A national trial probes the relationship between diabetes and cardiovascular disease

Mary Ellen Harvey ’58 has known about her type 2 diabetes for nearly 20 years. She wasn’t, however, managing it very well on her own.

The 70-year-old retired social worker knew she had a serious disease and that she should be more careful about it, but it was so easy to cheat. If she knew her blood sugar was going to be high because of something she had eaten, she simply didn’t test it.

What she didn’t know wouldn’t worry her, right?

All that changed when she signed up to participate in ACCORD (Action to Control Cardiovascular Risk in Diabetes), a nation-wide type-2-diabetes management trial. Washington State University Spokane is one of the 70 sites where the ACCORD trial is occurring. Harvey’s participation in the trial, along with that of thousands of other diabetics throughout the country, is helping researchers learn more about preventing the high blood glucose, high blood pressure, and high cholesterol that often accompany diabetes and subsequently cause cardiovascular disease.

For nearly four years now, Harvey has been writing down what she eats and when, and information about anything else that may affect her blood sugar level. About once a month, she carries her diabetes journal and her blood glucose meter to the third floor of WSU’s Health Sciences Building in Spokane.

For an hour or two, she reviews her journal with a researcher and talks about her diabetes. She has her blood pressure checked and blood drawn for an A1C test, which measures the amount of sugar that has attached to her red blood cells, indicating how well her diabetes has been controlled. Researchers download the readings of her blood glucose meter into a computer so they can track trends and make adjustments to her medications.

“My A1C was like 8.2 when I started, and today it was 6.0,” Harvey says during an exam.

That 6.0 level is exactly what the researchers want their higher glycemic patients to shoot for, or a little lower if possible. It’s the first time since joining the trial that Harvey has achieved this low number.

As Harvey talks, WSU researcher Peter Huynh examines her journal and meter readings. He points to a high blood sugar reading and asks what happened.

“I had the samples at Costco,” she says. “It was probably too late in the afternoon, or too close to meal time.”

Huynh makes some notations, then continues to examine her readings.

“You would never get this kind of follow-up with a regular doctor,” Harvey says. “It’s very helpful, so you know what to do later.”

But knowing what to do, and being able to do it, is complicated.

Part of Harvey’s task in the trial is to estimate how many carbohydrates she will consume at a meal, give herself an injection of enough insulin to compensate for those carbohydrates, and then use the blood glucose meter a couple of hours later to see how she is doing.

“It’s very difficult to estimate carbs if you haven’t prepared the food,” Harvey says. “Like eating at a buffet. That is just dynamite.”

Timing of meals is important, too, she says.

“It kind of cuts down on the spontaneity of your life. You don’t shop an extra half an hour. You have to have your meal.”

The incidence of type 2 diabetes in the United States has skyrocketed in the last 10 years, and the U.S. Centers for Disease Control and Prevention projects that at the current rate, one in three Americans born in 2000 will develop diabetes during his or her lifetime.

Diabetes is now the sixth leading cause of death in the United States. The cost is enormous. One in 10 health care dollars spent in 2002 was for diabetes, according to the American Diabetes Association. Type 2 diabetes is often referred to as a lifestyle disease, because it is closely associated with obesity and physical inactivity. It accounts for 90 to 95 percent of all diagnosed cases of diabetes in the country, according to the ADA.

Other factors associated with type 2 include older age, a family history of diabetes, an impaired glucose tolerance, and a history of diabetes during pregnancy.

On average, Hispanics and African-Americans are twice as likely to be diagnosed with diabetes as whites, while Native Americans are more likely yet, at 2.6 times the rate for whites, according to the CDC. Some Asian Americans, Native Hawaiians, and other Pacific Islanders also are at higher risk.

In type 2 diabetes, the body either does not produce enough insulin or, more commonly, the cells ignore the insulin, precipitating a gradual decline in the ability of the pancreas to produce insulin.

The body needs insulin to use sugar, which is the basic fuel for the body’s cells.

When sugar builds up in the blood instead of going into cells, it causes higher blood sugar levels, which over time can damage the eyes, kidneys, nerves, or heart, and the cells of the body become starved for energy.

Type 1 diabetes, on the other hand, develops when the body’s immune system destroys the cells in the pancreas that make insulin. Type 1 usually strikes children and young adults and accounts for 5 to 10 percent of all diagnosed cases.

The complications from type 2 diabetes are many, ranging from gum disease to kidney failure, amputations, and blindness.

A government diabetes prevention and control program in the Washington State Department of Health reported in August 2004 that 11 people die every day in the state of Washington from preventable complications of diabetes.

Furthermore, three people suffer an amputation every day, two people experience kidney failure, one person goes blind, and 176 people are hospitalized because of complications that could have been prevented.

Every Tuesday morning, Dr. Carol Wysham of the Rockwood Clinic in Spokane visits the third floor of the Health Sciences Building to see patients in the trial.

It was Wysham who took the first step to make Spokane a site for the ACCORD trial. Wysham asked John White, a pharmacy professor at WSU, to share leadership with her on the project.

White is a certified physician’s assistant as well as a doctor of pharmacy and has been involved in diabetes teaching and research since he was a student at the University of California at San Francisco in 1987. He is co-author of a book for the American Diabetes Association called Medications for the Treatment of Diabetes.

Wysham and White enlisted a professor in the WSU food science and human nutrition program in the same building who was willing to educate new patients about how to count carbohydrates. Peter Huynh, a pharmacy graduate doing a residency at Virginia Mason Medical Center in Seattle, became interested in doing a fellowship in diabetes with White.

Wysham’s medical practice in endocrinology in Spokane comprises a large number of patients with diabetes. She has practiced nearly 20 years, but she thought participating in a National Institutes of Health clinical trial might give her some additional experience.

“We spend an inordinate amount of time, energy, and dollars managing patients’ diabetes and trying to meet the American Diabetes Association standards on blood pressure, glucose, and cholesterol,” Wysham says, “but there are no studies that say how low you are supposed to go with blood sugars. It just appears lower is better.”

The ACCORD trial will at least show what happens to blood pressure and cholesterol levels when blood sugar is down to 6.0 or below, she says.

The researchers had enrolled 122 patients in the study by early summer.

Harvey was diagnosed with type 2 diabetes when she was in her early 50s after she was treated with prednisone and chemotherapy for a kidney disease.

“It may have been related to that, but I probably would have gotten it anyway,” she says. “My mother and a brother were diabetic.”

She was a good candidate for the clinical trial. This trial wants patients who have had complications, says Debbie
Weeks, the licensed practical nurse and certified clinical research coordinator who was the first person hired after the grant was awarded. She coordinates the trial.

Weeks and Peter Huynh, the pharmacy graduate who was hired after Weeks and who is working to become a certified diabetes educator, spend 30 to 40 percent of their time recruiting patients into the trial, which they have found to be the hardest part of their jobs.

They have to find patients willing to check their blood sugar several times a day, take their medications as prescribed, write down their food choices and other factors that may affect their blood sugar, and submit to the equivalent of a doctor’s examination regularly.

In exchange, the patients receive free medicine, insulin syringes, other supplies, and more intense health care than they would receive elsewhere.

“We do a lot of counseling, a lot of troubleshooting,” Weeks says.

One woman couldn’t afford to buy fresh fruits and vegetables for her diet, so they worked with her and helped her figure out how she could make that a priority. Another woman just couldn’t seem to get her blood sugar under control until Weeks and Huynh asked her to demonstrate her insulin technique. They then discovered she wasn’t drawing any insulin into the syringe but didn’t know it, because her cataracts kept her from seeing the syringe clearly.

From then on, either the woman’s husband helped her, or one of the clinical trial staff pre-filled her syringes, Weeks says.

Many of the patients don’t like the idea of taking insulin, Weeks says. “We try to be supportive of them. We start preparing them right away that they may need to take insulin. Peter and I have given ourselves injections in front of people. It helps take the initial shock out of doing it to themselves.”

At last count, more than 9,000 people were participating in the ACCORD study nationwide. William Foster, 63, of Spokane heard about it from his doctor and enrolled about two years ago.

Foster had heart bypass surgery in 1991 and again in 2001. After he experienced blurry vision about nine years ago, he was diagnosed with diabetes. He was taking 12 medications when his doctor said enrolling in the clinical trial might be helpful.

He had never taken insulin before and had always understood his doctors to say it was bad for him. But now he gives himself a shot of insulin before bed and then one shot of another fast-acting insulin before meals.

“There’s nothing difficult about giving shots,” Foster says now.

He is checking his blood sugar more frequently than he did before, because he is accountable to the researchers.

“They supply me with a meter, pills, and shots, check my A1C monthly instead of every six months,” Foster says. “They keep right on top of you. Where if you go to a regular doctor, they tell you it’s up to you. Here, it’s still up to you, but they would chew me out or give me the boot if I didn’t do it.”

He is watching his diet more closely, too, since he learned how to count carbohydrates.

A baked potato is 85 on the glycemic index, whereas table sugar is 65. “I don’t eat too many baked potatoes anymore,” Foster says.

He notes meats and salads are all zero on the glycemic index, which is a measure of a food’s effect on blood sugar levels.

“You go and eat a hamburger, and it’s the bun that’s bad for you,” he says. “After a while, you bite into that stuff, and you feel bad, not because you’re fat or skinny, but because it’s killing you. A person needs more exercise and less food.”

Foster says he doesn’t think he has a choice but to stick with the clinical trial to the end. It offers him medications he couldn’t pay for and close monitoring that is helping him.

“You don’t have any choice really, if you still want to do things.”

Diabetes determines professor’s direction

R. Keith Campbell knows a lot about diabetes. He’s lived with it
for more than 55 years.

The Washington State University professor of pharmacotherapy was
diagnosed long before people were able to test their own blood
sugar levels, but he was lucky enough to have a doctor who taught
him how to help himself.

Campbell claims that teaching others how to better manage their
diabetes has been his own biggest contribution to people with the

He was eight years old when he was diagnosed.

During a family reunion, his father noticed his behavior was a
little odd.

He ate an entire loaf of bread, kept running off to the
bathroom, and repeatedly stuck his head under the faucet in the
kitchen to drink.

The next day, a pediatrician tested and diagnosed him.

“I was lucky to catch it early,” Campbell says. “What was really
great was, I was sent to a new diabetes specialist in Spokane, Dr.
O.C. Olson, who believed that it was important to educate a person
with diabetes to take care of himself and keep blood sugars as
close to normal as possible.”

He learned that high blood sugars could damage his eyes,
kidneys, and nerves.

He also learned abnormal blood glucose levels could affect his
personality, making him tired, lethargic, irritable, or silly, so
he taught others around him to keep an eye on him and give him
sugar if he started acting strange.

Diabetes also steered his career. Campbell joined WSU’s College
of Pharmacy in 1968. Once word of his illness got around, he was
asked to give lectures on the topic.

“I was thus motivated,” he says, “to keep up on all the latest
information about diabetes for two reasons-to help myself and to
help me educate students, patients, and health care providers about

In his mid-30s, Campbell nearly went blind from his illness.

He had been unable to monitor his blood glucose for many years,
because the technology was simply not available until 1969.

“You just made it through the day without having too many
insulin reactions or going into a diabetic coma from too high blood
sugars,” Campbell says.

He awoke one morning with floaters in his eye-black specs
floating across his field of vision-caused by blood leaking from
the small blood vessels that feed the retina of the eye.

He consulted with an optometrist, who told him they were just
signs of aging and that he shouldn’t worry.

A few hours later, his left eye filled with blood, and he
couldn’t see.

Telling him he would probably be blind within six months, a
Seattle specialist administered laser treatment to his good eye and
later, to the eye with the problem. The eye healed.

Twenty years later, Campbell developed a second common diabetes
complication-heart trouble. He had quadruple by-pass surgery.

Campbell has type 1 diabetes, also known as juvenile-onset
diabetes, as opposed to the more common type 2, or adult-onset
variety, which accounts for 90 to 95 percent of the diagnosed cases
in the United States.

Much of the care and treatment of the two types of diabetes is
the same. Campbell tells other diabetics not only to keep their
blood sugars down and their blood pressure and cholesterol normal,
but to take one aspirin every day.

Over the years, Campbell has lectured across the country on the
subject, written hundreds of articles, and received numerous awards
from state and national organizations.

In 1989 he was named Outstanding Diabetes Educator in the U.S.
by the American Diabetes Association. A year later he received a
distinguished service award from the American Association of
Diabetes Educators.

He has been a consultant to the U.S. Centers for Disease Control
and Prevention and to the U.S. Food and Drug Administration.

Campbell and fellow faculty member John R. White, who was drawn
to WSU to work with Campbell, co-authored a book a few years ago
for the American Diabetes Association, titled Medications for
the Treatment of Diabetes.

Six faculty members in the College of Pharmacy are now actively
engaged in diabetes research and education. Desiring to preserve
its expertise in diabetes, the College of Pharmacy is raising money
to establish a faculty position named after Campbell, permanently
dedicated to diabetes research, teaching, and service.

Campbell, of course, would be the first faculty member appointed
to the position.

More information is available from the college at

Diabetes research at WSU

What do the women in a
Russian-speaking community in Spokane
know about diabetes?

Does high blood sugar damage certain cells in
the kidneys?

Researchers at Washington State University are
pursuing the answers to these and many other questions about

Washington State University researchers have contributed
share of information over the years to questions about

They will continue to do their part.

The following
is a summary of diabetes research now in progress
at WSU.

College of Nursing

Margaret A. Bruya,
professor and assistant dean for
academic health services, and Ruth C. Bindler, associate professor,
College of Nursing, worked with a group of students at Havermale
High School in Spokane during the 2004-2005 academic year to
investigate the effects of information provision and adolescent
goal setting on diet, activity, and stress reduction. Body
measurements, serum analysis, and questionnaires were used in the
fall and repeated before school terminated for summer. Weekly noon
meetings were held with the teens during the year. Data are now
being analyzed to determine the effect of the “Healthy Choices for
Life” program with students in an alternative high school. This is
the latest in a series of studies Bruya, Bindler, and other
researchers have conducted with different groups of children and
adolescents and their potential risk of type 2 diabetes and
cardiovascular disease. Their work has been integrated into the
activities at the People’s Clinic in the College of Nursing, where
Bruya is director. Numerous graduate nursing students completed
theses and clinical practicum courses with Bruya and Bindler in
this latest study.

Jacquelyn L. Banasik, associate
professor, College of
Nursing, is studying whether a change in a prediabetic patient’s
activity level could restore normal insulin and glucose levels in
the blood and prevent the patient from progressing to diabetes. To
do that, she is focused on describing the relationships between a
patient’s fat mass, the chemical signals issued by the fat cells,
insulin production by the pancreas, and the patient’s blood glucose

In the early stages of type 2 diabetes, the pancreas
produces a
higher than normal amount of insulin to overcome tissue resistance
to its activity and therefore keeps the blood glucose in the
near-normal range. Eventually, the pancreas is unable to keep pace,
and the blood glucose climbs. After a time, this process is
difficult to reverse. It is better to prevent type 2 diabetes by
making lifestyle changes in the early hyperinsulinemic stage, while
the pancreas is still functional and blood sugar remains relatively
normal, Banasik says.

Previous pilot work has revealed complex
motivational issues
affecting whether sedentary, overweight women at risk of diabetes
are able to change their activity levels, Banasik says. Her
research may lead to a better understanding of how the fat cell
signals or other signaling molecules may affect an overweight,
sedentary person’s behavior. That knowledge could lead to more
effective prevention strategies, she says.

Cynthia L. Corbett,
associate professor, College of Nursing,
is just finishing a two-year study on whether a particular six-week
group workshop will have any lasting positive effects on the
behavior of older adults with diabetes. She presented the workshop,
developed at Stanford University and titled “Chronic Illness Self
Management Workshop,” at independent living retirement communities
in Spokane and compared it to similar communities where the
workshop was not presented. The workshop includes information about
exercise, diet, stress, and setting goals. The study was funded by
Pfizer Inc.

Corbett also recently finished a collaborative
study with a
nurse practitioner at a physician’s clinic in Spokane to see
whether two face-to-face meetings with a family counselor could
positively impact the behavior of teenagers with diabetes. The
meetings involved some role playing to provide behavior choices in
the face of peer pressur-as, for example, when a group of teenagers
goes to a fast food restaurant to eat together.

“The bottom line
was the intervention did not impact glucose
control or decision-making skills as measured in the study,”
Corbett says. “We did find that the kids on insulin pumps have
better glucose control.”

“We also obtained interesting information
from the teenagers
about their behaviors and that will add to the literature on the
topic,” she says.

Exercise Science

Katherine R.
Tuttle, Rick Meek, and E. Carolyn Johnson

are jointly studying how excess amino acids-the building blocks of
protein-and high glucose can injure cells from small blood vessels
in the kidney.

It is known that eating a lot of protein is
injurious to kidneys
of patients with chronic kidney disease, and until recently it was
thought that this damage was induced by the increase in blood
pressure caused by high protein intake.

However, it is becoming
clear that high levels of amino acids
can also cause direct injury to cells in the small blood vessels in
the kidney.

Specifically, these researchers are studying mesangial
endothelial cells from the kidney glomerulus, which is the
filtration unit of the kidney.

Tuttle and Meek developed the
original hypotheses and cell
culture model for mesangial cells, and were joined later by
Johnson, who studies glomerular endothelial cells in a similar

Tuttle is a physician, a professor of basic medical
sciences at
WSU in the WWAMI program, and the director of research at The Heart
Institute of Spokane.

Johnson is an associate professor in the WSU
Spokane exercise
science graduate program and the new undergraduate program in
exercise physiology and metabolism.

Meek is the senior scientist
for basic research at The Heart
Institute of Spokane.

Funding for some of the work done by the
team has been supplied
by the Diabetes Action Research and Education Foundation, the
Northwest Kidney Centers, and the local Fraternal Order of

Food Science and Human Nutrition

Armstrong Shultz,
professor, Food Science and Human
Nutrition, is studying low-income Latino and Caucasian diabetes
patients in central Washington to quantify how they carry out their
dietary goals, with the purpose of managing their type 2 diabetes.
Her research also seeks to identify any personal, family, and
social issues that either motivate the patients to achieve their
goals or act as barriers to them. Shultz has been working on this
project since 2001 with doctoral student Kathy Briggs-Early.

administrators of the health care clinics that serve both
Latino and Caucasian clients, the research will help them identify
similarities and differences in the educational needs of patients
for diet and meal planning, and it will also aid them in evaluating
the success of their education. The project recently received
funding from the Diabetes Action Research and Education

Cooperative Extension

Sue Nicholson
nutrition specialist, Puyallup, is
director of the Diabetes Education Project for WSU Extension, which
is a five-lesson seminar series held in schools, churches,
community centers, extension offices, and other locations around
the state to educate people about diabetes. The Extension Office
started presenting the “On the Road to Living Well With Diabetes”
seminar series in September 2003. After the first 10 months, more
than 400 people in a dozen different communities, including members
of several Native American tribes, had been through the series. WSU
developed the seminars in collaboration with the Joslyn Diabetes
Center in Boston.

The series starts with a health screening to
measure blood
pressure, blood sugar, and cholesterol and is followed by
information about diet and exercise. Funding is from a
congressional appropriation administered by the U.S. Department of

Butkus also is involved in a pilot project to
train the
caregivers of elderly Hispanics with diabetes about the illness.
The project is funded through the Aging and Long Term Care office
of the Washington Department of Social and Health Services.


L. Corbett,
associate professor, College of
Nursing, is primary investigator on a study of why women with type
2 diabetes in the Russian speaking community in Spokane seem to
have higher blood pressure and cholesterol levels than other
Caucasian women in Spokane with type 2 diabetes.

began collecting data in June 2004 and completed
data collection in March 2005. The 30 women immigrants from the
former Soviet Union, on average, had higher blood pressures and
worse lipid profiles compared to an age- and weight-matched group
of 30 non-immigrant, non-Hispanic Caucasian women in the Pacific
Northwest. The medications taken by both groups was not as optimal
as it could have been for blood pressure and lipid control.

there was some indication that the immigrant group
was not treated as aggressively with medications as the
non-immigrant, non-Hispanic Caucasian group.

Quantitative and
qualitative analysis comparing the two groups’
dietary and activity patterns is ongoing. “If we find it is the way
they eat or exercise, then we could target certain behaviors for
change,” Corbett says. “But maybe the data won’t show anything at
all, and then we’ll wonder if it’s something genetic and not

A WSU Spokane seed grant is providing funding for the
Other researchers involved are faculty members Stephen M. Setter
and Jason L. Iltz in Pharmacy, Sue Nicholson Butkus of WSU
Extension in Puyallup, Carol B. Allen of Nursing, Jill Armstrong
Shultz of Food Science and Human Nutrition, one graduate student,
and one undergraduate student.

Robert A. Short, assistant
director of the Washington
Institute for Mental Illness Research and Training, is currently
studying data from about 800 individuals from the Spokane Heart
Study to see if it’s possible to establish longitudinal statistical
models that predict the onset of the metabolic syndrome (often a
precursor to type 2 diabetes), hypertension, and obesity based on
the levels of uric acid in a patient’s blood. He is working on the
study with Dr. Katherine R. Tuttle, director of research at the
Heart Institute of Spokane. The investigators have developed
similar statistical models for high-risk patients of myocardial
infarction and have now developed a National Institute of Diabetes
and Digestive and Kidney Diseases proposal to test these models in
the general population.

A Cookbook for Latinos from the American

Olga Fusté, director of Pierce County Extension and a
dietitian, compiled Cocinando para Latinos con Diabetes
(Diabetic Cooking for Latinos) for those who want to get
their blood sugar levels where they want them while still enjoying
delicious Latin cooking. Published by the American Diabetes
Association, the book includes chapters on soups, rice dishes,
beans, vegetables, chicken, meats, desserts, and more, offering 87
recipes in Spanish and English from most of the countries in
Central and South America.

Lorraine Nelson is communications coordinator in the College of