A look at the latest research

Treating Alcoholism with OXYTOCIN

Patients seeking help for alcohol addiction are normally treated with benzodiazepines, a class of sedativehypnotic drugs that can also be addictive. A new study finds intranasal oxytocin might be a better alternative.

“Patients who have received benzodiazepines for medical detoxification remain highly sedative-hypnotic tolerant,” explained lead researcher Cort Pedersen, M.D., of the University of North Carolina at Chapel Hill. “After detox, they have symptoms related to that high tolerance, including anxiety, alcohol craving, and difficulty coping with stress as well as sleeping, all of which increase their chance of relapsing back to drinking.” Oxytocin treatment may not only block withdrawal but also reverse sedative-hypnotic tolerance, thereby decreasing risk of relapse.

The study, published in Alcoholism: Clinical and Experimental Research, included 11 alcoholdependent patients who had consumed alcohol heavily each day for two weeks before being admitted to a detoxifi- cation unit. They were randomly assigned to receive either 24 IU of intranasal oxytocin twice a day for three days or a placebo.

Patients’ withdrawal symptoms were measured at least every four hours using the CIWA-Ar scale. If their CIWA-Ar scores rose to or above 12, they received a dose of the benzodiazepine, lorazepam, every hour until their scores fell below 10. Patients who received intranasal oxytocin required much less lorazepam to complete detoxification and had far lower CIWA scores as well as less alcohol craving than those given the placebo.

—Glenda Fauntleroy

Exposure to Light at Night Tied to OBESITY

Dark bedroom curtains could be the easiest weight-control option yet, according to recent findings that link light exposure during sleep to metabolic disruptions.

The research team of Kenji Obayashi, M.D., at Nara Medical University in Japan, measured light levels in the home bedrooms of more than 500 elderly volunteers. Based on the results, the participants were then divided into a dim light group and a LAN (light at night) group.

The researchers took a variety of metabolic measurements in each individual, and then compared the groups. The LAN group was associated with a host of bad metabolic indicators: significantly higher body weight, waist circumference, triglyceride levels, and low-density lipoprotein cholesterol levels, and significantly lower high-density lipoprotein levels.

One hypothesized metabolic disruption did not pan out. Light at night is known to suppress secretion of melatonin, a pineal gland hormone that is key to circadian rhythm, but is also involved in body mass regulation and lipid and glucose metabolism. The researchers measured the urinary excretion of a major melatonin metabolite as an index of melatonin secretion but found no significant difference between the groups.

In a paper awaiting publication in The Journal of Clinical Endocrinology & Metabolism [jcem. endojournals.org], the researchers say that their study supports the many epidemiological findings that associate night-shift work with obesity and dyslipidemia, but is the first to demonstrate this link in a home setting.

—Eric Seaborg

What’s Your BMI?

The United States Preventive Services Task Force recommends physician screening of all adults for obesity via body mass index (BMI) calculation.

Patients with a BMI of 30 kg/m2 or higher should be referred to intensive counseling about diet, exercise, or both, along with behavioral interventions.

—Joanne McAndrews, Ph.D.

Androgens Linked to BABY ACNE

Androgens cause sebaceous gland hypertrophy (SGH) and acne during puberty, but infants also often have SGH and acne-like blemishes. The goal of a study, led by Ulla Sankilampi, M.D., Ph.D., at University of Eastern Finland and Kuopio University Hospital in Finland, and to be published in an upcoming issue of The Journal of Clinical Endocrinology & Metabolism [jcem.endojournals. org], was to investigate in infants the association of postnatal urinary androgens with SGH.

Fifty-four full-term infants (28 girls and 26 boys) and 48 preterm infants (26 girls and 22 boys) were followed monthly starting at one week of age and continuing until six months of age. During each visit, researchers noted the occurrence of SGH and the prevalence of acne and collected the infants’ urine to determine levels of dehydroepiandrosterone sulfate (DHEAS) and testosterone.

SGH was found in 89 percent of the full-term infants and 96 percent of preterm infants. Acne (defined as more than five papules) was present in 91 percent of full-term infants and in 75 percent of the preterms. SGH and acne were associated with elevated urinary DHEAS and testosterone in infants of both sexes and terms. Peak urinary androgen levels preceded the peak occurrence of acne, researchers noted.

This study is the first to link SGH and acne in infants with urinary androgen secretion, according to the authors.

—Joanne McAndrews, Ph.D.

HUMAN EGGS from Stem Cells

Scientists may be on the brink of developing a means of increasing a woman’s fertility by creating a supply of reproductively viable eggs. In a study published in Nature Medicine, Jonathan L. Tilly, Ph.D., from Massachusetts General Hospital in Boston, led a team of researchers who devised a method to generate human oocytes from stem cells.

The researchers used a fluorescence-activated cell-sorting technique to isolate and culture egg-producing stem cells from ovaries of adult mice and found that the cells, once delivered back to the ovaries, could produce fertilization-competent eggs. They then took stem cells from women’s ovaries, marked them with the fluorescent material, and injected them into human ovarian tissue grafted under the mice’s skin. Human follicles containing fluorescently marked oocytes derived from the stem cells were found one to two weeks later.

This discovery “opens the door for development of unprecedented technologies to overcome infertility in women and perhaps even delay the timing of ovarian failure,” wrote Tilly.

—Glenda Fauntleroy

TESAMORELIN Improves Older Adult Cognitive Function

Because growth hormone–releasing hormone (GHRH), growth hormone, and insulin-like growth factor 1 (IGF-1) levels decrease with aging, these hormones could be implicated in the onset of agerelated cognitive impairment.

Laura D. Baker, Ph.D., at the University of Washington, Seattle, led a team of scientists who studied the effects of the GHRH analog tesamorelin on cognitive function in older adults. Study participants, age 55-87 years, included 76 healthy adults and 61 adults with mild cognitive impairment. Participants injected one mg of tesamorelin daily for 20 weeks, then took a series of cognitive tests to evaluate both visual and verbal memory and executive function.

In their paper, originally published online in Archives of Neurology, the researchers report that tesamorelin increased IGF-1 levels 117 percent, to a level comparable to that in young adults. The high levels lasted a day. Both executive function and verbal memory improved. In healthy adults, overall cognitive function improved; in those with mild cognitive impairments, tesamorelin administration staved offthe typical decline, which commonly results in Alzheimer’s disease.

The researchers conclude that tesamorelin exerts positive effects on older adult cognitive function in both healthy older adults and those with mild impairment. The next step is a trial lasting one year to determine whether the results hold up and to try to uncover the pathways at work.

—Kelly Horvath

VITAMIN D Offers No Immunity from Colds

For those hoping to ward offa cold by taking vitamin D3 , a new study finds the supplements give no protection. Vitamin D has long been considered to play a role in immune function. Lead researcher David Murdoch, M.D., from the University of Otago, Christchurch, New Zealand, said he was anticipating there might be some benefit in preventing upper respiratory tract infections, such as colds, flu, and sinus infections.

In their study, appearing in JAMA, the researchers randomly divided 322 healthy adults into two groups. One group received an initial dose of 200,000 IU of oral vitamin D3 , then 200,000 IU one month later, and 100,000 IU every month for 18 months. The second group was given a placebo in the same dosing increments.

No significant differences were seen in the outcomes of the adults in the groups. Participants taking vitamin D3 had 593 respiratory infections, and those on the placebo had 611. The number of missed work days and the duration of symptoms per episode (about 12 days per episode) were about the same.

Although his team did not find immunity properties in vitamin D supplements for healthy adults, Murdoch said further research of populations with low baseline vitamin D levels or at risk for vitamin D insufficiency is justified.

—Glenda Fauntleroy

Calcium Supplements and HYPERPARATHYROIDISM

Primary hyperparathyroidism affects up to 2 percent of postmenopausal women in the U.S., leaving them with fragile bones, fatigue, depression, nausea, loss of appetite, and increased risk of kidney stones. An analysis of the long-running Nurses’ Health Study, however, suggests an association between increased calcium intake and a reduced risk of the condition. The analysis appeared in the BMJ.

The Nurses’ Health Study has enrolled and tracked 121,700 female registered nurses since 1976. Every two years, the participants complete questionnaires on exercise and other lifestyle choices, as well as newly diagnosed diseases; every four years they report on their diets. Researchers at Brigham and Women’s Hospital and Harvard University analyzed data amassed between 1986 and 2008 from more than 58,000 participants and learned that 277 participants were diagnosed with hyperparathyroidism in that 22-year period. The team then divided the women into five equal groups according to nutrient intake and found that women who took at least 500 mg of calcium per day had a 40 to 70 percent lower risk of developing the condition than those who didn’t take calcium supplements, depending on variables such as age, body weight, smoking, alcohol use, and protein, vitamin A, and vitamin D intake.

A few caveats, however: The researchers noted that the study population included only women, and nearly all of the participants were white, so the results do not automatically apply to men or to women of other races.

—Terri D’Arrigo

BPA EXPOSURE Lowers Thyroid Hormone in Newborns

Evidence of the endocrine-disrupting properties of the ubiquitous chemical bisphenol A (BPA) continues to mount, with the latest finding an association between exposure to BPA during pregnancy and altered thyroid function in pregnant women and their male babies.

BPA has been found in placental tissue and amniotic fluid, raising the question of how it might affect the fetus. A team led by Jonathan Chevrier, Ph.D., of the University of California, Berkeley, tested about 500 low-income pregnant women and their newborns for a relation of BPA to thyroid hormones because of the essential role these hormones play in early growth and brain development. The researchers measured BPA concentrations in two urine samples collected from the women during the first and second half of pregnancy and compared them with measurements of free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in the women and TSH in their newborns.

In a study published in Environmental Health Perspectives, they note that BPA’s effects can be hard to document because the chemical’s short half-life in the body—less than six hours. When the BPA measurements were made in close time proximity to the hormone measurements, BPA was associated with reduced T4 levels in the women.

Higher BPA concentrations in women during pregnancy were associated with lower TSH levels in male newborns, but not in female infants. This association was stronger when BPA was measured in the third trimester compared with earlier in the pregnancy.

— Eric Seaborg

Benefits of Extended Endocrine Therapy for
BREAST CANCER PATIENTS

Despite treatment, women with estrogen receptor (ER)-positive breast cancer are more likely to die of the cancer 5 to 10 years after diagnosis than are ER-negative patients.A new study now offers physicians a method for determining which ER-positive patients are at highest risk.

Researchers at the Cancer Center and Cancer Institute at Fudan University in Shanghai, China, report that although the standard therapy for patients with ER-positive, early-stage breast cancer is five-year adjuvant endocrine therapy (tamoxifen and aromatase inhibitor), their study aimed to help resolve whether some patients might benefit from 5 or 10 additional years of endocrine therapy.

The study, appearing in The Journal of Clinical Endocrinology & Metabolism [jcem.endojournals.org], used data from the National Cancer Institute’s Surveillance Epidemiology and End-Results (SEER) Cancer database and included nearly 112,000 female patients with invasive breast cancer. Researchers stratified patients by ER status, age, and lymph node status.

The researchers, led by Ke-Da Yu, M.D., concluded that some subpopulations of ERpositive patients at high risk of breast cancer death 5–10 years after diagnosis can be identified by age and lymph node status.

—Glenda Fauntleroy

Don’t Just
SIT THERE

Want to avoid getting diabetes or cardiovascular disease? You might try standing up and moving around more often, a study led by E.G. Wilmot, M.B., Ch.B., research fellow in the Diabetes Research Group, University of Leicester, United Kingdom, suggests.

With the average adult spending 50 to 60 percent of the day in sedentary pursuits, the couch potato lifestyle’s health effects are a growing concern among healthcare providers. Two earlier narrative reviews with small sample sizes suggested a moderateto-strong association between diabetes and sedentary lifestyle, and an earlier metaanalysis found a link between television time and diabetes. The current meta-analysis study looked more broadly at sedentary behavior rather than time spent watching television and considered cardiovascular effects and overall mortality in addition to diabetes.

The researchers examined data on 794,577 participants in 18 studies, of which 16 were prospective. The rest were cross-sectional, and 10 of the 18 looked specifically at diabetes. Sedentary time was associated with increases in relative risk for all conditions studied, but the predictive effects and intervals were significant only for diabetes. Diabetes risk increased 112 percent for the most sedentary subjects. Researchers also noted a 147 percent increased risk of cardiovascular events and a 49 percent increased risk of death in these extreme subjects.

The study, published in Diabetologia, may have important implications for future research and public health policy. The researchers concluded that an urgent need for follow-up exists to determine whether reductions in sedentary time will translate into health benefits and how to best change sedentary behavior in adult populations.

—Carol Bengle Gilbert

DIABETES’
OBESITY Paradox

In a shocking reversal of what we have come to expect about health and weight status, scientists report that normal-weight people with diabetes, particularly older adults and nonwhites, have double the risk of death compared to overweight or obese people who have diabetes.

In their paper, published in The Journal of the American Medical Association, Mercedes R. Carnethon, Ph.D., at Northwestern University, Chicago, and her team of scientists suggest that the “obesity paradox” may occur because genetic factors make normal-weight people more susceptible to adverse complications of diabetes.

Other possible explanations are that diabetes is undiagnosed by physicians not expecting it in normal-weight patients, or that obesity itself protects against disease progression by providing greater fuel reserves for those in chronic illness–induced catabolic states.

—Kelly Horvath

STARVATION HORMONE Increases Life Span

Eat hearty, live long? UT Southwestern Medical Center researchers say a recent study shows that transgenic mice with higher-than-normal fibroblast growth factor-21 (FGF21) levels were able to achieve the longevity gains typically associated with calorie restriction.

Cornell University researchers demonstrated in 1934 that a low-calorie diet containing sufficient nutrients to avoid malnutrition could increase life spans in laboratory mice. It wasn’t until 2007, however, that scientists identified the starvation-averting effects of FGF21. FGF21 promotes survival during prolonged fasting by facilitating the burning of fatty acids, suppressing growth, and inducing hibernation-like behavior. Although extra FGF21 can extend life, too little may cause insulin resistance, cancer, and other diseases.

A recent study showed that the hormone can reduce obesity in mice. The current research is the first to explore its effects on longevity in non-obese mice. Without decreasing food intake, male mice chronically exposed to FGF21 experienced longevity gains of about 30 percent, whereas female mice lived 40 percent longer, equivalent to human life span increases observed in calorie restriction research.

The mechanism for FGF21’s lifeextending effects seems to be an increase in insulin sensitivity and blocking of the growth hormone/ insulin-like growth factor-1 signaling pathway. The researchers say these findings, published in eLIFE [www. elifesciences.org], could have important implications for investigating hormone therapies to increase human life spans.

Although FGF21 offered longevity benefits, its drawbacks include infertility in female mice, and smaller size and bone density loss in both sexes. Researcher Steven Kliewer, Ph.D., professor of molecular biology and pharmacology, described the experimental mice as “spry” despite their reduced bone density and suggested it didn’t impair their quality of life. He said future studies are needed to try to separate the bone density and infertility effects of FGF21 from the life-extending qualities.

—Carol Bengle Gilbert

Obesity During Pregnancy May Increase INSULIN IN OFFSPRING

A mother’s obesity during pregnancy and lactation may increase insulin levels in her baby’s blood—a condition known as hyperinsulinemia—and change the baby’s heart structure and function.

In the past, the mechanisms underlying the relationship between maternal obesity and offspring cardiac function have eluded researchers. It is not known if detrimental effects on the heart were simply a consequence of increased weight and adiposity in the offspring that leads to cardiac hypertrophy. A new study, pending publication in Endocrinology [endo. endojournals.org], using a mouse model, sheds light on this question.

An earlier investigation noted heavier and fatter mouse offspring at 3 and 6 months when their mothers consumed an obesitypromoting diet. This current study refined those results. Comparing heart structure in mouse pups at 8 weeks, before overt signs of obesity developed in the experimental (Mat-Ob) group, researchers identified cardiac changes.

The pups in both Mat-Ob and control groups had similar body weights up to 8 weeks. Despite their similar weights, the MatOb pups had higher heart weight and greater absolute cardiac mass. Their hearts displayed physical changes consistent with cardiac hypertrophy. Researchers also observed several molecular markers of hypertrophy. Left ventricular hypertrophy is a predictor of heart disease and mortality.

By focusing on their hearts’ condition before the Mat-Ob pups showed overt signs of obesity, researchers answered the chicken-and-egg question, eliminating increased weight and adiposity as causes of the hypertrophy. The Mat-Ob pups, however, were hyperinsulinemic at 8 weeks of age. The presence of hyperinsulinemia arising in the absence of adiposity implicates primary insulin resistance in tissues, such as the skeletal muscle, involved in regulating glycemia. Because the heart tissue remains insulin responsive, it becomes over-stimulated by insulin, leading to cardiac hypertrophy.

With the rising incidence of pregnant obese women and an accompanying surge in gestational diabetes, more babies are born at risk for insulin resistance, myocardial hypertrophy (increased heart cell size and thickening of the heart muscle), and cardiovascular disease. The researchers propose that increased plasma insulin resulting from maternal obesity affects the development of the heart and, therefore, has potential as a possible treatment target.

—Carol Bengle Gilbert

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