You are viewing the Ward Rounds Online Archive. To view the current issue, click here.

Departments

Research Briefs

Online Extra

Twice as Many Women to be Diagnosed with Gestational Diabetes

Two to three times more pregnant women may soon be diagnosed and treated for gestational diabetes based on new measurements for determining risky blood sugar levels for the mother and her unborn baby, according to a study that was coordinated by investigators at Northwestern University Feinberg School of Medicine.

“As result of this study, more than 16 percent of the entire population of pregnant women qualified as having gestational diabetes,” said lead author Boyd Metzger, MD, the Tom D. Spies Professor of Metabolism and Nutrition at Feinberg and a physician at Northwestern Memorial Hospital. “Before, between 5 to 8 percent of pregnant women were diagnosed with this.”

Blood sugar levels that were once considered in the normal range are now seen as causing a sharp increase in the occurrence of overweight babies with high insulin levels, early deliveries, cesarean section deliveries, and potentially life-threatening preeclampsia, a condition in which the mother has high blood pressure that affects her and the baby.

The study was published in the March issue of Diabetes Care, a journal of the American Diabetes Association.

The good news, Metzger noted, is recent studies show women with mild gestational diabetes, who were treated with lifestyle and diet changes as well as blood sugar monitoring, greatly reduced their risk of complications. As a result of treatment, the women had smaller babies, fewer cesarean deliveries and less preeclampsia, Metzger said.

For the past decade, the rate of gestational diabetes as previously measured has soared as much as 50 percent. "We shouldn't be surprised," Metzger said. "The fact that we have a lot of gestational diabetes to deal with is consistent with the major impact that diabetes and obesity are having in our population at large. How could we expect pregnancy to escape that?”

Online Extra

A Better Way to Predict Heart Attacks

Every year, thousands of people get heart scans that provide pictures of calcium deposits in their coronary arteries. Studies have shown that the coronary artery calcium score (CACS) can point to signs of atherosclerosis and predict future heart attacks.

A new Northwestern University Feinberg School of Medicine study shows for the first time that using the CACS, while also considering traditional risk factors for heart disease (age, gender, tobacco use, blood pressure, antihypertensive medication use, cholesterol levels and race/ethnicity), is a better method than using traditional measures alone to predict future heart attacks. 

"Almost one-quarter of the people in the study who had heart attacks were considered intermediate risk based on traditional risk factors alone, but were considered high risk once we included their CACS," said lead author Tamar Polonsky, MD, post-doctoral fellow in cardiovascular epidemiology and prevention at Feinberg.
Polonsky, senior author Philip Greenland, MD, the Harry W. Dingman Professor of Cardiology at Feinberg, and a team of researchers explained their discovery in a paper published in the Journal of the American Medical Association on April 28, 2010.

Beginning in July 2000, more than 6,000 volunteers from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort, were evaluated for heart disease risk using traditional risk factors and the CACS test. The volunteers, between the ages of 45 and 84, identified themselves as white, black, Hispanic or Chinese and had no known cardiovascular disease.

Nearly six years later, 209 of the participants had some type of coronary heart disease event. When looking at the risk levels of those who experienced a heart attack or serious chest pain, researchers found that the CACS was key in classifying people in the most extreme categories.

"Ours is the first study to show that the CACS test, applied in a large population, actually puts more people who experience events in the high-risk category and more people who do not have events in the low-risk category," said Greenland. "So the test is effective. It sorts people properly."

Getting your CACS is not without additional cost — it is rarely covered by insurance — and there are risks.

"It is a test that has radiation exposure — about the same as two mammograms," Greenland said. "It is not a test your family doctor can do in the office when you do your blood work. You would have to go to a separate radiology clinic."

While the study suggests that a CACS could help doctors better identify people who would benefit from more aggressive treatment of their risk factors or who might be able to hold off on starting medication, Greenland said more research needs to be done before the test is routinely recommended.

Online Extra

Researchers Discover Genetic Link Between Both Types of ALS

Researchers from Northwestern University Feinberg School of Medicine have discovered a link between sporadic and familial forms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease also known as Lou Gehrig’s disease.

Researchers found that a protein called FUS forms characteristic skein-like cytoplasmic inclusions in spinal motor neurons in most cases of ALS. Mutations in this gene have been previously linked to a small subset of familial ALS cases. Researchers thus linked a rare genetic cause to most cases of ALS, clearing the way for rational therapy based on a known molecular target.

The study was recently published online in the Annals of Neurology.

ALS is a disease in which muscle-controlling nerve cells in the brain and spinal cord (motor neurons) die, resulting in rapidly progressive paralysis and death usually within three to five years of the onset of symptoms. Most cases of ALS are of unknown etiology and appear as sporadic ALS. About 5 to 10 percent of ALS cases are familial. Some forms of familial ALS are caused by genetic mutations in specific genes. Mutations in the Cu/Zn superoxide dismutase gene (SOD1) account for approximately 20 percent of these cases. Mutations in the TAR DNA-binding protein gene (TDP43) and FUS gene occur in about 4 to 5 percent of familial ALS cases. Altogether, mutations in specific genes have been identified in about 30 percent of these cases. 

In contrast to familial ALS, the etiology and the pathogenic mechanisms underlying sporadic ALS — 90 percent of all ALS — has remained largely unknown and is a major challenge.

For this study, researchers examined the post-mortem spinal cords and brains of 100 cases, 78 with ALS and 22 in a control group. They found FUS pathology in the spinal cords of all the ALS cases, except for a few with SOD1 mutations. But FUS pathology was not present in control cases without ALS.

“This is a game changer because it establishes a connection in the development of sporadic ALS with a known cause of familial ALS,” said senior author Teepu Siddique, M.D., the Les Turner ALS Foundation/ Herbert C. Wenske Professor of the Davee Department of Neurology and Clinical Neurosciences at Feinberg and a neurologist at Northwestern Memorial Hospital.

“Our finding opens up a new field of investigation for rational therapy for all of ALS,” Siddique added. “This is the holy grail of researchers in this field.”

"There hasn’t been a therapy for most of ALS, because the cause was unknown," Siddique said. “Three genes have been identified in ALS, but the problem has been connecting inherited ALS to sporadic ALS.”

“We identified the FUS pathology in sporadic ALS and most familial ALS cases,” said Han-Xiang Deng, M.D., associate professor of neurology at Feinberg and lead author of the paper. “The patients with the FUS pathology may account for about 90 percent of all ALS cases. Our findings suggest that pathological interaction of FUS with other proteins is a common theme in motor neuron degeneration in the vast majority of the ALS cases. We believe that this is a major step forward in formulating a common pathogenic pathway for motor neuron degeneration. Importantly, it may offer a novel avenue for developing therapies through targeting these FUS-containing inclusions.”

The one exception to the new finding is when familial ALS is associated with a mutation on the SOD1 gene. In those patients, and in the mutant SOD1 transgenic mouse models, researchers did not find evidence of FUS pathology.

“This tells us that it follows a different pathway of pathogenesis, so treatment for this form of the disease would have to be different,” Deng said.

The study is supported by the National Institutes of Health, the Les Turner ALS Foundation, the Vena E. Schaff ALS Research Fund, the Harold Post Research Professorship, the Herbert and Florence C. Wenske Foundation, the David C. Asselin MD Memorial Fund and the Les Turner ALS Foundation/Herbert and Florence C. Wenske Professorship.

Online Extra

Can Exercise Prevent Disability in Older Adults?

A new study will test if exercise can prevent or delay the declining ability to walk in older adults.

Called the Lifestyle Interventions and Independence for Elders, or LIFE study, which is being funded by the National Institutes of Health, will enroll 1,600 sedentary older adults between the ages of 70 and 89 who are at risk of mobility disability. Northwestern, one of eight institutions around the country conducting the trial, will enroll 200 participants. It is the largest randomized, controlled trial ever conducted on physical activity in older adults.

"The results will provide definitive evidence, for the first time, about whether exercise can prevent decline in walking ability in an older, frail population," said lead investigator Mary McDermott, M.D., professor of medicine at Feinberg and a physician at Northwestern Memorial Hospital. "The study is of utmost importance given the aging of the population and the fact that older men and women are living longer with chronic disease. Maintaining independence is one of our public health priorities for older adults."

Little is known about whether specific interventions can help prevent major mobility disability, defined as the inability to walk a quarter of a mile or four blocks. For older adults, staving off disability could help them maintain their physical independence and enhance the quality of their later years.

The LIFE study will compare the long-term effectiveness and practicality of two interventions: a physical activity program and a successful aging health education program.

Eligible participants will be randomly assigned to take part in either a structured physical activity program that includes moderate- intensity physical activity such as walking and exercises to improve strength, balance and flexibility, or in a successful aging program that includes health education workshops and supervised stretching. 

Individuals will be followed for up to approximately four years. To enroll or learn more about the LIFE study, call 312-503-5223 or toll-free 866-386-7730.