http://www.medscape.com/viewarticle/832424

Healthy Lifestyle Cuts Risk of MI by 86% in Swedish Cohort Study

Michael O'Riordan

September 26, 2014

 

STOCKHOLM, SWEDEN — A healthy diet, moderate alcohol consumption, a smaller waist circumference, and not smoking were each independently associated with a lower risk of MI in a large cohort of healthy Swedish men[1].

When these four lifestyle behaviors were combined with physical activity, individuals who adhered to all five healthy practices had an 86% lower risk of MI when compared with a high-risk group of individuals who didn't adhere to any to healthy behaviors. When compared with the rest of the study cohort, which included individuals who practiced some but not all of the healthy lifestyle behaviors, the risk of MI was reduced 79% compared with those who adhered to all five.

"The benefit of combined diet, lifestyle, and healthy body weight may prevent up to approximately four of five cases of MI in this healthy study population," write Dr Agneta Åkesson (Karolinska Institutet, Stockholm, Sweden) and colleagues in the September 30, 2014 issue of the  Journal of the American College of Cardiology. "A decrease in risks with increasing adherence to the low-risk behaviors was also observed in men with hypertension and high cholesterol."

Overall, just 1% of the 20 721 men adopted all five of what the researchers referred to as "low-risk behaviors." While the number is dismal, the researchers say that these lifestyle behaviors are modifiable and that previous studies have shown that adopting components of such a healthy lifestyle can reduce the incidence of coronary heart disease.

"It is, however, also clear that extensive prevention can be achieved only through inhibiting the initiation and establishment of any high-risk behavior," write Åkesson et al. "Preferably, also to control healthcare expenditures, prevention should focus on ensuring that ideal low-risk behaviors are introduced early and continued throughout life."

Diet Neither Extreme Nor Exceptional

In the study, men aged 45 to 79 years old filled out a questionnaire that included approximately 350 items related to diet and lifestyle factors. A "low-risk" diet was defined on the basis of a recommended food score adopted by the National Health and Nutrition Examination Survey (NHANES). Moderate alcohol consumption was defined as 10 to 30 g/day, while a low-risk physical-activity behavior was defined as at least 40 minutes of walking or cycling per day. Finally, a waist circumference less than 95 cm was defined as healthy.

After 11 years of follow-up, individuals who combined a low-risk diet, one that included fruits, vegetables, reduced-fat dairy, whole grains, and fish, with moderate alcohol consumption had a 35% lower risk of MI compared with a high-risk group of individuals who adhered to none of the healthy lifestyle behaviors. A healthy diet, moderate alcohol consumption, and not smoking were associated with a 64% lower risk of MI. Adding physical activity to the model reduced the risk of MI by 76%, while all five healthy behaviors, including low abdominal adiposity, reduced the risk by 86%.

In an editorial[2], Dr Dariush Mozaffarian(Tufts University, Boston, MA) notes that simply eating the healthy diet was associated with a 20% lower risk of MI. The diet, he said, was "neither extreme nor exceptional, but reasonable and consistent with dietary guidelines." Also, the dietary evidence showed that the benefit was attributed to eating healthier foods rather than a lower intake of unhealthy food, such as red and processed meat, fried potatoes, and sweets, among other items.

Not adhering to the healthy diet and drinking alcohol more excessively accounted for nearly one in four MIs in the study population, while the combined absence of three healthy behaviors—diet, alcohol, and not smoking—explained nearly half of the MIs.

"These findings highlight the primacy of healthy lifestyle," writes Mozaffarian. "For both individual patients and populations, lifestyle goals should not be formulated solely for control of weight or blood pressure, cholesterol, and glucose levels. Although lifestyle has major benefits on these physiological factors, a healthier diet, greater activity, and nonsmoking influence numerous other pathways of risk and produce substantial additional benefits for cardiovascular and noncardiovascular health."

The authors have reported they have no conflicts of interest. Mozaffarian has received royalties from UpToDate; is on the advisory board of Unilever North America; is a consultant for Foodminds, Nutrition Impact, Amarin, AstraZeneca, and Life Sciences Research Organization; and has received honoraria from Quaker Oats, Pollock Institute, and Bunge.

Sclerostin Linked with Reduce short-term Mortality Risk in Dialysis Patients

Among 673 incident dialysis patients enrolled in a prospective cohort study in the Netherlands, those with the highest levels of circulating sclerostin had a 71% and 61% decreased risk for cardiovascular death and all-cause mortality, respectively, within 18 months compared to those with the lowest levels of the glycoprotein. The findings are published in Nephrology Dialysis Transplantation. Sclerostin is secreted by osteocytes and inhibits bone formation. While recent research suggests that sclerostin may play a role in uremic and non-uremic cardiovascular calcification processes, additional studies are needed to reveal the mechanisms involved.

Soda giants agree to cut calories consumed by 20 percent by 2025.

News that soft drink giants Coke, Pepsi and Dr Pepper Snapple Group agreed Tuesday to work to reduce the calories Americans get in their beverages by 20 percent over the next decade received wide coverage, with many major newspapers and news agencies offering their respective takes. Several media outlets note some experts weren’t impressed with the move, pointing out that Americans have already begun scaling back on soda consumption. Others note that the move is an implicit acknowledgment of the role of the soda industry in rising obesity rates across the country. The New York Times(9/24, Strom, Subscription Publication) reports that the commitment, made Tuesday at the 10th annual Clinton Global Initiative in New York, “was an acknowledgment by the companies of the role their products play in the country’s obesity crisis and the escalating rates of diabetes and heart disease that accompany it.” The paper notes the companies agreed to “expand the presence of low- and no-calorie drinks, as well as drinks sold in smaller portions,” and also make efforts to inform consumers “and encourage them to reduce the calories they are drinking.” Still, the paper notes, health advocates “generally dismissed the Tuesday announcement as little more than another example of the industry’s marketing prowess.”

        USA Today (9/23, Horovitz, Today) clarifies that the pledge does not cut “the actual calories in a 12-ounce can of conventional soda, which is about 150 calories.” Instead, the paper notes, the soda companies agreed “to take specific actions to reduce soft drink calorie consumption – like selling smaller portion sizes and increasing promotion of products such as bottled water.” The paper provides details of the agreement, noting that the companies “jointly pledged to provide calorie counts and promote calorie awareness on the vending machines, fountain dispensers and retail coolers that they control nationwide.”

        In an analytical piece, the Wall Street Journal (9/24, Esterl, Subscription Publication) notes that the industry’s move effectively recognizes the role of sugary drinks in the country’s obesity issues.

        The Washington Post (9/23) quotes Susan K. Neely, president and chief executive of the American Beverage Association, the industry trade group, “This is the single-largest voluntary effort by an industry to help fight obesity and leverages our companies’ greatest strengths in marketing, innovation and distribution.”

        But the AP (9/24, Choi) reports that the commitment to reduce the calorie consumption “follows the way customers’ tastes are already changing: People have been moving away from soda on their own for several years.” The news was also covered Reuters (9/24, Athavaley), the Christian Science Monitor (9/23), TIME (9/23) and New York Daily News (9/24).

FIFA expected to approve new rule to mitigate risk of concussions.

The New York Times (9/24, Borden, Subscription Publication) reports that FIFA is “expected to confirm a new policy” in the coming days that will “allow referees to stop games for up to three minutes so that an injured player can be examined by a team doctor.” At issue is the threat of concussions, which “became even more inflamed” last summer during the World Cup final after “several players appeared to sustain serious injuries only to continue playing.” In a statement FIFA said, “The incidents at the World Cup have shown that the role of team doctors needs to be reinforced in order to ensure the correct management of potential cases of concussion.” Bloomberg News (9/24, Duff) and TIME (9/24, Stampler) also report on this story.

AMA releases fact sheet to help physicians comply with new hydrocodone regs.

Medical News Inc. (9/24) reports that on Sept. 18, the American Medical Association “released a new fact sheet...to assist physicians in complying with new federal regulations on prescribing hydrocodone and help avoid disruptions in patient care.” A new “rule, effective October 6, 2014, reschedules hydrocodone combination products (HCPs) into Controlled Substance Schedule II.” In a statement, AMA president Robert M. Wah, MD, said, “This new fact sheet explains how new regulatory changes impact both physicians and pharmacists, which will help ensure patients continue having access to the care they need under the new federal rule.” The fact sheet can be seen here. For more information, please visit AMA Wire.

US T2D rates appear to be slowing.

The Wall Street Journal (9/24, A3, McKay, Subscription Publication) reports that, according to a study published Sept. 24 in the Journal of the American Medical Association and conducted by researchers from the US Centers for Disease Control and Prevention, US type 2 diabetes (T2D) rates appear to be plateauing. For the study, researchers analyzed data from the National Health Interview Survey covering some 655,000 adult patients.

        USA Today (9/24, Painter) reports the study found that “8.3% of adults had been diagnosed with diabetes as of 2012.” However, “the rates at which new cases are accumulating and overall counts are climbing have slowed in recent years.” Study co-author Ann Albright, director of the CDC’s division of diabetes translation, said, “It gives us hope,” adding, “It’s important that we begin to slow down this runaway train.”

        The Los Angeles Times (9/24, Healy) reports that the CDC researchers “said the plateau may be a downstream effect of another positive trend: a stabilization of obesity rates in the U.S. first seen in 2003 and 2004.” But, diabetes “continues to spread among African Americans and Latinos,” and “among Americans ages 20 to 44 and those with a high school education or less.”

        Bloomberg News (9/24, Pettypiece) points out that in 2010, the CDC “estimated that one in three adult Americans would have diabetes by 2050 as the population ages and there are more minorities at high risk for the disease.” Now, “the slowdown in new cases may mean the epidemic can be avoided, said...Albright.” Also covering the story are Reuters (9/24, Seaman), TIME (9/24, Oaklander), HealthDay (9/24, Thompson) and Medscape (9/24, Tucker).

Greater Body Mass Index May Increase Risk of Gout

A systematic review and meta-analysis of 10 prospective studies found each 5-unit increment in BMI was associated with a 55% increased relative risk of gout. The study included a total of 27,944 cases among 215,739 participants. Compared to individuals who had a BMI of 20 kg/m², those with a BMI of 25, 30, 35, and 40 kg/m² had a 1.8-, 2.7-, 3.6-, and 4.6-times increased relative risk of gout. The findings are published in the European Journal of Nutrition.

FDA Advisory Panel Urges Restrictions on Testosterone Use

http://www.medscape.com/viewarticle/831897

Miriam E. Tucker

September 18, 2014

 

A combined US Food and Drug Administration (FDA) advisory panel has voted nearly unanimously to change the labeling for testosterone-replacement products, with the aim of tamping down on their current widespread use for "age-related" hypogonadism. The panel also indicated that large studies are needed to demonstrate both clinical benefit and safety of the products.

The votes of the joint Bone, Reproductive, and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee were 20 to 1 in favor of label changes, and the panel voted as follows for these respective outcomes:

• Not requiring a safety study (1 vote).

• Requiring a safety study only for certain indications (16 votes).

• Requiring a safety study regardless of indication (4 votes).

Testosterone products have 2 current indications. The first — for replacement of testosterone in men with congenital or acquired primary hypogonadism, including conditions such as cryptorchidism, Klinefelter's syndrome, or testicular damage from chemotherapy or heavy metals — was not in dispute.

The panel primarily addressed the second indication, currently worded as "Hypogonadotropic hypogonadism (congenital or acquired): Idiopathic gonadotropin or luteinizing-hormone–releasing (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation."

The "idiopathic" wording has led to the widespread use of testosterone products for men with relatively low testosterone levels related to aging as well as for men with signs and symptoms of "low T" but who in reality have either normal testosterone levels or, in many cases, do not even have testosterone levels tested.

"Benefit is unclear in men diagnosed with hypogonadism due to no apparent cause other than older age. Yet testosterone is being predominantly prescribed to men 40 to 64 years of age. This has prompted the FDA to question whether labeling accurately reflects the appropriate indicated population," Hylton V. Joffe, MD, director of the Division of Bone, Reproductive, and Urologic Products at the FDA, told the panel in his introductory remarks.

Call for Much Tighter Wording of Second Indication 

The 2010 publication of a study showing a signal of cardiovascular risk among 209 men aged 65 and older taking testosterone-replacement therapy prompted the FDA's initial investigation into this area, and  more recently published studies suggesting both cardiovascular risk and possible protection prompted further inspection, Dr. Joffe said.

An FDA analysis of national sales data found that use of testosterone therapy rose 65% from 2009 to 2013 in the United States, and the number of prescriptions rose from 1.3 million in 2010 to 2.3 million by 2013. Men aged 40 to 64 accounted for 70% of those prescribed testosterone products and were the group in whom usage rose the most during the 5-year period, FDA epidemiologist Mohamed A. Mohamoud, PharmD, told the panel.

Data also show that only about half of men taking testosterone therapy had been diagnosed with hypogonadism. Furthermore, there was no evidence in 25% of users to show they had had their testosterone concentrations tested prior to initiating therapy, and 21% of those prescribed testosterone replacement had not had their levels tested at any time while they were on the therapy, Dr. Mohamoud said.

Brian Tran, PharmD, an FDA regulatory reviewer, also noted that direct-to-consumer advertisements claiming benefits such as improved quality of life and sexual performance with testosterone products have prompted warning letters from the agency.

A few panel members advised restricting the indication to primary hypogonadism alone, while others said that the second indication should be tightened, by removing the "idiopathic" and including recommendations in the label for confirming the diagnosis of low testosterone and for monitoring throughout treatment, along with more information about cardiovascular safety.

Several said the labeling should include the Endocrine Society's 2010 diagnostic guidelines, which call for symptoms and signs consistent with hypogonadism and "unequivocally low" serum testosterone of less than 300 ng/mL, measured in the morning, and confirmed by a second test.

Panel member Marc Garnick, MD, clinical professor of medicine at Beth Israel Deaconess Medical Center, division of oncology, Boston, Massachusetts, said, "The aging male andropause patient is an appropriate population for consideration, but the criteria must be much more precise."

He said the label should call for "appropriately valued" low testosterone levels, along with documentation of symptoms such as erectile dysfunction, loss of libido, and/or diminution of bone-mineral density, as well as a detailed cardiovascular history, baseline ECG, and routine measurements of quality of life in order to determine when the product should be stopped for lack of efficacy.

"I believe the Madison Avenue catch-all of 'Low T' has some validity, but it has been totally misused and misrepresented," Dr. Garnick commented.

Trials Needed for Cardiovascular Safety

Regarding the safety question, Tobias Gerhard, PhD, from the Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, said: "The evidence regarding cardiovascular safety is obviously very insufficient. We need more data. At this point, I don't think there's evidence for a clear causal association, but I believe we do have a signal of reasonable strength."

Given the magnitude of off-label use "and lack of strong data on effectiveness in this population, I think it's important to include something about cardiovascular safety in the label. Maybe not to the level of black box, but certainly that there are serious concerns that have not yet been adequately addressed," he added.

Several panelists said that a large, randomized clinical trial would be needed to determine whether or not the cardiovascular signal was real, noting that men with low testosterone are already at increased cardiovascular risk. Others felt that an observational trial would allow for the collection of more end points.

Toby C. Chai, MD, professor and vice chair of the department of urology at Yale University School of Medicine, New Haven, Connecticut, said, "For a population it was not originally intended to be used [in]…if we want to look at reality we have to do safety studies....Whether it should be randomized or observational, I think we'll be prospectively looking at those cardiovascular risks."

In a statement provided to Medscape Medical News, Androgel manufacturer Abbvie said, "Testosterone-replacement therapy is an important men's health topic. AbbVie is committed to our patients, and we will work with the FDA during its review."

FDA advisory panel members are vetted for conflicts of interest and waivers granted for participation if necessary. For this hearing, Dr. Garnick was granted a waiver after disclosing that he holds stock valued between $25,001 and $50,000 in one of the affected companies.

Cooled Dialysate May Protect Patients from Brain Damage

Hemodialysis drives progressive white matter brain injury due to blood pressure instability; however, patients in a recent study who dialyzed at 0.5°C below body temperature were completely protected against such white matter changes. Investigators randomized 73 new dialysis patients to dialyze with body temperature dialysate or dialysate cooled to 0.5°C below body temperature for 1 year. The findings are published in JASN. Previous research has shown that conventional dialysis can cause significant circulatory stress that damages multiple organs.

The A-Z on latest understanding about diet. Right here in 30 mins flat.

http://www.medpagetoday.com/PrimaryCare/DietNutrition/47745

Welcome to another edition of the MedPage Today Tweet of the Week! Every Friday, the editorial team highlights its favorite 140-character contribution from the healthcare twittersphere.

This week's winner is ... Isabel Schmidt, a personal trainer and nutritional adviser from Urban Energy Fitness! She shared this video of three physicians debating which kinds of eating habits and diets are the most beneficial, and why.

Interesting discussion about diet 

http://t.co/GNz4m30IpW

Artificial Sweeteners Linked to Glucose Intolerance

http://www.medscape.com/viewarticle/831873

The artificial sweeteners aspartame, sucralose, and saccharin cause blood glucose abnormalities in mice and some humans, a team reports in an article published online September 17 in Nature. The changes in glucose tolerance seem to be driven by the microbiome and can be reproduced in germ-free mice by giving them gut microbes from a person who has consumed the sweeteners.

"We found that artificial sweeteners may drive...an exaggerated elevation in blood glucose levels, the very same condition that we often aim to prevent by consuming them," Eran Elinav, MD, PhD, from the Department of Immunology at the Weizmann Institute of Science, Rehovot, Israel, said at a press briefing.

The investigators began with experiments in mice, giving each animal 1 of 3 artificial sweeteners in its water: aspartame, sucralose, or saccharin. Because commercial preparations of these sweeteners also contain some glucose, researchers used glucose, fructose, or plain water for the control mice to ensure it was the artificial sweetener and not any added sugar that was responsible for the effect. "To our surprise, we found they all induced a blood sugar disturbance even compared to mice who drank sugary water," Dr. Elinav said. This effect occurred on both a normal diet of rat chow (P < .001) and a high-fat diet in which 60% of calories came from fat (P < .03).

Because these artificial sweeteners are not digested or absorbed by the human body, the investigators hypothesized that gut microbes were responsible for the results. They administered antibiotics to the mice: 1 group received ciprofloxacin and metronidazole, a broad-spectrum approach focusing on gram-negative bacteria, and another group received vancomycin, aimed against gram-positive bacteria. Both treatments, when given for 4 weeks, eliminated the differences in glucose tolerance between sweetener-fed mice and controls.

The symptoms could also be triggered by a microbial transplant. Microbes from mice who had been drinking saccharin were transplanted via feces into germ-free mice and caused the recipients to show impaired glucose tolerance, whereas microbes from mice who had been drinking glucose did not (P < .03). Further, to show that the microbes were responsible, and not some other component of the feces, the researchers cultured bacteria from mice who were not eating sweeteners and added saccharin to the growth media. These bacteria were then transplanted into germ-free mice, resulting in impaired glucose tolerance compared with mice that received a control culture (P < .002).

Bacterial Profiles

The researchers performed both 16S sequencing, to identify the bacteria that were over- or underrepresented in mice with impaired glucose tolerance, and metagenomic sequencing, to identify what those bacteria are doing. In the microbial ecosystems from mice that ate artificial sweeteners, the pathways that were overrepresented included several that had previously been linked to diabetes and glucose intolerance. Glycan degradation, for example, occurs when microbes digest certain chains of sugars and create short-chain fatty acids that the body can use for energy, providing extra calories. The investigators confirmed that the sweetener-fed mice had increased amounts of this end product, the short chain fatty acids, in their guts.

In Humans

Artificial sweeteners caused changes in glucose tolerance in humans, as well, but only for some participants the investigators consider to be "responders." A group of 7 healthy volunteers who do not normally consume artificial sweeteners were given saccharin for 6 days at a dose that met the US Food and Drug Administration's maximum acceptable daily intake of saccharin for humans. No participants saw improvements in glucose tolerance, but 4 showed impairment.

Even before the experiment began, the microbial ecosystems from the 4 responders were different from those of the 3 nonresponders, suggesting their microbiome was somehow more susceptible. These results, said Dr. Elinav, "point to the personalized nature of our food responses and the need to understand this personalized effect in order to fight the metabolic syndrome, which as we all know, is one of the most common and serious epidemics in all history."

Bacteria from responders, sampled at the end of the trial, were able to induce glucose intolerance when introduced into germ-free mice (P < .02), whereas baseline samples from the responders (taken before they had consumed the artificial sweeteners) did not have this effect, nor did bacteria from the nonresponders.

Trend Seen With Long-Term Consumption

A further experiment involving 381 nondiabetic participants showed that long-term consumption of artificial sweeteners was associated with measures of central obesity and glucose intolerance, even when corrected for body mass index.

The authors caution that the results from the human experiments are not yet enough to make recommendations about whether or not people should consume sweeteners. They also point out that the mechanism for the sweeteners' effect is unknown: it may be causing less desirable bacteria to thrive, or it may be poisoning certain normal bacteria, allowing detrimental species to take their place.

In an accompanying editorial, Taylor Feehley, BA, and Cathryn Nagler, PhD, both from the Department of Pathology at the University of Chicago, note that "Whether the bacterial populations or metabolic pathways altered by the consumption of [artificial sweeteners] are similar to those described in people with or developing diabetes remains to be seen."

The authors have disclosed no relevant financial relationships.

Nature. Published online September 17, 2014. Abstract

-------------------------

Major newspapers, wire sources, and Internet consumer health outlets cover a study suggesting that the use of artificial sweeteners may interfere with how the body metabolizes sugar and in some individuals may even alter bacteria in the gut.

        USA Today (9/18, Weintraub) reports that according to a study published online Sept. 17 in the journal Nature, “reaching for artificial sweeteners to avoid sugar may be trading one evil for another.” Researchers from the Weizmann Institute of Science in Israel posit that “differences in gut microbes may explain why some people can handle artificial sweeteners just fine while in an unknown percentage of others the sweeteners lead to diabetes.”

        The Wall Street Journal (9/18, A6, Naik, Subscription Publication) reports that in work with mice and then with people, researchers examined the effects of sucralose, aspartame and saccharin on the gut microbiota and on levels of blood glucose.

        The Washington Post (9/18, Dennis) reports that mice fed the artificial sweeteners experienced “increased risk of glucose intolerance, a condition that can lead to diabetes.” Researchers then “monitored what happened to seven human volunteers who did not typically use artificial sweeteners but were given regular doses of saccharin over the course of a week.” Four volunteers went on to develop “significant glucose intolerance.” The Post also notes that “the American Medical Association and the American Diabetes Association have cautiously backed the use of non-caloric sugar substitutes as a way to fight obesity and diabetes, saying that the products can be part of a healthy diet as long as the calories saved aren’t replaced by consuming more food over the course of a day.”

        The Los Angeles Times (9/18, Netburn) “Science Now” blog reports “genetic analysis” also “revealed that the composition of the gut bacteria in mice had indeed changed after exposure to the artificial sweetener – some types of bacteria became more abundant, while others shrank.” The researchers also “said a computer algorithm looked at the gut microbes of the seven people and clustered them into two groups,” one group with people “affected by the artificial sweeteners, and the other group” with people who seemed to be unaffected by them.

        The New York Times (9/18, Chang) “Well” blog reports that the latter finding “suggests that any effects of artificial sweeteners are not universal.” In addition, it “suggests probiotics – medicines consisting of live bacteria – could be used to shift gut bacteria to a population that reversed the glucose intolerance.”

        According to the AP (9/18, Ritter), the study “authors said they are not recommending any changes in how people use artificial sweeteners based on their study.” Instead, they, along with “outside experts, said more study is needed, while industry groups called the research limited and said other evidence shows sweeteners are safe and useful for weight control.” The Food and Drug Administration, in a statement, “said the sweeteners ‘have been thoroughly studied and have a reasonable certainty of no harm to consumers.’”

        Also covering the study are the NBC News (9/18, Fox) website, Reuters (9/18, Kelland), Nature (9/18, Abbott), TIME (9/18, Park), HealthDay (9/18, Thompson) and Medscape (9/18, Skwarecki).

Improved Fitness May Delay Blood Pressure Increases as Men Age

Systolic blood pressure increases with age, but men with higher fitness levels experience abnormal systolic blood pressure (>120 mm Hg) later than those with low fitness levels. The finding comes from a study of 13,953 men 20–90 years of age who were initially free of hypertension, cardiovascular disease, and cancer and were followed over a 36-year period (1970–2006). The Journal of the American College of Cardiologystudy also found that men in the higher fitness category had lower body mass index scores, percent of body fat, and cholesterol, compared to men who were less fit.

Insulin Pumps: Safer than Injections?

Compared to multiple daily insulin injections, use of insulin pumps resulted in a 29% reduction in all-cause mortality and a 43% reduction in the risk of fatal cardiovascular disease in a study of 18,000 patients with type 1 diabetes. When considering just coronary heart disease, pump use was associated with an 18% reduced risk. The studyincluded 2441 Swedish patients using insulin pumps and 15,727 patients using multiple daily insulin injections who were followed for an average of almost 7 years. It was presented at the annual meeting of the European Association for the Study of Diabetes in Vienna, Austria.

Studies: Extensive Walking Combats Effects of Fructose

The New York Times reported that two new studies indicate that “walking at least 12,000 steps a day effectively wiped out all of the disagreeable changes wrought” by consuming 75 grams of fructose in two sodas per day. The second of these studies published this month in The European Journal of Clinical Nutrition, “focused on blood-sugar responses to fructose and activity, and found equally striking changes among the young people when they didn’t move much. Two weeks of extra fructose left them with clear signs of incipient insulin resistance, which is typically the first step toward Type 2 diabetes.” The earlier study in May showed that “after two weeks of fructose loading and relative inactivity, these young, healthy volunteers displayed a notable shift in their cholesterol and health profiles. There was a significant increase in their blood concentrations of dangerous very-low-density lipoproteins, and a soaring 116-percent increase in markers of bodily inflammation.”

Benzodiazepines associated with increased risk for Alzheimer’s.

The Los Angeles Times (9/10, Healy) reports that according to a study published online Sept. 9 in the BMJ, “older people who have relied on a class of drugs called benzodiazepines to reduce anxiety or induce sleep are at higher risk of going on to develop Alzheimer’s disease...with those whose use of the medications is most intensive almost twice as likely to develop the mind-robbing disorder.” For the study, researchers “compared the pattern of benzodiazepine use in 1,796 people elderly people diagnosed with Alzheimer’s with that of 7,184 similar people who had no such diagnosis.” The medications “specifically considered by the researchers were the short-acting anti-anxiety medications alprazolam (Xanax), lorazepam (Ativan), oxazepam (Seresta) and diazepam (Valium), and the longer-acting anti-seizure and ‘hypnotic’ drugs frequently used to treat insomnia: clonazepam (Klonopin), flurazepam (Dalmane), midazolam (Versed), nitrazepam (Mogadon), temazepam (Restoril) and triazolam (Halcion).”

        The NBC News (9/10, Fox) website reports that the study “found that elderly people who used...benzodiazepines for three months or longer had a 43 percent to 51 percent higher risk of later developing Alzheimer’s.” It remains unclear, however, “whether the drugs are causing the Alzheimer’s directly, or if people perhaps use the drugs to treat other symptoms that may be early signs of Alzheimer’s, such as depression or insomnia.”

        HealthDay (9/10, Norton) reports that two years ago, “the American Geriatrics Society (AGS) put benzodiazepines on its list of drugs considered ‘potentially inappropriate’ for seniors, because of risks like confusion, dizziness and falls.” Malaz Boustani, MD, MPH, of the Regenstrief Institute, Indiana University Center for Aging Research, an expert “who cowrote an editorial published with the study said older adults have to be cautious about using the drugs, or any medication that can affect mental function.”

Report: Twenty US States Have Obesity Rates At or Above 30 Percent

The Washington Post “Wonkblog” reported that “nowhere in the U.S. are Americans more overweight than in Mississippi and West Virginia, where more than 35 percent of the adult population is now obese, according to a new report from the Trust for America’s Health and the Robert Wood Johnson Foundation.” Those “states, however, are hardly alone in their alarmingly high obesity rates—another 18 U.S. states, including just about all of the U.S. south, have obesity rates at or above 30 percent.”

Most AIN Cases in the Elderly Are Caused by Proton Pump Inhibitors and Antibiotic

Drug-induced acute interstitial nephritis (AIN), a common cause of acute kidney injury, occurred in 87% of elderly individuals in a recent study, compared to 64% of younger participants. AIN due to proton pump inhibitors was more common in elderly participants compared to younger ones (18% vs. 6%), while AIN due to autoimmune or systemic causes was more common among younger individuals (27% vs. 7%). The 2 most common culprit drugs in the elderly were penicillin and omeprazole. The Kidney International study investigated the causes and characteristics of AIN in 45 elderly (≥65 years) and 88 younger (18–64 years) adults.

Lower Serum Bicarbonate Levels Linked with Lower Bone Mineral Density in US Adults

In a study of 9724 adults who participated in NHANES 1999–2004, each 2.2 mEq/L increment in serum bicarbonate level among women was associated with a 0.007 g/cm² greater lumbar bone mineral density (BMD) and 0.005 g/cm² greater total BMD. Among men, it was associated with a 0.008 g/cm² increase in lumbar BMD and a non-significant increase in total BMD. In a subgroup analysis of 2805 pre- and post-menopausal women, there was a significant association between serum bicarbonate levels and total BMD only in postmenopausal women. Thefindings are published in the American Journal of Kidney Diseases.

FDA allows marketing of the first test to assess risk of developing acute kidney injury

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm412910.htm

For Immediate Release

September 5, 2014

Release

Today the U.S. Food and Drug Administration allowed marketing of the NephroCheck test, a first-of-a-kind laboratory test to help determine if certain critically ill hospitalized patients are at risk of developing moderate to severe acute kidney injury (AKI) in the 12 hours following the administration of the test. Early knowledge that a patient is likely to develop AKI may prompt closer patient monitoring and help prevent permanent kidney damage or death.

The kidneys filter waste and extra water out of the blood and are important in controlling blood pressure and other essential body functions. When kidneys are not functioning properly, waste builds up in the body and can cause serious health problems. 

AKI is a sudden decline in kidney function, often without early signs or symptoms, following an injury to the kidney caused by a co-existing disease, infection, or other condition. AKI can cause fluid to build up in the body, chest pain, muscle weakness, and permanent kidney damage or chronic kidney disease (the gradual loss of kidney function). Critically ill patients are the most at risk for AKI, particularly patients who meet certain factors such as advanced age, diabetes and high blood pressure.

Current laboratory tests can only assess whether a patient may already have AKI; often, the patient has progressed to moderate to severe AKI before the test results confirm the clinical diagnosis. NephroCheck detects the presence of insulin-like growth-factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases (TIMP-2) in the urine, which are associated with acute kidney injury. Within 20 minutes, the test provides a score based on the amount of the proteins present that correlates to the patient’s risk of developing AKI within 12 hours of the test being performed. No other tests currently on the market are FDA-approved or cleared to assess the risk of developing AKI in at-risk patients.  

“Early assessment and timely treatment for AKI can help prevent kidney damage and potential associated complications,” said Alberto Gutierrez, director of the Office of In Vitro Diagnostics and Radiological Health at the FDA’s Center for Devices and Radiological Health. “The NephroCheck provides health care providers with a quick, validated method of assessing a patient’s AKI risk status which may inform patient management decisions.”

The FDA reviewed the data for NephroCheck through the de novo premarket review pathway, a regulatory pathway for some low- to moderate-risk medical devices that are not substantially equivalent to an already legally marketed device.

The FDA’s review included two clinical studies evaluating the test’s safety and effectiveness. The two studies compared the clinical diagnoses of more than 500 critically ill subjects at 23 hospitals to NephroCheck test results. NephroCheck accurately detected 92 percent of AKI patients in one study and 76 percent in the other. In both studies, NephroCheck incorrectly gave a positive result in about half of patients without AKI. 

The NephroCheck Test System is manufactured by Astute Medical based in San Diego, California.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. FDA also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

FDA approves new immunotherapy for melanoma.

There was wide coverage of the news that Merck & Co. on Thursday received FDA approval for a novel cancer medication called Keytruda (pembrolizumab), with major newspapers, news agencies and trade journals reporting. Many media outlets highlighted the significance of the medication, noting that Keytruda belongs to a new class of medications for treating advanced melanoma, using the body’s own immune system. The Wall Street Journal (9/5, Loftus, Subscription Publication) discusses the importance of the approval, noting that it is aimed at treating patients who have exhausted other therapies, including those people who did not respond adequately to Bristol-Myers Squibb Co.’s immunotherapy Yervoy (ipilimumab).

        Writing about the mechanism of action of the new therapy, the New York Times (9/5, Pollack, Subscription Publication) reports that cancer researchers have been struggling to solve how cancerous cells manage “to evade the body’s immune system” and the “answer is that tumors activate brakes on the immune system, preventing it from attacking them.” The paper notes that Keytruda “is the first drug approved that inhibits the action of one of those brakes, a protein known as PD-1, or programmed death receptor 1.” The Times notes that the general approach could “work for many types of cancer, though so far the main successes in clinical trials have come against the deadly skin cancer melanoma, lung cancer and kidney cancer.”

        Discussing the results of trials that facilitated the approval of the medicine, the Los Angeles Times (9/5, Healy) reports the FDA disclosed Keytruda “showed promising early results in 173 clinical trial participants with advanced melanoma whose disease progressed after prior treatment.” About a quarter who were given one of two doses of Keytruda “saw their tumors shrink.” According to the piece, “the effect lasted at least 1.4 to 8.5 months and continued beyond this period in most patients.”

        According to Bloomberg News (9/5, Edney, Koons)melanoma “accounts for 2 percent of skin cancer cases and causes the majority of deaths from the disease,” including nearly 10,000 expected this year, citing the American Cancer Society. The article notes that the treatment “was approved under the FDA’s accelerated approval program,” but Merck will still have to show “the benefits through an improvement in survival or disease-related symptoms.”

        The treatment, however, does not come cheap, with “early shipments” of Keytruda costing “$112,000 a year for an average patient,” and later versions reaching $150,000 a year, reports the Philadelphia Inquirer (9/5), citing Bernstein Research analyst Tim Anderson. In a note to clients Thursday Anderson expects “that Merck’s sales from Keytruda will be about $3.5 billion in 2020,” the paper adds

Twice-Weekly Hemodialysis May Help Preserve Residual Kidney Function in ESRD Patients

Among 85 maintenance hemodialysis (MHD) patients, the percent of patients with residual kidney function loss was significantly lower in those receiving twice-weekly dialysis compared to those receiving thrice-weekly dialysis, especially during the first year of HD initiation (60% vs. 82). In a subcohort of 48 incident MHD patients, there were no significant differences between the 2 groups except for variations in the HD frequency. On multivariate analysis, male gender, HD frequency, urea reduction ratio, and intradialytic hypotension episodes were associated with residual kidney function loss. The findings are published in the American Journal of Nephrology.

Obesity driving force behind escalating type 2 diabetes rates.

TIME (9/3, Oaklander) reports that according to a study published Sept. 2 in the Annals of Internal Medicine, obesity appears to be the “single biggest culprit to blame” for escalating rates of type 2 diabetes (T2D). After analyzing “data from five National Health and Nutrition Examination Surveys of a nationally representative U.S. sample of 23,932 people,” researchers found that body mass index (BMI) “explained most of the increase in the prevalence of diabetes, even more than other big factors like race, ethnicity and age.”

        HealthDay (9/3, Doheny) reports that the study also “found that the prevalence of diabetes in men rose from about five percent to more than 11 percent. In women, it rose from under six percent to nearly nine percent.”

Studies Add to the Growing Uncertainty about Blood Pressure Treatment Targets

Two studies question blood pressure targets in patients with hypertension. In a JAMA Internal Medicine study of 77,765 CKD patients with uncontrolled hypertension who were followed for a median of 6 years, patients with strict systolic blood pressure (SBP) control (<120 mm Hg) had a 70% increased risk of death compared to patients with SPB between 120 and 139 mm Hg, after adjustments. In aJournal of the American College of Cardiology study of 398,419 treated hypertensive patients, systolic and diastolic pressures higher and lower than 130–139 mm Hg systolic and 60–79 mg Hg diastolic were linked with an increased risk of death and ESRD.

Low-carb diets may be better than low-fat diets for protecting against heart disease.

On the front of its Science Times section, the New York Times (9/2, D1, O'Connor, Subscription Publication) reports that individuals “who avoid carbohydrates and eat more fat, even saturated fat, lose more body fat and have fewer cardiovascular risks than people who follow the low-fat diet that health authorities have favored for decades,” according to a National Institutes of Health-financed study published Sept. 2 in the Annals of Internal Medicine. The study “included a racially diverse group of 150 men and women...who were assigned to follow diets for one year that limited either the amount of carbs or fat that they could eat, but not overall calories.” By the time the study ended, “people in the low-carbohydrate group saw markers of inflammation and triglycerides...plunge,” while HDL increased.

        The Washington Post (8/29, Searing) “Health & Science” blog points out caveats to the study, including the fact that “the study measured risk factors for cardiovascular disease but did not last long enough to measure actual development of the disease.” In addition, “dietary data came from the participants’ responses on questionnaires.”

        Also covering the story are Reuters (9/2, Seaman),TIME (9/2, Oaklander), the NPR (9/2, Aubrey) “The Salt” blog, HealthDay (9/2, Norton), MedPage Today (9/2, Walsh), and Medscape (9/2).

Low Carb Beats Low Fat for Weight Loss, CV Risk

Direct link: http://www.medpagetoday.com/Cardiology/Prevention/47447

Low Carb Beats Low Fat for Weight Loss, CV Risk

Published: Sep 1, 2014

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By Nancy Walsh, Senior Staff Writer, MedPage Today

Reviewed by F. Perry Wilson, MD, MSCE; Assistant Professor, Section of Nephrology, Yale School of Medicine

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For weight loss and for reducing cardiovascular risk, cutting down on carbs was a more effective strategy than limiting fat intake in a randomized trial, researchers found.

Action Points

• Note that this small randomized trial demonstrated that a low-carbohydrate diet was superior to a low-fat diet in terms of weight loss at 1 year.
• Be aware that dietary adherence was assessed by self-report.

At 12 months, individuals on a low-carbohydrate diet had lost 5.3 kg (11.7 lb), while those on a low-fat diet with similar caloric value had lost 1.8 kg (3.9 lb), for a mean difference of -3.5 kg, or 7.7 lb (95% CI minus 5.6-minus 1.4, P=0.002), according to Lydia Bazzano, MD, PhD, of Tulane University in New Orleans, and colleagues.

They also had significantly greater increases in HDL cholesterol, with a mean difference of 7 mg/dL (95% CI 3-11,P<0.001), along with a greater decrease in the ratio of total to HDL cholesterol, with a mean difference of -0.44 (95% CI minus 0.71-minus 0.16, P=0.002), the researchers reported in the Sept. 2 Annals of Internal Medicine.

Previous studies on low-carbohydrate diets and cardiovascular risk have had conflicting results and were limited by a lack of population diversity and the inclusion primarily of patients with the metabolic syndrome or diabetes.

To assess the effect of the diet in a broader population, Bazzano and colleagues enrolled 148 individuals whose mean age was 47 and whose mean body mass index was 35 kg/m2. More than 85% were women, and half were black.

At baseline, none had cardiovascular disease (CVD), kidney disease, or diabetes, and they were not allowed to take prescription weight-loss drugs.

Half were randomized to a diet limiting digestible carbohydrates to less than 40 grams per day, and the others to a diet in which less than 30% of energy intake was in the form of fats and 55% was from carbohydrates.

Both groups were provided with detailed dietary information. All participants met with a dietitian individually each week for the first month and then regularly in small group counseling sessions for the duration of the study.

Adherence to the diet was assessed in two 24-hour dietary recalls at 3, 6, and 12 months, in which participants reported food consumption for the previous day.

Throughout the study, physical activity and caloric intake were similar in the two groups -- the 12-month average caloric content of the low-carb and low-fat diets was 1,448 and 1,527 calories, respectively -- and approximately 80% of participants in both groups completed the yearlong trial.

Numerous parameters showed greater benefits for the low-carbohydrate diet. The mean difference in fat mass decrease at 12 months was -1.5% (95% CI minus 2.6-minus 0.4, P=0.011), and the mean difference in increased lean mass was 1.7% (95% CI 0.6-2.8, P=0.003).

Triglyceride levels fell in both groups, but more so in the low-carbohydrate group, with a mean difference of -14.1 mg/dL (95% CI minus 27.4-minus 0.8, P=0.038).

"A major concern that has been frequently raised about low-carbohydrate diets is their potential to elevate LDL cholesterol levels, an established risk factor for CVD," the researchers noted.

However, in this study both groups had decreases in LDL cholesterol that did not differ significantly.

C-reactive protein levels also decreased more in the low-carbohydrate group, but glucose levels and blood pressures didn't show significant decreases in either group.

Finally, the 10-year Framingham risk score for coronary heart disease was significantly lower at 12 months in the low-carbohydrate group, with a mean difference of -1.4% (95% CI minus 2.1%-minus 0.6%, P<0.001).

"For a number of years, a host of outlets have been touting the low carbohydrate diet as a successful way to weight loss," said William E. Downey, MD, director of interventional cardiology and chair of the secondary prevention task force, Carolinas HealthCare System in Charlotte, N.C., who was not involved in the study.

"What has been the big concern is that often that diet is relatively high in fat and the question has been, is there a tradeoff with respect to cardiovascular outcomes?" he said.

"While this trial didn't look specifically at outcomes, they did look in a very rigorous way at changes in cholesterol, changes in CRP and inflammatory markers, changes in blood pressure, all those things that we think are tightly linked to outcomes," Downey toldMedPage Today.

Some previous studies had also indicated that the low-carb approach was superior, but these had observational designs that made them vulnerable to a host of confounding factors, Downey said.

That the current study was a randomized trial makes the findings far more credible, he suggested.

The study authors noted that most findings were similar for white and black participants, with the exception of a slightly greater increase in HDL for blacks on the low-fat diet.

"Our study found that a low-carbohydrate diet induced greater weight loss and reductions in cardiovascular risk factors at 12 months than a low-fat diet among black and white obese adults who did not have diabetes, CVD, or kidney disease at baseline," Bazzano and colleagues wrote.

"Restricting carbohydrates may be an option for persons who are seeking to lose weight and reduce cardiovascular risk factors and should be studied further," they concluded.

Limitations of the study were the self-report of diet and the possibility that the results would not be generalizable to populations who don't have the close dietary counseling that was provided in this study.

The authors disclosed no financial conflicts of interest. The study was funded by the National Institutes of Health.

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Primary source: Annals of Internal Medicine
Source reference: Bazzano L, et al "Effects of low-carbohydrate and low-fat diets: a randomized trial" Ann Intern Med 2014; DOI:10.7326/M14-0180.