DEFEATING A DANGEROUS DUO
Willa Hsueh takes on the fight against diabetes and high blood pressure afflicting the Latino community.
by Christopher Tedeschi
In the neighborhoods surrounding LAC+USC Medical Center, one in ten Latino adults develops diabetes. The number is startling, nearly twice the rate of diabetes in the general population. High blood pressure often accompanies the disease-the two tend to travel as a dangerous pair throughout extended families.
Willa Hsueh, M.D., professor of medicine and chief of the division of endocrinology, diabetes, and hypertension, has been tracing the roots of those conditions, specifically in Latinos, for the better part of her career.
"Adult-onset diabetes is epidemic in the local community," Hsueh says. "And our division has received grant after grant to study diabetes and high blood pressure with projects specifically geared to Latinos," with grants totaling $15 million from the National Institutes of Health.
For more than 15 years, Hsueh, whose last name is pronounced "shoi," has been at USC investigating the connections between diabetes and high blood pressure, or hypertension, and trying to discover how the two conditions behave specifically in Latino populations.
The high concentration of Latinos in the areas surrounding USC's School of Medicine has been a naturally-occurring source of case studies since the medical center opened a ward for diabetic patients in 1934. By the mid 1960s, the diabetes service was treating more than 3,000 inpatients each year.
Many of those patients were Latino, and their physicians soon came to realize that the incidence of adult-onset, or type-II, diabetes in the Latino population seemed to be much higher than the rate of incidence for other ethnic groups. Ever since, USC researchers have been trying to understand why, and looking toward therapies for both diabetes and hypertension tailored particularly to the needs of the Latino community.
Hsueh became part of that research effort in 1979, when she became an assistant professor of medicine in what was then called the section of endocrinology. Richard Horton, M.D., professor of medicine and chief of endocrinology at the time, recalls Hsueh then as "clearly a young potential star."
"Looking at what she had done in her fellowship, when she was young and just starting her career, you could tell that she had great talents and abilities," Horton recalls.
Hsueh was one of several key diabetes and hypertension researchers recruited to USC in the late '70s and early '80s. Shortly afterward, Horton recruited Adina Zeidler, M.D., now a professor of medicine conducting research on the prevention of type-1, or insulin-dependent diabetes.
At about the same time, Diabetes Division Chief George Bray, M.D., recruited Thomas Buchanan, M.D., to the division's rapidly growing research core. Buchanan, an associate professor of medicine and obstetrics and gynecology, joined the diabetes division in 1986. He now investigates the link between increased insulin resistance during pregnancy and diabetes onset later in life.
The addition of Hsueh, Zeidler and Buchanan "started our division on a heavily research-oriented pathway," says Horton.
Hsueh began serving as chief of the division of diabetes, hypertension and nutrition in 1989. When her division merged with Horton's endocrinology section in 1993, she became chief of the newly formed division of endocrinology, diabetes and hypertension.
She's now ready to zero in on the molecular underpinnings of high blood pressure. The National Heart, Lung and Blood Institute, part of the National Institutes of Health, recently awarded Hsueh's research team a five-year, $7 million grant to investigate the molecular genetics of hypertension among Latinos.
Some diseases, like cystic fibrosis or sickle-cell anemia, result when a single gene fails to work correctly. But it takes the cumulative influence of many genes to lead to a propensity for hypertension.
Hsueh's project will focus on characterizing genetic similarities in groups of people with hypertension, while trying to determine if families with certain genetic markers are prone to the disease. Results could point towards treatments designed for particular genetic varieties of the problem.
A new SCOR grant-for Specialized Centers of Research-will propel the division's already-strong research core into the multidisciplinary worlds of epidemiology and molecular genetics.
Over the next four and a half years, Hsueh and her colleagues plan on enrolling nearly 1,200 participants in the hypertension study. Since the researchers are examining hereditary patterns of high blood pressure, they will concentrate on recruiting closely-related family groups. A typical family enrolled in the project might consist of an individual with high blood pressure, as well as that individual's adult children, brothers, sisters, and parents.
The molecular studies could point to strong links between high blood pressure and diabetes. Scientists have already learned that certain factors, like the body's sensitivity to salt and resistance to the hormone insulin, may play a role in the onset of both diseases. The SCOR project will allow researchers to work with large numbers of families to understand better the dubious relationship.
Hsueh hopes to learn how several genes might work together to influence particular kinds of hypertension specifically in Latinos. "The impact of certain genes could be different in different populations," she says.
The research could eventually have an impact on treatment for high blood pressure. Many different classes of hypertension drugs exist, Hsueh says, and physicians often need to find the best one for their patients in a costly, inefficient trial-and-error fashion. But knowing the most likely genetic roots of hypertension in particular populations would eventually allow doctors to select the proper medication the first time around.
"Finding genetic explanations for the disease will help us to understand the specific disease characteristics relevant to our population, and then suggest a way to tailor a treatment to that population," she predicts.
So the nearly 100 Latino families ready to take part in the SCOR program will be providing information that could improve future diagnosis and treatment of high blood pressure, while receiving care from one of the best teams in the game.
o o o
PHENOMENAL FOOD
For years, Barbara Averill suffered nightly blood sugar drops so severe they threatened to plunge her into a diabetic coma as she slept.
To maintain her blood sugar levels, she used to get up three times a night to test her blood and snack on the candy, graham crackers and orange juice that remained in arm's reach on her nightstand.
"I used to have bad nights once a week because my blood sugar wouldn't go back up. Now I barely have them at all," said Averill, 32, of Grand Rapids, Mich.
Averill is one of the first people to benefit from a new medical food, called "Zbar," designed to reduce the incidence of hypoglycemia among insulin-dependent diabetics.
Created by Francine Kaufman, M.D., associate professor of pediatrics at the USC School of Medicine and an endocrinologist and researcher at Childrens Hospital Los Angeles (CHLA), Zbar helps diabetics like Averill to maintain a more stable blood sugar level, especially overnight.
Kaufman, who has been with CHLA since serving her internship in 1976, worked with Baker Norton Pharmaceuticals Inc., to formulate uncooked cornstarch, which usually has an unpleasant taste, into a tasty 110-calorie bar that is low in fat.
The uncooked cornstarch, the bar's active ingredient, is a complex carbohydrate which triggers gradual and consistent absorption of glucose by the body.
Kaufman said the bar is not designed to rescue people suffering from hypoglycemia, but is effective in preventing the condition.
While most carbohydrates are completely absorbed by the body within three hours, Zbar can take as long as nine hours to absorb, assuring a steady supply of glucose for the body.
In a recent study at a summer camp for diabetics, age 14 to 30, Kaufman showed that the bar decreased hypoglycemia events by as much as 78 percent among those who consumed it compared to those who did not.
Reducing the number of low blood sugar episodes also indirectly reduces the number of hyperglycemia-excessive blood sugar- episodes because people have a tendency to overtreat a low reaction, Kaufman said.
Zbars, available in chocolate crunch, mandarin orange and peanut butter flavors, sell for about a dollar each. Although consumers can purchase Zbars without a prescription, they are intended for use under medical supervision and will be marketed exclusively through pharmacies.
About 8 million Americans are currently under treatment for diabetes and of those, 3.8 million are on insulin therapy.
"So far, the positive response has been overwhelming," Kaufman said. "I've spent my life in academic medicine and it feels pretty good when you realize where your contribution can be made."
Averill, who has suffered from diabetes for 21 years, said, "I tell everyone about Zbar. It's phenomenal. There's no other way to describe it."
Jon Nalick
