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CONFERENCE COVERAGE
MORE NEWS FROM THE 69TH ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN DIABETES ASSOCIATION (ADA)
NEW ORLEANS - JUNE 5–9, 2009
Automated 'Artificial Pancreas' Controls Blood Glucose Levels in Diabetes Patients for First Time
An automated artificial pancreas system (APS) can safely and effectively maintain desired blood glucose levels in patients with type 1 diabetes, according to scientists from UC Santa Barbara (UCSB) and Sansum Diabetes Research Institute.
The researchers, working with the Schneider Children's Medical Center of Israel, tested an automated insulin delivery system comprising the OmniPod System (Insulet Corp., Bedford, Mass.) and the DexCom STS7 continuous glucose monitor (DexCom, San Diego) linked and controlled through UCSB's artificial pancreas software. The software's insulin delivery algorithm, optimized for each patient, includes a unique safety feature, based on clinical parameters, which prevents insulin-induced hypoglycemia.
Without any outside intervention, the system restored normal blood glucose levels following both induced hyperglycemia and unanticipated meals, while avoiding hypoglycemia. This was achieved through the automatic delivery of insulin to correct for the induced high blood glucose levels, and an insulin infusion rate moderated to ensure a smooth return to normal levels and avoid low blood glucose levels, according to a news release from UCSB Engineering.
"This study demonstrates for the first time a completely automated insulin delivery system that frees the patients from controlling their pumps manually, eliminating the question of compliance in treatment," said principal investigator Frank Doyle, Professor of Chemical Engineering at UCSB. "We pulled together a talented team of engineers and medical doctors who created the critical element of the artificial pancreas—a unique algorithm that is robust and straightforward to implement. It's become the gold standard."
The UCSB APS software platform is also being used by a number of other teams working on the artificial pancreas project, but no other team has advanced yet to wholly-automated clinical trials. Closed-loop trials were performed in four patients for a mean duration of 5 hours (range of 2–7 hours) and included a meal of 30 g of carbohydrates. The mean Low Blood Glucose Index was 0.02 (range 0-0.06), the mean High Blood Glucose Index was 9 (range 4.2-15), and the median Daily Risk Range was low (range low to moderate).
The research is part of the artificial pancreas project, which is funded by the Juvenile Diabetes Research Foundation and is being conducted by an international group of diabetes research centers. The project's first goal is to integrate an insulin pump and continuous blood glucose monitor to closely replicate a healthy pancreas for patients with type 1 diabetes.
Genes Play a Role in Glycemic Control in Type 1 Diabetes
Glycemic control in type 1 diabetes is not fully dependent on the individual's behavior, but is in part subject to genetic influence, according to a presentation by Andrew D. Paterson, MBChB, Senior Scientist in the Program for Genetics and Genome Biology, Hospital for Sick Children in Toronto.
"We identified four genes related to glycemic control in type 1 diabetes," said Dr. Paterson. "Two of these genes also affect risk for complications . . . and one gene has a strong effect on the rate of hypoglycemia. This finding does not give people with diabetes the freedom to slack off on their careful nutrition, exercise, and medication regimens because behavior clearly plays the major role in glycemic control," he added in an ADA news release.
"Eventually, the genetic variations we found may be used to identify individuals at risk for poor glycemic control and for diabetic complications, so that steps could be taken to intensify control or implement other measures. But in the interim, this knowledge may influence the design and analysis of genetic studies attempting to identify risk factors for long-term diabetic complications and lead us in new research directions to better understand the mechanisms of glycemic control."
The first data suggesting that A1C might be influenced by genetics came in 2001 in a British study looking at identical twins, where one twin had type 1 and the other did not.
"It was found that when the twin without diabetes had an A1C in the high normal range, the twin with diabetes would have an A1C in the high range for someone with diabetes," said Dr. Paterson. "Essentially, they were playing to the same drummer but in a different key."
In the current study, researchers mined data available from the DCCT (Diabetes Control and Complications Trial). Conventional control during the DCCT required only one or two insulin injections and blood checks daily, with the aim of preventing overt diabetes symptoms, and typically yielded A1C ≥9%. Intensive control to bring A1C levels as close to normal as possible (≤6%) required at least three insulin injections a day or treatment with an insulin pump, guided by at least four glucose self-monitoring checks a day.
The initial results, reported in 1993, demonstrated dramatic reductions in the development of microvascular complications. Intensive control also lowered the risk of heart disease according to data published in 2005 as part of the ongoing EDIC (Epidemiology of Diabetes Interventions and Complications) follow-up.
Researchers had access to every quarterly A1C test from the original DCCT. They performed high resolution genome-wide studies using the mean A1C values and capillary glucose of people in the conventional treatment group and compared loci of interest to people in the intensive treatment group. They determined the genotypes of a million single-nucleotide polymorphisms (SNPs) across the genome for more than 1,300 participants.
Investigators identified four major gene loci related to A1C levels: One in both treatment groups reached genome-wide significance—SORCS1 gene 10q25.1 Three achieved close to genome-wide significance: 14q32.13 (GSC) and 9p22 (BNC2) in the combined treatment groups; and 15q21.3 (WDR72) in the intensive group. Further, evidence indicated that SORCS1 was associated with hypoglycemia and BNC2 was associated with kidney and eye complications.
Mealtime Pramlintide Added to Basal Insulin Showed Similar Improvements in Glycemic Control Versus Rapid-Acting Insulin
Mealtime pramlintide (Symlin, Amylin) injection improved glucose control, treatment satisfaction, and quality of life for patients with type 2 diabetes, according to oral and poster presentations here.
The 36-week, randomized, open-label study was designed to compare the efficacy and safety of mealtime pramlintide, rapid-acting insulin, or both agents in patients with type 2 diabetes using basal insulin therapy. The multicenter study included 112 patients with type 2 diabetes with an average age of 54 years, baseline A1C of 8.2%, fasting plasma glucose of 160 mg/dL and body mass index (BMI) of 36 kg/m2.
"The effect of [pramlintide] was similar to that of mealtime rapid-acting insulin when added to basal insulin treatment in this study, with [pramlintide] use resulting in no weight gain and less hypoglycemia," said Dennis Karounos, MD, Associate Professor of Internal Medicine, Lexington Veterans Affairs Medical Center and University of Kentucky College of Medicine. "For patients recently requiring basal insulin, adding mealtime therapy with pramlintide may be a preferable alternative to mealtime rapid-acting insulin," he said in an Amylin news release.
Fenofibric Acid in Combination With Rosuvastatin Helps Diabetes Patients With Mixed Dyslipidemia Reach Goal
Fenofibric acid delayed-release capsules (Triplipix, Abbott) in combination with rosuvastatin (Crestor, Astra Zeneca) helped patients achieve individual and combined lipid targets in those with mixed dyslipidemia and type 2 diabetes. The combination helped up to three times more patients simultaneously reach all three key lipid targets—high-density lipoprotein (HDL) cholesterol, triglycerides, and low-density lipoprotein cholesterol—than the predetermined monotherapy, according to a news release from Abbot.
"Because diabetes is a risk factor for heart disease, it is particularly important that patients with diabetes and mixed dyslipidemia manage all three key lipid parameters," said Robert Rosenson, MD, State University of New York, Brooklyn. "The results of this analysis are promising for combination therapy with [fenofibric acid] and rosuvastatin."
According to Abbott, Trilipix, is the first and only fibrate to be approved for use in combination with a statin. In certain patients, treatment guidelines recommend the combination of a fibrate with a statin to improve lipids.
Aleglitazar Could Be a Safe, Effective Therapy for Type 2 Diabetes
Findings from a phase 2 study show that aleglitazar (a novel peroxisome proliferator-activated receptor co-agonist from Roche) could be a safe and effective for the treatment of type 2 diabetes, and thus will be entered into phase 3 trials. The data were presented here and were published online in The Lancet.
Robert R. Henry, MD, University of California, San Diego, and colleagues conducted a phase 2, multicenter study in patients with type 2 diabetes (either drug-na•ve or treated with ≤2 oral agents). Following a 5-week run in period with all patients on placebo, 332 were randomized to 16 weeks' treatment with aleglitazar at once-daily doses of 50, 150, 300, 600 µg, or matching placebo (55 in each group), or to pioglitazone (Actos, Takeda) 45 mg once daily (n = 57) as a reference.
The primary endpoint was the change in A1C from baseline to the end of treatment. Researchers found that aleglitazar reduced baseline A1C versus placebo in a dose-dependent manner, from -0.36% with 50 µg to -1.35% at 600 µg. The trend of changes over time suggested that the maximum effect of aleglitazar on A1C concentration was not yet reached after 16 weeks of treatment.
Side effects (edema, hemodilution, and weight gain) occurred in a dose-dependent manner, and at doses <300 µg, no patients had congestive heart failure, frequency of edema (one case at 150 µg) was less than placebo (three cases) and also less than with pioglitazone (four cases). Furthermore, at a dose of 150 µg, bodyweight gain was less than half that with pioglitazone (0.52 kg vs 1.06 kg).
Qnexa Showed Improved Blood Sugar Control Through Weight Loss in Type 2 Diabetes
Data from a year-long phase 2 trial evaluating the investigational agent Qnexa (Vivus, Inc.) in patients with type 2 diabetes showed that treatment significantly reduced patients' A1C and helped patients achieve and maintain significant weight loss. The study also showed that Qnexa—a proprietary, low dose, controlled release formulation of phentermine and topiramate that simultaneously addresses both appetite and satiety—had a positive impact on other risk factors associated with diseases prevalent in people living with diabetes.
"While it is widely known that type 2 diabetes can be treated through weight loss, the currently approved weight-loss therapies have limitations. The optimal diabetes therapy will not only enable patients to control their blood sugar by lowering glucose levels to the desired range, but will also help patients achieve meaningful weight loss," said W. Timothy Garvey, MD, Professor of Medicine and Chair of the Department of Nutrition Sciences at the University of Alabama at Birmingham in a news release. "The A1C reduction seen in this study is significant. The 9.4% weight loss observed in these patients—on average more than
20 lbs—is compelling, not only because of the amount, but more importantly the ability to maintain the weight loss over 1 year. These results suggest that this agent has the potential to play an important role in diabetes management with respect to blood sugar control and sustained weight loss."
Lorcaserin Demonstrated Weight Loss, Improvements in Endpoints Associated with Cardiovascular Risk
Positive results from BLOOM (Behavioral Modification and Lorcaserin for Overweight and Obesity Management), evaluating the safety and efficacy of lorcaserin for weight management, showed that treated patients achieved highly significant categorical and absolute weight loss in year 1. Continued treatment with lorcaserin (Arena Pharmaceuticals) in year 2 of BLOOM helped significantly more patients maintain their weight loss as compared to those on placebo.
According to a company news release, treatment with lorcaserin—a novel single agent that represents the first in a new class of selective serotonin 2C receptor agonists—also resulted in highly significant improvements as compared to placebo in multiple secondary endpoints associated with cardiovascular risk. Lorcaserin did not result in increased risk of depression and was not associated with the development of cardiac valvular insufficiency.
Previously announced BLOOM data demonstrated that lorcaserin was highly efficacious, achieving statistical significance on all three coprimary efficacy endpoints, and was very well tolerated.
"These data provide reason for new optimism for the millions of people who struggle with managing their weight and are in need of novel, well-tolerated treatments to help improve their overall health," said Steven R. Smith, MD, Co-Principal Investigator and Professor and Assistant Director for Clinical Research at the Pennington Biomedical Research Center.
"Lorcaserin's positive impact on multiple secondary measures has important implications for improving comorbidities associated with excess weight and further demonstrates the medically significant benefits of 5% or more weight loss, a mark two-thirds of the lorcaserin patients who completed the BLOOM trial achieved."
Once-Weekly Exenatide Provided Sustained Improvements Glycemic Control, Weight Loss
Interim results from the DURATION-1 study that showed sustained glucose control with weight loss, as well as improvements in systolic blood pressure and triglycerides, through 2 years of treatment with exenatide once weekly (Amylin and Eli Lilly), an investigational therapy for type 2 diabetes. A new drug application for exenatide once weekly was recently submitted to the US Food and Drug Administration.
In the controlled portion of the open-label study, patients received exenatide once weekly or exenatide (Byetta) injection for 30 weeks, followed by 74 weeks of treatment with exenatide once weekly for all patients during an open-ended assessment period. Significant reductions in A1C of 1.7% and fasting plasma glucose of 40 mg/dL were maintained after 2 years of treatment, according to a company news release. Sixty-five percent of patients achieved an A1C of ≤7%.
Body weight was significantly reduced, with patients losing an average of 5.8 lbs. Serum lipid profiles were significantly improved, and there was a significant reduction in systolic blood pressure.
MORE NEWS FROM THE ENDOCRINE SOCIETY'S 9TH ANNUAL MEETING (ENDO 09)
WASHINGTON, DC - JUNE 10–13, 2009
Men With Low Testosterone See Multiple Doctors Before Being Diagnosed; Many Dissatisfied with Current Treatment Options
About 63% of men who suffered from low testosterone saw two or more doctors before the condition was diagnosed, and once treated, nearly 30% of men said they stopped taking their medicine, according to results of a survey of more than 100 men.
The most frequent symptoms respondents reported were lack of energy (87%), decreased concentration (83%), loss of sex drive (82%) and the inability to get or maintain an erection (80%).
An estimated 13.9 million American men have hypogonadism, yet only 9% of men are currently being treated with testosterone replacement therapy, according to a news release from Endo Pharmaceuticals. The condition takes a significant toll on men's lives: Among men polled, 97% said low testosterone had a somewhat or very negative impact on the sexual aspect of their lives, and 90% said it adversely affected their self esteem.
"Low testosterone levels may have a marked impact on a man's sense of well being," said Raymond Rosen, PhD, Chief Scientist of the New England Research Institutes in Watertown, Mass. Among men polled, 61% said they were generally unsatisfied with their lives before being treated.
Low testosterone is associated with a broad range of physical, psychological, and sexual symptoms including decreased energy and mood, fatigue, loss of muscle mass, depressed libido, and erectile dysfunction. In addition, low testosterone has been associated with other serious medical conditions including diabetes, cardiovascular disease and metabolic syndrome.
"These symptoms are vague and nonspecific, which may account for the apparent underdiagnosis of low testosterone," said Martin M. Miner, MD , Co-Director of the Men's Health Center Miriam Hospital and Clinical, Providence, RI, and Associate Clinical Professor of Family Medicine Warren Alpert School of Medicine of Brown University, said. According to the survey, 36% of respondents saw two physicians before being diagnosed while 19% saw three doctors and 9% saw four. "This clearly speaks to the need for greater awareness among physicians of the condition and also for more patient-friendly treatments, since most men with this hormone deficiency will need to stay on treatment for life," Dr. Miner said.
Current treatment options include transdermal patches and gels that must be applied to the skin on a daily basis. Patients using gels must take care to prevent any transfer of testosterone to partners or children, as they have been associated with inappropriate genitalia enlargement and aggression in children. Short-acting testosterone injections are another, less popular treatment option that must be administered every 2 to 4 weeks.
"Despite the benefits of treatment, staying on therapy can be a problem for some men," Dr. Rosen said. According to the survey, 64% of men had used two or more testosterone replacement medicines, and 28% of men reported that they had stopped taking their medication at some point.
New long-acting injections that only need to be administered five times in the first year following the initial injection and every 10 weeks thereafter are in development and may offer patients a convenient new option for treatment. A majority of men polled said five shots in a year would be an improvement over their current therapies.
Endo Pharmaceuticals, sponsor of the survey, is developing the first and only long-acting injectable testosterone replacement treatment in the United States.
Bariatric Surgery Increases Risk of Fractures
After weight-loss surgery, people have nearly twice the expected risk of breaking a bone and an even higher risk of a foot or hand fracture, a new study has found.
"This finding is unexpected," said study coauthor Jackie Clowes, MD, PhD, Assistant Professor of Medicine at Mayo Clinic, Rochester, Minn. "The established opinion is that obesity protects against osteoporosis and, therefore, fractures."
Past research shows that bariatric surgery results in an increased bone turnover, the rate of bone breakdown and bone formation; however, it is not clear whether this change is clinically relevant. Dr. Clowes and her group suspected that the accelerated bone turnover after weight loss surgery would increase fracture risk.
According to an Endocrine Society news release, the researchers reviewed the medical records of patients who had bariatric surgery to treat medically complicated obesity, performed at Mayo Clinic between 1985 and 2004, and looked at data, including postoperative fractures. So far, the authors have analyzed data for 97 of the 292 patients whose records are available.
Of the 97 patients, 86 are women, and their average age was 44 years. Ninety percent of the patients had gastric bypass and the other patients had either vertical banded gastroplasty or biliopancreatic diversion. The average length of follow-up was 7 years.
After bariatric surgery, 21 patients suffered one or more fractures, for a total of 31 fractures. Compared with the fracture rate expected in an age- and sex-matched population in southeastern Minnesota, the patients who underwent bariatric surgery were 1.8 times likelier to have a first fracture at any site of the body. Fractures were especially common at the hand and foot, with the risk of hand fracture being more than three times greater than average, and foot fracture risk nearly four times greater.
"It is currently unclear why fractures are more common after bariatric surgery, especially at the hand and foot," Dr. Clowes said. "Although aggressive calcium and vitamin D supplementation after surgery may well help, it may still be insufficient to prevent the increased risk of fracture."
Successful Weight Loss With Dieting Linked to Vitamin D
Vitamin D levels in the body at the start of a low-calorie diet predict weight loss success, a new study found. The results suggest a possible role for vitamin D in weight loss, according to a news release from the Endocrine Society.
"Vitamin D deficiency is associated with obesity, but it is not clear if inadequate vitamin D causes obesity or the other way around," said the study's lead author, Shalamar Sibley, MD, MPH, Assistant Professor of Medicine at the University of Minnesota.
In this study, the authors attempted to determine whether baseline vitamin D levels before calorie restriction affect subsequent weight loss. They measured circulating blood levels of vitamin D in 38 overweight men and women before and after the individuals followed a diet plan for 11 weeks consisting of 750 calories a day fewer than their estimated total needs. Patients also had their fat distribution measured with dual energy X-ray absorptiometry scans.
On average, individuals had vitamin D levels that many experts would consider to be in the insufficient range, according to Dr. Sibley. The investigators found that baseline, or prediet, vitamin D levels predicted weight loss in a linear relationship. For every increase of 1 ng/mL in level of 25-hydroxycholecalciferol, individuals ended up losing almost a half pound more on their calorie-restricted diet. For each 1-ng/mL increase in active 1,25-dihydroxycholecalciferol, patients lost nearly one-quarter pound more.
Additionally, higher baseline vitamin D levels predicted greater loss of abdominal fat.
"Our results suggest the possibility that the addition of vitamin D to a reduced-calorie diet will lead to better weight loss," Dr. Sibley said. She cautioned, however, that more research is needed. "Our findings need to be followed up by the right kind of controlled clinical trial to determine if there is a role for vitamin D supplementation in helping people lose weight when they attempt to cut back on what they eat."
Nanotechnology May Allow Easier Detection of Small Pituitary Tumors
Researchers at UCLA have found a way using nanotechnology to safely light up and identify the cells of small endocrine tumors, whose size makes it difficult for surgeons to locate and completely remove them.
Nanotechnoloyis rapidly finding widespread applications in biomedicine, including labeling cells. Such identification would be useful during surgery to remove small pituitary tumors, such as the usually noncancerous tumors that are responsible for the chronic, debilitating disorder Cushing's disease, according to a news release from the Endocrine Society.
Because these tumors often are small and difficult to locate, surgeons sometimes are unable to remove the entire tumor. Long-term recurrence rates currently exceed 20%, said study coauthor Anthony Heaney, MD, PhD, Associate Professor of Medicine and Neurosurgery at the David Geffen School of Medicine at UCLA.
Many nanoparticles, however, are made of heavy metal and thus are likely to be toxic in the body, Dr. Heaney said. Therefore, he and his coworkers tested a ceramic-based, phosphorescent nanoparticle, known as YAG: Y3A15O12:Ce (Nanogram Corp., Milpitas, CA), in cultured pituitary tumor cells obtained from mice and humans. The investigators first showed that this nanoparticle was not toxic to either mouse or human cells.
Then Dr. Heaney and colleagues tagged the nanoparticle with specific peptides that are expressed on the surface of pituitary tumors. This new approach carried the nanoparticle into the tumor cells of both mice and humans, and the researchers then applied light. The resulting phosphorescence made the tumor cells shine brightly for up to 20 hours, the authors reported. Dr. Heaney's research group plans to conduct animal studies of this nanotechnology approach.
"If successful, our use of specifically targeted nanoparticles may enable novel therapeutic approaches for pituitary and other neuroendocrine tumors, including cancers," Dr. Heaney said.
Hormone Therapy Plus Physical Activity Reduce Abdominal Adiposity After Menopause
Older women who take hormone therapy (HT) to relieve menopausal symptoms may get the added benefit of reduced body fat if they are physically active, according to a new study that provides information on the health benefits of any type of physical activity, not just exercise.
Lead author Poli Mara Spritzer, MD, PhD, a Professor at the Federal University of Rio Grande do Sul in Porto Alegre, Brazil, and Chief of the Gynecological Endocrinology Unit at the university's Hospital de Clinicas de Porto Alegre said that after menopause, a woman's percentage of body fat tends to increase and redistribute to the abdomen. Excess belly fat is a risk factor for diabetes and heart disease.
According to an Endocrine Society news release, postmenopausal women who exercise have a lower percentage of body fat than sedentary women, past research shows. Dr. Spritzer said less is known about the influence on body fat composition of physical activity in women receiving HT. Some data suggest that estrogen treatment may add to the effect of exercise in reducing fat.
Dr. Spritzer and her colleagues studied 34 healthy women aged an average of 51 years, who had menopause for <3 years and sought HT to relieve hot flashes, night sweats, and vaginal dryness. They evaluated the women's cholesterol levels, BMI, waist circumference, and percentage of body fat before and after 4 months of HT. The women received estrogen plus progesterone therapy in either non-oral (nasal and vaginal) or low-dose oral preparations.
For 6 consecutive days before starting HT and 6 days at the end of HT, women wore a pedometer to estimate their level of physical activity. The device measured the steps they took, including walking, working, and doing house chores and leisure activities. They were instructed to not change their usual activities. Most of the women did not play sports or do any structured physical exercise, according to Dr. Spritzer.
Results showed that 24 of the women were physically active—defined as taking 6,000 steps or more per day—and 10 were inactive (less than 6,000 steps a day). For active women, the higher the number of steps they took, the lower was their waist measurement and the better their HDL-C, the authors reported. The inactive women did not have any changes in body fat or cholesterol.
"Data from our study suggest that active women could benefit from [HT] beyond the relief of menopausal symptoms—by preserving a good body fat percentage and distribution," Dr. Spritzer said. "Further studies with [more patients] are needed in order to answer whether a specific physical activity is better than others."
Genetic Predisposition to High TSH Linked to Long Life
Results of a new study challenge the current medical practice of treating a mildly underactive thyroid in older people by showing that the condition may actually contribute to healthy aging—at least in some people.
According to the Endocrine Society, millions of older people have a very small increase in the level of thyroid-stimulating hormone (TSH) in the blood (mild or subclinical hypothyroidism). Although it is unclear whether mild hypothyroidism worsens health, most doctors treat it with thyroid medication, according to study co-author Martin Surks, MD, professor of medicine and pathology at Albert Einstein College of Medicine, Bronx, NY.
Dr. Surks and his colleagues at Albert Einstein speculated that genes are responsible for mild hypothyroidism in Ashkenazi Jews and possibly other people, and that this increase is beneficial, because recent research shows that TSH increases with age in people who do not have thyroid disease, even those who live 100 years. The researchers studied a group of 236 Ashkenazi Jews who were about 100 years old, as well as their children: 444 men and women, with a median (midpoint) age of 69 years. For the control group, they included 188 spouses of the offspring (median age, 70). None of the individuals had known thyroid disease.
The TSH levels in the children were higher than in others of the same age (the children's spouses), but still lower than in their long-lived parents. On heritability analysis, TSH levels in parents and their children were closely related, indicating that heredity and genes could be involved, Dr. Surks said.
Further testing found SNPs in the TSH receptor. Those individuals who had these genetic variants had higher TSH levels than did individuals without the variants, the authors found. Furthermore, the parents and their children were much more likely to have the genetic variants than the unrelated group who were the same age as the children.
"The fact that genetic changes appear to underlie the increase in TSH in older Ashkenazi Jews suggests that this increase in TSH contributes to healthy aging and does not necessarily indicate hypothyroidism," Dr. Surks said. "If these findings are confirmed in other populations, the current designation of subclinical hypothyroidism in elderly people as an illness that needs treatment should be changed."
Ghrelin May Help Combat Frailty in Older Women
Frail elderly women with unexplained weight loss may benefit from supplementation with the body's appetite-stimulating hormone, ghrelin, or with similar agents, according to a new study.
Unexplained weight loss is a common problem in older adults. It can lead to the development of frailty, a debilitating syndrome of declines across multiple body systems. Frail individuals have much higher rates of functional decline, hospitalization, and death than healthier people their age, said study lead investigator Anne Cappola, MD, ScM, assistant professor of medicine at the University of Pennsylvania School of Medicine, Philadelphia, in an Endocrine Society news brief.
"There are no good medical treatments for frailty or unintentional weight loss at this time," Dr. Cappola said.
The pilot study enrolled five women aged ≥70 years who had unintentional, unexplained weight loss of >5% of their body weight in a year and who met at least two of the other standard criteria for frailty: self-reported exhaustion, weakness (grip strength), slow walking speed and low physical activity. The control group included five healthy women of similar age.
Each woman received two infusions into a vein, 1 week apart, of ghrelin or placebo (saline). The order was assigned randomly, and neither the women nor the person giving the infusion knew which one it was. During the 180-minute infusion, blood samples were taken to measure ghrelin levels in the body. Also measured was growth hormone response, because past studies showed an increase in growth hormone to ghrelin stimulation, and there could be benefit to raising growth hormone levels in this population, according to Dr. Cappola.
After the infusion, the women received a standardized meal, and the researchers quantified how much they ate. Women in both groups ate 51% more calories after the ghrelin infusion than the placebo infusion, because of increased carbohydrate and protein intake, not fat, the authors reported. Blood levels of growth hormone and ghrelin were higher at every time point during the ghrelin infusion than during the placebo infusion. The only side effect of treatment was a transient sensation of warmth that four women experienced during the ghrelin infusion.
"Our study is the first to show an improvement in appetite and growth hormone levels after administration of the hormone ghrelin to frail older women with unexplained weight loss," Dr. Cappola said.
Future studies, she said, should examine the potential therapeutic role of ghrelin or ghrelin mimetic agents in this population. These agents are available only for research use now.
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