News — September/October 2009

Rates of Severe Childhood Obesity Have Tripled Over the Last 25 Years
Rates of severe childhood obesity have tripled in the last 25 years, putting many children at risk for diabetes and heart disease, according to a report in Academic Pediatrics by an obesity expert at Brenner Children's Hospital, part of Wake Forest University Baptist Medical Center.

"Children are not only becoming obese, but becoming severely obese, which impacts their overall health," said Joseph Skelton, MD, lead author and director of the Brenner FIT (Families in Training) Program. "These findings reinforce the fact that medically based programs to treat obesity are needed throughout the United States, and insurance companies should be encouraged to cover this care."

Dr. Skelton and colleagues compared data from the NHANES (National Health and Nutrition Examination Survey). According to a news release from Wake Forest, they looked at the prevalence of obesity and severe obesity in a study population of 12,384 children, representing approximately 71 million US children aged 2 to 19 years.

Severe childhood obesity—a new classification for children—describes those with a body mass index (BMI) ≥99th percentile for age and gender. The research by Dr. Skelton and colleagues is the first of its kind to use the new classification and detail the severity of the problem. They found that the prevalence of severe obesity tripled (from 0.8% to 3.8%) from 1976 to 1980 and 1999 to 2004. Based on the data, there are 2.7 million children in this country who are considered severely obese.

Researchers also looked at the impact of severe obesity and found that one-third of children in the severely obese category were classified as having metabolic syndrome. "These findings demonstrate the significant health risks facing this morbidly obese group," wrote the researchers in their report. "This places demands on health care and community services, especially because the highest rates are among children who are frequently underserved by the health care system."

Short-Term Risks Post-Bariatric Surgery are Low
Short-term complications and death rates were low following bariatric surgery to limit the amount of food that can enter the stomach, decrease absorption of food, or both, according to LABS-1 (Longitudinal Assessment of Bariatric Surgery). The study—funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)—was reported in the New England Journal of Medicine.

According to coauthor Myrlene Staten, MD, Senior Advisor for Diabetes Translation Research at NIDDK, and colleagues, <1% of patients died within 30 days of surgery, further supporting the short-term safety of bariatric surgery as a treatment for patients with extreme obesity. Although bariatric surgery can have dramatic health benefits, such as improved blood sugar control or even reversal of type 2 diabetes, it carries serious risks. LABS-1 sought to evaluate the short-term safety of bariatric surgery to help doctors and patients understand these risks.

"Evaluating the 30-day safety outcomes of bariatric surgery in large populations is an essential step forward," said Dr. Staten in a news release from NIDDK. "And LABS-1 data are from all patients who had their procedure performed by a surgeon participating in the study, not from just a select few patients."

The LABS-1 consortium followed 4, 776 patients who had bariatric surgery for the first time, evaluating complications and death rates within the first 30 days postoperatively. Patients were aged ≥18 years and had an average BMI of 44 kg/m².

HF, Death Risk Higher With Rosiglitazone Vs Pioglitazone
Rosiglitazone (Avandia, GlaxoSmithKline) is associated with an increased risk of heart failure and death among older patients compared with pioglitazone (Actos, Takeda), according to a study in the British Medical Journal.

The researchers said it is difficult to advocate continued use of rosiglitazone for most patients, according to a news release from the journal. It has been unclear whether there are clinically important differences in the cardiac safety of these two drugs; therefore, researchers in Canada compared the risk of myocardial infarction (MI), heart failure, and death in patients treated with rosiglitazone and pioglitazone. Using prescription records, they identified nearly 40,000 patients aged ≥66 years who started treatment with either rosiglitazone or pioglitazone between April 2002 and March 2008.

Data on hospital admission for either MI or heart failure during the 6-year study period were recorded, and deaths were identified from a national database. Detailed analysis showed that patients treated with pioglitazone had a significantly lower risk of heart failure and death compared with patients treated with rosiglitazone, but there was no significant difference in the risk of MI. The researchers estimated that, for every 93 patients treated with rosiglitazone rather than pioglitazone, one additional cardiovascular event or death would be predicted to occur annually.

Liraglutide Improved Glycemic Control, Weight in Blacks
When taken by itself, once-daily liraglutide (Victoza, Novo Nordisk), an investigational treatment for type 2 diabetes, leads to statistically significant and sustained reductions in blood sugar and weight in blacks with type 2 diabetes, as compared to glimepiride. The data were presented at the 114th National Medical Association Annual Convention & Scientific Assembly.

According to a news release from the drug's manufacturer, blacks are 1.6 times more likely to have diabetes than non-Hispanic whites, and almost 15% of all blacks aged ≥20 years have diabetes. In the study, 64% of black patients treated with liraglutide 1.8 mg once a day and 29% treated with liraglutide 1.2 mg once daily reached and maintained the American Diabetes Association's A1C target, versus 11% of patients treated with glimepiride 8 mg once daily after 52 weeks.

"Because African Americans are among the most affected by diabetes, it is important that we consider how these patients respond to potential treatments," said Mansur Shomali, MD, Union Memorial Hospital, Baltimore, and lead author of the study. "In this study, liraglutide not only lowered blood sugar, but patients lost weight as well. This is good news for these patients who are often struggling to control their disease."

Type 1 Diabetes Complications Halved By Tight Control
Near-normal control of glucose beginning as soon as possible after diagnosis would greatly improve the long-term prognosis of type 1 diabetes, concluded a study in the Archives of Internal Medicine. The study also found that the outlook for people with long-standing type 1 diabetes has greatly improved in the past 20 years due to a better understanding of the importance of intensive glucose control as well as advances in insulin formulations, insulin delivery, glucose monitoring, and the treatment of cardiovascular risk factors.

"The demonstration that near-normal glucose control substantially lowers microvascular and cardiovascular complications has heralded a new era of type 1 diabetes care," said lead author David M. Nathan, MD, of Massachusetts General Hospital in a news release from the NIDDK. Dr. Nathan is co-chair of the landmark DCCT (Diabetes Control and Complications Trial) and its follow-up study, EDIC (Epidemiology of Diabetes Interventions and Complications), both funded by the National Institutes of Health.

"The remarkable improvement in long-term outcomes achieved with intensive glucose control should encourage clinicians and patients alike to implement intensive therapy as early in the course of type 1 diabetes as possible."

DCCT found that intensive glucose control was superior to conventional control in delaying or preventing the complications of type 1 diabetes. EDIC continues to follow DCCT participants to determine the long-term effects of prior intensive versus conventional blood glucose control.

MRI May Help Diagnosis, Staging, Treatment of Diabetes
Magnetic resonance imaging (MRI) may aid physicians in the early diagnosis, staging, and treatment of diabetes, according to a study published in the American Journal of Roentgenology.

This is the first study of its kind to apply noninvasive imaging techniques to diabetes research, according to a news release from the American Roentgen Ray Society.

"With noninvasive MRI, we have the ability to evaluate beta-cell mass, a major factor of insulin secretion that is significantly reduced in type 2 diabetes and almost gone in type 1," said lead author Anna Moore, MD, Molecular Imaging Laboratory, Massachusetts General Hospital and Harvard Medical School. "We are also able to detect inflammation of the pancreas and vascular changes associated with type 1 and type 2 diabetes. This opens a huge area that is closed right now," said Dr. Moore. "Knowing the number of functional beta cells left would allow physicians to develop the most appropriate treatment plans for their patients. It would also allow them to respond, change, or manipulate those treatment plans at any time. Noninvasive MRI could … assist in achieving insulin independence in patients with diabetes."

FDA Approves Saxagliptin for Type 2 Diabetes Patients
Bristol-Myers Squibb Company and AstraZeneca announced US Food and Drug Administration (FDA) approval of saxagliptin (Onglyza), a dipeptidyl peptidase-4 (DPP-4) inhibitor. According to the company's news release, the agent is indicated as an adjunct to diet and exercise to improve glycemic control in adults for the treatment of type 2 diabetes.

Saxagliptin once daily can be used in combination with commonly prescribed oral antidiabetic medications or as a monotherapy to significantly reduce A1C.

The approval is based on a clinical development program, which included approximately 5,000 patients, more than 4,000 of whom received saxagliptin. As part of the development program, saxagliptin, with diet and exercise, was studied as add-on therapy with other oral antidiabetic medications, including metformin, the sulfonylurea glyburide, and thiazolidinediones; in adults new to diabetes therapy starting metformin and saxagliptin together; and as a monotherapy.

FDA Approves Pitavastatin for Primary Hypercholesterolemia
The FDA has approved pitavastatin (Livalo, Kowa Pharmaceuticals America, Inc), an HMG-CoA reductase inhibitor (statin), for the primary treatment of hypercholesterolemia and combined dyslipidemia.

"[Pitavastatin] has a robust safety, efficacy, and tolerability profile and offers an attractive alternative for patients with primary hypercholesterolemia or combined dyslipidemia," said Antonio M. Gotto Jr, MD, DPhil, the Stephen and Suzanne Weiss Dean of Weill Medical College of Cornell University, in a company news release. "[Pitavastatin] has very positive attributes that will help continue to fill current unmet needs in the statin market for clinically complex patient populations, such as the elderly, patients with diabetes or patients who take multiple medications for co-morbid conditions."

Pitavastatin differs from other statins in that it has a unique cyclopropyl group on the base structure. This cyclopropyl group contributes to a more effective inhibition of the HMG-CoA reductase enzyme to inhibit cholesterol production, and potentially affords greater low-density lipoprotein cholesterol clearance and reduction of plasma cholesterol, according to Kowa. Additionally, it is only minimally metabolized through the cytochrome P450 pathway.

Medicare: Cover DXA in Men With Testosterone Deficiency
Hypogonadism affects 4 to 5 million men in the United States placing them at risk for developing osteoporosis. Despite the clear association of testosterone deficiency with low bone density and osteoporosis, Medicare does not provide coverage for bone density testing for these individuals. To address this concern, The Endocrine Society issued a Position Statement, endorsed by the National Osteoporosis Foundation, calling for Medicare coverage of bone mineral density (BMD) testing for this at-risk population.

BMD measured by dual energy x-ray absorptiometry (DXA), is an excellent predictor of the risk of fractures in both men and women. Nationally, Medicare currently provides coverage for DXA scans in men only when an individual has been previously diagnosed with osteoporosis, osteopenia or has had a vertebral bone fracture. This means that most men found to have osteoporosis are diagnosed only after a hip or spine fracture.

"The lack of Medicare coverage for DXA scans in men with hypogonadism results in underdiagnosis and undertreatment of osteoporosis, resulting in significant morbidity, mortality,and cost to society," said Robert Vigersky, MD, Endocrine Society President. "The Endocrine Society recommends widening the scope of Medicare coverage to include bone density scans for men with testosterone deficiency."

Takeda Initiates Cardiovascular Outcomes Trial for Alogliptin
Takeda Pharmaceutical Company announced that it has received notification from the FDA agreeing to the study design for a cardiovascular outcomes trial for alogliptin. Alogliptin is a selective DPP-4 inhibitor under investigation for the treatment of type 2 diabetes as an adjunct to diet and exercise.

The EXAMINE (Examination of Cardiovascular Outcomes: Alogliptin vs Standard of Care in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome) trial is designed to comply with the new FDA guidance regarding additional cardiovascular safety trials in diabetes.