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Archive - 02 - 2013
February 28, 2013 (Baylor College of Medicine) — Bone marrow cells that produce brain-derived eurotrophic factor (BDNF), known to affect regulation of food intake, travel to part of the hypothalamus in the brain where they "fine-tune" appetite, said researchers from Baylor College of Medicine and Shiga University of Medical Science in Otsu, Shiga, Japan, in a report that appears online in the journal Nature Communications. "We knew that blood cells produced BDNF," said Dr. Lawrence Chan, professor of molecular and cellular biology and professor and chief of the division of diabetes, endocrinology & metabolism in the department of medicine and director of the federally funded Diabetes Research Center, all at BCM. The factor is produced in the brain and in nerve cells as well. "We didn't know why it was produced in blood cells." Fluorescent marker reveals surprise Dr. Hiroshi Urabe and Dr. Hideto Kojima, current and former postdoctoral fellows in Chan's laboratory respectively, looked for BDNF in the brains of mice who had not been fed for about 24 hours. The bone marrow-derived cells had been marked with a fluorescent protein that showed up on microscopy. To their surprise, they found cells producing BDNF in a part of the brain's hypothalamus called the paraventricular nucleus. "We knew that in embryonic development, some blood cells do go to the brain and become microglial cells," said Chan. (Microglial cells form part of the supporting structure of the central nervous system. They are characterized by a nucleus from which "branches" expand in all directions.) "This is the first time we have shown that this happens in adulthood. Blood cells can go to one part of the brain and become physically changed to become microglial-like cells." However, these bone marrow cells produce a bone marrow-specific variant of BDNF, one that is different from that produced by the regular microglial cells already in the hypothalamus. Only a few of these blood-derived cells actually reach the hypothalamus, said Chan. "It's not very impressive if you look casually under the microscope," he said. However, a careful scrutiny showed that the branching nature of these cells allow them to come into contact with a whole host of brain cells. "Their effects are amplified," said Chan. Curbing the urge Mice that are born lacking the ability to produce blood cells that make BDNF overeat, become obese and develop insulin resistance (a lack of response to insulin that affects the ability to metabolize glucose). A bone marrow transplant that restores the gene for making the cells that produce BDNF can normalize appetite, said Chan. However, a transplant of bone marrow that does not contain this gene does not reverse overeating, obesity or insulin resistance. When normal bone marrow cells that produce BDNF are injected into the third ventricle (a fluid-filled cavity in the brain) of mice that lack BDNF, they no longer have the urge to overeat, said Chan. All in all, the studies represent a new mechanism by which these bone-marrow derived cells control feeding through BDNF and could provide a new avenue to attack obesity, said Chan. He and his colleagues hypothesize that the bone marrow cells that produce BDNF fine tune the appetite response, although a host of different appetite-controlling hormones produced by the regular nerve cells in the hypothalamus do the lion's share of the work. "Bone marrow cells are so accessible," said Chan. "If these cells play a regulatory role, we could draw some blood, modify something in it or add something that binds to blood cells and give it back. We may even be able to deliver medication that goes to the brain," crossing the blood-brain barrier. Even a few of these cells can have an effect because their geometry means that they have contact with many different neurons or nerve cells. He credits Urabe and Kojima (now with Shiga University of Medical Science in Japan) with doing most of the experiments involved in the research. Others who took part include: Tomoya Terashima, Nobuhiro Ogawa, Miwako Katagi, Kazuori Fujino, Asako Kumagai, Hiromichi Kawai, Akhiro Asakawa, Akio Inui, Hitoshi Yasuda, Yutaka Eguchi, Kazuhiro Oka, Hiroshi Maegawa, Atsunori Kashiwagi and Hiroshi Kimura, all of Shiga University of Medical Science. Funding for this work came from the Ministry of Education, Culture, Sports, Science and Technology, Japan, the President's Discretionary Fund from Shiga University of Medical Science and the U.S. National Institutes of Health grant HL-51586 and the Diabetes Research Center (P30 DK79638).
February 28, 2013 (Newswise) — An analysis of a free online weight loss program revealed that members who were more active on the website lost more weight than members who were less active, report researchers at The University of Texas Health Science Center at Houston (UTHealth) Medical School. The study in the Journal of Medical Internet Research focused exclusively on members of SparkPeople.com, America's largest diet and fitness site by unique visitors, according to comScore, an Internet technology company. Lead researcher Kevin Hwang, M.D., M.P.H., of the UTHealth Medical School and his colleagues analyzed a variety of factors and found that the frequency of weigh-ins and the number of posts on the program's message boards were associated with significant weight loss. Members who entered their weight at least four times a month lost 11 pounds per month more than those who did not, regardless of the duration of their membership. Likewise, members who posted at least one message on a message board lost more than 3 pounds more than those who did not. Hwang said that they considered the possibility that "members made weight entries only when they were losing (rather than gaining) weight," but found that 71 percent of subjects in the study posted at least one instance of weight gain. "The findings suggest that, if used in a certain way, an online weight loss program can be effective in producing significant weight loss by helping people keep track of their weight," Hwang said. "Some people who want to lose weight but avoid a scale for weeks on end can be engaging in a form of denial that can hamper weight loss." More than a third of adults in the United States are considered obese and many are turning to free online programs to shed unwanted pounds. In the study, the authors wrote, "Because this online program is free, scalable, and widely disseminated, the potential public health impact is significant." The researchers started with a random sample of members who had at enrolled in SparkPeople during a three month period in 2008 and included all available follow-up data for these members through May 10, 2010. The final study sample included 1,258 members who had at least two weight entries and adequate data to allow complete analysis. Ninety one percent of the subjects studied were female and the average body mass index was 31.6. Hwang and his colleagues report that to their knowledge this is the first analysis of a natural cohort of members of a free online weight loss community, so findings reflect the "real world" rather than a prospective research study in which members must meet strict enrollment criteria. Hwang's collaborators included Amber Trickey, Ph.D., UTHealth Medical School; Jing Ning, Ph.D., The University of Texas MD Anderson Cancer Center; and Christopher Sciamanna, M.D., M.P.H., Penn State College of Medicine. Hwang is with the UT Physicians' Medical Weight Loss Program. This work was supported by a Clinical Investigator Award from UTHealth, the university's Center for Clinical Research & Evidence-Based Medicine and The UTHealth-Memorial Hermann Center for Healthcare Quality and Safety.
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