Eylea outperforms Avastin for diabetic macular edema with moderate or worse vision loss

NIH-funded clinical trial shows Eylea, Avastin, and Lucentis perform similarly when vision loss is mild.

A two-year clinical trial that compared three drugs for diabetic macular edema (DME) found that gains in vision were greater for participants receiving the drug Eylea (aflibercept) than for those receiving Avastin (bevacizumab), but only among participants starting treatment with 20/50 or worse vision.  Gains after two years were about the same for Eylea and Lucentis (ranibizumab), contrary to year-one results from the study, which showed Eylea with a clear advantage. The three drugs yielded similar gains in vision for patients with 20/32 or 20/40 vision at the start of treatment. The clinical trial was conducted by the Diabetic Retinopathy Clinical Research Network (DRCR.net), which is funded by the National Eye Institute, part of the National Institutes of Health.
“This rigorous trial confirms that Eylea, Avastin, and Lucentis are all effective treatments for diabetic macular edema,” said NEI Director Paul A. Sieving, M.D., Ph.D. “Eye care providers and patients can have confidence in all three drugs.”
Eylea, Avastin, and Lucentis are all widely used to treat DME, a consequence of diabetes that can cause blurring of central vision due to the leakage of fluid from abnormal blood vessels in the retina. The macula is the area of the retina used when looking straight ahead. The drugs are injected into the eye and work by inhibiting vascular endothelial growth factor (VEGF), a substance that can promote abnormal blood vessel growth and leakage. Although the drugs have a similar mode of action, they differ significantly in cost. Based on Medicare allowable charges, the per-injection costs of each drug at the doses used in this study were about $1850 for Eylea, about $60 for Avastin, and about $1200 for Lucentis.
DRCR.net investigators enrolled 660 people with DME at 89 clinical trial sites across the United States. When the study began, participants on average were 61 years old with 17 years of type 1 or type 2 diabetes. Only people with a visual acuity of 20/32 or worse were eligible to participate (to see clearly, a person with 20/32 vision would have to be 20 feet away from an object that a person with normal vision could see clearly at 32 feet). At enrollment, about half the participants had 20/32 to 20/40 vision. The other half had 20/50 or worse vision. In many states, a corrected visual acuity of 20/40 or better in at least one eye is required for a driver’s license that allows both day- and nighttime driving.
Each participant was assigned randomly to receive Eylea (2.0 milligrams/0.05 milliliter), Avastin (1.25 mg/0.05 mL), or Lucentis (0.3 mg/0.05 mL). Participants were evaluated monthly during the first year and every 4-16 weeks during the second year. Most participants received monthly injections during the first six months. Thereafter, participants received additional injections of assigned study drug until DME resolved or stabilized with no further vision improvement.  Subsequently, injections were resumed if DME worsened. Additionally, laser treatment was given if DME persisted without continual improvement after six months of injections. Laser treatment alone was the standard treatment for DME until widespread adoption of anti-VEGF drugs a few years ago.
Among participants with 20/40 or better vision at the trial’s start, all three drugs improved vision similarly on an eye chart. On average, participants’ vision improved from 20/40 vision to 20/25.
Among participants with 20/50 or worse vision at the trial’s start, visual acuity on average improved substantially in all three groups. At two years, Eylea participants were able to read about 3.5 additional lines on an eye chart; Lucentis participants were able to read about three additional lines, and Avastin participants improved about 2.5 lines, compared with visual acuity before treatment. Eylea outperformed Avastin at the one- and two-year time points. While Eylea outperformed Lucentis at the one-year time point, by the two-year time point gains in visual acuity were statistically no different. At the end of the trial, average visual acuity was 20/32 to 20/40 among participants in all three groups.
“The results of the DRCR Network’s comparison of Eylea, Avastin, and Lucentis will help doctors and their patients with diabetic macular edema choose the most appropriate therapy,” said John A. Wells, M.D., the lead author of the study and a retinal specialist at the Palmetto Retina Center, Columbia, South Carolina. “The study suggests there is little advantage of choosing Eylea or Lucentis over Avastin when a patient’s loss of visual acuity from macular edema is mild, meaning a visual acuity of 20/40 or better. However, patients with 20/50 or worse vision loss may benefit from Eylea, which over the course of the two-year study outperformed Lucentis and Avastin.”
The number of injections participants needed was about the same for all three treatment groups. Eylea, Avastin, and Lucentis participants on average required nine injections in the first year of the study and five in the second year.
The need for laser treatment varied among the three treatment groups. By two years, 41 percent of participants in the Eylea group received laser treatment to treat their macular edema, compared with 64 percent of participants in the Avastin group and 52 percent in the Lucentis group.
The risk of heart attack, stroke, or death from a cardiovascular condition or an unknown cause by end of the trial was higher among participants in the Lucentis group. Twelve percent of Lucentis participants had at least one event, compared with five percent of participants in the Eylea group and eight percent of participants in the Avastin group. This difference in cardiovascular rates has not been seen across all other studies, and therefore may be due to chance. Continued assessment of these serious cardiovascular events and their association with these drugs is important in future studies. Cardiovascular events such as heart attack and stroke are common complications of diabetes. The occurrence of eye complications, such as eye infections and inflammation, was similar for all three drugs.
Results of the study were published online today in Ophthalmology, the journal of the American Academy of Ophthalmology. Eylea and Lucentis were provided by drug manufacturers Regeneron and Genentech, respectively. Additional research funding for this study was provided by the National Institute of Diabetes and Digestive and Kidney Diseases, also a part of NIH.

“This important study would not have happened without funding from the National Institutes of Health and the cooperation of two competing companies,” said Adam R. Glassman, M.S., principal investigator of the DRCR.Net Coordinating Center at the Jaeb Center for Health Research.

The U.S. Food and Drug Administration has approved a new treatment certain diabetic foot ulcers

The U.S. Food and Drug Administration has approved a new indication for the Integra Omnigraft Dermal Regeneration Matrix (Omnigraft) to treat certain diabetic foot ulcers. The matrix device, which is made of silicone, cow collagen, and shark cartilage, is placed over the ulcer and provides an environment for new skin and tissue to regenerate and heal the wound. 

An estimated 29 million people in the United States have been diagnosed with diabetes, according to the Centers for Disease Control and Prevention, and about 25 percent of them will experience a foot ulcer during their lifetime. Chronic diabetic foot ulcers are associated with tissue and bone infections and result in 50,000 amputations each year.

“We are excited to see a new innovation in diabetes care with the potential to improve the number of foot ulcers that heal,” said William Maisel, M.D., M.P.H., acting director of the Office of Device Evaluation in the FDA’s Center for Devices and Radiological Health. “Healing of these painful and debilitating ulcers is essential for patients to resume walking and other daily activities.” 

The FDA first approved Integra Dermal Regeneration Template (which the company now also calls Omnigraft) in 1996 for the treatment of life threatening burn injuries when the use of a patient’s own skin for a graft was not possible.  In 2002, Integra Dermal Regeneration Template was approved for a new indication to treat patients undergoing reconstructive surgery for burn scars when they cannot have skin grafts. Now, Omnigraft is approved to treat certain diabetic foot ulcers that last for longer than six weeks and do not involve exposure of the joint capsule, tendon or bone, when used in conjunction with standard diabetic ulcer care. 

Omnigraft’s new indication is based on a clinical study that demonstrated that the matrix device improved ulcer healing compared to standard diabetic foot ulcer care, which includes cleaning and covering the wound with a surgical bandage and keeping weight off of the foot with the ulcer. In the study, 51 percent of patients treated with Omnigraft had healed ulcers after 16 weeks compared to 32 percent of patients treated with standard diabetic foot ulcer care alone. 

Adverse events observed in the clinical trial included infections, increased pain, swelling, nausea, and new or worsening ulcers.

Omnigraft shouldnot be used in patients with allergies to cow (bovine) collagen or chondroitin (cartilage from any source) since serious allergic reactions may occur. Omnigraft should also not be used on infected wounds.

Omnigraft is manufactured by Integra LifeSciences Corporation of Plainsboro, New Jersey.

New treatment options, better hope of preventing vision loss from diabetes

There is some good news for people with eye complications from diabetes. A network of researchers supported by the National Eye Institute (NEI) found that the drug Lucentis (ranibizumab) can be highly effective for treating proliferative diabetic retinopathy, an eye disease that can occur as a complication of diabetes. The researchers, part of the Diabetic Retinopathy Clinical Research Network, say this is the first major advance in therapy in 40 years.

Diabetic retinopathy is the leading cause of vision loss and blindness among working-age Americans. An advanced stage, called proliferative diabetic retinopathy, occurs when abnormal blood vessels grow near the retina, the light-sensitive tissue at the back of the eye. These new vessels can leak blood, which can obscure vision and damage the retina. Lucentis is one of several drugs called VEGF inhibitors that can block this process.

In the new study, Lucentis was compared to scatter laser therapy (or panretinal photocoagulation), which has been the standard treatment for proliferative diabetic retinopathy since the 1970s. Although laser therapy is effective in improving central vision, it can cause decreased night and side vision. The study found that Lucentis produced more improvement in central vision and little change in side vision when compared to laser therapy.

An injection into the eye might sound scary, but it's one of the most common procedures performed by ophthalmologists. VEGF inhibitors have been used for several years to treat diabetic macular edema, a swelling of the retina that can occur as blood leaks around it. The new study suggests that VEGF drugs may even help prevent macular edema. Study participants who were treated with Lucentis were less likely to develop macular edema than those treated with laser therapy.

As better treatments for diabetic retinopathy emerge, it's important to remember that an early diagnosis is the first step to getting treatment and saving your sight. If you have diabetes, you should get a comprehensive dilated eye exam at least once a year. Diabetic retinopathy often has no symptoms in its early stages. But an eye care professional can detect it before symptoms occur. And with early detection and appropriate treatment, the risk of severe vision loss from the disease can be reduced by 95 percent.

"Only about half of all people with diabetes get an annual comprehensive dilated eye exam, which is essential for detecting diabetic eye disease early, when it is most treatable," said NEI Director Paul A. Sieving, M.D., Ph.D.

Keeping diabetes under control is also key to preventing vision loss. If you have diabetes, NEI's National Eye Health Education Program recommends these important steps to keep your health on TRACK:

• Take your medications as prescribed by your doctor.

• Reach and maintain a healthy weight.

• Add physical activity to your daily routine.

• Control your ABC's -- A1C, blood pressure, and cholesterol levels.

• Kick the smoking habit.

Diabetes expert warns Paleo Diet is dangerous and increases weight gain

UNIVERSITY OF MELBOURNE

    SHARE

 PRINT  E-MAIL

IMAGE: THE MICE INVOLVED IN THE STUDY WERE FED A SPECIAL DIET. THOSE ON A DIET MIMICKING THE PALEO DIET GAINED WEIGHT. view more 

CREDIT: THE UNIVERSITY OF MELBOURNE.

A new study has revealed following a low-carbohydrate, high-fat diet for just eight weeks can lead to rapid weight gain and health complications.

The surprise finding, detailed in a paper in Nature journal Nutrition and Diabetes, has prompted University of Melbourne researchers to issue a warning about putting faith in so-called fad diets with little or no scientific evidence.

Lead author, Associate Prof Sof Andrikopoulos says this type of diet, exemplified in many forms of the popular Paleo diet, is not recommended - particularly for people who are already overweight and lead sedentary lifestyles.

He says mass media hype around these diets, particularly driven by celebrity chefs, celebrity weight-loss stories in the tabloid media and reality TV shows, are leading to more people trying fad diets backed by little evidence. In people with pre-diabetes or diabetes, the low-carb, high-fat (LCHF) diet could be particularly risky, he said. 

"Low-carbohydrate, high-fat diets are becoming more popular, but there is no scientific evidence that these diets work. In fact, if you put an inactive individual on this type of diet, the chances are that person will gain weight," Assoc Prof Andrikopoulos, President of the Australian Diabetes Society, said.

"There is a very important public health message here. You need to be very careful with fad diets, always seek professional advice for weight management and always aim for diets backed by evidence." 

Researchers at the University of Melbourne's originally sought to test whether high-fat and low-carbohydrate foods would benefit the health of people with pre-diabetes.

They took two groups of overweight mice with pre-diabetes symptoms and put one group on the LCHF diet. The other group ate their normal diet. The mice were switched from a three per cent fat diet to a 60 per cent fat diet. Their carbs were reduced to only 20 per cent. 

After eight weeks, the group on the LCHF gained more weight, their glucose intolerance worsened, and their insulin levels rose. The paleo diet group gained 15 per cent of their body weight. Their fat mass doubled from 2 per cent to almost 4 per cent.

"To put that in perspective, for a 100 kilogram person, that's the equivalent of 15 kilograms in two months. That's extreme weight gain," Assoc Prof Andrikopoulos said. 

"This level of weight gain will increase blood pressure and increase your risk of anxiety and depression and may cause bone issues and arthritis. For someone who is already overweight, this diet would only further increase blood sugar and insulin levels and could actually pre-dispose them to diabetes. 

"We are told to eat zero carbs and lots of fat on the Paleo diet. Our model tried to mimic that, but we didn't see any improvements in weight or symptoms. In fact, they got worse. The bottom line is it's not good to eat too much fat."

Prof Andrikopoulos says the Mediterranean diet is the best for people with pre-diabetes or diabetes. 

"It's backed by evidence and is a low-refined sugar diet with healthy oils and fats from fish and extra virgin olive oil, legumes and protein."

Diabetics who use verapamil have lower glucose levels

---

A new University of Alabama at Birmingham research paper published in the journal Diabetes Research and Clinical Practice shows for the first time that there is an association of verapamil use and lower fasting glucose levels in humans with diabetes. It is a promising finding at UAB, where the Comprehensive Diabetes Center is currently conducting a first-of-its-kind, JDRF-funded clinical trial using verapamil, a drug that researchers in the School of Medicine have shown completely reverses the disease in mice models.

Yulia Khodneva M.D., Ph.D., a research associate and postdoctoral scholar in UAB's Division of Preventive Medicine and junior member of the Comprehensive Diabetes Center, examined the association of calcium channel blockers and verapamil use with fasting serum glucose among almost 5,000 adults with diabetes who were part of the REGARDS study. The Reasons for Geographic and Racial Differences in Stroke project, sponsored by the National Institutes of Health, is a national study focusing on learning more about the factors that increase a person's risk of having cardiovascular disease.

The sample of diabetic adults included 1,484 calcium channel blocker users, of whom 174 were verapamil users. The findings showed that calcium channel blocker users had 5 mg/dL lower serum glucose compared to non-users. Verapamil users had on average 10 mg/dL lower serum glucose compared to calcium channel blocker non-users. And the numbers showed a substantially greater difference among insulin users who also took verapamil. Verapamil users who took insulin in combination with oral medication had a 24 mg/dL lower serum glucose, and verapamil users who took insulin alone to manage their diabetes showed a 37 mg/dL lower serum glucose.

"This is a cross-sectional observational study unlike the current prospective randomized UAB verapamil clinical trial, so we can't infer causal relationship between using verapamil and lower glucose levels; but we can say there is an association with lower glucose levels, and that is absolutely encouraging," Khodneva said.

Khodneva says the findings in the final subgroup, which used insulin alone and included participants who had mostly Type 1 or severe Type 2 diabetes, were quite striking.

"The change in glucose for that group compared to those not taking verapamil -- 37 mg/dL -- is almost four times higher than when you look at the whole sample of diabetic adults," Khodneva said. "That made us think that verapamil is predominantly active for participants who have Type 1 diabetes or those with Type 2 diabetes who have really damaged beta cells. There seems to be something that works on the structural level, especially for those who have stronger beta-cell damage."

"Dr. Khodneva has done a tremendous job analyzing these large data sets and discovering for the first time that verapamil use is associated with lower glucose levels in patients with diabetes," said Anath Shalev, M.D., director of UAB's Comprehensive Diabetes Center and principal investigator of the verapamil clinical trial. "Strikingly, the observed difference in glucose levels is comparable to an approximately 1 percent reduction in HbA1C and to what would be expected from the addition of an approved diabetes drug. Moreover, the large difference in glucose levels especially in the groups taking insulin is consistent with our underlying hypothesis that verapamil promotes functional beta-cell mass."

UAB announced its verapamil clinical trial in November 2014 and began enrolling patients in January 2015. The first results that will assess verapamil's effectiveness on Type 1 diabetes are still approximately 18 months away.

The trial is testing an approach different from any current diabetes treatment by focusing on promoting pancreatic beta cells, which produce insulin the body needs to control blood sugar. UAB scientists have proved through years of research that high blood sugar causes the body to overproduce a protein called TXNIP, which is increased within the beta cells in response to diabetes, but had never previously been known to be important in beta-cell biology. Too much TXNIP in the pancreatic beta cells leads to their death and thwarts the body's efforts to produce insulin, thereby contributing to the progression of diabetes.

But UAB scientists have also uncovered that verapamil, which is widely used to treat high blood pressure, irregular heartbeat and migraine headaches, can lower TXNIP levels by decreasing calcium concentration in the beta cells -- to the point that, when mouse models with established diabetes and blood sugars above 300 milligrams per deciliter were treated with verapamil, the disease was eradicated.

'Beiging' white fat cells to fight diabetes

Researchers are getting closer to learning how to turn white fat cells into brown fat cells, in a process called "beiging," to bring down blood sugar levels and fight diabetes. The team, led by Joseph Baur, PhD, an assistant professor of Physiology in the Perelman School of Medicine at the University of Pennsylvania published their findings this month in the journal Diabetes.

"Beiging of white fat could be harnessed to fight diabetes by burning excess calories to cause a decrease in blood sugar," Baur said. "Our work suggests that activation of the mTOR pathway plays a critical role in this process." Induction of beige fat cells is considered a promising strategy to combat obesity because of this cell type's ability to metabolize glucose and lipids, dissipating the resulting energy as heat.

Brown and white fat cells, or adipocytes, play different roles in the body. While white adipocytes store energy as large fat droplets, brown adipocytes contain smaller fat droplets and are specialized to burn fat to produce heat. To do this brown adipocytes are packed with the powerhouses called mitochondria that contain iron, which gives them their brown color. In fact, babies are born with brown fat along the upper back and shoulders to keep warm.

In adult humans, the recent discovery of brown fat "depots" is also associated with lower body weight. Brown-like fat cells, called beige adipocytes, also appear within white fat deposits in response to cold and other signals. The energy balance within the body is influenced by brown and beige adipocytes, which are stimulated into action by cold temperatures and other signals to burn fat and carbohydrates.

The primary tool used in these studies was rapamycin, a drug that inhibits the protein mTOR (mechanistic target of rapamycin), which can be found in two distinct protein complexes. It was first discovered as a byproduct of Streptomycin hygroscopicus, a bacterium found in a soil sample from Easter Island, an island also known as Rapa Nui, hence the name. Rapamycin is currently used as an immunosuppressant in organ transplant, but has recently attracted attention when it was discovered to extend lifespan in mice.

Interestingly, in 2012, Baur's lab discovered that rapamycin also causes insulin resistance due to its ability to inhibit both arms of the mTOR signaling pathway controlled by the protein complexes mTORC1 and mTORC2. They showed in an animal model that these two arms could, in principle, be separated to dissect which pathway controls longevity versus endocrine effects.

In terms of physiology, mTOR signaling is involved in the control of blood sugar and cholesterol levels, and its inhibition increases the risk of diabetes. While previous studies suggested that mTORC1 inhibition would promote beiging of white fat cells, Baur's present work supports the notion that mTORC1 activity is actually required for cold-induced beiging of white fat cells. If activating mTORC1 directly can bring about the same result, then this approach could potentially be applied to combat diabetes.

In the Diabetes study, the team shows that rapamycin blocks the ability of cold or drugs that activate a specific neurotransmitter pathway to induce the appearance of beige fat cells. Accordingly, rapamycin-treated mice are cold-intolerant and fail to maintain body temperature and weight when moved to a colder environment.

The findings demonstrate a positive role for mTORC1 in the recruitment of beige fat cells to white fat depots, which could explain some of the negative metabolic effects of mTOR inhibition.

"Our study highlights the complex interconnection between mTOR signaling and metabolism," said first author Cassie Tran, PhD, a postdoctoral fellow in the Baur lab. "It will be critical in moving forward to determine the specific targets downstream of mTOR that are causing the negative metabolic effects in order to create better drugs and one day drugs that might also extend heathspan. The discovery of a critical signaling pathway for beige-fat formation also suggests the opportunity to target this pathway to therapeutically increase the number of heat-producing cells in obese or diabetic patients."

Diabetes drug may prevent recurring strokes

Pioglitazone, a drug used for type 2 diabetes, may prevent recurrent stroke and heart attacks in people with insulin resistance but without diabetes. The results of the Insulin Resistance Intervention after Stroke (IRIS) trial, presented at the International Stroke Conference 2016 in Los Angeles and published in the New England Journal of Medicine, suggest a potential new method to prevent stroke and heart attack in high-risk patients who have already had one stroke or transient ischemic attack.  This large, international study was supported by the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (NINDS).

The IRIS trial is the first study to provide evidence that a drug targeting cell metabolism may prevent secondary strokes and heart attacks even before diabetes develops. Insulin regulates metabolism and keeps blood sugar levels from getting too high, along with many other processes, in the body. Insulin resistance is a condition in which the body produces insulin but does not use it effectively.

“This study represents a novel approach to prevent recurrent vascular events by reversing a specific metabolic abnormality thought to increase the risk for future heart attack or stroke,” said Walter J. Koroshetz, M.D., director of the NINDS.

“The IRIS trial supports the value of more research to test the vascular benefits of other interventions such as exercise, diet and medications that have similar effects on metabolism as pioglitazone,” said Walter N. Kernan, M.D. professor of general medicine at Yale University School of Medicine, New Haven, Connecticut, and lead author of the study.  

More than 3000 patients from seven countries who had experienced an ischemic stroke or transient ischemic attack within the previous six months were randomized to receive pioglitazone or placebo for up to five years in addition to standard care. Ischemic stroke and transient ischemic attacks can occur when a cerebral blood vessel becomes blocked, cutting off the delivery of oxygen and nutrients to brain tissue.

In this study, stroke or heart attack occurred in 9 percent of participants taking pioglitazone and 11.8 percent of patients on placebo, which was a relative decrease of 24 percent. The results suggest that 28 strokes or heart attacks may be prevented for every 1000 patients who take pioglitazone for up to five years. 

Insulin resistance is a hallmark of type 2 diabetes but also occurs in more than 50 percent of people with ischemic stroke who do not have diabetes. People with diabetes are known to have increased risk of stroke. Previous research suggested that insulin resistance increases risk for stroke, but the IRIS trial was the first to treat it and suggested that the therapy reduced the risk of recurrent stroke and heart attacks. However, pioglitazone is not FDA-approved for the uses studied in the IRIS trial.

In this study, pioglitazone also reduced the risk of diabetes by 52 percent in the study participants.
The study evidenced an additional known side effect of the drug, which is an increased risk of bone fractures.  To help doctors and patients choose the best strategy for preventing recurring strokes, future studies will attempt to identify a person’s risk of bone fractures due to pioglitazone. As approved for use in medical practice, the drug also carries additional side effects (drug label (link is external)).


“More research is needed to determine the mechanisms by which pioglitazone decreases risk for stroke and heart attack and increases bone fracture risk, with the hope of developing strategies that maximize benefit and minimize serious side effects in our patients,” said Dr. Kernan.

Type 2 diabetes drug can exhaust insulin-producing cells

Long-term use of liraglutide, a substance that helps to lower blood sugar levels in patients with type 2 diabetes, can have a deteriorating effect on insulin-producing beta cells, leading to an increase in blood sugar levels. This according to a study on mice implanted with human insulin-producing cells conducted by a team of scientists from Karolinska Institutet, Sweden, and the University of Miami, USA. The researchers flag the possible consequences of this popular form of therapy in the next issue of the journal 'Cell Metabolism'.

Blood-sugar suppressors in the form of analogues of the incretin hormone GLP-1 are commonly used in the treatment of type 2 diabetes, since they stimulate the glucose response of the pancreatic beta cells to make them secrete more insulin. There is now compelling evidence that liraglutide therapy is efficacious at least in the short term, since it produces an initial reduction in blood sugar. However, many patients do not respond to the treatment and some even display adverse reactions such as nausea, vomiting and diarrhoea.

To study the long-term effects of incretin therapy, which has never previously been assayed, researchers at Karolinska Institutet and the University of Miami worked with humanised mice, generated by transplanting human insulin-producing cells into the anterior chamber of the eye. The mice were given daily doses of liraglutide for more than 250 days, during which time the researchers were able to monitor how the pancreatic beta cells were affected. The results showed an initial improvement in the insulin-producing cells, followed by a gradual exhaustion, with reduced secretion of insulin as a response to glucose. This, they say, was unexpected.

"Given the lack of clinical studies on the long-term effect of these drugs in diabetes patients, this is a very important discovery," says Midhat Abdulreda, researcher at the Diabetes Research Institute, University of Miami Miller School of Medicine.

"We also need to take these results into account before prescribing blood-sugar suppressing GLP-1 analogues when planning long-term treatment regimens for patients," says Per-Olof Berggren, PhD, Professor at the Rolf Luft Research Centre for Diabetes and Endocrinology at Karolinska Institutet's Department of Molecular Medicine and Surgery. "Our study also shows in general how to carry out in vivo studies of the long-term effects of drugs on human insulin-producing cells, which should be extremely important to the drug industry."

New Iowa State research holds promise for diabetics with vitamin D deficiency

A simple change in diet could boost vitamin D levels for millions of Americans suffering from Type 2 diabetes, according to new research from Iowa State University published in the Journal of Agricultural and Food Chemistry.
Vitamin D is important for bone health and protecting against cancer and other diseases, but diabetics have trouble retaining it and other nutrients because of poor kidney function. A team of Iowa State researchers found diabetic rats fed an egg-based diet had higher concentrations of vitamin D, improved blood glucose levels and gained less weight.

Iowa State researchers are most interested in 25-hydroxyvitamin D-3 (25D) -- the form of vitamin D in the blood that reflects vitamin D status. For that reason, it made sense to test eggs in the diet rather than other foods containing vitamin D or a supplement.

"Eggs are the richest source of 25-hydroxyvitamin D-3 in the diet, and there isn't any conversion required to make it into the blood. If you take it in a supplement or food fortified with vitamin D, it has to be converted to that form," said Matthew Rowling, an associate professor of food science and human nutrition.

The variation in results was significant. Blood glucose levels dropped nearly 50 percent for diabetic rats on an egg-based diet compared to diabetic rats fed a standard diet. Concentrations of 25D were 148 percent higher for the egg-fed group and plasma triglyceride concentrations -- a risk factor for cardiovascular disease -- dropped 52 percent.

Rowling and colleagues Kevin Schalinske, professor of food science and human nutrition, and Samantha Jones, a graduate research assistant, are still working to understand why more vitamin D is retained from eggs than supplements. They say it may be related to other components found in eggs.

Don't skip the yolk

Eggs are not only a good source of vitamin D and other nutrients; they are also inexpensive and readily available. However, researchers say you need to eat the whole egg.

"If you just ate egg whites you wouldn't get any of the vitamin D, because the 25D is only in the yolk. The whites are fine if you're focused just on protein, but the nutrients are all in the yolk. From a vitamin D standpoint, you want to consume the whole thing," said Jones, lead author of the paper.

The next step is to determine the minimal amount of eggs needed in the diet to yield a benefit. The study was designed to replace protein in the diet, so the rats were fed the equivalent of 17 to 18 eggs daily. However, based on the results and the severity of the rats' diabetes, researchers expect a much lower dosage will be effective in humans. They also want to know if health benefits are enhanced when additional dietary constituents that promote the maintenance of vitamin D status and reduction of diabetic symptoms, such as fiber, are added to the diet.

"You may need even less egg if you combine it with something else that does not provide vitamin D per se, but rather protects the kidney and prevents loss of vitamin D," Schalinske said. "We want to make sure we understand what's going on with egg consumption and promoting vitamin D balance and make sure there's a linkage to outcomes whether it's bone health or kidney health."

Barley can help improve blood sugar levels and reduce appetite

A recent study from Lund University in Sweden shows that barley can rapidly improve people's health by reducing blood sugar levels and risk for diabetes. The secret lies in the special mixture of dietary fibres found in barley, which can also help reduce people's appetite and risk for cardiovascular disease.

"It is surprising yet promising that choosing the right blend of dietary fibres can -- in a short period of time -- generate such remarkable health benefits", says Anne Nilsson, Associate Professor at the Food for Health Science Centre and one of the researchers behind the study.

The study was conducted with healthy middle-aged participants who were asked to eat bread largely made out of barley kernels (up to 85%) for three days -- at breakfast, lunch and dinner. Approximately 11-14 hours after their final meal of the day participants were examined for risk indicators of diabetes and cardiovascular disease.

The researchers found that the participants' metabolism improved for up to 14 hours, with additional benefits such as decreases in blood sugar and insulin levels, increases in insulin sensitivity and improved appetite control. The effects arise when the special mixture of dietary fibres in barley kernel reaches the gut, stimulating the increase of good bacteria and the release of important hormones.

"After eating the bread made out of barley kernel, we saw an increase in gut hormones that regulate metabolism and appetite, and an increase in a hormone that helps reduce chronic low-grade inflammation, among the participants. In time this could help prevent the occurrence of both cardiovascular disease and diabetes", says Anne Nilsson.

In a previous related study conducted with a team from the University of Gothenburg in Sweden researchers also found that dietary fibres from barley kernel generate an increase of the gut bacteria Prevotella copri, which have a direct regulatory effect on blood sugar levels and help decrease the proportion of a type of gut bacteria that is considered unhealthy.

The effects from barley kernel are influenced by the composition of the individual's gut microbiota, meaning people with low concentrations of the Prevotella copri bacteria experienced less effect from their intake of barley products. Eating more barley could, however, help stimulate growth of the bacteria.

The results are timely as rates of obesity and type 2 diabetes have significantly increased in the past few years. Researchers hope that more knowledge about the impact of specific dietary fibres on people's health will result in stores keeping more food products with healthy properties such as barley kernels. The ambition is also to get more people to use barley in meals, for example in salads, soups, stews, or as an alternative to rice or potatoes.

The researchers' advice for how to maintain a healthy blood sugar level:

• Choose bread with as much whole grains as possible. Feel free to mix with other grains, for example rye
• Avoid white flour
• Add barley kernel grains in soups and stews
• Replace for example white rice with cooked barley
• Eat beans and chickpeas with your meal as they too have a good blend of dietary fibres and like barley kernels a low glycaemic index with positive health effects.

The bread used in the study was 85% made out of barley grains, which had been boiled and mixed with wheat flour. If you want to reduce the amount of barley grains, you can replace some of it with whole grains.

High-salt diet doubles threat of cardiovascular disease in people with diabetes

People with Type 2 diabetes who eat a diet high in salt face twice the risk of developing cardiovascular disease as those who consume less sodium, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

Diabetes occurs when there is too much sugar in the bloodstream. People develop Type 2 diabetes when their bodies become resistant to the hormone insulin, which carries sugar from the blood to cells.

According to the U.S. Centers for Disease Control and Prevention, about 29.1 million Americans have some form of diabetes. This population is at risk for heart disease. Between 2003 and 2006, cardiovascular disease death rates were about 1.7 times higher among adults diagnosed with diabetes than those who were not, according to the CDC's 2014 National Diabetes Statistics Report.

"The study's findings provide clear scientific evidence supporting low-sodium diets to reduce the rate of heart disease among people with diabetes," said the study's first author, Chika Horikawa, RD, MSc, CDE, of the University of Niigata Prefecture in Niigata, Japan. "Although many guidelines recommend people with diabetes reduce their salt intake to lower the risk of complications, this study is among the first large longitudinal studies to demonstrate the benefits of a low-sodium diet in this population."

The nationwide cohort study surveyed participants in the Japan Diabetes Complications Study who were between the ages of 40 and 70 and had been diagnosed with diabetes. Participants were identified at 59 outpatient centers and universities across Japan. In all, 1,588 people responded to a survey about their diets, including sodium intake. The researchers reviewed data on cardiovascular complications participants experienced over the course of eight years.

Researchers divided the participants into four groups based on their sodium intake. The analysis found people who ate an average of 5.9 grams of sodium daily had double the risk of developing cardiovascular disease than those who ate, on average, 2.8 grams of sodium daily. The effects of a high-sodium diet were exacerbated by poor blood sugar control.

"To reduce the risk of developing cardiovascular disease, it is important for people who have Type 2 diabetes to improve their blood sugar control as well as watch their diet," Horikawa said. "Our findings demonstrate that restricting salt in the diet could help prevent dangerous complications from diabetes."

Study shows heart calcium scan predictive of diabetes-related death from cardiovascular disease

People with Type 2 diabetes have two to four times the risk of cardiovascular disease compared to people without the disease. The best way for doctors to predict which diabetes patients are at the greatest risk for heart disease is to use a coronary artery calcium (CAC) test in addition to the most commonly used assessment tool, according to researchers at Wake Forest Baptist Medical Center.

Current medical guidelines recommend treating all diabetes patients as high risk, but the Wake Forest Baptist study found that CAC can identify diabetes patients who are at very high risk for developing potentially fatal cardiovascular disease, as well as those who are at low risk.

"Our observations challenge accepted medical knowledge that all people with diabetes have the same risk. CAC is key in predicting the specific risk level," said Donald Bowden, Ph.D., professor of biochemistry at Wake Forest Baptist and senior author of the study, which is published online in the December issue of the journal Diabetes Care.

"People at very high risk are 11 times more likely to die from cardiovascular diseases as compared to those at low risk. Diagnosing a more precise risk level should help doctors provide more effective treatments and hopefully improve outcomes," he said.

The community-based Diabetes Heart Study was designed to determine if CAC provided additional information about cardiovascular disease and mortality beyond the Framingham Risk Score, the most commonly used assessment tool. A total of 1,123 people with Type 2 diabetes between 34 to 86 years old were followed for an average of 7.4 years. The study participants were recruited from clinics in western North Carolina and reflect a cross section of families with diabetes-affected members in the region.

CAC uses a CT scan to detect calcium build-up in the arteries of the heart. According to Bowden, the cost of the test is relatively low and the radiation exposure is about half of what someone would get in a year "by just walking around."

"Based on our study, we think that CAC should be added to the Framingham tool as the standard of care for all people with diabetes," Bowden said.

Tree nuts appear to help blood sugar levels in people with Type 2 diabetes

Eating tree nuts appears to help lower and stabilize blood sugar levels in people with Type 2 diabetes compared to those on a control diet, a new study has found.

A systematic review meta-analysis of the totality of the evidence from 12 clinical trials in 450 participants found that eating about two servings a day of tree nuts improved the two key markers of blood sugar: the HbA1c test, which measures blood sugar levels over three months, and the fasting glucose test, where patients are not allowed to eat or drink anything but water for eight hours before their blood glucose levels are tested.

The best results were seen when tree nuts replaced refined carbohydrates rather than saturated fats, said Dr. John Sievenpiper, a physician and researcher in the Clinical Nutrition and Risk Factor Modification Centre of St. Michael's Hospital. The results of his study were published today in the online journal PLOS ONE.

Dr. Sievenpiper said participants in the clinical trials reviewed ate 56 grams of tree nuts a day. One serving of tree nuts is about ¼ cup or 30 grams. He said that people in North America consume on average less than one serving a day, so this is one way they can adapt their diets to take advantage of the metabolic benefits.

Tree nuts are such things as almonds, Brazil nuts, cashews, chestnuts, coconuts, hazelnuts, pecans, macadamia nuts, walnuts, pine nuts and pistachios. They do not include peanuts, which are legumes.

Dr. Sievenpiper said that while nuts are high in fat, it's healthy unsaturated fat and while they can also be high in calories, participants in the clinical trials did not gain weight. "Tree nuts are another way people can maintain healthy blood sugar levels in the context of a healthy dietary pattern," he said.

Metformin May Lower Cancer Risk in People with Type 2 Diabetes

A commonly prescribed diabetes drug, metformin, reduces the overall cancer risk in people with Type 2 diabetes, a large systematic review study finds. The results will be presented Monday at The Endocrine Society’s 94th Annual Meeting in Houston.

“Type 2 diabetes increases the risk for several types of cancer,” said lead author Diego Espinoza-Peralta, MD, an endocrinologist with Mexico’s National Institute of Medical Sciences and Nutrition (Instituto Nacional de Ciencias Medicas y Nutricion) in Mexico City. “Our findings suggest that the regular use of metformin—a low-cost medication— reduces this risk, compared with not taking metformin.”

Espinoza-Peralta and his colleagues conducted a systematic review and meta-analysis, or combined statistical analysis, of reported studies that evaluated cancer risk in patients with Type 2 diabetes. They analyzed seven relevant studies that included more than 32,400 Type 2 diabetic patients who had no other known condition that increased their cancer risk.

The investigators found that the odds of getting any type of cancer was 0.62 times less—an estimated 38 percent relative risk reduction—with daily continuous use of metformin than for those with no exposure to metformin.

“This risk reduction with metformin use extended to certain types of cancers, specifically colon and breast cancer,” Espinoza-Peralta said.

Colorectal cancer and breast cancer are among the cancers that studies have found to occur more often in people with Type 2 diabetes. There was no risk reduction, however, in pancreatic cancer, another type of cancer for which people with Type 2 diabetes are at increased risk, the authors reported.

Metformin, which is the standard recommended initial treatment of Type 2 diabetes, may protect against cancer because it regulates activity of an enzyme that suppresses cell growth, according to Espinoza-Peralta.

“There is growing evidence that metformin brings more benefits to diabetic patients beyond glucose control,” he said.