Interrupting sitting time improves blood sugar control in people with type 2 diabetes

A new study published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]) suggests that a 'Sit Less' intervention ? breaking sitting with standing and light-intensity walking ? may be an alternative to structured exercise to promote blood sugar control in patients with type 2 diabetes, giving improved 24-hour glucose levels and improved insulin sensitivity.

The use of moderate to vigorous exercise is one of the cornerstones of prevention and treatment of type 2 diabetes, with current physical activity guidelines recommending a performance of at least 150 min per week of exercise at these intensities. Despite the proven effectiveness of such a regime, however, over 90% of the healthy population does not adhere to the guidelines. Non-compliance is likely to be even higher in those with type 2 diabetes, in which related comorbidities such as muscle weakness and peripheral neuropathy can be a barrier to physical exercise. An alternative approach is needed.

This study considered the possible benefits of a 'Sit Less' programme, replacing sitting time with standing and light-intensity walking, in comparison to the use of a conventional structured exercise regimen of the same energy expenditure. It was conducted by Bernard Duvivier, Department of Human Biology and Movement Science, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Netherlands, and colleagues.

The study involved 19 adults (13 men and 6 women) with type 2 diabetes, with a mean disease duration of 6 years, a mean HbA1c of 6.7% and a mean fasting plasma glucose of 7.88 mmol/l during screening. Their mean age was 63 years and the mean BMI was 30.5 kg/m2 (just within the definition of obese). A total of 14 participants were using glucose-lowering diabetes drugs and 13 were using lipid-lowering drugs (most often statins).

The participants followed three activity regimens - 'Sitting', 'Exercise' and 'Sit Less' - each lasting 4 days. During the sitting regimen participants were restricted to 1 hour/day of walking and 1 hour/day standing, with the remaining 14 hours spent sitting. During the exercise regimen approximately 1 hour/day of sitting time was replaced by supervised cycling on an ergometer at the research centre, in 20 minute bouts separated by 5 minutes rest. In the sit less regimen, 5 hours/day sitting were replaced by 2 hours walking and 3 hours standing, with participants encouraged to break up their sitting time every 30 minutes with small bouts of walking and standing throughout the day. The exercise and sit less regimens were designed to have comparable energy expenditure for each participant. The order of the regimens was randomised, and 10 days of usual lifestyle was maintained as a 'wash-out' period before and between regimens.

Diet was controlled with use of the participants' normal diet, supplemented during the last 36 hours of each regimen by the provision of pre-packed meals based on their energy requirements for each regimen. Glucose levels were measured continuously using a subcutaneous glucose monitor and also via the collection of blood glucose samples four times daily. The use of light-intensity walking was diarised and verified using advanced accelerometry (which monitors motion via multiple parameters). 24-hour glucose levels were analysed during the last 24 hours of each four-day regimen. On the day after each regimen, between 08.30 and 09.30 hours, after an overnight fast, blood was collected for glucose, insulin and lipid measurements.

The data were analysed to provide: 24 hour glucose concentration; incremental AUC for glucose (incremental area under the curve - a summary measure of glucose usage - the increase above fasting level over 24 hours); duration of hyperglycaemia; an average glucose concentration for each 30 minutes to indicate any bouts of hypoglycaemia; an estimate of insulin sensitivity; fasting triacylglycerol levels and non-esterified fatty acid (NEFA) levels.

The study found that the use of the sit less regimen led to significant improvements in insulin sensitivity, mean 24-hour glucose levels, 24-hour glucose excursions, durations of hyperglycaemia and fasting triacylglycerol levels, compared with sitting. Whilst positive effects for most variables (other than 24-hour glucose) were also found in the traditional exercise regimen, these were generally less potent than the improvements found for the sit less group. In addition, glucose level reductions, which can lead to hypoglycaemia and render some diabetic patients reluctant to perform structured exercise, were found to be less for the sit less regimen.

Previously it has been noted that a sedentary (inactive) lifestyle is associated with an increased risk of type 2 diabetes, and that regular interruption of sitting using small bouts of walking may be beneficial to insulin action and glucose control. This study, however, is the first to consider the effects of a sit less regimen for people with type 2 diabetes in free-living conditions. The outcome of the study fits the emerging picture that breaking up sedentary behaviour by light-intensity activities may be a potent way to help improve blood glucose control.

The authors suggest that sustained compliance with exercise programmes, especially by individuals with type 2 diabetes, is at best mediocre. Strategies to reduce sitting time are generally considered to be less demanding than structured exercise programmes and hence are more likely to have long-term compliance. The authors say that their findings "provide indications favouring the implementation of interventions targeting the breaking-up of sitting time over interventions involving structured exercise". As the volume of activities in this proof-of-concept study was high (an additional 2 hours walking and 3 hours standing during the sit less regimen in comparison to the other regimens), the authors suggest "that future long-term studies are needed to determine the volume of light-intensity activity that is feasible in daily life".

Diabetes drug, metformin, lowers risk of heart disease deaths better than sulfonylureas

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A new analysis of 204 studies involving more than 1.4 million people suggests that metformin, the most frequently prescribed stand-alone drug for type 2 diabetes, reduces the relative risk of a patient dying from heart disease by about 30 to 40 percent compared to its closest competitor drug, sulfonylurea.

The study, designed to assess the comparative -- not absolute or individual -- benefits and risks of more than a dozen FDA-approved drugs for lowering blood sugar in type 2 diabetes, is described in the April 19, 2016 issue of the Annals of Internal Medicine. Diabetes now affects almost 10 percent of the U.S. population and poses a growing public health threat, and most people will eventually need drug treatment, the researchers say.

"Metformin looks like a clear winner," says Nisa Maruthur, M.D., M.H.S., assistant professor of medicine at the Johns Hopkins University School of Medicine. "This is likely the biggest bit of evidence to guide treatment of type 2 diabetes for the next two to three years." 

Maruthur, the lead author on the meta-analysis, notes that cardiovascular fatalities -- heart attacks and strokes -- are major risks for people with uncontrolled blood sugar, but it has never been clear if one diabetes drug is better than another at lowering these fatalities. Other diabetes-related complications include blindness, kidney failure and limb amputations.

This review, Maruthur says, provides a much-needed update to two previous analyses, the last one published in 2011. Since then, researchers have published more than 100 new studies comparing the effectiveness of various blood sugar-lowering drugs, and several new drugs have also come on the market since the last report.

Of the total 204 studies analyzed, 50 spanned several continents, while others were conducted across Europe, Asia and the United States. Most of the studies were short term, with only 22 mostly observational studies lasting more than two years. Participants in the studies were generally overweight with uncontrolled blood sugar levels. Many studies excluded the elderly and those with significant health problems. Just shy of half of the studies made no mention of race or ethnicity. When researchers did report that information, only 10 to 30 percent of participants were nonwhite. 

Maruthur says the new analysis not only looked at cardiovascular disease but also other drug effects, including glucose control, and common side effects, such as weight gain, hypoglycemia and gastrointestinal problems. Because the majority of patients with type 2 diabetes end up using multiple blood sugar-lowering drugs, Maruthur and her team also evaluated how the drugs performed when used alone or in combination. While some of the various studies' participants were on insulin, this injectable drug was only evaluated when used in combination with other drugs. 

Among other findings, the new review revealed that DPP-4 inhibitors, a class of anti-diabetic drugs that were very new at the time of the 2011 review, were clearly less effective at lowering blood sugar levels compared to metformin and sulfonylureas.

In terms of side effects, a new class of drugs known as SGLT-2 inhibitors, which work by shuttling excess glucose out of the body through urine, caused yeast infections in 10 percent of users, a side effect unique to this drug, Maruthur says. However, SGLT-2 inhibitors, along with another drug class known as GLP-1 receptor agonists, helped patients lose weight. Sulfonylureas, on the other hand, caused weight gain and resulted in the highest rates of hypoglycemia, or too-low blood sugar, among the oral medications.

Cautioning that such meta-analyses can be limited because of differences in research protocols and measurements across studies, Maruthur and her colleagues took steps to ensure that only studies using similar methods were combined. Also, they excluded from their analysis any studies that included patients taking additional, nonstudy diabetes drugs. 

Overall, Maruthur says, the results indicate that metformin, which has been around since the late 1990s, works just as well, if not better, than sulfonylureas, which have been on the market since the late 1950s/1960s, and diabetes drugs that have appeared on the market more recently. She says the new findings are in line with the current recommendation that metformin be used as a first-line therapy. The real question arises, Maruthur says, when patients and doctors must choose a second drug to be used in combination with the metformin. 

"The medications all have different benefits and side effects, so the choice of second-line medications must be based on an individual patient's preferences," Maruthur says. 

Maruthur and her team's work will be published alongside the report they wrote for the Agency for Healthcare Research and Quality, the funding agency for the study, detailing the hundreds of studies included in Maruthur's analysis and an exhaustive summary. Both the American College of Physicians and the Veterans Association plan to use these publications to update their guidelines. 

The cost of diabetes drugs is a major consideration when prescribing. While metformin is available as a relatively cheap generic, many newer drugs carry a hefty price tag. In 2014, per-person spending was higher for diabetes drugs for any other class of traditional drugs, in part because over half the prescriptions filled for diabetes were for nongenerics.

Additional benefits of type 2 diabetes treatment found for non-alcoholic fatty liver disease patients

A type 2 diabetes treatment has been found to also have 'off-label' benefits for glucose control in the liver and in fatty cells known as adipose.1 Presented at The International Liver CongressTM 2016 in Barcelona, Spain, today, the study shows that exenatide, a treatment that targets the pancreas to improve glucose absorption, enhances glucose uptake and reduces insulin resistance in the liver and in adipose tissue.

Non-alcoholic fatty liver disease (NAFLD) is a condition in which fat builds up in the liver. In some cases this accumulation of fat can cause inflammation of the liver and eventually lead to permanent scarring (cirrhosis), which can seriously impair the liver's ability to function. NAFLD is closely associated with obesity and diabetes and the consequences of the condition can be grave, representing a major global public health problem.2 Two large European studies reported NAFLD prevalence rates of between approximately 43% and 70% in adults with type 2 diabetes.3

"There has been much discussion around the benefit of using injectable diabetes treatments, such as exenatide, on other tissues than the pancreas to improve glucose control," said Dr Amailia Gastaldelli, Institute of Clinical Physiology, CNR, Pisa, Italy, University of Texas Health Science Center, San Antonio, USA, and lead author of the study. "This is why we set out to evaluate the effects of exenatide on the liver and adipose tissue; to better understand the benefits this treatment could offer to a wider group of patients."

Male participants (n=15) with a fatty liver index score of >30 (a classification system that ranges from 0 to 100)4 were tested on two occasions. Those with a score <30 are deemed to have a negative likelihood of having fatty liver. Exenatide or placebo was injected 30 minutes before an oral glucose test in the double blinded study. The test measured glucose uptake in liver tissue and abdominal adipose tissue glucose uptake. 

The results showed that acute exenatide administration (5mcg) decreased glucose production and insulin resistance (p=0.02) in the liver tissue when blood sugars were low. The treatment also improved liver tissue uptake of glucose when it is eaten (p=0.039). Furthermore, exenatide decreased insulin resistance in fatty adipose tissue (p=0.009).

"This interesting study shows promising findings for the many people around the world who suffer from non-alcoholic fatty liver disease," says Professor Tom Hemming Karlsen, EASL Vice-Secretary. "The authors have succeeded in identifying an existing treatment that can improve liver metabolism, which is an important step forward for the hepatology community."

Controlling blood pressure, sugar, cholesterol linked to lower cardiovascular disease

While controlling blood pressure, blood sugar and LDL-cholesterol levels reduces the risk of cardiovascular disease in people with diabetes, only 7 percent of diabetic participants in three major heart studies had recommended levels of these three factors, according to research from the Heart Disease Prevention Program at the University of California, Irvine School of Medicine.

The findings illustrate the need for persons with diabetes to better manage their blood pressure, blood sugar and LDL-cholesterol levels, which are prime indicators of future cardiovascular disease. The diabetic participants surveyed in the UCI review were enrolled in the three heart studies between the late '80s and early 2000s, when treatment was not as good as it is now. Still, more recent data show that only 25 percent of Americans with diabetes achieve all three of these targets.

The good news is that those in the heart studies who did control all three factors had a 62 percent lower risk of developing cardiovascular disease, according to Nathan D. Wong, lead author of the UCI report, which appears online in Diabetes Care.

"But we have done a dismal job nationally at getting most of our patients with diabetes controlled for even just these three measures," said Wong, director of the Heart Disease Prevention Program and a cardiology professor at UCI.

"Since cardiovascular diseases - including coronary heart disease, stroke and heart failure - are leading causes of death for people with diabetes, these findings underscore the value of achieving target or lower levels of these modifiable risk factors," he added.

Wong and colleagues studied 2,018 adults (57 percent female) with diabetes mellitus but without known cardiovascular diseases who participated in the Atherosclerosis Risk in Communities Study, the Multi-Ethnic Study of Atherosclerosis or the Jackson Heart Study. Fifty-five percent were African American, 30 percent white, 11 percent Hispanic and 4 percent Asian/Pacific Islander.

The researchers compared measurements of the three key factors to American Diabetes Association guidelines that were in effect at the time - blood pressure under 130/80 mmHg, LDL (or bad) cholesterol less than 100 mg/dL and blood HbA1c (glycated hemoglobin) under 7 percent. Forty-one percent of the study group were on target in one of the three categories; 27 percent had achieved two of the benchmarks; but only 7 percent met the recommended scores in all three.

Study participants' control of individual and composite factors was also examined in relation to the occurrence of new cardiovascular events (including heart attacks, coronary deaths, strokes, heart failure, percutaneous interventions and bypass surgeries) over an average follow-up of 11 years.

Wong said that proper management of any one factor translated to a 36 percent lower risk, proper management of any two factors was linked to a 52 percent lower risk, and proper management of all three factors correlated to a 62 percent lower risk of cardiovascular events compared to those without any factors controlled.

Blood pressure management appeared to benefit African Americans and women more than other ethnic groups or men; however, the converse was true for LDL control.

"Our analysis of three large U.S. cohorts including persons in whom diabetes has been diagnosed shows those who were at target levels for HbA1c, blood pressure and LDL to have substantially lower risks for cardiovascular disease than persons with diabetes who were not at target levels for such factors," Wong said. "These findings emphasize the importance of composite control of these modifiable risk factors to better address the cardiovascular disease risks seen in persons with diabetes, the need for the development of healthcare strategies to better ensure such management, and the need for studies to evaluate and eliminate barriers to risk factor control in persons with diabetes."

New proteins discovered that link obesity-driven diabetes to cancer

For the first time, researchers have determined how bromodomain (BRD) proteins work in type 2 diabetes, which may lead to a better understanding of the link between adult-onset diabetes and certain cancers. 

The findings, which appear in PLOS ONE, show that reducing levels in pancreatic beta cells of individual BRDs, called BET proteins, previously shown to play a role in cancer, may also help patients who are obese and diabetic.

The research was led by Gerald V. Denis, PhD, associate professor of pharmacology and medicine at Boston University School of Medicine, who was the first to show that BET protein functions are important in cancer development. 

Adult-onset diabetes has been known for decades to increase the risk for specific cancers. The three main members of the BET protein family, BRD2, BRD3 and BRD4, are closely related to each other and often cooperate. However at times, they work independently and sometimes against each other. 

According to the researchers new small molecule BET inhibitors have been developed that block all three BET proteins in cancer cells, but they interfere with too many functions. 

"The BET proteins provide a new pathway to connect adult-onset diabetes with cancer, so properly targeting BET proteins may be helpful for both," explained Denis, who is the corresponding author of the study. 

He believes this discovery shows the need for deeper analysis of individual BET proteins in all human cell types, starting with boosting insulin and improving metabolism in the pancreas of adults who are obese. 

"Without better targeted drugs, some ongoing cancer clinical trials for BET inhibitors are premature. These new results offer useful insight into drug treatments that have failed so far to appreciate the complexities in the BET family."

CPAP may not improve glycemic control in people with diabetes

People with type 2 diabetes and obstructive sleep apnea (OSA) may not experience improved glycemic control by using continuous positive airway pressure, or CPAP, as some studies have suggested, according to the results of a randomized, controlled trial published online ahead of print in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

"Many studies have indicated that OSA may contribute towards the development and progression of type 2 diabetes," said lead study author Jonathan Shaw, MD, associate professor and head of population health at Melbourne's Baker IDI Heart and Diabetes Institute "However, proving that link, and determining if treating OSA could have benefits for glucose control, requires intervention studies. Some uncontrolled studies had reported improved glucose control after starting CPAP, but some small controlled trials did not support this." 

In "The Effect of Treatment of Obstructive Sleep Apnea on Glycemic Control in Type 2 Diabetes," researchers in Australia and the U.S. randomly assigned 298 patients with "relatively well-controlled" type 2 diabetes and newly diagnosed OSA to either treat their sleep apnea with CPAP or receive usual care. 

In addition to measuring the change in glycemic control, researchers studied changes in blood pressure, daytime sleepiness and quality of life over six months. Researchers found:

• No difference between those receiving CPAP and the control group in change in glycated hemoglobin (HbA1c) at three and six months. 
• Greater fall in diastolic blood pressure over six months in the CPAP group compared to controls -- a finding that was statistically significant only among those who used CPAP for at least four hours a night.
• Daytime sleepiness improved significantly among those using CPAP as measured by the Epworth Sleepiness Index.
• Quality of life between the two groups was not statistically significant overall as measured by the RAND 36-Item Short Form Health Survey. Among those using CPAP for at least four hours a night, there was a significant difference with controls on vitality and mental health subscores.

Authors offered several possible explanations for why participants using CPAP did not experience better glycemic control. OSA may play a bigger role in the development of diabetes than in the control of established diabetes. The bar for adherence to CPAP -- set at four hours a night -- may have been set too low. And, lastly, CPAP may only benefit those with severe OSA and/or poor glycemic control. Participants with those characteristics were not well represented in the study, the authors noted.

"OSA is common in people with type 2 diabetes, and although we did not find a glycemic benefit for its treatment, clinicians should have a high index of suspicion for its presence when patients experience daytime sleepiness, snoring and resistant hypertension," Dr. Shaw said. "Identification and treatment of OSA in these patients may lead to clinically meaningful benefits."

Anthocyanins in Strawberries Improve Insulin Resistance

A new study in Molecular Nutrition & Food Research found that anthocyanin-rich strawberries may improve insulin sensitivity.

Insulin resistance (IR) is a hallmark of metabolic syndrome and a risk factor for heart disease and type 2 diabetes. Typically, after a meal, the pancreas produces an appropriate amount of insulin to usher glucose from the bloodstream into the cells. People with IR have built up a tolerance to insulin, so the pancreas must churn out extra insulin to coax blood sugar into the cells. Over time, this process can lead to type 2 diabetes.

Researchers observed the effect of anthocyanins on the postprandial insulin response of 21 obese adults with insulin resistance. Subjects were served a typical ‘Western-style’ meal high in carbohydrates and fat plus a beverage that contained freeze-dried whole strawberry powder. The beverages were controlled for fiber, and the amount of strawberry powder ranged from 0 grams to 40 grams (equivalent to 3 cups of fresh strawberries). When subjects drank the most concentrated beverage, they didn’t produce as much insulin as when they drank the least concentrated versions. In other words, they didn’t need as much insulin to metabolize their meal after drinking the anthocyanin-rich strawberry shake.

While the exact mechanisms are unclear, strawberry anthocyanins may alter insulin signaling at a cellular level.

These results add to the collective evidence that consuming strawberries may help improve insulin action, says study author Britt Burton-Freeman, Ph.D.

Eunyoung Park, et al. A dose-response evaluation of freeze-dried strawberries independent of fiber content on metabolic indices in abdominally obese individuals with insulin-resistance in a randomized, single-blinded, diet-controlled crossover trial. Molecular Nutrition & Food Research, February 2016.

- See more at: http://www.strawberrynutritionnews.com/#sthash.ib0OehCn.dpuf

Combination injection improves glucose control for patients with type 2 diabetes

 A multinational clinical trial led by UT Southwestern Medical Center and others found that injection of a new long-acting insulin combined with another drug improves glucose control in patients with Type 2 diabetes and, additionally, is associated with weight loss.

The trial compared glucose control of participants receiving daily injections of either basal insulin glargine or IDegLira, which is a mixture of insulin degludec and liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist. Liraglutide stimulates cells in the pancreas to produce insulin. The study findings were published today in the Journal of the American Medical Association.

"Many patients who are on an oral agent and basal insulin are unfortunately not at goal glycemia. Treatment options for such patients are to either increase the basal insulin dose or to add additional shots of insulin at mealtimes. The downside of both of these approaches is weight gain and hypoglycemia (low blood sugar)," said the study's lead author, Dr. Ildiko Lingvay, Associate Professor of Internal Medicine and Clinical Sciences at UT Southwestern. In addition, taking multiple injections per day also increases the burden on the patient.

Currently, about two-third of patients with Type 2 diabetes who are treated with basal insulin are not in good glucose control, Dr. Lingvay said. 

"The clinical trial found that participants treated with the combination product had more improvement in their HbA1C (hemoglobin A1C) test than those treated with basal insulin alone, they had weight loss rather than weight gain, and they had many fewer episodes of hypoglycemia," she added.

The phase 3 trial, conducted from September 2013 to November 2014, enrolled 557 participants with uncontrolled Type 2 diabetes in 75 treatment centers located in 10 countries. At the time they enrolled, study participants were taking an oral diabetes medication, metformin, as well as basal insulin glargine. All remained on the oral medication. 

Participants were then randomly assigned to continue on insulin glargine - or to switch to daily injections of IDegLira. Those who were assigned to the insulin glargine group had their insulin dose sequentially increased as high as necessary to bring their glucose levels under control. For those taking IDegLira, dosage was also increased based on glucose readings, but there was a cap on the amount their dosage could be increased because of limits on liraglutide dosage. 

Participants who took the combination product saw their glucose levels drop faster. On average, the HbA1C blood sugar level for participants on IDegLira dropped from 8.4 to 6.6. On average, the HbA1C level for participants on insulin glargine dropped from 8.2 to 7.1. The HbA1C test indicates the average blood glucose level over a three-month period; participants with an HbA1C level below 7 are considered within normal range.

Those taking IDegLira lost an average of about 3 pounds compared with an average weight gain of nearly 4 pounds for the glargine group. Only 6.1 percent of participants on the combination product experienced confirmed episodes of nighttime hypoglycemia compared with 24.4 percent of the patients on the basal glargine. 

"The advantage of the combination product is that the treatment burden is the same as taking a basal insulin - one shot a day - but you are getting an additional product that works through a different mechanism and addresses different pathophysiologic defects of the disease. The liraglutide affects satiety and induces weight loss, while also stimulating insulin secretion. The combination product addresses more underlying abnormalities present in this disease," said Dr. Lingvay.

Insulin degludec, which was approved last fall by the Food and Drug Administration, is the longest-acting insulin currently available. 

"Patients on IDegLira did better overall, especially when factoring in weight loss and decreased hypoglycemia risk," said Dr. John Buse, Professor of Medicine at the University of North Carolina School of Medicine and senior author on the study.

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

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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."