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HHAL MEDICAL NEWS JULY 2012
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HHAL MEDICAL NEWS JULY 2012

Caloric Restriction Plus Physical Activity For Longevity


Fruit flies on dietary restriction (DR) need to be physically active in order to get the lifespan extending benefits that come from their Spartan diet. If the same axiom holds true in humans, those practicing caloric restriction in hopes of living longer need to make sure they eat enough to avoid fatigue. 

According to research at the Buck Institute, flies on DR shift their metabolism toward increasing fatty acid synthesis and breakdown, specifically in muscle tissue. "Dietary restriction is known to enhance spontaneous movement in a variety of species including primates, however this is the first examination of whether enhanced physical activity is necessary for its beneficial effects," said Buck faculty Pankaj Kapahi, PhD, who runs the lab where the research took place. "This study establishes a link between DR-mediated metabolic activity in muscle, increased movement and the benefits derived from restricting nutrients," he said, adding that flies on DR who could not move or had inhibited fat metabolism in their muscle did not exhibit an extended lifespan. "Our work argues that simply restricting nutrients without physical activity may not be beneficial in humans," said Kapahi. The research is published in the July 3, 2012 edition of Cell Metabolism. 

The research also points to a potential target that could yield a drug that mimics the beneficial effects of DR. Lead author, Subhash D. Katewa, PhD, Buck Institute staff scientist, said flies genetically engineered to overexpress the circulating peptide AKH (the fly equivalent of glucagon in mammals) showed increased fat metabolism, spontaneous activity and extended lifespan even though their diet was unrestricted. AKH plays a critical role in glucose and lipid metabolism. "Our data suggests that DR may induce changes in muscle similar to those observed under endurance exercise and that molecules like AKH could serve as potential mimetics for DR that enhance activity and healthspan," said Katewa. 

"A better understanding of the dynamics of fat metabolism is needed in order to clarify its role in aging and disease," Katewa said. "These current results suggest that enhanced fat metabolism could help slow aging and the onset of age-related disease."

http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=247351

 

Why Does Spinach Give Us Strength?

 

Spinach has long been associated with strength, but why the leafy vegetable makes us stronger has remained unknown until now. 

Researchers at the Karolinska Institute say that nitrate, found naturally in spinach and several other vegetables, significantly increases muscle strength.

In the study, the team placed nitrate directly into the drinking water of a group of mice for seven days and then compared their muscle strength to a control group. According to the researchers, the amount of nitrate given to the mice was roughly the equivalent to that which a human would obtain by consuming 200 to 300 grams of fresh spinach or 2 to 3 beetroots a day.

Spinach and beetroot are two of the main sources of nitrate, but it is also found in several other vegetables, such as chard and lettuce.

After 7 days, the researchers examined different muscles on the mice's legs and feet. They discovered that those given nitrate had significantly stronger muscles than mice in the control group. According to the researchers the greatest effect were observed in the extensor digitorum longus muscle, which extends down the tibia, and the flexor digitorum brevis muscle of the foot.


Nitrate, found naturally in spinach, significantly increases muscle strength, say researchers

Furthermore, the team found that the nitrate mice had higher concentrations of two different proteins, CASQ1 and DHPR, found naturally in the muscles. These proteins, which is assumed to explain the greater muscle strength, are used for storing and releasing calcium, which is essential for making muscles contract.

The researchers now want to conduct further studies in order to determine how their findings can be applied to individuals with muscle weakness.

Dr Andrés Hernández, researcher at the Department of Physiology and Pharmacology, explained:


"From a nutritional perspective our study is interesting because the amount of nitrate that affected muscle strength in mice was relatively low. Translated to humans it means that we can obtain the equivalent volume by eating more of a vegetarian diet, as nitrate is found naturally in several leafy vegetables, especially in beetroot juice, for example. There are currently no dietary supplements containing nitrate."

http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=247156

 

Larger Waist Sizes In Women Related To Increased Risk Of Infertility And Cancer

Nuffield Health, the UK's largest health charity, published an

article today showing that women with larger waist sizes are at

great risk of cancer, including breast cancer. They also have increased chance of infertility.

The data was compiled from nearly 55,000 women taking the Nuffield 'Health MOT', a series of tests that

takes about an hour and assesses overall fitness and health. Parameters included body mass index (BMI),

resting heart rate, cholesterol, aerobic fitness, blood pressure, and sugar levels. Patients also had an

opportunity to discuss health issues such as hydration, alcohol consumption, sleep quality and any existing

injuries. MOT is the UK abbreviation for the annual safety checks required to keep a vehicle on the road,

so the name is a play on that. Patients are given a score from 6-100. Presumably 0 would mean a person

was already deceased.

Those chosen for the analysis were the ones who said they aimed to improve their health. 57% had waist

lines considered to be in the highest category of risk for future illness, including infertility, breast, womb

and ovarian cancer, heart disease and type 2 diabetes. The average waistline was almost 5cm larger than

the healthy size recommended of 80cm. The women contrasted with the men whose sizes mainly fell within

the healthy band.

Fat stored around waistline was seen to cause a variety of complications for women, and was specifically

associated with disturbed ovarian function, irregular ovulation cycles and anovulation, all of which hinder

fertility, this is seen in other data where 50-60% of women with polycystic ovarian syndrome were found to

be abdominally obese. Furthermore, the chances of heart disease, liver disease and type 2 diabetes are

all increased by being overweight.

Adding to the fertility concerns was the younger age of women in the group, with 50% being between 26

and 46. Britain seems to be following the United States, with expanding waistlines and warnings of a major

future health issue on the brew. The pattern of public awareness is following that of tobacco in the 70s and

80s, but in the meantime, healthcare services are bracing for a tidal wave of obesity related chronic illness

that is set to put a major strain on healthcare providers. The situation is highlighted by a recent incidence

of a teenager in Wales, UK, that had to be cut out from her house, with the bedroom wall demolished, as

she'd become so fat, weighting in at over 400kg, nearly ½ a ton, that she couldn't exit her parents home

normally, and this occurred after she'd already received significant support to lose weight, including an

extended trip to a weight loss facility in the US.

The weight problem in the UK doesn't stop there. More than ½ of all women in the MOT tests had body

mass indexes higher than the healthy range of 18-25, and nearly one fifth were considered moderately or8/3/12 Medical News Today News Article - Printer Friendly

www.medicalnewstoday.com/printerfriendlynews.php?newsid=247106 2/3

morbidly obese. Waist-to-hip ratios have blown out into more of an apple shape at 0.83, where the classic

pear shape is considered a more natural and lower health risk

http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=247106

 

 

Metformin Makes Brain Cells Grow

The discovery is an important step toward therapies that aim to repair the brain not by introducing new stem cells but rather by spurring those that are already present into action, says the study's lead author Freda Miller of the University of Toronto-affiliated Hospital for Sick Children. The fact that it's a drug that is so widely used and so safe makes the news all that much better. 

Earlier work by Miller's team highlighted a pathway known as aPKC-CBP for its essential role in telling neural stem cells where and when to differentiate into mature neurons. As it happened, others had found before them that the same pathway is important for the metabolic effects of the drug metformin, but in liver cells.
 

"We put two and two together," Miller says. If metformin activates the CBP pathway in the liver, they thought, maybe it could also do that in neural stem cells of the brain to encourage brain repair.
 

The new evidence lends support to that promising idea in both mouse brains and human cells. Mice taking metformin not only showed an increase in the birth of new neurons, but they were also better able to learn the location of a hidden platform in a standard maze test of spatial learning.
 

While it remains to be seen whether the very popular diabetes drug might already be serving as a brain booster for those who are now taking it, there are already some early hints that it may have cognitive benefits for people with Alzheimer's disease. It had been thought those improvements were the result of better diabetes control, Miller says, but it now appears that metformin may improve Alzheimer's symptoms by enhancing brain repair.
 

Miller says they now hope to test whether metformin might help repair the brains of those who have suffered brain injury due to trauma or radiation therapies for cancer.

http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=247517

 

Muscle Power Boosted By Caffeine In The Elderly


A new study to be presented at the Society for Experimental Biology meeting on 30th June has shown that caffeine boosts power in older muscles, suggesting the stimulant could aid elderly people to maintain their strength, reducing the incidence of falls and injuries. 

For adults in their prime, caffeine helps muscles to produce more force. But as we age, our muscles naturally change and become weaker. 

Sports scientists at Coventry University looked for the first time at whether these age-related changes in muscle would alter the effect of caffeine. They found that caffeine continued to enhance muscle performance in two different muscles from mice, although it was less effective in older muscles. 

Jason Tallis, the study's primary author, said: "Despite a reduced effect in the elderly, caffeine may still provide performance-enhancing benefits." 

For adults in their prime, caffeine helps muscles to produce more force. But as we age, our muscles naturally change and become weaker. So, sports scientists at Coventry University looked for the first time at whether these age-related changes in muscle would alter the effect of caffeine. 

Caffeine's effect was smallest for juvenile muscles, suggesting caffeine may not have an enhancing effect in developing muscles. 

The decline in muscle strength that occurs as we age contributes to injuries and reduces quality of life. The process is not well understood, but it is clear that preserving muscle tone is key. 

Tallis said: "With the importance of maintaining a physically active lifestyle to preserve health and functional capacity, the performance-enhancing benefit of caffeine could prove beneficial in the aging population." 

The researchers isolated muscles from mice ranging in age from juvenile to elderly, then tested their performance before and after caffeine treatment. They looked at two different skeletal muscles, which are the muscles we can control voluntarily. The first was the diaphragm, a core muscle used for respiration; the second was a leg muscle called the extensor digitorum longus (EDL), used for locomotion.

http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=247239

 

Raisins Help Control Blood Sugar Levels


Consuming raisins three times per day may reduce postprandial (post-meal) sugar levels significantly, according to a new study.

The research, conducted by Harold Bays, MD, medical director and president of Louisville Metabolic and Atherosclerosis Center (L-MARC), was presented at the American Diabetes Association's 72nd Annual Scientific Session. 

The study involved 46 adults who had slight increases in glucose levels, but no previous diagnosis of diabetes mellitus. The researchers randomly assigned participants to two groups. The first group was told to snack on raisins three times per day for 12 weeks, while the second group snacked on pre-packaged commercial snacks that did not contain raisins or other fruits or vegetables.

The researchers found that raisins considerably reduced mean post-meal glucose levels by 16% and reduced mean hemoglobin A1c by 0.12% from baseline. Pre-packaged commercial snacks on the other hand, did not significantly reduce mean post-meal glucose or hemoglobin A1c.

Dr. Bays explained:


"Compared to the snacking control group, the group consuming raisins had a significant statistical reduction in their after-liquid meal blood sugar levels among study participants who had mean baseline fasting glucose levels between 90 and 100 mg/dl. 

This favorable glucose effect of raisins was further supported by the statistically significant reduction in hemoglobin A1c (a standard test for overall blood sugar control in diabetes mellitus) in the within group comparison to baseline. The within group comparisons from baseline with snacks did not demonstrate a reduction in hemoglobin A1c."

http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=247222

 

Meta-Analysis: Cranberries Offer Protection Against UTIs

Cranberry intake appears to lower the risk for urinary tract infections, according to a meta-analysis in the Archives of Internal Medicine.

In 13 randomized controlled trials comprising some 1600 participants, those consuming cranberry products showed a roughly 30% lower rate of urinary tract infection than controls. The effect was most notable in women with recurrent infections (relative risk, 0.53), female populations (0.49), and children (0.33). The authors urge "great caution" in interpreting their analysis, given the heterogeneity found among study designs.

Long used as a folk preventive for urinary tract infections, cranberries were thought to exert their protective effect through urinary tract acidification. That notion, the authors write, was disproved a half century ago. Current explanations include cranberries' effect on limiting the ability of bacteria to attach to uroepithelial cells.

Archives of Internal Medicine article

 

Glucose Deprivation Activates Feedback Loop That Kills Cancer Cells


Compared to normal cells, cancer cells have a prodigious appetite for glucose, the result of a shift in cell metabolism known as aerobic glycolysis or the "Warburg effect." Researchers focusing on this effect as a possible target for cancer therapies have examined how biochemical signals present in cancer cells regulate the altered metabolic state. 

Now, in a unique study, a UCLA research team led by Thomas Graeber, a professor of molecular and medical pharmacology, has investigated the reverse aspect: how the metabolism of glucose affects the biochemical signals present in cancer cells. 

In research published in the journal Molecular Systems Biology, Graeber and his colleagues demonstrate that glucose starvation - that is, depriving cancer cells of glucose - activates a metabolic and signaling amplification loop that leads to cancer cell death as a result of the toxic accumulation of reactive oxygen species, the cell-damaging molecules and ions targeted by antioxidants like vitamin C. 

The research, which involved UCLA scientists from the Crump Institute for Molecular Imaging, the Institute for Molecular Medicine, the California NanoSystems Institute, the Jonsson Comprehensive Cancer Center, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, and the Department of Pathology and Laboratory Medicine, demonstrates the power of systems biology in uncovering relationships between metabolism and signaling at the network level. 

"Most strikingly, our discovery that glucose withdrawal causes both cell death and increased tyrosine phosphorylation is intriguing because increased tyrosine kinase signaling is normally associated with cell growth," said Nicholas A. Graham, a senior postdoctoral scholar in Graeber's lab who helped design the project. 

To explain the seemingly contradictory result that glucose deprivation reduced viability and at the same time increased signaling, the authors used an unbiased systems-biology approach that included phospho-tyrosine mass spectrometry and other biochemical profiling techniques. 

Assessing the "crosstalk" between metabolism and signaling, they discovered that the glucose deprivation activates a positive feedback loop whereby the withdrawal of glucose induces increased levels of reactive oxygen species, which in turn inhibit negative regulators of tyrosine signaling. The resulting supra-physiological levels of tyrosine phosphorylation then generate additional reactive oxygen species. 

"Because cancer cells live on the edge of what is metabolically feasible, this amplifying cycle of oxidative stress ultimately overwhelms and kills the cancer cell," Graeber explained. "These findings illustrate the delicate balance that exists between metabolism and signaling in the maintenance of cancer cell homeostasis." 

In addition, the authors showed the possibility of exploiting this positive feedback loop for therapeutic intervention. Combining short-term glucose deprivation with an inhibitor of tyrosine phosphatases, they demonstrated synergistic cell death in a cancer cell line. 

"Understanding the links between metabolism and signaling will empower new therapeutic approaches toward inducing this metabolic catastrophe," Graham said. "This study provides a framework for rational design of combinatorial therapeutics targeting both metabolism and signaling in cancer." 

The findings by Graeber and his colleagues add to the emerging concept of systems integration between oncogenic signaling networks and the metabolism of malignant tumors. The work lays a foundation for future studies delineating how signaling and metabolism are linked, with the ultimate goal of refining therapeutic strategies targeting cancer metabolism.

http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=247124

 

Shingles Vaccine Seems Safe for Patients with Immune-Related Diseases

Patients vaccinated against herpes zoster while under treatment for immune-related diseases do not face increased hazards for herpes zoster, a JAMA study suggests. Current guidelines consider vaccination contraindicated in such patients while on immunosuppressive drugs.

The retrospective cohort study comprised over 450,000 Medicare patients with immune-related diagnoses such as rheumatoid arthritis and inflammatory bowel disease. Roughly 20,000 received the vaccine — over 600 of whom were on immunosuppressive treatment around the time of vaccination. The investigators found no increase in risk for herpes zoster among vaccinated patients, even those vaccinated during treatment.

Writing in Journal Watch Infectious Diseases, Dr. Richard Ellison comments that the results "suggest both a benefit from the vaccine and relatively low risk."

JAMA article 

High Doses of Vitamin D Linked to Modestly Reduced Fracture Risk

High doses of vitamin D were associated with reduced fracture risk in older adults in a meta-analysis in the New England Journal of Medicine. This follows a rash of recent vitamin D studies with inconsistent findings.

Researchers analyzed data from 11 studies comprising some 31,000 people aged 65 and older who were randomized to oral vitamin D supplements or placebo. Among participants in the highest actual-intake quartile (792 to 2000 IU daily), there was a 30% reduction in hip fracture incidence, relative to controls. In addition, the highest intake conferred a 14% risk reduction for any nonvertebral fracture. There were no significant reductions in fracture risk at lower intakes.

An editorialist concludes: "It would appear to be prudent ... to ensure an intake at the upper end of the range at which [the authors] found a reduction in fracture risk."

NEJM article 

http://www.nejm.org/doi/full/10.1056/NEJMoa1109617?query=TOC#t=articleResults

 

People Gain an Average of 10 Pounds 1 Year After Quitting Smoking

One year after quitting smoking, people have gained an average of 10 lb, according to a meta-analysis in BMJ.

Researchers analyzed 62 randomized trials that measured weight gain following smoking cessation. Regardless of the cessation treatment used, all groups gained about 2 lb per month for the first 3 months. Then, weight gain slowed until 1 year, at which point people had gained an average of 9 to 11 lb. However, there was a large variation in weight change — about 16% of participants lost weight, while about 13% gained more than 22 lb.

Editorialists caution that the results may not be generalizable to all smokers because these participants volunteered for cessation clinics. They conclude: "Although obesity is positively associated with an increased risk of all cause mortality, cohort studies indicate that modest weight gain does not increase the risk of death; smoking does."

BMJ article

Moderate Alcohol Consumption Linked to Reduced Risk for Rheumatoid Arthritis in Women

Long-term, moderate alcohol consumption is associated with reduced risk for rheumatoid arthritis, according to a prospective cohort study in BMJ.

Some 34,000 Swedish women reported on their alcohol consumption in 1987 and 1997 and then were followed from 2003 through 2009 (when they were roughly 54 to 89 years old). During follow-up, some 200 participants developed RA. After adjustment for smoking status, those who consumed more than three drinks a week in both 1987 and 1997 had about half the risk for RA as those who did not drink.

As a potential mechanism, the authors note that alcohol downregulates immune responses. They point out, however, that they could not make conclusions about heavy alcohol use, as just 1% of the women consumed more than two drinks a day.

BMJ article 

 

Epigenetic Cause Of Osteoarthritis Discovered

In what could be a breakthrough in the practical application of epigenetic science, U.K. scientists used human tissue samples to discover that those with osteoarthritis have a signature epigenetic change (DNA methylation) responsible for switching on and off a gene that produces a destructive enzyme called MMP13. This enzyme is known to play a role in the destruction of joint cartilage, making MMP13 and the epigenetic changes that lead to its increased levels, prime targets for osteoarthritis drug development. In addition to offering a new epigenetic path toward a cure for osteoarthritis, this research also helps show how epigenetic changes play a role in diseases outside of cancer. This finding was recently published online in the FASEB Journal. 

"As the population gets older, osteoarthritis presents increasing social and economic problems," said David A. Young, Ph.D., a researcher involved in the work from the Musculoskeletal Research Group at the Institute of Cellular Medicine at Newcastle University in Newcastle upon Tyne in the United Kingdom. "Our work provides a better understanding of the events that cause cartilage damage during osteoarthritis and provides hope that tailored drug development to prevent the progress of disease will improve the quality of life and mobility of many arthritis sufferers."
 

To make the discovery, Young and colleagues compared the extent to which DNA methylation was different in cartilage from patients suffering from osteoarthritis and healthy people of similar age. They found that at one small position, the gene for MMP13 had less DNA methylation in diseased patients. Then they confirmed that reduced methylation of this gene increases levels of the destructive enzyme MMP13.
 

"We've already seen how epigenetics has advanced our approach to cancer. Now we're seeing it with other diseases and even exercise." said Gerald Weissmann, M.D., Editor-in-Chief of the
 FASEB Journal. "This study not only lays the groundwork for a new understanding of osteoarthritis, but also shows that the old 'either/or' nature v. nurture argument is outdated: epigenetics teaches us that nature (the daily wear and tear of joints) regulates nurture (the genes in our cartilage) to cause arthritis."

http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=247572

Why Does A Diet High In DHA Improve Memory?

In a study published in the journal Applied Physiology, Nutrition, and Metabolism, researchers at the University of Alberta say they have discovered a potential explanation for why a diet high in DHA, an omega-3 fatty acid found in fish, improves memory.

In an animal study, lead researcher Yves Sauve and colleagues discovered mice that consumed a diet high in DHA had 30% higher levels of DHA in the hippocampus region of the brain, compared with mice fed on a regular, healthy diet. 

Sauve, a researcher in the Faculty of Medicine & Dentistry, who works in the department of physiology, the department of ophthalmology and the Center of Neuroscience, explained:


"We wanted to find out how fish intakes improves memory. What we discovered is that memory cells in the hippocampus could communicate better with each other and better relay messages when DHA levels in that region of the brain were higher. This could explain why memory improves on a high-DHA diet."



The researchers confirmed that when DHA is added to a diet, additional stores of DHA are deposited in the brain. Sauve explains that consuming more fish or taking supplements could prevent DHA levels decreasing in the brain as we age. 

In an earlier study, Sauve found that consuming DHA stops a toxic molecule at the back of the eye that causes age-related vision loss from accumulating.

DHA stands for Docosahexaenoic acid - it is an omega-3 fatty acid that is a main structural component of the retina, sperm, testicles, and human brain cerebral cortex.

Cold-water oceanic fish oils are rich in DHA. DHA can also be manufactured commercially from microalgae.

The following foods are rich in DHA:

·         Algae

·         Anchovies

·         Bluefin or Albacore Tuna

·         Breast milk (also infant formula milk)

·         Caviar or Fish Roe

·         Herring

·         Salmon

·         Sardines

·         Swordfish

http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=247456

 

The Search for the Perfect Diet Continues

A Swedish study suggests that the long-term cardiovascular consequences of a low-carb, high-protein diet are negative.

Short-term, rapid weight loss has made Atkins-type, low-carbohydrate, high-protein diets popular, but concerns about the long-term effects of these diets continue to mount. In a large, population-based sample of 43,396 Swedish women aged 30 to 49 who completed a dietary questionnaire, investigators assessed the impact of low carbohydrate intake, high protein intake, or both on cardiovascular outcomes during an average follow-up of 15.7 years.

Each 10% decrease in carbohydrate intake (20 g — a small roll — per day), each 10% increase in protein intake (5 g — one boiled egg — per day), or each 2-unit increase in low-carbohydrate/high-protein score (scale: 2–20, with 20 representing very low carbohydrate and very high protein intake) was associated with a significant 4%–5% increase in the risk for cardiovascular events. In absolute terms, this represents an additional eight or nine cardiovascular events per 10,000 patient-years in women with low-carbohydrate/high-protein scores of 16 or more, as compared with those with scores of 6 or less.

Lagiou P et al. Low carbohydrate-high protein diet and incidence of cardiovascular diseases in Swedish women: Prospective cohort study. BMJ 2012

·     Original article (Subscription may be required)

·     Medline abstract (Free)

Moderate Alcohol Consumption Is Associated with Lower Risk for Rheumatoid Arthritis

In a prospective study, risk was 40% to 50% lower in older women who weren't teetotalers.

Alcohol consumption lowers production of proinflammatory molecules, and an inverse relation between alcohol consumption and risk for rheumatoid arthritis (RA) has been observed previously in case-control studies. To test this association prospectively, researchers conducted a population-based cohort study of more than 34,000 Swedish women (age,  39 in 1987). Participants provided data on alcohol consumption in 1987 and 1997.

During follow-up from 2003 until 2009, 197 new cases of RA were identified. The multivariable adjusted relative risk for RA during follow-up was 37% lower in women who drank >4 glasses of alcohol (1 glass = 15 g of ethanol) weekly in 1997 than in women who drank <1 glass of alcohol weekly. Similarly, adjusted risk for RA was 52% lower in women who drank >3 glasses of alcohol weekly in both 1987 and 1997 than in never drinkers.

Comment: This prospective study affirms that moderate alcohol consumption is associated with lower risk for rheumatoid arthritis in women. The investigators note that their results are consistent with the known inverse relation between alcohol consumption and coronary heart disease risk (JW Gen Med Mar 15 2011) and "add to the evidence that moderate alcohol consumption is not harmful and can be protective against" chronic disease.

Original article (Subscription may be required)

Medline abstract (Free)

 

New Position Statement for Managing Type 2 Diabetes

A one-size-fits-all approach is rejected.

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) have published a new position statement entitled, "Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach." The document outlines basic elements of lifestyle modification, oral agents, noninsulin injectable agents, and insulin, and provides management tips that even experienced clinicians might find helpful. Two aspects of the report are particularly noteworthy:

 

·         Acknowledging "mounting concerns about . . . potential adverse effects [of drug therapies] and new uncertainties regarding the benefits of intensive glycemic control on macrovascular complications," the authors emphasize a patient-centered approach with individualized targets for glycemic control. For example, they recommend more-stringent control (e.g., glycosylated hemoglobin [HbA1c] target, <7%) for motivated patients with new-onset diabetes and long life expectancies, and less-stringent control (e.g., HbA1c goal, 8% or even higher) for less-motivated patients with longstanding diabetes, limited life expectancies, and high risk for adverse outcomes from hypoglycemia.

·         Because the authors reject a one-size-fits-all approach, they make this important statement: "Utilizing the percentage of diabetic patients who are achieving an HbA1c <7% as a quality indicator, as promulgated by various health care organizations, is inconsistent with the emphasis on individualization of treatment goals."

Original article 

Medline abstract (Free)

 

High intake of vitamin E cuts risk of liver cancer in study
Vitamin E intake from diet and supplements significantly reduced the likelihood of developing liver cancer in patients ages 40 to 70, a Chinese study found. Researchers said the link between vitamin E intake and liver cancer seemed stronger in women and was consistent in patients with and without liver disease or a family history of liver cancer. The findings appear on the website of the Journal of the National Cancer Institute. MedPage Today

 

http://www.medpagetoday.com/Gastroenterology/GeneralHepatology/33789

 

 

Don't worry if you take longer to recover from your workout
This study found that late heart rate recovery after treadmill exercise stress adds prognostic value for all-cause mortality to a multivariable model including early, one-minute heart rate recovery. The American Journal of Cardiology

 

Heparin use -- Think twice for percutaneous coronary intervention
This study concluded that therapeutic warfarin treatment seems to provide sufficient anticoagulation for percutaneous coronary intervention and additional heparins are not needed and may increase access site complications. The American Journal of Cardiology 

 

Obesity alone does not raise mortality risk, study finds
A study in The Journal of American Board of Family Medicine found excess body weight was not associated with increased mortality risk in obese adults aged 18 to 90. However, severely obese participants with diabetes or hypertension were 1.26 times more likely to die than their normal-weight counterparts, University of California, Davis, researchers said. International Business Times (7/8), Daily News (New York)/Indo-Asian News Service

 

Less sitting is linked to a longer life expectancy
Reducing the amount of time sitting to less than three hours per day could extend a person's life expectancy by up to two years, according to an analysis of five previous studies and data from the National Health and Nutrition Examination Survey. Researchers also found that limiting the amount of time watching TV to less than two hours a day would boost a person's life expectancy by an additional 1.38 years. The findings appeared online in BMJ Open. Google/The Press Association (U.K.)

 

Omega-6 is linked to lower risk of coronary heart disease
U.K. researchers assessed the fatty-acid levels of 7,354 patients and found that those with the highest levels of omega-6 polyunsaturated fatty acids in their blood were less prone to coronary heart disease than were those with the lowest concentrations. They also found a significant but not strong association between coronary heart disease risk and high levels of saturated fatty acids. The findings of the nested case-control study appear in the journal PLoS Medicine. MedPage Today

 

n–3 Fatty Acids and Cardiovascular Outcomes in Patients with Dysglycemia

 

CONCLUSIONS

Daily supplementation with 1 g of n–3 fatty acids did not reduce the rate of cardiovascular events in patients at high risk for cardiovascular events. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number,

http://www.nejm.org/doi/full/10.1056/NEJMoa1203859?query=TOC#t=articleResults

 

Natural History of Subclinical Hypothyroidism in Older Adults

Some people revert back to euthyroid status.

Somwaru LL et al. 1962

 

 

New Lipid Biomarkers of Little Use in Predicting Cardiovascular Risk

A pooled analysis provides no justification for routinely adding any new tests to current lipid panels.

During the past decade, a myriad of new lipid biomarkers have been purported to correlate better than traditional lipid measures with cardiovascular risk. To assess the value of these novel biomarkers for routine use in risk prediction, investigators pooled data from 37 cohorts including more than 165,000 individuals with a median follow-up of 10 years.

The combination of apolipoprotein B (apoB) and apolipoprotein A-I (apoA-I), lipoprotein(a) (Lp[a]), and lipoprotein-associated phospholipase A2 (Lp-PLA2) all performed worse than total cholesterol and HDL at predicting cardiovascular risk, and adding the newer markers to conventional risk factors improved risk prediction only slightly. By the authors' estimate, 13,622 of every 100,000 adults aged 40 or older would be classified at intermediate risk by conventional risk factors alone; the addition of combined apoB and apoA-I, Lp(a), or Lp-PLA2 would reclassify 1.1%, 4.1%, and 2.7%, respectively, to high risk. The estimated numbers requiring screening to prevent one cardiovascular event over 10 years were about 4500 for combined apoB and apoA-I, 800 for Lp(a), and 1000 for Lp-PLA2.

The Emerging Risk Factors Collaboration. Lipid-related markers and cardiovascular disease prediction.JAMA 2012 Jun 20; 307:2499.

Medline abstract (Free)

 

 

Prostatectomy vs. Observation for Prostate Cancer: PIVOT

Prostatectomy did not lower 10-year mortality overall; the exception was men with PSA levels >10 ng/mL.

CONCLUSIONS

Among men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up. Absolute differences were less than 3 percentage points. (Funded by the Department of Veterans Affairs Cooperative Studies Program and others; PIVOT ClinicalTrials.gov number, NCT00007644.)

http://www.nejm.org/doi/full/10.1056/NEJMoa1113162?query=TOC#t=articleResults

Wilt TJ et al. N Engl J Med 2012 Jul 19; 367:203

 

Must We Stop Prophylactic Aspirin in Patients Who Develop Peptic Ulcers?

Proton-pump inhibitors usually heal aspirin-associated ulcers, even if aspirin is continued.

Liu C-P et al. Am J Gastroenterol 2012 Jul 107:1022

 

Rhythm vs. Rate Control in Older Atrial Fibrillation Patients

Rhythm control might be superior in the long term.

 Ionescu-Ittu R et al. Arch Intern Med 2012 Jul 9; 172:997

 

Weight Changes Vary After Smoking Cessation

At 12 months, about half of smoking abstainers gained >5 kg, but 16% of abstainers lost weight.

Aubin H-J et al. BMJ 2012 Jul 10; 345:e4439

 

Effect on Resting Energy Expenditure of Three Maintenance Diets

A low-carbohydrate diet, even if higher in fat, produced the best results.

 Ebbeling CB et al. JAMA 2012 Jun 27; 307:2627

 

Metformin for Antipsychotic-Induced Adverse Effects in Women with Schizophrenia

The medication reversed amenorrhea, promoted weight loss, and improved insulin resistance.

Wu R-R et al. Am J Psychiatry 2012 Jun 15;

 

Testing Strategies to Rule Out Acute Coronary Syndromes: Which Is Most Efficient?

Compared with standard evaluation, early CCTA shortened hospital stay but increased subsequent testing and radiation exposure with no reduction in overall cost of care.

CONCLUSIONS

In patients in the emergency department with symptoms suggestive of acute coronary syndromes, incorporating CCTA into a triage strategy improved the efficiency of clinical decision making, as compared with a standard evaluation in the emergency department, but it resulted in an increase in downstream testing and radiation exposure with no decrease in the overall costs of care. (Funded by the National Heart, Lung, and Blood Institute; ROMICAT-II ClinicalTrials.gov number, NCT01084239.)

http://www.nejm.org/doi/full/10.1056/NEJMoa1201161?query=TOC#t=articleResults

Hoffmann U et al. N Engl J Med 2012 Jul 26; 367:299

Redberg RF. N Engl J Med 2012 Jul 26; 367:375

 

 

USPSTF: Don't Screen Asymptomatic, Low-Risk Adults for Coronary Disease with ECG

Asymptomatic, low-risk adults should not be screened for coronary heart disease with resting or exercise ECG, according to a statement from the U.S. Preventive Services Task Force in theAnnals of Internal Medicine. Evidence was insufficient to recommend for or against screening in higher-risk patients.

ECG testing doesn't offer improved risk stratification over conventional risk factors such as obesity, hypertension, and lipodystrophy among those at low risk, the USPSTF concluded. For all risk categories, ECG screening could lead to unnecessary procedures and overtreatment.

The group points to the Framingham calculator as a reasonable tool for stratifying risk.

USPSTF statement in Annals of Internal Medicine 

Framingham risk calculator

 

Estimating Rates of Metastatic Prostate Cancer in the Absence of PSA Screening

In the absence of PSA screening for prostate cancer, the number of men presenting with metastatic disease annually would triple, according to an estimate published in Cancer.

Using federal cancer registry data, researchers compared rates of men presenting with metastatic disease in the pre-PSA era (starting in 1983) with recent clinical experience. They found that the benefit of reducing metastatic disease at presentation as a result of PSA screening increased with age.

They estimate that the absence of PSA screening (as recommended by the U.S. Preventive Services Task Force) would lead to an additional 17,000 cases of metastatic disease in the U.S. each year.

Cancer article

 

 

FDA Approves Three New Treatments

The FDA approved new treatments for several conditions last week, including:

·         Chronic obstructive pulmonary disease: Aclidinium bromide (marketed as Tudorza Pressair) is a new long-acting antimuscarinic agent, given twice daily as a dry powder inhaler, for the long-term maintenance treatment of bronchospasm in COPD patients.

·         Severe hypertriglyceridemia: A new omega-3 pill containing icosapent ethyl (Vascepa) may be used in addition to dietary changes to reduce triglycerides in adults whose levels reach 500 mg/dL or greater.

·         Advanced breast cancer: Everolimus (Afinitor), previously approved for advanced renal cancer and other conditions, is now indicated for use with exemestane to treat postmenopausal women with hormone receptor–positive, HER2-negative breast cancer whose illness has recurred or progressed after receiving letrozole or anastrozole.

COPD drug news release (Free)

Hypertriglyceridemia drug news release (Free)

Breast cancer drug news release (Free)

 

Meta-Analysis: ACE Inhibitors Associated with Lower Pneumonia Risk

Angiotensin-converting–enzyme inhibitors may offer some protection against pneumonia, according to a BMJ meta-analysis. An editorialist isn't so sure.

Researchers looked at almost 40 studies — including cohort studies, case-control studies, and randomized trials — that reported pneumonia outcomes after use of ACE inhibitors, angiotensin-receptor blockers, and control treatments. The data revealed that ACE inhibitors conferred a roughly 30% decrease in risk for pneumonia, when compared with ARBs or control treatments. The effect was particularly pronounced in Asian patients.

The authors speculate that the cough often associated with ACE inhibitors may actually play a part in the protective effect by clearing respiratory tract secretions.

An editorialist finds it "difficult to agree" with the authors' enthusiasm. She calls for more studies "before we advise patients to put up with their cough because it may prevent them from getting pneumonia."

BMJ article (Free PDF)

 

Vitamin D Supplementation Prevents Fractures

A meta-analysis suggests benefit at a dose of >800 IU daily, but factors relating to treatment adherence could have biased the results

Clinical trials have not consistently confirmed that vitamin D supplementation in older adults prevents fractures. To reconcile conflicting data, researchers pooled participant-level data from 11 randomized controlled trials of vitamin D supplementation that involved 31,000 older people (age,  65).

In intent-to-treat analyses, vitamin D supplementation lowered risks for hip fracture (hazard ratio, 0.90; P=0.07) and any nonvertebral fracture (HR, 0.93; P=0.03), but these reductions were not significant (for statistical reasons, a P-value of 0.0125 was considered significant). However, the researchers conducted additional analyses that incorporated treatment adherence and supplement use outside the trial: Participants in the highest quartile of daily vitamin D intake (median, 800 IU; range, 792–2000) did have significantly lower risks for both hip fracture (HR, 0.70) and any nonvertebral fracture (HR, 0.86), compared with controls. In contrast, participants in the lowest three quartiles did not benefit from vitamin D supplementation. Some trials also involved calcium supplementation, but the vitamin D findings were independent of additional calcium intake. Vertebral fractures were not documented consistently in these trials.

Medline abstract (Free)

Heaney RP. Vitamin D — Baseline status and effective dose. N Engl J Med 2012 Jul 5; 367:77. (http://dx.doi.org/10.1056/NEJMe1206858)

Medline abstract

 

FDA: Zofran May Lead to Abnormal Heart Rhythm

The FDA is alerting clinicians that a single 32-mg intravenous dose of ondansetron (Zofran and generics) may lead to QT interval prolongation, which in turn may put patients at risk for torsades de pointes.

In response, the manufacturer is removing the 32-mg dose from the drug's label. The drug, a 5-HT3 receptor antagonist that prevents nausea and vomiting associated with chemotherapy, may still be used at the lower intravenous dose — 0.15 mg/kg given every 4 hours for three doses. No dose should exceed 16 mg.

The following patients may be at particularly high risk for QT prolongation: those with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those taking concomitant medications that prolong the QT interval. Before ondansetron is administered, electrolyte abnormalities, such as hypokalemia or hypomagnesemia, should be corrected.

Dosing for oral ondansetron remains the same.

FDA MedWatch safety alert

 

 

Outcomes of Evaluation for Visible Hematuria

At a referral clinic, 18% of patients had bladder cancer; no cause was found in half the patients.

Mishriki SF et al. J Urol 2012 May 187:1561

 

 

What Can Adenosine Tell Us About Neurocardiogenic Syncope?

 

Adenosine plasma levels and A2A adenosine receptor expression seem to correlate with different responses to different provocation tests.

Deharo J-C et al. Heart 2012 Jun 98:855

 

 

 

Metformin Makes Brain Cells Grow
http://mnt.to/l/476p

 

Alzheimer's Patients Benefit From Nutrient Mix
http://mnt.to/l/477W

 

Alzheimer's Treatment Halts Symptoms For 3 Years
http://mnt.to/l/47jb

 

How Are Alzheimer's Disease And Diabetes Linked?
http://mnt.to/l/47kg

 

Risk Of Developing Rheumatoid Arthritis May Be Reduced In Women By Moderate Drinking
http://mnt.to/l/47h6

Four Drinks A Week May Keep Rheumatoid Arthritis Away
http://mnt.to/l/47bF

Postmenopause Moderate Alcohol Consumption May Help Prevent Bone Loss
http://mnt.to/l/47bf

 

Mammography Screening Shows Limited Effect On Breast Cancer Mortality In Sweden
http://mnt.to/l/47hW

 

Risk Of Cholesterol-Related Cardiovascular Diseases Is Not Lowered By Vitamin D Supplements
http://mnt.to/l/47k8

 

Increased Risk For Diabetes When Obesity And Low Vitamin D Are Present
http://mnt.to/l/47j4

 

New Therapeutic Target For The Management Of Diabetes
http://mnt.to/l/47j3

 

How Exercise Improves Heart Function In Diabetics: Study
http://mnt.to/l/47gB

 

Healthy Fatty Acid Levels Return When Weight Normalizes In Girls With Eating Disorders
http://mnt.to/l/47h9

 

Sexual Dysfunction May Be A Tip-off To Heart Disease In Diabetic Men
http://mnt.to/l/47mx

 

Exploring The Healing Powers Of Singing
http://mnt.to/l/47cz

What Is Atherosclerosis? What Causes Atherosclerosis?
http://mnt.to/l/47dV

 

Molecule Discovered That May Prevent Atherosclerosis
http://mnt.to/l/47cw

 

Effective Weight Loss - Keep A Food Journal, Don't Skip Meals, Don't Eat Out
http://mnt.to/l/47dX

 

 

 

Dopamine-Releasing Nerve Cells Crucial To The Formation Of Both Punished And Rewarded Memories
http://mnt.to/l/47jD

 

Cutting Salt Could Reduce Stomach Cancer
http://mnt.to/l/47nw

 

The Ancients Knew A Thing Or Two About Plants' Healing Qualities
http://mnt.to/l/47js

 

How We Can Innovate Our Way Out Of A Double Crisis - Hunger And Obesity
http://mnt.to/l/47nD

 

New Measure For Obesity: A Body Shape Index Strongly Correlated To Premature Death
http://mnt.to/l/47jy

 

Why Do Some People Exercise And Others Don't?
http://mnt.to/l/47gM

 

Localized Prostate Cancer: Removal No Better Than Observation, Study
http://mnt.to/l/47n9

 

The Presence Of Oxidants Early In Life May Help Determine Life Span
http://mnt.to/l/47kw

 

Study Examines How Muscles Are Paralyzed While We Sleep
http://mnt.to/l/47pj

Brain Maps Created During Study Of Aging Reveal That Alzheimer's Patients Drive Differently
http://mnt.to/l/47fL

Gait Changes May Signal Cognitive Decline, Presage Alzheimer's
http://mnt.to/l/47fr

Alzheimer's Early Timeline Of Changes Identified By Scientists
http://mnt.to/l/47cT

Anxiety Linked To Accelerated Aging
http://mnt.to/l/47cZ

Accelerated Aging, Anxiety And Shortened Telomeres Linked
http://mnt.to/l/47bZ

LRP4 Protein Important For Communication Between Brain And Muscle Cells
http://mnt.to/l/47ft

 

Coronary Heart Disease More Likely Indicated By Measuring HDL Particles As Opposed To HDL Cholesterol
http://mnt.to/l/47c3

 

 

 

 

 

 

Discovery That Bees Can Reverse Brain Aging Has Implications For Alzheimer's Disease
http://mnt.to/l/474Q

 

Epigenetic Cause Of Osteoarthritis Discovered
http://mnt.to/l/477w

 

Discovery Of Epigenetic Links In Cell-Fate Decisions Of Adult Stem Cells Could Pave Way Toward Treatments For Bone Diseases Like Osteoporosis
http://mnt.to/l/478d

Vitamin D Supplementation Effective In Fracture Risk Reduction In Older Adults
http://mnt.to/l/476y

 

Why Do Cancer Rates Increase As We Age?
http://mnt.to/l/476S

A Single Cancer Cell Can Produce Up To 5 Daughter Cells
http://mnt.to/l/476t

Good Cholesterol Levels Increased By Algae Extract
http://mnt.to/l/477p

Sunburn Is Consequence Of RNA Damage To Skin Cells
http://mnt.to/l/477M

The Key (Proteins) To Self-Renewing Skin
http://mnt.to/l/476x

Risk Of Bladder Cancer May Increase With Some Diabetes Drugs
http://mnt.to/l/4744

Glycemic Index Varies From One Type Of Rice To Another With Most Varieties Scoring A Low To Medium GI
http://mnt.to/l/478t

Drinking Coffee: More Good Than Harm?
http://mnt.to/l/477K

American Diet Fuelling Heart Disease And Diabetes Rates In Southeast Asia
http://mnt.to/l/476N

Why Does A Diet High In DHA Improve Memory?
http://mnt.to/l/4758

How A Protein Meal Lets Your Brain Know You're Full
http://mnt.to/l/476r

Discovery Of Mechanism That Controls Obesity, Atherosclerosis And Potentially Cancer
http://mnt.to/l/475H

 

Molecular Link Identified Between Metabolic Diseases And Cancer
http://mnt.to/l/474w

A More Realistic Indicator Of Health Expectancy
http://mnt.to/l/474C

The Secret To Longevity? High Levels Of Brain-Protecting Protein Are Unique In The Naked Mole Rat
http://mnt.to/l/473p

Fighting Alzheimer's Disease With Exercise
http://mnt.to/l/46WM

Neuronal Stress And Brain Insulin Resistance Linked To Worsening Alzheimer's Disease
http://mnt.to/l/46Wp

Glucose Deprivation Activates Feedback Loop That Kills Cancer Cells
http://mnt.to/l/46Wn

Coffee In Moderation May Benefit Heart Slightly
http://mnt.to/l/46W4

Depressive Symptoms Alleviated With Vitamin D Deficiency Treatment
http://mnt.to/l/46Zs

 

In Some Postmenopausal Women, Low Vitamin D Levels Linked To Weight Gain
http://mnt.to/l/46TT

Women With Depression May Benefit From Vitamin D
http://mnt.to/l/46VB

How To Have Healthy Skin
http://mnt.to/l/46Ys

The Most Successful Strategy For Diabetes Is Early, Intensive Treatment
http://mnt.to/l/46Yt

Second Line Diabetes Drug Linagliptin Effective
http://mnt.to/l/46Zn


Raisins Help Control Blood Sugar Levels
http://mnt.to/l/46Yn

 

Prediabetic Men Can Boost Testosterone Levels With Weight Loss
http://mnt.to/l/46WT

Sitagliptin Improves Reactive Hypoglycemia Symptoms
http://mnt.to/l/46Vd

 

Diabetics' Use Of Aspirin May Not Be Effective For Preventing Blood Clots That Cause Heart Attacks And Strokes
http://mnt.to/l/46V6

 

Symptoms Of Metabolic Syndrome Improved By Testosterone-Replacement Therapy
http://mnt.to/l/46VC

 

Muscle Power Boosted By Caffeine In The Elderly
http://mnt.to/l/46YJ

 

Larger Waist Sizes In Women Related To Increased Risk Of Infertility And Cancer
http://mnt.to/l/46VZ

Gastric Emptying Rate May Be Key To Preventing Obesity
http://mnt.to/l/46Vp

Why Does Spinach Give Us Strength?
http://mnt.to/l/46X2

Potential Link Between Long-Term Calcium, Vitamin D Supplement Use And Increased Risk Of Kidney Stones
http://mnt.to/l/46Wf

Caloric Restriction Plus Physical Activity For Longevity
http://mnt.to/l/472Z

 

Evidence Behind Healthy Eating Advice
http://mnt.to/l/46ZB

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