanted to determine whether those with diabetes and psoriasis were more likely to be prescribed diabetic treatments in comparison with those who had DM but no psoriasis.
They declare: "We observed no difference in use of oral hypoglycemic agents or insulin among patients with mild psoriasis; however, patients with severe psoriasis were more likely to be prescribed oral hypoglycemic agents and had a trend toward being more likely to be prescribed insulin."
Fructose In Moderation Could Be Beneficial For Diabetics
A new study by researchers at St. Michael's Hospital suggests that fructose may not be as bad for us as previously thought and that it may even provide some benefit.
"Over the last decade, there have been connections made between fructose intake and rates of obesity," said Dr. John Sievenpiper, a senior author of the study. "However, this research suggests that the problem is likely one of overconsumption, not fructose."
The study reviewed 18 trials with 209 participants who had Type 1 and 2 diabetes and found fructose significantly improved their blood sugar control. The improvement was equivalent to what can be achieved with an oral anti-diabetic drug.
Even more promising, Dr. Sievenpiper said, is that the researchers saw benefit even without adverse effects on body weight, blood pressure, uric acid (gout) or cholesterol.
Fructose, which is naturally found in fruit, vegetables and honey, is a simple sugar that together with glucose forms sucrose, the basis of table sugar. It is also found in high-fructose corn syrup, the most common sweetener in commercially prepared foods.
In all the trials they reviewed, participants were fed diets where fructose was incorporated or sprinkled on to test foods such as cereals or coffee. The diets with fructose had the same amount of calories as the ones without.
"Attention needs to go back where it belongs, which is on the concept of moderation," said Adrian Cozma, the lead author of the paper and a research assistant with Dr. Sievenpiper.
"We're seeing that there may be benefit if fructose wasn't being consumed in such large amounts," Cozma said. "All negative attention on fructose-related harm draws further away from the issue of eating too many calories."
Overall Post-Meal Blood Sugar Levels Reduced By Snacking On Raisins
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Compared to control snacks, raisins significantly decreased mean post-meal glucose levels by 16 percent
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Compared to baseline within group paired analysis, raisins significantly reduced mean hemoglobin A1c by 0.12 percent
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Consumption of the control snacks in the study did not significantly reduce mean post-meal glucose or hemoglobin A1c
New research debuted at the American Diabetes Association's 72nd Annual Scientific Session suggests eating raisins three times a day may significantly lower postprandial (post-meal) glucose levels when compared to common alternative snacks of equal caloric value. The study was conducted at the Louisville Metabolic and Atherosclerosis Center (L-MARC) by lead researcher, Harold Bays, MD, medical director and president of L-MARC.
The study was conducted among 46 men and women who had not previously been diagnosed with diabetes mellitus, but who had mild elevations in glucose levels. Participants were randomly assigned to snack on raisins or pre-packaged commercial snacks that did not contain raisins or other fruits or vegetables, three times a day for 12 weeks. Findings included:
The study was funded by the California Raisin Marketing Board through a grant to the L-MARC Research Center in Louisville, Kentucky.
"Raisins have a relatively low glycemic index and contain fiber and antioxidants, all factors which contribute to blood sugar control," said James Painter, Ph.D., R.D., and nutrition research advisor for the California Raisin Marketing Board. "Decreasing blood sugar and maintaining normal hemoglobin A1c levels is important because it can prevent long-term damage to the heart and circulatory system."
Gene May Link Diabetes and Alzheimer's
In recent years it became clear that people with diabetes face an ominous prospect -- a far greater risk of developing Alzheimer's disease. Now researchers at The City College of New York (CCNY) have shed light on one reason why. Biology Professor Chris Li and her colleagues have discovered that a single gene forms a common link between the two diseases.
They found that the gene, known to be present in many Alzheimer's disease cases, affects the insulin pathway. Disruption of this pathway is a hallmark of diabetes. The finding could point to a therapeutic target for both diseases. The researchers report their finding in the June 2012 issue of the journal Genetics.
"People with type 2 diabetes have an increased risk of dementia. The insulin pathways are involved in many metabolic processes, including helping to keep the nervous system healthy," said Professor Li, explaining why the link is not far-fetched.
Although the cause of Alzheimer's is still unclear, one criterion for diagnosis of the disease after death is the presence of sticky plaques of amyloid protein in decimated portions of patients' brains.
Mutations in the human "amyloid precursor protein" (APP) gene, or in genes that process APP, show up in cases of Alzheimer's that run in families. In the study, Professor Li and her colleagues scrutinized a protein called APL-1, made by a gene in the worm Caenorhabditis elegans (C. elegans ) that happens to be a perfect stand-in for the human Alzheimer's disease gene.
"What we found was that mutations in the worm-equivalent of the APP gene slowed their development, which suggested that some metabolic pathway was disrupted," said Professor Li. "We began to examine how the worm-equivalent of APP modulated different metabolic pathways and found that the APP equivalent inhibited the insulin pathway."
This suggested that the human version of the gene likely plays a role in both Alzheimer's disease and diabetes.
They also found that additional mutations in the insulin pathway reversed the defects of the APP mutation. This helped explain how these genes are functionally linked.
The APL-1 is so important, they found, that "when you knock out the worm-equivalent of APP, the animals die," Li explained. "This tells us that the APP family of proteins is essential in worms, as they are essential in mammals," like us.
Professor Li and her colleagues hope that this new insight will help focus research in ways that might lead to new therapies in the treatment of both Alzheimer's disease and diabetes.
"This is an important discovery, especially as it comes on the heels of the U.S. government's new commitment to treat and prevent Alzheimer's disease by 2025," said Dr. Mark Johnston, editor-in-chief of "Genetics." "We know there's a link between Alzheimer's and diabetes, but until now, it was somewhat of a mystery. This finding could open new doors for treating and preventing both diseases."
The research has identified one link in the chain, an Alzheimer's disease-related protein to the insulin pathway. This may provide insights into why type II diabetes patients are at higher risk for Alzheimer's. However, the protein fragments into many parts, each of which may attach to and signal neurons and other cells along the way. "The big question," said Professor Li, "Is how the amyloid precursor protein and its cleavage products intersect with the insulin pathway."
Each intersection offers a possible target for drugs and other treatment. Professor Li plans to continue down the pathway, mapping its crossroads as she goes.
Professor Li conducted the research with then CUNY Graduate Center -- City College graduate student, Collin Y. Ewald, and research assistant, Daniel A. Raps.
The research was funded by grants from the Alzheimer's Association, the National Institutes of Health (NIH), the National Science Foundation (NSF), and a NIH Research Centers in Minority Institutions grant to The City College of New York.
Peaches, Plums, Nectarines Give Obesity, Diabetes Slim Chance
Peaches, plums and nectarines have bioactive compounds that can potentially fight-off obesity-related diabetes and cardiovascular disease, according to new studies by Texas AgriLife Research.
The study, which will be presented at the American Chemical Society in Philadelphia next August, showed that the compounds in stone fruits could be a weapon against "metabolic syndrome," in which obesity and inflammation lead to serious health issues, according to Dr. Luis Cisneros-Zevallos, AgriLife Research food scientist.
"In recent years obesity has become a major concern in society due to the health problems associated to it," said Cisneros-Zevallos, who also is an associate professor at Texas A&M University. "In the U.S., statistics show that around 30 percent of the population is overweight or obese, and these cases are increasing every year in alarming numbers."
While he acknowledged that lifestyle, genetic predisposition and diet play a major role in one's tendency toward obesity, "the major concern about obesity is the associated disease known as metabolic syndrome.
"Our studies have shown that stone fruits -- peaches, plums and nectarines -- have bioactive compounds that can potentially fight the syndrome," Cisneros-Zevallos said. "Our work indicates that phenolic compounds present in these fruits have anti-obesity, anti-inflammatory and anti-diabetic properties in different cell lines and may also reduce the oxidation of bad cholesterol LDL which is associated to cardiovascular disease."
What is unique to these fruits, he said, is that their mixture of the bioactive compounds work simultaneously within the different components of the disease.
"Our work shows that the four major phenolic groups -- anthocyanins, clorogenic acids, quercetin derivatives and catechins -- work on different cells -- fat cells, macrophages and vascular endothelial cells," he explained. "They modulate different expressions of genes and proteins depending on the type of compound.
"However, at the same time, all of them are working simultaneously in different fronts against the components of the disease, including obesity, inflammation, diabetes and cardiovascular disease," he explained.
Cisneros-Zevallos said this is believed to be the first time that "bioactive compounds of a fruit have been shown to potentially work in different fronts against a disease."
"Each of these stone fruits contain similar phenolic groups but in differing proportions so all of them are a good source of health promoting compounds and may complement each other," he said, adding that his team plans to continue studying the role of each type of compound on the molecular mechanisms and confirm the work with mice studies.
The studies on the health benefits of stone fruit are funded by the California Tree Fruit Agreement, The California Plum Board, the California Grape and Tree Fruit League and the Texas Department of Agriculture. The Cisneros-Zevallos lab team in this study included Freddy Ibanez, Paula Castillo, Paula Simons and Dr. Congmei Cao.
Diabetics now living for longer
New research from the United States has highlighted that people who have developed diabetes are now living longer than ever before.
The study, by the Centers for Disease Control (CDC) and the National Institutes of Health, which was based on data from 250,000 adults from 1997 to 2006 and reported in the journal Diabetes Care, found that diabetics are living a lot longer and that patient deaths had been reduced by 23 per cent. This was explained by improved medical therapies, especially for high blood pressure and cholesterol, and people smoking less and taking more exercise. Deaths from heart disease and stroke were also reported to be down by a huge 40 per cent.
However, although the rate of reduction, which is the same for men and women, is good news it does mean that because people are living longer and an increasing amount of people are being diagnosed with diabetes, the total number of diabetics is expected to continue to go up. In the US, the number of those diagnosed has more than tripled since 1980, and there are now thought to be 25.8 million people with diabetes in the country.
Ann Albright, from the CDC, pointed out "Taking care of your heart through healthy lifestyle choices is making a difference, but Americans continue to die from a disease that can be prevented."
Sex and Insulin Pumps
Insulin pump users often ask what to do with their pump during sex
A common question for people starting off on an insulin pump, or considering going onto a pump, is what should I do with my pump during sex?
We take a look at some of the options available and show you how other people with diabetes deal with their insulin pumps for sex.
Taking off the insulin pump
You can take your insulin pump off before having sex. This is one of the more popular options.
Diabetes UK recommends not spending longer than an hour disconnected from your pump.
When disconnected, you may find your blood glucose levels start to rise. If convenient, a blood test before and after sex will show you whether or how much your blood sugar has risen whilst disconnected.
Here’s what members of a Diabetes Forum say about taking their pumps off for sex:
"Take it off, have fun and put it back on when you're ready, as long as it’s not 3 hours later?! Just give a bit more a bolus when you reconnect, it works for me, but then everyone is different."
"I'm male. I take my pump off when I have sex. It's never been an issue. Given the exercise you need less insulin anyways"
"Depending on what your comfortable with I tend to unclip mine before and then just reclip it back on, think everyone finds their own way which you will yourself with time."
Leaving the pump on
Another option is to leave your pump on. You’ll need to take a bit of care so as not to accidentally tug sharply on any of the tubing.
If you leave your pump on, you’ll need to treat sex as a form of exercise and beware of going hypo.
You may wish to adjust your insulin delivery or have some carbohydrate before starting to prevent your blood glucose from dipping too low.
Here’s what the Forum members say about leaving their insulin pumps on during sex:
"I haven't had to disconnect yet and frankly, I've hardly noticed I'm attached!! It's caused a couple of giggles as we've had to quickly shove the pump out of the way and then the tube got tangled but as soon as it did we were both aware, had a giggle and carried on! I honestly wouldn't worry about it too much, give it a go and have fun practicing"
"Luckily my boyfriend is very understanding, and doesn’t find it a problem. Sometimes I stay attached with it in my bra, other times it gets unattached and thrown on the bed to be found later! If you don’t let it be an issue, then it shouldn’t be."
Letting the moment dictate
Sometimes you may not want to adopt a different approach at different times:
"Sometimes I take it off if things are moving slowly enough if you know what I mean but if it is mad, spontaneous sex that you don't have time to think about, then I have left it on. Yeah it sometimes gets in the way but we have a laugh about it then chuck it out the way. If I do take it off, even without insulin for short while, I tend to go hypo after sex anyway!"
Sex Drive and Libido
Diabetes can cause loss of sex drive in men and women. Loss of sex drive and libido can affect people of all ages and both genders. Loss of libido tends to become more likely the older we get and this has been found to be more pronounced in women.
Complications of diabetes, including depression and nerve damage, can also have an impact on libido.
Which factors affect libido?
The NHS lists the following factors which can play a role towards a lower sex drive:
- If your relationship is having problems
- If you have certain diabetic complications
- Low sex hormone levels
- If you are approaching the menopause
- Stress
- Exhaustion
- Depression
- Over consumption of alcohol
- An underactive thyroid (hypothyroidism)
- If you are on certain medications
Relationship issues
The NHS notes relationship issues as one of the most common factors in a loss of sex drive.
Talking about your feelings with your partner can be beneficial. You can also get help by talking with Relate, a charity that offers relationship counselling - contact Relate on 0300 100 1234
Your GP can also be able to refer you to speak with a psychosexual therapist.
Diabetic complications
The presence of certain diabetic complications, such as nerve damage (neuropathy) or circulation difficulties, can lead to difficulties in arousal, which can also affect libido.
Achieving good control of blood sugar levels is generally recommended for men and women.
- Read more on female sexual dysfunction
- Read more on male sexual dysfunction
Low sex hormone levels
Low testosterone levels in men and women can lead to a lower sex drive. Women produce testosterone albeit in much smaller quantities than males.
If you have low testosterone levels, your GP may be able to prescribe treatments to help.
Approaching the menopause
Women approaching the menopause will typically experience a reduction of oestrogen in their blood which can lead to a loss of libido.
Hormone replacement therapy (HRT) can help but does have side effects. You can discuss with your GP whether hormone replacement is appropriate
Type 2 Diabetes and Harmful Medication
Reading the fine print is an easy step to skip when you are prescribed a new medication, but you risk taking something that may be more harmful than helpful.
When it comes to type 2 diabetes, there are several classes of drugs that your doctor can choose from. They include sulfonylureas, meglitinides, biguanides (metformin) and thiazolidinediones (Actos).
Every medicine should be approached with caution. You’ll want to watch for these serious side effects:
Weight Gain
Gaining 2 to 12 pounds when you begin many type 2 diabetes mediations is normal. However, if you gain more weight than this or continue to gain weight after taking the medicine for some time, you may be retaining water. Water retention is dangerous, because it is often an indicator of heart problems.
Hypoglycemia
Sulfonylureas and meglitinides stimulate the release of insulin, which can cause your blood sugar to drop too much. Hypoglycemia needs to be dealt with right away. It can be detected by increased heartbeat; sweating; paleness; anxiety; numbness in fingers, toes and lips; sleepiness; confusion; headache and slurred speech.
Bladder Cancer
Actos, which is the world’s best-selling diabetes drug, has been linked to higher rates of bladder cancer. Watch for these signs of Actos bladder cancer: blood in the urine, frequent need to urinate and pain while urinating. Talk to your doctor right away if you notice any of these symptoms.
Actos bladder cancer Lawsuits are in the thousands, patients have sued the maker of Actos after developing complications.
Lactic Acidosis
Metformin carries the Food and Drug Administration’s black-box warning because it can lead to lactic acidosis in rare cases. This life-threatening condition occurs when oxygen levels in the body drop and lactic acid builds up in the bloodstream faster than it can be removed.
Lactic acidosis can be detected by checking electrolyte levels. Also watch for nausea, vomiting, lethargy abdominal pain, anxiety and an irregular heart rate.
No matter which medication you and your doctor choose, it’s important to be fully informed about the risks that come with it. Talk to your doctor about any concerns or questions you have.
Alanna Ritchie is a writer for Drugwatch.com. An English major, she is an accomplished technical and creative writer.
Maxonidine, A Second-Generation Drug Used For Hypertension Aids Heart Function Independent Of Blood Pressure
Heart failure is the most common cause of death throughout the world, typically the result of chronic high blood pressure, also known as hypertension. As a result, research efforts have focused on an array of approaches aimed at preventing and treating high blood pressure. Recently, Japanese researchers examined the utility of an anti-hypertensive drug, moxonidine, which acts on the imidazoline receptors in the cardiovascular center of the brainstem. They found, using an animal model, that the drug can improve heart function and survival independent of its effect on blood pressure. They also found the drug had a favorable effect on oxidative stress, which is related to insulin resistance, the underlying abnormality in diabetes, which is common in people with heart failure.
An abstract presentation about the findings was offered at the meeting Experimental Biology 2012, being held April 21-25 at the San Diego Convention Center. The study was conducted by Yoshitaka Hirooka, Nobuhiro Honda, Ryuichi Matsukawa, Koji Itou and Kenji Sunagawa, all of the Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences in Fukuoka, Japan. It is entitled, "Central sympathoinibition improves left ventricular function during the transition from hypertrophy to heart failure in Dahl salt-sensitive rats." The abstract is sponsored by the American Society for Investigative Pathology (ASIP), one of six scientific societies sponsoring the conference which last year attracted some 14,000 attendees.
Heart failure is a chronic disease that takes many forms and a variety of medications are used to treat it. Drugs such as ACE inhibitors and beta blockers target the causes of systolic heart failure. Clonidine, a first-generation central sympathoinhibitory drug, targets brain receptors that reduce cardiac output and lower blood pressure. Moxonidine, a second-generation drug, targets diastolic heart failure and function by reducing the effect of the central nervous system (CNS) receptors to decrease sympathetic activation and thus reduce blood pressure. In the study, salt-sensitive, hypertensive rats either received Moxonidine or were assigned to the control group. Researchers later found that the animals who received the drug had a marked inhibition of the sympathetic activity (an area of the brain) compared to those that did not. The findings suggest that inhibition of the central sympathetic outflow is important in the mechanism of hypertension. According to Dr. Hirooka, "The findings are important because they suggest that moxonidine may be useful in targeting the central receptors in the brain that are known to occur in patients with hypertension."
Next Steps
The study is the latest in a series conducted by the research team whose focus is on neural control of circulation in hypertension and heart failure. Looking ahead, they will work to identify the precise mechanisms involved in the beneficial effect of moxonidine, Dr. Hirooka said. They will also study other ways to see if the compound is a possible therapeutic tool for hypertensiveheart disease to prevent heart failure. As the drug had beneficial effects on insulin resistance, they would like to further investigate the issue, he added.
Maxonidine is available in select countries in Europe and Asia. It is not currently available in the United States.
Ultra-Long-Acting Insulin Degludec, Two Phase 3 Studies Published
Two Phase III studies, published in The Lancet, reveal that ultra-long-acting insulin degludec considerably reduced rates of nocturnal hypoglycemia in patients with type 1 and type 2 diabetesby 25%, compared to insulin glargine.
Insulin degludec is an investigational compound developed by Novo Nordisk.
1,635 individuals with diabetes were enrolled to participate in the trials in order to examine insulin degludec, compared to insulin glargine, in a basal-bolus regimen.
In both studies, researchers adjusted patient insulin doses systematically in order to allow them to achieve a targeted fasting glucose level. Due to this, participants in both studies successfully achieved similar improvements in sugar control. This allowed the researchers to closely determine disparity in hypoglycemia rates.
Alan Garber, M.D., Professor, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA, and lead research of one of the studies, explained:
"Hypoglycemia is a major concern for both people with diabetes and their physicians and can often lead to under- and sub-optimal treatment. Of particular concern are hypoglycemic events that occur in the overnight hours during sleep when patients are unaware and therefore unable to take measures to reverse it. Newer insulins such as insulin degludec may be able to mitigate this concern."
The studies found that participant with type 2 diabetes who took insulin degludec had a considerably lower rate of overall hypoglycemic events (11.1 episodes/patient-year), compared to individuals assigned to insulin glargine (13.6). This figure was similar between both groups in individuals with type 1 diabetes.
Furthermore, results showed that insulin degludec reduced nocturnal hypoglycemia by 25% in both type 1 and type 2 diabetes (4.4 vs 5.9 episodes/patient-year), compared to participants taking insulin glargine (1.4 vs. 1.8).
Mads Krogsgaard Tomsen, executive vice president and chief science officer at Novo Nordisk, said:
"We are proud that The Lancet has recognized the clinical potential of insulin degludec by publishing these two pivotal studies. Novo Nordisk is very excited about the potential of insulin degludec to lower the rates of hypoglycemia in people with diabetes using basal insulin analogues."
Improving Mood, Blood Sugar In Diabetes With Naturopathic Care
About 26 million Americans suffer from type 2 diabetes. A study in BMC Complementary and Alternative Medicine has now revealed that complementary and alternative medicine (CAM), in adjunction to conventional medicine, holds various positive benefits for people with type 2diabetes, compared with those who only receive conventional medicine. For instance, better eating and exercise habits lower blood sugar levels, improve moods and give the person a stronger sense of control over their condition.
Ryan Bradley, ND, MPH, director of the Diabetes and Cardiovascular WellnessClinic at Bastyr Center for Natural Health declared:
"The news is encouraging for those fighting the disease. Patients involved in the study cited the benefits of trying different approaches to find the best ways to minimize the effects of type 2 diabetes. In many ways, that strategy mirrors our partnership with Group Health in this research study - working together to discover the best possible solutions."
The study, a joint collaboration between the Group Health Research Institute and the Bastyr University Research Institute provided 40 type 2 diabetes patients with diet and exercise counseling and glucose monitoring from four naturopathic physicians (NDs).
A large proportion of participants also received stress-management care and dietary supplements, all of which was in addition to the standard diabetes care and prescription drugs they received from their medical doctors. The participants were then compared with 329 patients who only received conventional diabetes care.
The outcome, after 6 months and after around four naturopathic treatments, demonstrated that the 40 patients displayed improved self-care, improved moods and were more consistent in monitoring their glucose levels, with their hemoglobin A1c rates being almost a full percentage point lower, compared with the patients in the conventional care group, whose rates only dropped by 0.5% over the same period of time.
Dr. Bradley said although the findings of this small observational study are very encouraging, they need to be confirmed with larger numbers of participants in a randomized trial. Given that type 2 diabetes is one of the top-10 causes of death in Americans, it is important to find more alternative effective options for treating the disease. The fight against the disease is also very costly at $178 billion annually, which means that 1$ out of every $10 spend on health care in the U.S. goes to treat type 2 diabetes.
Senior researcher Daniel Cherkin, PhD, at the Group Health Research Institute declares:
"Our number-one goal is to help patients. Collaboration with our research colleagues at Bastyr University allows us to explore a broader range of ways to help meet the needs of our patients."
Fighting Harmful Free Radicals Tied To Aging And Cancer With Avocado Oil: The 'Olive Oil Of The Americas'?
Atmospheric oxygen facilitated the evolution and complexity of terrestrial organisms, including human beings, because it allowed nutrients to be used more efficiently by those organisms, which in turn were able to generate more energy. However, as we find out more about how oxygen molecules work inside the body, more attention is being paid to their not-so-good effects, and researchers are seeking ways to thwart them.
A number of environmental factors - such as pollution, cigarette smoke and radiation - can turn the oxygen molecules found in mitochondria, the power plants of cells, into free radicals. These unstable molecules destroy virtually all the normal molecules forming cells, such as lipids, proteins and even DNA, by turning them into free radicals, too. This destructive phenomenon is associated with aging and occurs in a variety of diseases, including hypertension and diabetes, which represent major challenges for health systems due to their great social and economic costs. Those costs have motivated scientists worldwide to undertake intensive searches for substances that bolster cell resistance to the harmful effects of free radicals.
Many studies of antioxidants in vegetables and fruits, such as carrots and tomatoes, have been completed with few encouraging results, says Christian Cortés-Rojo, a researcher at Universidad Michoacana de San Nicolás de Hidalgo in Morelia, Michoacán, México. "The problem is that the antioxidants in those substances are unable to enter mitochondria. So free radicals go on damaging mitochondria, causing energy production to stop and the cell to collapse and die. An analogy would be that, during an oil spill, if we cleaned only the spilled oil instead of fixing the perforation where oil is escaping, then the oil would go on spilling, and fish would die anyway."
But Cortés-Rojo is prepared to reveal the first research results showing the protective effects of avocado oil against free radicals in mitochondria. Cortés-Rojo presented his group's work at the annual meeting of the American Society for Biochemistry and Molecular Biology, held in conjunction with the Experimental Biology 2012 conference in San Diego.
The research team used yeast cells - those used in wine and beer production - to examine avocado oil's properties.
"The reason why we have chosen yeast," explains Cortés-Rojo, "is that (a) this microorganism is easier to study than other biological models due to its relative simplicity and (b) because studies our group published in 2009 and 2011 found that yeast mitochondria are very resistant to free radicals due to the sort of fat that forms its envelope, which is highly resistant to oxidation. The same kind of fat can be found in avocado oil; but, in addition, avocados also contain some plant pigments that inhibit oxidation. That is why we decided to test whether these avocado properties could increase even more the yeast's resistance to mitochondrial oxidation."
The results of this research, he says, show that avocado oil allowed the yeast cells to survive exposure to high concentrations of iron, which produces a huge amount of free radicals, "even to higher levels to those found in some human diseases."
He continues: "These results could be attributed to the fact that avocado oil caused accelerated respiration in mitochondria, which indicate that the use of nutrients for producing energy for cell functions remains effective even in cells attacked by free radicals and that mitochondria itself could produce little amounts of damaging free radicals."
Cortés-Rojo emphasized that these findings reinforce the good reputation the avocado has when it comes to health maintenance. He points to pioneering research by Mario Alvizouri-Muñoz, a doctor at the Morelia General Hospital, who demonstrated that avocado lowers the blood concentration of cholesterol and certain fats that are increased in diabetic patients and that may lead to stroke or heart attack.
"Our results are promising because they indicate that avocado consumption could improve the health status of diabetic and other patients through an additional mechanism to the improvement of blood lipids," he says. "We'll need to confirm that what has been observed in yeasts could occur in higher organisms, such as humans. We hope this will be the case, because there are many vital processes conserved in organisms that seem very dissimilar to humans."
Moreover, Cortés-Rojo says, the findings, and the fact that México is the largest producer of avocados in the world, could promote the use of avocado oil or some of its components to reduce the socioeconomic impact of chronic degenerative diseases. "In some Mediterranean countries, low or almost no appearance of these kinds of diseases has been associated with the high olive oil consumption," he explains. "Olive oil has a fat composition similar to that found in avocado oil. Therefore, avocado oil could eventually be referred to as the olive oil of the Americas."
When Using Oxygen To Regenerate Bone, Timing Is Everything
A research team at Tulane University will report this week that the application of high levels of oxygen to a severed bone facilitates bone regrowth, study results that may one day hold promise for injured soldiers, diabetics and other accident victims.
The results of the Department of Defense-funded study were presented at the American Society for Biochemistry and Molecular Biology annual meeting, held in conjunction with the Experimental Biology conference in San Diego.
"One out of every 200 Americans is an amputee," emphasizes Mimi Sammarco, who led the study at Tulane. "This number is expected to double in the next 40 years and is of particular concern given that amputation injuries have increased considerably due to combat casualties and the increasing amputation issues associated with the rise in diabetes and other related diseases."
The only vertebrate capable of regenerating lost limbs is the salamander, which has been the focus of a number of studies by the laboratory where the work was done. Run by Ken Muneoka, a professor at Tulane's cell and molecular biology department, the lab has been exploring the molecular underpinnings of limb regeneration under various circumstances. The work spearheaded by Sammarco, meanwhile, uses a mouse model.
"While salamanders are able to regenerate entire limbs, rodents, monkeys and humans are only able to regenerate the digit tip after amputation," she explains. "The third phalangeal element, the very end bone on your finger, if you amputate one-third back or anywhere toward the tip, it will grow back. If you go just a fraction of a millimeter closer, it won't. If you amputate in the middle bone, it won't."
Multiple research teams have been trying to figure out what makes that huge difference between regrowth here but no regrowth there. The Tulane lab, in particular, has been investigating which genes are turned on, which proteins are expressed and which molecular activities change at the site of amputation over time.
"What it boils down to is genes (that spur regeneration) don't just turn themselves on. They turn on because something signals them. So I thought, maybe it's oxygen that's turning them on," Sammarco says. "Oxygen is often the primary signal that turns on various genes."
Sammarco used a special incubator to expose a thin bone sample taken from an amputation site to high levels of oxygen. "What we found is that when you expose regenerating bone to 20 percent oxygen, it'll respond very favorably but only at a certain time. If you try it too early, like right after amputation, it doesn't do a whole lot."
The air we breathe is made of about 20 percent oxygen, but that's a lot higher than the level in the body, which is closer to around 6 percent, she explains. "In some areas of injury, the oxygen level is going to go down to 1 percent," because the blood vessels that deliver oxygen to tissue naturally retract after injury. "And maybe we're only talking millimeters or fractions of millimeters. They're naturally contractile."
What to do about the drop in oxygen levels is something of a puzzle for those in the wound-healing field, Sammarco says. Many researchers are trying to figure out how to reinvigorate vasculature and how to oxygenate the wound site.
"There are two opposing fields: We get injured, so we need to drop the oxygen concentration to encourage vasculature. And then there's the other side that says, no, we need to flood it with oxygen to oxygenate the tissue. And neither works particularly well," she admits.
The way Sammarco sees it, maybe it's not an either-or situation: "I think you have to know when to apply each one. It's all about timing. Obviously, there's a sequence in growing things back. And oxygen can push the button that has to be applied at a certain time."
Ultimately, battlefield doctors must be able to assess in what stage a patient is in the spectrum of injury and repair.
"Further on down the line, how do we make that treatable in the field in the middle of the desert? How do you make it portable and usable? There's general public usable and there's where it is going to be most useful, and that's in the field - immediate treatment for a soldier so we can have maximal bone growth down the line."
Sammarco emphasizes that even just partial regeneration of a limb would make a world of difference to any amputee and that soldiers in particular are excellent candidates for rehabilitation, because they are usually in fantastic physical shape.
"They're the fittest people out there. They're not diabetics receiving amputations. They're not the average American who received an amputation after a car crash. These are the most viable people for rehabilitation, and these are the people who can benefit from getting an extra inch of stump length and be able to ski - to do things they were doing before, because their level of activity is so much higher than everybody else's," she says. "Thus, every effort to direct and control the extension of amputation stump length contributes to the rehabilitation of amputees, while keeping in mind the long-term goal of complete regeneration."
Animal Model For Xenotransplantation As A Therapy For Type 1 Diabetes
Type1 diabetes is caused by autoimmune destruction of the insulin-producing beta cells. Over 250,000 patients suffer from type 1 diabetes in Germany who are treated with daily insulin injections to maintain glucose metabolism. Replacement of the destroyed beta cells by transplantation of either a complete pancreas organ or isolated human beta cells is the only effective way to cure the disease. However, due to the shortage of organ donors this method can be offered to only few patients.
As an alternative approach researchers are exploring xenotransplantation, i.e. transplantation of the organ from another species. The most obvious barrier in xenotransplantation is the strong immune rejection against the transplant. A research team led by LMU's Professor Eckhard Wolf and Professor Jochen Seissler has now generated a genetically modified strain of pigs whose beta-cells restores glucose homeostasis and inhibit human-anti-pig immune reaction. So far, the efficacy of this approach has been demonstrated only in an experimental mouse model. "Whether the strategy will work in humans remains to be demonstrated," says Professor Wolf. "Nevertheless, we consider the approach as very promising and plan to test it further in other settings."
Type 1 diabetes is caused by an autoimmune reaction which ultimately leads to the destruction of the insulin-producing cells in the pancreas, and usually becomes manifest during adolescence. Thereafter, insulin must be administered by regular insulin injections. Since insulin therapy cannot reproduce the complex pattern of physiologically controlled insulin secretion, patients are at risk of hypoglycemia and many patients develop severe vascular complications such as myocardial infarction or stroke.
Transplantation of a healthy pancreas or pancreatic beta cells that synthesize insulin may represent the best treatment option. Unfortunately, the availability of donor organs falls far short of requirements. Over the course of the last several years, fewer than 200 pancreas transplantations have been carried out. "Pigs represent a possible alternative source, because glucose metabolism in this species is very similar to that in human beings," Professor Seissler points out.
Pig insulin differs from its counterpart in humans at only a single amino acid, and has been used successfully in the treatment of diabetic patients for decades. However, pig cells inevitably provoke an immune reaction leading to the destruction of the transplanted tissue. One way of avoiding this difficulty is to encapsulate the foreign tissue in a biologically inert material that is permeable to insulin but not to cells of the immune system. However, the drawback of this approach is the restricted supply of oxygen and essential nutrients to the transplanted cells, thereby reducing its lifespan.
Wolf and his team chose a different route. For the first time they generated genetically modified pigs that express the protein LEA29Y specifically in beta cells. LEA29Y effectively inhibits the activation of a class of immune cells that are required to initiate a rejection reaction. The researchers then transplanted these cells into a diabetic mouse strain that has a humanized immune system. Seissler's group showed that these mice were able to restore glucose metabolism and were protected form human-anti-pig rejection. As Wolf is quick to point out, "It is not yet clear whether this will also work in humans. However, we will now attempt to validate the effects of this very promising approach using beta-cells expressing immune modulators in other transplantation models."
Two Takeda Diabetes Drug Applications, FDA Asks For More Info
Takeda says it has received a complete response letter from the FDA regarding NDAs (new drug applications) for alogliptin and fixed-dose combination alogliptin and pioglitazone - both diabetes type 2 investigational therapies. Takeda says it has recently been providing the FDA (Food and Drug Administration) with post marketing data from markets outside the USA. Takeda believes it can provide the additional information from post marketing data from non-USA markets, as well as findings from its current clinical trial program.
Thomas Harris, vice president, regulatory affairs, Takeda Global Research & Development Center, Inc., said:
"We will immediately request a meeting with the FDA to determine the appropriate next steps and are committed to addressing outstanding issues. We remain confident in the benefit that alogliptin will bring to patients with type 2 diabetes in the U.S., if approved.
Takeda has built a strong foundation in and maintained a robust focus on diabetes over the past 20 years, and we will continue to invest in developing a diverse range of innovative products for the growing type 2 diabetes population."
What is Alogliptin?
Alogliptin is a DPP-4i (selective dipeptidyl peptidase IV inhibitor). It is an investigational drug for diabetes type 2 treatment in the USA, alongside exercise and diet.Alogliptin slows down the inactivation of GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide). GLP-1 and GIP are incretin hormones which are involved in regulating blood glucose levels.
The most common adverse effects linked to alogliptin, according to a phase 3 program, include upper respiratory tract infection, headache, urinary tract infection, and nasopharyngitis.
Pioglitazone
Drugs containing pioglitazone have been available in the United States since 1999 for diabetes type 2 treatment, alongside exercise and diet.In a communiqué online, Takeda wrote:
"The FDC (fixed dose combination) alogliptin and pioglitazone combines two complementary agents with distinct mechanisms of action, and if approved, will be the first type 2 diabetes treatment option in the U.S. to include both a DPP-4i and the thiazolidinedione (TZD) pioglitazone in a single tablet."
Adverse events related to alogliptin and pioglitazone co-administration include influenza, urinary tract infection, back pain and nasopharyngitis.
According to the Wall Street Journal, shares of Furiex Pharmaceuticals Inc. dropped 26%. Furiex is a partner drug developer with Takeda.
Long-Overlooked Protein May Be The Gateway To The Storage And Burning Of Fat, Diabetes Treatment
Humans are built to hunger for fat, packing it on during times of feast and burning it during periods of famine. But when deluged by foods rich in fat and sugar, the modern waistline often far exceeds the need to store energy for lean times, and the result has been an epidemic of diabetes, heart diseaseand other obesity-related problems.
Now, scientists at the Salk Institute for Biological Studies have identified the linchpin of fat metabolism, a protein known as fibroblast growth factor 1 (FGF1), which may open new avenues in the treatment of diabetes.
In a paper published in Nature, the Evans lab reports that FGF1 activity is triggered by a high-fat diet and that mice lacking the protein swiftly develop diabetes. This suggests that FGF1 is crucial to maintaining the body's sensitivity to insulin and normal levels of sugar in the blood.
"Because humans are good at storing fat during times of plenty, we are also excellent at surviving times of famine," says Ronald M. Evans, a professor in Salk's Gene Expression Laboratory and lead author of the paper. "The fat tissues of our body are like batteries, providing us with a steady source of energy when food is scarce. FGF1 governs the expansion and contraction of fat and thus controls the ebb and flow of energy throughout our body."
Obesity rates have soared in the United States in recent decades, with more than one third of U.S. adults and 17 percent of children and adolescents now considered obese, according to the Centers for Disease Control and Prevention.
As the number of overweight people has grown, so too has the incidence of metabolic disease, with nearly 26 million Americans estimated to have obesity-related type 2 diabetes. With annual costs exceeding well over $200 billion, obesity is a chronic disease that is consuming a huge portion of our health care dollars.
Although exercise and calorie restriction are known to be effective at preventing and treating diabetes, the obesity epidemic continues to grow and new drugs to treat the problem are desperately needed. Against this backdrop, the Evans' lab discovery is an important breakthrough - and a surprise.
"The discovery of FGF1 was unexpected - and intriguing - because it was believed to do nothing," says Jae Myoung Suh, a postdoctoral researcher in Evans' laboratory and co-first author on the paper. "If you deplete FGF1 from the body, nothing happens when the mice are fed a steady low fat diet. But when given a high-fat, "Western-style" diet the mice develop an aggressive form of diabetes and experience a system-wide breakdown of their metabolic health."
"These abnormalities cause abdominal or stomach fat to become inflamed," says Michael Downes, a senior staff scientist in Salk's Gene Expression Laboratory and co-lead author on the paper. "This is important because inflamed visceral fat has been linked to heightened risk for diabetes and other obesity-related diseases, such as heart disease and stroke."
The scientists also found that FGF1 is regulated by the antidiabetic drug Actos, which is used to increase the body's sensitivity to insulin. But Actos and related drugs, though helpful, have side effects that limit their use.
Thus, Evans and his colleagues plan to explore whether FGF1 might point to a new way to control diabetes by avoiding the drawbacks of Actos and providing a more natural means of increasing insulin sensitivity.