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.”