Angela: RISE-ing Above Diabetes
In 2015, Angela had just obtained health insurance, so she saw her doctor for an overdue physical examination. A massage therapist in her fifties who sees her clients at their homes and businesses, she is dependent on her health to be able to carry her equipment to appointments and stay on her feet to work. In general, her health was good, but her health care provider did identify one area of concern: elevated blood sugar (glucose) levels—termed prediabetes—that suggested she was at risk to develop type 2 diabetes. “When I was diagnosed as prediabetic, that made me very nervous,” says Angela, who was aware that her family history of type 2 diabetes also increased her risk of developing the disease.
A Disease that Runs in the Family
Born in Trinidad to a family of South Asian descent, Angela immigrated to the United States as a child and grew up in Miami with five of her siblings—three sisters and two brothers. (Another sister moved from Trinidad to England.) Angela knew that her mother, who recently passed away, had type 2 diabetes for the last 2 decades of her life. The family history runs deeper, however. “My father died at 75,” Angela relates, and she and her siblings “didn’t know this [at the time]—but he also had diabetes.” The complications of the disease had taken their toll: her father developed kidney failure and was on dialysis for 10 years, before dying from cardiovascular complications of the disease. In fact, the family’s history “stems way back,” Angela says, as her mother’s father had the disease as well.
Two in her generation—Angela and one of her sisters—have developed prediabetes. Angela is concerned about her and her siblings’ health, but also is thinking of the next generation. “So far, none of my [three] kids have” developed diabetes or prediabetes, Angela notes, gratefully. “Thank you, God, for that.” But Angela isn’t taking her future health—or theirs—for granted. She agreed to participate in a clinical trial, she says, “for my years of life and my children’s, and the generations to come!”
Diabetes and Prediabetes
When we eat, sugars and other nutrients enter our bodies through the digestive process. The pancreas responds by producing the hormone insulin, which signals cells throughout the body to absorb sugar. However, while the body needs blood sugar levels to remain above a certain level to maintain brain and other functions, higher levels lead to organ damage. Thus, a healthy pancreas helps keep blood sugar levels within a narrow, optimal range.
Unfortunately, some people develop a condition called insulin resistance, in which their cells no longer respond as strongly to insulin. Aging and excess weight—as well as genetics and other NIDDK Recent Advances & Emerging Opportunities 2019: Diabetes, Endocrinology, and Metabolic Diseases 37 factors—can increase risk for insulin resistance. At first, the pancreas compensates for this by simply producing more insulin, but gradually it may lose the ability to do so. At that point, blood sugar levels begin to rise, often reaching levels in excess of the diagnostic threshold for type 2 diabetes. Although this form of diabetes can occur in anyone, people of African, Hispanic, Native American, or Asian descent (like Angela) are at particularly high risk.
The Restoring Insulin Secretion Clinical Studies
In 2013, the NIDDK-supported Restoring Insulin Secretion (RISE) consortium formed to conduct three related clinical studies. Each stems from an important observation: previous research suggesting that lowering blood glucose levels with certain diabetes drugs during prediabetes or early in the course of type 2 diabetes may slow or perhaps even reverse the loss of pancreatic function. Although it is not clear why this works, possibilities include that such treatments may limit the exposure of the pancreas to damage from chronically high levels of sugar and other nutrients, or that they may simply relieve the burden on a person’s pancreas.
The RISE studies, two in adults, and one in youth, were therefore designed to test the potential for different methods to improve and preserve the production of insulin in people with prediabetes or recently diagnosed type 2 diabetes. “I hope that is accomplished,” Angela says fervently. Fortuitously, her prediabetes diagnosis coincided with a timely offer to participate in one of the three RISE clinical trials. “I was very fortunate that RISE sent me a letter in the mail,” Angela relates, “and I said well, you know, there’s no harm in trying … to see if they can do something about it.” She was quick to call and was soon enrolled in a RISE study. As she says, “I am very happy to participate in the RISE study … to help [people with or at-risk for diabetes] maintain function [and] a healthy life.”
Participating in the RISE Adult Medication Study
The RISE clinical trial Angela is participating in— the RISE Adult Medication Study—is comparing the capability of various blood glucose-lowering medication regimens to preserve or restore the ability of the pancreas to secrete insulin. The four approaches being compared are: 1) early intensive insulin treatment with a long-acting form of insulin called “glargine,” followed by the first-line type 2 diabetes drug, metformin; 2) an injected diabetes medication called liraglutide delivered along with metformin; 3) metformin by itself; and 4) placebo. Each participant was randomly assigned to receive one of the four treatment approaches for 12 months. Just before starting treatment, as well as periodically during and afterward, the participants received a variety of tests to ascertain how well their bodies responded to insulin, and to test the ability of their bodies to produce and release their own insulin in response to glucose in a drink or delivered intravenously. The participants also received cognitive testing to determine whether any of the treatments had beneficial effects on mental function.
Angela agreed to participate in a clinical trial, she says, “for my years of life and my children’s, and the generations to come!”
In addition, the RISE studies have enabled an important substudy having to do with obstructive sleep apnea (OSA)—pauses of breathing due to closing of the airway during sleep due to relaxation of the muscles in the throat. OSA can cause excessive daytime sleepiness, and severe cases are associated with high blood pressure, a risk factor for cardiovascular disease. There is now evidence that OSA may increase the risks of type 2 diabetes, and vice versa. To improve our understanding of the relationship between apnea and diabetes, researchers enrolled a subset of RISE participants—including Angela—in a RISE sleep substudy. In this way, Angela learned that she has a mild case of OSA, primarily when she slept on her back. As a result, she now makes an effort to ensure that she sleeps on her side.
Angela was randomized to receive either metformin or placebo. Although she didn’t know which she was taking, she didn’t mind. “You know I just kind of left it up to them.… Sometimes I thought I was taking placebo, and other times I’m like, maybe I am taking metformin.” In any case, she was pleased with the result. As she says, “maybe my mind was just playing games with me, but I lost 10 pounds during the whole treatment.”
Angela has high praise for the RISE study and its staff: “The bunch of people that I came in contact with, you know, I love them, and I would love to continue to be a participant, because I feel I could trust them. They showed me a great amount of kindness, and it’s very supportive as well.”
And that wasn’t the only benefit of participating in the trial: Angela says the study also helped her track her own health. “They were very efficient at giving me a list of all my test results,” noting they also sent the results to her doctor. “They kept me informed of what’s going on, and ... I felt good about that.” This meant that if a major health issue had arisen, whether or not it was related to diabetes, it might have been caught early. For example, Angela recalls, “At one point they said I had a little bit low blood count ... and I spoke to the doctor about it.” Fortunately, it turned out to be nothing serious.
Angela speaks glowingly of her experience in the trial, especially of the staff with whom she worked. “It’s just amazing the amount of testing they were doing, and they were very safe—I felt safe…. Everybody was friendly—super friendly—and I felt like I can trust them.” Regarding the metabolic testing, she notes, “I was totally feeling good when they were doing all that.” She has more mixed feelings about the cognitive testing: “Every time I went in and did a cognitive test … that was hard, but it was a great challenge!”
Taking Charge of Her Health
“They were very efficient at giving me a list of all my test results,” she said, noting they also sent the results to her doctor. “They kept me informed of what’s going on, and… I felt good about that.”
After she was diagnosed with prediabetes, Angela worked on improving her diet and exercising more. She joined a gym, which she confesses she doesn’t like, but she enjoys going out walking. She even participated in a 3-day, 60-mile walk for breast cancer research and prevention, which not only reaped rewards for the breast cancer community but also personal ones for Angela. “I forced myself to go to the gym and get in shape for it, and it was awesome! I got to meet a lot of ladies that had had breast cancer and victory over it, and there were some that were … [still] in the midst of it all. And I heard a lot of testimonies, which was awesome…. It was fun, too!”
Angela credits participating in the RISE Adult Medication Study with helping change her outlook. “It has definitely shown me the importance of taking care of yourself,” she shares. She also has high praise for RISE and its staff: “The bunch of people that I came in contact with … I love them, and I would love to continue to be a participant, because I feel I could trust them. They showed me a great amount of kindness, and it’s very supportive as well…. A lot of care and love,” she says, was put into the RISE study.
Of the RISE staff who worked with her, Angela continues, “they’re wonderful. And I wouldn’t mind doing another study again so I can see them again, and just be willing to do something for the good of others. Or even for myself to benefit from it.” She adds that “I’ve learned more, come to appreciate my health more. I’m realizing that the more you know, the more you take care of yourself!”
"I thought that the RISE Study is a great study,” Angela says, and she adds “they are doing a tremendous good.”
At the end of the intervention period of the trial, the staff went over Angela’s test results with her, giving her and her health care provider information to help keep Angela as healthy as possible. “They said I’m doing really good.… They said my results turned out to be really good, and they also gave me a rundown on my good cholesterol and my bad cholesterol, and they said that it’s normal,” although “the bad is a little bit high.” In view of this, they reminded her of the importance of keeping a healthy diet.
Angela can’t say enough good things about her experience with RISE. “I thought that the RISE Study is a great study, and … they are doing a tremendous good,” she says. She notes that she is looking forward to finding out about results, as well: “When everybody that has participated [has] completed the study, they’re going to have a big party, and then all the participants will get the inside scoop: the results of what we were taking, and so forth, and it’s going to be exciting!”
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