Rapid and unexpected weight gain after fecal transplant

 

A woman successfully treated for a recurrent Clostridium difficile infection with stool from an overweight donor rapidly gained weight herself afterwards, becoming obese, according to a case report published in the new journal Open Forum Infectious Diseases. Fecal microbiota transplant (FMT) is a promising treatment for relapsing C. difficile infections, a common cause of antibiotic-related diarrhea that in severe cases may be life-threatening. The case suggests that clinicians should avoid selecting stool donors who are overweight. The report also raises questions about the role of gut bacteria in metabolism and health. At the time of the woman's fecal transplant in 2011, her weight was stable at 136 pounds, and her Body Mass Index (BMI) was 26. Then 32 years old, she had always been of normal weight. The transplant used donor stool from the woman's overweight but otherwise healthy teenage daughter, administered via colonoscopy, to restore a healthy balance of bacteria in the woman's gut, curing her C. difficile infection. Sixteen months later, the woman weighed 170 pounds, and her BMI was 33, meeting medical criteria for obesity. The weight gain persisted despite a medically supervised liquid protein diet and exercise program. Continuing efforts to diet and exercise did not lower her weight: Three years after the transplant, she weighed 177 pounds with a BMI of 34.5, and she remains obese today. "We're questioning whether there was something in the fecal transplant, whether some of those 'good' bacteria we transferred may have had an impact on her metabolism in a negative way," said Colleen R. Kelly, MD, of the Warren Alpert Medical School of Brown University, who wrote the case report with Neha Alang, MD, of Newport Hospital in Rhode Island. Such a link between bacteria in the gastrointestinal tract and weight is supported by previously published animal studies, where transfer of gut bacteria from obese to normal-weight mice can lead to a marked increase in fat. In light of the case and the animal data, the authors recommend selecting stool donors who are not overweight for fecal transplants. Importantly, the FMT was not the only possible cause of the woman's weight gain. In addition to treatment for C. difficile, she had also been treated with several antibiotics for Helicobacter pylori infection. Other possible contributing factors in the woman's weight gain include the resolution of her C. difficile infection, genetic factors, aging, and stress related to illness. However, as noted above, she had never been overweight before. The case raises many questions about donor selection and highlights the importance of studying long-term outcomes of FMT, according to Ana A. Weil, MD, and Elizabeth L. Hohmann, MD, both of Massachusetts General Hospital, who wrote a related editorial. "Careful study of FMT will advance knowledge about safe manipulation of the gut microbiota," they wrote. "Ultimately, of course, it is hoped that FMT studies will lead to identification of defined mixtures of beneficial bacteria that can be cultured, manufactured, and administered to improve human health." Fast Facts Fecal transplants are a promising approach for treating recurrent C. difficile infections, a common cause of potentially life-threatening diarrhea. In this case report, a woman successfully treated for a relapsing C. difficile infection with a fecal transplant rapidly became overweight for the first time in her life. The stool donor, the woman's daughter, was overweight. The report suggests that donor screening for these transplants should exclude those who are overweight.

 

Newly discovered protein has link to gestational diabetes

 

For at least 40 years, scientists who study how the body metabolizes sugar have accepted one point: there are four enzymes that kick-start the body's process of getting energy from food. The discovery of these four catalysts for energy production, called hexokinases, generated more research into how the body metabolizes carbohydrates, and how interfering with those enzymes through medications could help manage metabolic disorders such as diabetes. But this biochemical foursome may not deserve all of the credit. According to research by scientists at Duke and Northwestern universities, the hexokinase team actually has a fifth player. The findings appear in the online journal Nature Communications. "This swims against the past 40 years of research and what we thought we knew," said Tim Reddy, Ph.D., a senior author of the study and assistant professor of biostatistics and bioinformatics at Duke. "Hexokinases are critical to basically all of our energy production. Finding a fifth one opens the door to more study into how we metabolize sugar, as well as genetic links to metabolic disorders." The new protein is called HKDC1, and the researchers report that this enzyme may be a genetic predictor for whether an expectant mother develops hyperglycemia, or excess blood sugar, during pregnancy. Hyperglycemia is a potentially harmful environment for a growing fetus and can contribute to obesity and diabetes later in the child's life. While at least 4 percent of pregnant women develop diabetes during pregnancy, as many as 400,000 women each year in the U.S. have gestational hyperglycemia, which equals about 10 percent of expectant mothers. Hyperglycemia during pregnancy may have many of the same harmful long-term health effects as full-blown gestational diabetes, according to a landmark study published in the New England Journal of Medicine in 2008. "We know that these children may be more likely to be born large and be subject to health impacts down the road, such as obesity and diabetes," Reddy said. Doctors have counseled expectant mothers on the risks of high blood sugar and the benefits of proper diet and exercise to lessen the risk. But there currently isn't a method to screen women for their risk of developing high blood sugar while pregnant. Often, mothers are diagnosed too late, after they have developed diabetes. While all humans have this fifth hexokinase, it appears during pregnancy, women with less of this gene are not able to metabolize glucose as well, the study showed. Researchers hope the new findings could lead to a test for pregnant women that indicates their potential for developing hyperglycemia. "The discovery of this gene creates a path forward to better predicting a woman's risk," Reddy said. "Knowing that there is this new hexokinase at play could also give us more information on how to inhibit or activate it, and anything we can to do disrupt the cycle would be an important advance to stem the epidemic of diabetes we see today." Further investigation into the enzyme could create potential targets for new therapies for metabolic conditions, said William Lowe, M.D., a senior author of the study and professor of medicine at Northwestern University Feinberg School of Medicine. "This study shows the benefit of large-scale genetic studies as they begin to shed light on new molecules that are important for metabolism," Lowe said. The idea that this enzyme has been hidden in the human genome all these years is somewhat shocking, said Christopher Newgard, Ph.D., an author of the paper and director of the Duke Molecular Physiology Institute. "It's ancient history in the field of carbohydrate biochemistry that there were four members of the family," Newgard said. "Something like 40 years goes by, and then here comes this cowboy, showing up late to the party."

 

New study postulates the role of dietary advanced glycation end products in the risk of Alzheimer's disease

 

A new paper published in the Journal of Alzheimer's Disease provides evidence that cooking foods at high temperatures increases the risk of Alzheimer's disease. This study looked at the content of advanced glycation end products (AGEs) in national diets and clinical studies comparing and compared total AGEs to Alzheimer's disease rates. AGEs are a group of compounds that are combinations of sugars and proteins and other large molecules. They can be formed in the body, and there is a large body of literature on AGEs and Alzheimer's disease. However, AGEs are also formed when food is cooked at high temperatures or aged for a long time such as in hard cheese. AGEs increase the risk of various chronic diseases through several mechanisms including increased inflammation and oxidative stress. They can also bind to the receptor for AGEs (RAGE). RAGE transports beta-amyloid proteins across the blood-brain barrier and contributes to the development of Alzheimer's disease. Our newly published paper is the first that estimated the AGE content of diets from observational studies in various countries, which estimated the link between dietary factors and risk of Alzheimer's disease. For this purpose, the values for AGE for many types of food were taken from a study by researchers at the Mount Sinai School of Medicine in New York. They cooked 549 foods by different methods and measured the AGE content of the cooked food. They found that the higher the cooking temperature, the higher the AGE content. For example, 100 grams of raw beef had 707 kU of AGEs, but 100 grams of roast beef had 6071 kU. To use their findings in our study, we obtained information from observational studies in which diet was assessed using food frequency questionnaires or from national dietary supply values from the Food and Agriculture Organization of the United Nations. We then used either a range of cooking temperatures or methods for the observational studies or an estimate of average cooking methods and temperatures for the national dietary supply data. In typical national diets, we found that meat made the highest contribution of AGEs, followed by vegetable oils, cheese, and fish. Foods such as cereals/grains, eggs, fruit, legumes, milk, nuts, starchy roots, and vegetables generally make low contributions to the total amount of AGEs in a diet, either because they are generally prepared at low temperatures or since they comprise smaller portions of diets. According to Drs. Jaime Uribarri and Weijing Cai of The Icahn School of Medicine at Mount Sinai, "This epidemiological study supports our previous findings in animals and humans of an important role for dietary AGEs in Alzheimer's disease. We found that mice kept on a diet high in AGEs, similar to Western diet, had high levels of AGEs in their brains together with deposits of amyloid-β, a component of the plaques characteristic of Alzheimer's disease, while at the same time developed declines in cognitive and motor abilities. The mice fed a low AGE diet remained free of these conditions. In addition, clinical studies have shown that subjects with higher blood AGE levels, in turn resulting from high AGE diets, are more likely to develop cognitive decline on follow up. The findings point to an easily achievable goal that could reduce the risk of dementia through the consumption of non-AGE-rich foods, for example, foods that cooked or processed under lower heat levels and in the presence of more water, raising the importance of not just what we eat, but also how we prepare what we eat."

 

FDA approves new drug for binge eating disorder (BED)

 

The United States Food and Drug Administration (FDA) recently approved lisdexamfetamine dimesylate, under the brand name Vyvanse, to treat moderate to severe binge eating disorder (BED) in adults, a first of its kind prescription drug specifically indicated for BED. "TOS has long supported new tools to assist with treating obesity," says Martin Binks, PhD, TOS Secretary Treasurer and Associate Professor of Nutritional Sciences at Texas Tech University. "Given that if untreated, BED has shown in some people to lead to reduced long-term success in behavioral weight-loss programs and following bariatric surgery, this new tool may prove useful in the obesity treatment setting." For clinicians, TOS says that understanding the differences between obesity and BED is important. BED is an eating disorder that affects only a portion of those with the medical disease obesity. While as many as 30% of people seeking obesity treatment may report some degree of binge eating, those who meet clinical criteria for BED likely represent only 7-10% of all obesity treatment seekers. "It is important to consider treating BED in the context of other treatments specifically targeting obesity," says Susan L. McElroy, MD, a TOS member who specializes in both obesity and BED treatment, and Chief Research Officer, Lindner Center of HOPE and Professor of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine. "Vyvanse is approved for treating BED, but it is not approved for weight-loss or obesity treatment and should not be considered a replacement for this treatment." Research shows that obesity is a far more complex condition than simply being a matter of eating less and exercising more. In most cases, obesity is chronic and challenging to treat and puts individuals at risk for more than 30 health conditions. "For the subset of people with obesity who also have binge eating disorder the availability of this new, safe and effective tool to treat BED may provide some long-awaited support," said Dr. McElroy, who previously coordinated clinical research on Vyvanse.

 

FDA approves new drug for binge eating disorder (BED)

 

The United States Food and Drug Administration (FDA) recently approved lisdexamfetamine dimesylate, under the brand name Vyvanse, to treat moderate to severe binge eating disorder (BED) in adults, a first of its kind prescription drug specifically indicated for BED. "TOS has long supported new tools to assist with treating obesity," says Martin Binks, PhD, TOS Secretary Treasurer and Associate Professor of Nutritional Sciences at Texas Tech University. "Given that if untreated, BED has shown in some people to lead to reduced long-term success in behavioral weight-loss programs and following bariatric surgery, this new tool may prove useful in the obesity treatment setting." For clinicians, TOS says that understanding the differences between obesity and BED is important. BED is an eating disorder that affects only a portion of those with the medical disease obesity. While as many as 30% of people seeking obesity treatment may report some degree of binge eating, those who meet clinical criteria for BED likely represent only 7-10% of all obesity treatment seekers. "It is important to consider treating BED in the context of other treatments specifically targeting obesity," says Susan L. McElroy, MD, a TOS member who specializes in both obesity and BED treatment, and Chief Research Officer, Lindner Center of HOPE and Professor of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine. "Vyvanse is approved for treating BED, but it is not approved for weight-loss or obesity treatment and should not be considered a replacement for this treatment." Research shows that obesity is a far more complex condition than simply being a matter of eating less and exercising more. In most cases, obesity is chronic and challenging to treat and puts individuals at risk for more than 30 health conditions. "For the subset of people with obesity who also have binge eating disorder the availability of this new, safe and effective tool to treat BED may provide some long-awaited support," said Dr. McElroy, who previously coordinated clinical research on Vyvanse.

 

Older adults: Double your protein to build more muscle

You are what you eat, especially when it comes to how your body builds protein. It is well known that consuming protein stimulates the body's cells to build protein. However, getting older combined with eating less protein can lead to a decline in the body's muscle-building efficiency. Maintaining and building muscle is especially important for older individuals. Increased muscle mass can contribute to a healthier weight, better fitness and an improved quality of life. New research in the American Journal of Physiology -- Endocrinology and Metabolism explores whether the amount and timing of protein consumption make a difference in the body's net protein gains. Current US recommendations for daily dietary protein intake are 0.8 grams/kilogram of body weight (roughly 62 g of protein per day for a 170-pound person). Previous research has shown that older adults need a protein intake of at least 0.40 g/kg of body weight at each meal (roughly 31 g of protein per meal or 93 g per day for a 170-pound person) to encourage maximum protein synthesis. This represents a significantly higher amount of protein than the recommended dietary allowance (RDA) suggests. Researchers at the Center for Translational Research in Aging and Longevity at the Donald W. Reynolds Institute on Aging at the University of Arkansas for Medical Sciences set out to measure whether daily protein intake greater than the average American adult consumption leads to a greater net protein gain in older adults. They also examined whether the timing of protein intake made a difference in protein synthesis -- the process by which cells make protein -- and net protein gains. The research team studied 20 healthy adults between 52-75 years of age, randomly assigning them to one of four groups over a four-day test period. Two groups ate the RDA of 0.8 g/kg per day of protein: one group had even protein distribution across meals (33% of total protein at breakfast, lunch and dinner) and the other had an uneven protein distribution at meals (15% at breakfast, 20% at lunch and 65% at dinner). The other two groups ate double the RDA (1.5 g/kg day of protein) following the same even and uneven protein distribution patterns as the first two groups. The group that consumed double the RDA was supplemented with a pre-weighed milk protein concentrate (equal parts whey and casein) to ensure that they achieved daily protein goals of 1.5 g/kg day. All meals were prepared in prepared in the Metabolic Kitchen at University of Arkansas Translational Research Institute. The subjects recorded time and other details about the food they ate. The research team found that while the distribution of protein across meals did not make a significant impact, total amount of protein consumed did. "Although there was no clear effect of the pattern of protein intake in our study, we observed a definitive effect of a higher amount of protein intake in mixed meals on whole body net protein balance and muscle protein synthesis," the authors wrote. "Whole body net protein balance was greater with protein intake above recommended dietary allowance." The article "Quantity of dietary protein intake, but not pattern of intake, affects net protein balance primarily through differences in protein synthesis in older adults" is published in the American Journal of Physiology -- Endocrinology and Metabolism. It is highlighted as one of this month's "best of the best" as part of the American Physiological Society's APSselect program.

 

FDA Panel Backs Appetite-Curbing Implant for Severely Obese

By Dennis Thompson
HealthDay ReporterLatest Diet & Weight Management NewsFDA Panel Backs Appetite-Curbing Implant for ObeseWhen School's Out, Weight Can Pile OnIs Breakfast the Key to Weight Control?Health Tip: If You Aren't Hungry, Don't EatDiabetes Drug Spurs Weight Loss in NondiabeticsWant More News? Sign Up for MedicineNet Newsletters!

TUESDAY, June 17, 2014 (HealthDay News) -- A new implant designed to curb the appetite by electrically stimulating stomach nerves may have moved closer to U.S. Food and Drug Administration approval on Tuesday.

The device is aimed at severely obese adults who have failed to slim down using traditional methods, but don't want, or can't have, weight-loss surgery, the device's manufacturer, EnteroMedics Inc., said in its application for FDA approval.

The FDA's nine-person Gastroenterology and Urology Devices Panel -- a key advisory committee -- voted 8 to 1 that the Maestro Rechargeable System is safe when used as designed, and 6 to 2 (with one abstention) that the device's benefits outweighed its risks.

The panel was less decisive on a third vote, on whether the device would be effective for patients: On that vote, 4 panelists voted yes while 5 voted no.

The FDA is not obligated to follow the decisions of its advisory committees, but it usually does.

In the United States, more than one-third of adults are obese, according to the U.S. Centers for Disease Control and Prevention. This increases their risk of serious health issues such as heart disease, diabetes, depression and cancer, experts say.

Despite this, "we have very few tools at our disposal compared with other chronic diseases," said Martin Binks, an associate professor of nutritional sciences at Texas Tech University who was scheduled to testify before the FDA panel on behalf of the Obesity Society.

"We certainly are encouraged by the FDA's recent willingness to review treatments for obesity," Binks said.

The Maestro Rechargeable System sends electrical signals to nerves around the stomach that help control digestion. These signals block the nerves, decreasing hunger pangs and making the person feel full, the St. Paul, Minn.-based manufacturer said.

In clinical trials, obese people with a Maestro implant lost an average 8.5 percent more weight than others who received a fake implant, the device maker said.

"The Maestro Rechargeable System is a safe and effective treatment option for obese individuals who have failed more conservative weight reduction interventions such as diet/exercise and pharmacotherapy, but are not able or willing to undergo more aggressive bariatric surgical options," the device company said in FDA briefing papers.

The Maestro consists of a "pulse generator" surgically implanted under the skin of the chest wall. This delivers high-frequency electrical pulses to leads laid along two trunks of the vagus nerve, which helps control the function of many organs in the abdomen.

The device is intended in use for people with a body mass index (BMI) of at least 40, which is extremely obese. BMI is a measurement of body fat based on height and weight.

EnteroMedics said the Maestro also could be used in people with a BMI of at least 35 who have health problems related to their obesity and have failed to lose weight through other programs. (A BMI of 30 is the threshold for obesity.)

The FDA advisory committee's review included results from a clinical trial that involved more than 200 morbidly (severely) obese people in the United States and Australia. Of those, 157 received a Maestro implant and 76 received a fake implant.

All of the participants then went through a standard weight management program, which consisted primarily of 15-minute counseling sessions. The program did not include more intense interventions such as very low calorie diets, mandatory exercise programs or portion-controlled meals.

Over the course of a year, study participants with the Maestro implant lost just over 24 percent of their excess weight on average, compared with nearly 16 percent of excess weight loss for people who received fake implants.

More than half the participants lost at least one-fifth of their excess weight, and 38 percent lost at least one-quarter of their excess weight, according to the researchers.

EnteroMedics added that people with fake implants regained about 40 percent of the weight they had lost within six months of the trial's end, while the people with the Maestro device appeared to sustain their weight loss.

The device appears to be largely safe, with only about 4 percent of patients suffering a health problem because of the implant, the FDA's report on Maestro said.

However, the Maestro is unsafe during MRI scans and would have to be removed if a person needed an MRI, according to the FDA.