News — November/December 2009

AACE Releases Algorithm for Treatment of Type 2 Diabetes Patients
A new, first-of-its-kind diabetes algorithm created to help achieve glycemic control in type 2 patients was published in Endocrine Practice.

This diabetes algorithm, released as a consensus statement from the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE), is a simple 1-page resource designed to assist primary care physicians, endocrinologists, and others in the management of type 2 diabetes.

“Depending on a patient’s current A1C level, a physician will use the algorithm to determine whether mono-, dual-, or triple-combination therapy should be considered,” said Helena Rodbard, MD, former AACE President and Co- Chair of the Algorithm Task Force. “To minimize the risk of diabetic complications, the algorithm will help achieve a[n] A1C value <6.5% when appropriate.”

According to a news release from AACE, until now, there has never been a treatment algorithm that considers currently approved classes of medications emphasizing safety and efficacy while also considering secondary factors such as the overall cost of care—not just the cost of medications. These drug classes include biguanides, dipeptidyl peptidase—4 inhibitors, incretin mimetics, thiazolidinediones, alpha-glucosidase inhibitors, sulfonylureas, meglitinides, bile-acid sequestrants, amylin analogs, and insulin therapy.

“We felt that an authoritative, practical algorithm for managing type 2 diabetes was essential,” former AACE President and Co-Chair of the Algorithm Task Force, Paul S. Jellinger, MD, said. “We believe that this algorithm represents the treatment preferences of most clinical endocrinologists. This is a point-of-care tool that helps clinicians make appropriate and safe treatment decisions.”

The algorithm also prioritizes medication choices according to risk of hypoglycemia, safety, efficacy, simplicity, and anticipated degree of patient adherence. It was created by a consensus group of leading endocrinologists combining very extensive clinical experience, clinical researchers, practitioners and academicians, and is based on the AACE/ACE Diabetes Guidelines and recent medical literature.

With nearly 80 million people suffering from diabetes and prediabetes in the United States, there is a shortage of endocrinologists to care for all patients. Many patients are treated by primary care physicians. The algorithm represents an important tool to assist and educate clinicians.

Smoking Bans Reduce Risk of Secondhand Smoke-Related MI
Smoking bans are effective at reducing the risk of myocardial infarction (MI) and coronary heart disease (CHD) associated with exposure to secondhand smoke, according to a new report from the US Institute of Medicine (IOM). The report also confirms there is sufficient evidence that breathing secondhand smoke boosts nonsmokers’ risk for heart problems, adding that indirect evidence indicating that even relatively brief exposures could lead to a[n] MI is compelling.

“It’s clear that smoking bans work,” said Lynn Goldman, professor of environmental health sciences, Johns Hopkins Bloomberg School of Public Health, and chair of the committee of experts that wrote the report. “Bans reduce the risks of [MI] in nonsmokers as well as smokers. Further research could explain in greater detail how great the effect is for each of these groups and how secondhand smoke produces its toxic effects. There is no question, however, that smoking bans have a positive health effect.”

About 43% of nonsmoking children and 37% of nonsmoking adults are exposed to secondhand smoke in the United States, according to public health data. Despite significant reductions in the percentages of Americans breathing environmental tobacco smoke over the past several years, roughly 126 million nonsmokers were still being exposed in 2000, according to a news release from the National Academies of Sciences.

A 2006 report from the US Surgeon General’s office concluded that exposure to secondhand smoke causes heart disease and indicated that smoke-free policies are the most economical and effective way to reduce exposure. The effectiveness of smoking bans in reducing heart problems has continued to be a source of debate, however.

The IOM committee conducted a comprehensive review of published and unpublished data and testimony on the relationship between secondhand smoke and short-term and long-term heart problems. Eleven key studies that evaluated the effects of smoking bans on MI rates informed the committee’s conclusions about the positive effects of smoke-free policies. The studies calculated that reductions in the incidence of MI range from 6% to 47%. Given the variations in how the studies were conducted and what they measured, the committee could not determine more precisely how great the effect is. Only two of the studies distinguished between reductions in MIs suffered by smokers versus nonsmokers. The repeated finding of decreased MI rates overall after bans were implemented conclusively demonstrates that smoke-free policies help protect people from the cardiovascular effects of tobacco smoke, the committee said.

The report also provides a detailed discussion of the evidence from animal research and epidemiological studies showing a cause-and-effect relationship between secondhand smoke exposure and heart problems.

FDA Investigates CV Risk Associated With Sibutramine
The US Food and Drug Administration (FDA) is reviewing preliminary data from a recent study suggesting that patients using sibutramine (Meridia, Abbott) have a higher number of cardiovascular events than patients using a placebo.

The analysis of these data is ongoing and the FDA is making no conclusions about the preliminary findings at this time, according to a news release. The findings highlight the importance of avoiding the use of sibutramine in patients with a history of coronary artery disease, congestive heart failure (CHF), arrhythmias, or stroke, as recommended in the current sibutramine labeling.

The SCOUT (Sibutramine Cardiovascular Morbidity/ Mortality Outcomes in Overweight or Obese Subjects at Risk of a Cardiovascular Event) study began in 2002. The analysis of the study results is ongoing by the manufacturer. The FDA was made aware of the preliminary results for the study primary endpoint—a combination of MI, stroke, resuscitated cardiac arrest, or death—in mid- November 2009. Part of a post-approval commitment between the European Medicines Agency and the manufacturer, the study was designed to show that weight loss with sibutramine and standard care was more effective in reducing the number of cardiovascular events compared with weight loss from a placebo and standard care.

The FDA stated that patients included in the study were aged ≥55 years, overweight or obese, and had a history of heart disease or type 2 diabetes plus one additional cardiovascular risk factor. Patients who recently had an MI or stroke, or had poorly controlled CHF, were not included in the study. Approximately 10,000 patients enrolled in the study.

The preliminary analysis of the primary endpoint suggests that patients using sibutramine experienced a higher number of cardiovascular events compared with those using a placebo. The preliminary data shows that cardiovascular events were reported in 11.4% of patients using sibutramine compared with 10% of patients using a placebo. This difference is higher than expected, suggesting that sibutramine is associated with an increased cardiovascular risk in the study population.

According to the FDA, health care professionals should continue to evaluate the benefits and risks of sibutramine, taking into account individual patient medical histories. Both health care professionals and consumers are encouraged to report side effects from the use of sibutramine to FDA's MedWatch Adverse Event Reporting program.

New Data Show CKD Rates Rising Due to Diabetes
New data confirms that the rate of chronic kidney disease (CKD) is inching upward, keeping pace with the rising rates of diabetes. In late September, the US Renal Data System published its 2009 Annual Data report, which showed the incidence of CKD in the United States. Medicare population is now 9.8%, up from 8.7% reported in last year’s data analysis.

According to a news release from the TMF Health Quality Institute, diabetes, the leading cause of kidney disease, moved closer to affecting one in four Medicare beneficiaries nationally: The newest data show 24.8% have the disease, up from the 23.6% one year earlier. The Texas Department of State Health Services estimates more than 1.8 million Texans have diabetes.

Dallas-based nephrologist Roberto Collazo-Maldonado, MD, is not surprised by the data. “Because Texas has a big problem with diabetes,” Dr. Collazo said, “more people will get kidney disease. If we find it early, we can effectively treat [CKD] to prevent and avoid dialysis. That is, if we find it early.”

The American Diabetes Association recommends people with diabetes have an annual microalbumin test.Fewer than 40% of Texas Medicare beneficiaries with diabetes received this screening in 2007, according to claims data from the Centers for Medicare & Medicaid Services.

“I regularly see patients who discover they have [CKD] when they come to the hospital for emergency treatment because their kidneys have failed,” Dr. Collazo continued. “This is too late. People with diabetes must check their kidney health every year.

Up to 40% of people with diabetes will experience kidney problems in their lifetime, according to the news release from. Minorities with diabetes are also disproportionately affected: blacks are four times more likely than whites to experience kidney failure, and Mexican Americans with diabetes are twice as likely as non-Hispanic whites to have diabetes.

Accounting for 44% of new cases, diabetes is the leading cause of CKD, the US Renal Data System reported in 2007. The second leading cause is high blood pressure. Other risk factors are age, obesity and a family history of kidney problems. TMF Health Quality Institute is an Austin, Texas-based nonprofit consulting company focused on promoting quality health.

Healthy Neighborhoods May Lower Diabetes Risk
Individuals living in neighborhoods conducive to physical activity and providing access to healthy foods may have a lower risk of developing type 2 diabetes in a 5-year period, according to a report in Archives of Internal Medicine.

“The worldwide epidemic of type 2 diabetes is largely driven by the combined rise in obesity, intake of energydense or nutrient-poor foods, and physical inactivity,” the authors wrote as background information in the article. Interventions to reduce risk on the individual level— including surgery, medication, and behavior change— have had mixed results. Large-scale behavior change may be necessary to reverse the diabetes epidemic, but such a change is difficult to achieve and may be unsustainable if the surrounding environment is not supportive, according to a news release from the journal’s publisher.

Amy H. Auchincloss, PhD, MPH, of Drexel University School of Public Health, Philadelphia, and colleagues studied 2,285 adults age 45 to 84 who were initially examined between 2000 and 2002. Study participants were from three of the sites in the MESA (Multi-Ethnic Study of Atherosclerosis) for which neighborhood level data were obtained: Baltimore; Forsyth County, NC; and New York City/Bronx. Blood glucose levels were obtained from study participants at baseline and at three follow-up examinations, during which other individual characteristics also were assessed (including diet, body mass index [BMI], and physical activity levels).

Measures of neighborhood resources were obtained from a separate assessment in which other residents of the same neighborhoods rated the suitability of their environment for physical activity and access to healthy foods. For instance, they were asked if it was pleasant or easy to walk in their neighborhood, and whether a large, high-quality selection of fruits, vegetables and other lowfat foods was available. Scores for physical activity and healthy foods were calculated for each neighborhood on scales of one to five.

Over a median of 5 years of follow-up, 233 of the 2,285 participants (10.2%) developed diabetes. Average neighborhood scores were 3.68 for physical activity and 3.36 for healthy foods.

“Better neighborhood resources, determined by a combined score for physical activity and healthy foods, were associated with a 38% lower incidence of type 2 diabetes,” the authors wrote. This was similar to the reduction in risk observed among individuals whose BMI was five points lower. “The association remained statistically significant after further adjustment for individual dietary factors, physical activity level and BMI.”

The increasing prevalence of type 2 diabetes in the past 30 years makes it urgent to identify environmental features that may mitigate risk, the authors concluded.

Diabetes Education Decreased Health Care Costs
A new study of an extensive database of Medicare and commercial (employee and dependent) member claims revealed that people with diabetes who received diabetes education had lower average health care costs than patients who did not participate in diabetes education. The study was published in The Diabetes Educator and conducted by Solucia Consulting of Farmington, Conn., and underwritten by a grant from the American Association of Diabetes Educators.

Diabetes education is the ongoing process of facilitating the knowledge, skill, and ability necessary for diabetes selfcare. Diabetes education aims to achieve optimal health status, better quality of life and reduce the need for costly health care. It is most often provided by diabetes educators, who are health care professionals that have speciaized training in diabetes care, traditionally drawn from nursing and dietetics and more recently involving pharmacists.

The authors studied 3 years of claims data that reflected care of 634,645 individuals with diabetes. The researchers compared claims from those who received diabetes education with those who did not. According to the analysis, commercially insured patients who received diabetes education cost, on average, 5.7% less than those who did not receive diabetes education. Medicare patients who participated in diabetes education cost the health care system 14% less than Medicare patients who did not participate. Moreover, those who belonged to physician practices that more frequently referred patients for diabetes education had better overall quality care for their diabetes.

AACE Issues Guidelines for Ethical Use of Growth Hormone
AACE has released new medical guidelines for the accurate diagnosis and effective ethical treatment of growth hormone deficiency in affected patients.

According to a news release, growth hormone replacement therapy has proven useful for children and adults with scientifically proven growth hormone deficiency. In recent years, however, human growth hormone (HGH) use for anti-aging and athletic enhancement has increased to the point that this use currently accounts for approximately 30% of growth hormone prescriptions in the United States. A number of professional athletes have now admitted or have been alleged to have used HGH to speed recovery from injury or to enhance performance. Anti-aging centers tout benefits of HGH to slow the aging process.

“Although there is not a wealth of medical data published concerning HGH as a recovery tool for injured athletes, it’s certainly not an approved indication for use,” David Cook, MD, Interim Division Chief of Endocrinology at the Oregon Health & Science University, and coauthor of the new medical guidelines said.

In addition to addressing the increasing misuse of growth hormone in anti-aging and sports, the AACE guidelines more importantly address the accurate diagnosis and effective therapy for growth hormone-deficient patients, as well as new cut points or benchmarks for growth hormone testing.

“These guidelines are the result of recent advancements in our understanding of the benefits of growth hormone replacement for patients,” Dr. Cook said. “Controlled trials, using strict dosing regimes and measuring clinical end points, such as body composition and insulin sensitivity, have shown us that growth hormone dosing should be individualized, with close attention to avoiding side effects,” he said.

According to the news release, the AACE guidelines also outline new cut points for stimulation testing of growth hormone deficiency. Stimulation testing measures normal secretion or low growth hormone secretion, making them an accurate barometer to gauge growth hormone deficiency.

Despite a growing body of evidence on the benefits of growth hormone therapy, there is still considerable inconsistency in the United States in the clinical practice of growth hormone replacement for adults.

“There are multiple factors accounting for this,” Dr. Cook said. “Such as the high cost of growth hormone therapy, the need for daily injections, the lack of awareness regarding its indications, diagnosis, long-term surveillance, and concerns about whether there are long-term risks involved.”

Consequences of untreated growth hormone deficiency include cardiovascular complications, metabolic complications, osteopenia/osteoporosis, and diminished quality of life.

Encouraging Data for Treatment of Low IGF-1
Ipsen announced preliminary results from a phase 2 open-label clinical trial that is evaluating the coadministration of recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor-1 (rhIGF-1) in two separate daily injections as a potential treatment for children with otherwise unexplained short stature associated with low IGF-1 levels.

Ipsen also announced results from a long-term study of rhIGF-1 in patients with severe primary insulin-like growth factor deficiency (sPIGFD) that demonstrated that longterm twice-daily therapy with rhIGF-1 improved the adult and near-adult heights of extremely short patients with sPIGFD. The data from these two studies were presented along with posters on rhIGF-1 (Increlex, mecasermin [rDNA origin] injection) at the 8th Joint Meeting of the Lawson Wilkins Pediatric Endocrine Society/European Society for Pediatric Endocrinology in New York, NY.

These studies were performed under investigational new drug application protocols, and the coadministration of rhGH and rhIGF-1 is not an approved administration regimen for Increlex. Increlex is currently marketed in the United States and other countries for the treatment of growth failure in children with severe primary IGFD using twice-daily injections.

“The data supporting the efficacy and safety of rhIGF-I continue to grow, and these results demonstrate that children with severe primary IGF-I deficiency can improve their adult/near-adult height with long-term IGF-I therapy,” said Philippe F. Backeljauw, MD, Professor of Pediatrics, Cincinnati Children’s Hospital Medical Center. “These results provide increased confidence to treat patients with severe primary IGFD with rhIGF-I.”

Women With Breast Cancer Have Low Vitamin D Levels
Women with breast cancer should be given high doses of vitamin D as a majority of them are likely to have low levels, which could contribute to decreased bone mass and greater risk of fractures, according to scientists at the University of Rochester Medical Center.

In a study of 166 women undergoing treatment for breast cancer, nearly 70% had low levels of serum vitamin D, according to a study presented at the American Society of Clinical Oncology’s Breast Cancer Symposium in San Francisco. The analysis showed women with latestage disease and non-Caucasian women had even lower levels, according to a University of Rochester Medical Center news release.

“Vitamin D is essential to maintaining bone health, and women with breast cancer have accelerated bone loss due to the nature of hormone therapy and chemotherapy. It’s important for women and their doctors to work together to boost their vitamin D intake,” said Luke Peppone, PhD, research assistant professor of Radiation Oncology, at Rochester’s James P. Wilmot Cancer Center. He is a member of the National Cancer Institute’s (NCI) Community Clinical Oncology Program research base in Rochester.

Scientists funded by the NCI analyzed vitamin D levels in each woman, and the average level was 27 ng/mL; more than two-thirds of the women had vitamin deficiency. Weekly supplementation with high doses of vitamin D&MDASH; &GE;50,000 IU or more—improved the levels, according to Dr. Peppone’s study.

The IOM suggests that blood levels nearing 32 ng/mL are adequate. This problem is not unexpected, Dr. Peppone said, because previous studies have shown that nearly half of all men and women are deficient in the nutrient, with vitamin D levels <32 ng/mL. Vitamin D, obtained from milk, fortified cereals and exposure to sunlight, is well known to play an essential role in cell growth, in boosting the body’s immune system and in strengthening bones. Symptoms of vitamin D deficiency include muscle pain, weak bones/fractures, low energy and fatigue, lowered immunity, symptoms of depression and mood swings, and sleep irregularities, many of which are common for women undergoing breast cancer treatment.

Link Found Between Osteoporosis and Celiac Disease
People with celiac disease may develop osteoporosis because their immune system attacks their bone tissue, a new study has shown. It is the first time an autoimmune responsehas been shown to cause damage to bones directly.

Researchers from the University of Edinburgh studied a protein called osteoprotegerin (OPG) in people with celiac disease—a digestive condition that affects 1 in 100 people. In healthy people, OPG plays a crucial role in maintaining bone health by controlling the rate at which bone tissue is removed. This research is reported in the New England Journal of Medicine.

According to a news release from University of Edinburgh, the latest research shows that 20% of celiac patients produce antibodies that attack the OPG protein and stop it from working properly. This results in rapid bone destruction and severe osteoporosis. It was previously thought that osteoporosis—a known complication of celiac disease—develops in celiac patients because they cannot properly absorb calcium and vitamin D from their diet. Both nutrients are essential for healthy bone development. The team found that although this new form of osteoporosis did not respond to calcium and vitamin D supplements, it can be easily treated with drugs that prevent bone loss.

Prof. Stuart Ralston, of the Institute of Genetics and Molecular Medicine at the University of Edinburgh, who led the team, said: “This is a very exciting step forward. Not only have we discovered a new reason to explain why osteoporosis occurs in celiac disease, but we have also found that it responds very well to drugs that prevent bone tissue removal. Testing for these antibodies could make a real and important difference to the lives of people with celiac disease by alerting us to the risk of osteoporosis and helping us find the correct treatment for them.”