Stories of patients who are benefitting from NIDDK-supported research.
With Type 1 Diabetes, “Time Is of the Essence”—
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Late in the summer of 2005, Lilo Cunningham noticed that her then 10-year-old daughter, Charlotte, was beginning to drink copious amounts of water. This seemed unusual to Lilo because Charlotte was not fond of drinking water. “But no matter where we went, she was always looking for a water fountain,” says Lilo. Lilo also noticed that Charlotte was using the bathroom more frequently.
Lilo recognized these changes in Charlotte’s behavior as potential symptoms of diabetes. As two of Lilo’s sisters have sons with the type 1 form of the disease, Lilo decided not to take a chance. Within days of her observations, Lilo made an appointment with Charlotte’s pediatrician and, sure enough, learned that Charlotte’s blood sugar level was 680—about seven times above normal.
Charlotte was diagnosed with type 1 diabetes—previously known as juvenile diabetes—a devastating illness that often strikes in infancy, childhood, or young adulthood.
The diagnosis was frightening, but Lilo was able to turn to her sisters for advice. In addition to offering many practical suggestions for dealing with diabetes on a day-to-day basis, one of Lilo’s sisters, who is very active in the Juvenile Diabetes Research Foundation International (JDRF), informed her that several diabetes research trials were under way. She suggested that the Cunninghams might want to investigate these trials for Charlotte.
Because the Cunninghams were informed of several clinical trials shortly after Charlotte’s diagnosis, she was eligible to participate in a clinical trial specifically designed for newly-diagnosed patients. The therapy being tested in this trial may slow down the progression of the disease, which could reap long-term benefits for patients and make it easier for them to control their blood sugar levels.
Controlling blood sugar levels is critical. The NIDDK’s landmark Diabetes Control and Complications Trial (DCCT) demonstrated that intensive blood sugar control offers remarkable long-term benefits when it comes to preventing or delaying complications frequently associated with type 1 diabetes, including eye, nerve, kidney, and cardiovascular disease.
Charlotte, now 13 years old and 3 1/2; years post-diagnosis, shows no signs of complications from diabetes. “Time is of the essence,” says Lilo. “The more we can slow the progression of this disease and keep Charlotte healthy, the better chance she has of leading a longer, healthier life.”
About the Study
Type 1 diabetes occurs when a person’s immune system mounts a misguided attack and destroys the insulin-producing beta cells found in the pancreas. Insulin is critical for the body to absorb sugar from the blood and to use it for energy. Those with type 1 diabetes need daily administration of externally-supplied insulin, either by injection or with a pump, and must monitor their blood sugar levels vigilantly. Researchers have discovered, however, that many individuals diagnosed with type 1 diabetes still make detectable amounts of insulin, even many years after they are diagnosed. The DCCT also showed that people with type 1 diabetes who still made some of their own insulin had fewer long-term disease complications, as well as reduced incidents of dangerously low blood sugar (hypoglycemia) from administration of too much insulin. These observations suggest that preserving patients’ remaining beta cell function, so that they still produce some of their own insulin, could have dramatic, long-term health benefits.
The trial in which Charlotte is participating is trying to do just that. A previous NIDDK-supported clinical trial indicated that an antibody, called hOKT3gamma1(Ala-ala) or “anti-CD3,” halted the destruction of insulin-producing beta cells in a small number of newly-diagnosed patients. Anti-CD3 alters the signal that triggers the disease-causing immune cells to attack the insulin-secreting cells. Charlotte is participating in a trial where researchers are determining if an additional treatment of anti-CD3 will provide further benefit, beyond that of the single treatment. This trial is being conducted by the Immune Tolerance Network, which is led by the National Institute of Allergy and Infectious Diseases, in collaboration with the NIDDK’s Type 1 Diabetes TrialNet. Both networks also receive funding from the Special Statutory Funding Program for Type 1 Diabetes Research. Because one of the requirements for participation in this particular trial was that patients enroll within 8 weeks of their diagnosis, the Cunninghams are very grateful that a family member counseled them to act quickly after Charlotte’s diagnosis.
“We were fortunate that Charlotte was diagnosed so early and was able to participate in this trial,” says Lilo. “As a result, she’s perhaps making more insulin than the average person in the early stages of diabetes and is doing very well.”
The trial requires Charlotte to be infused daily over a 14-day period with the anti-CD3 antibody. Each daily infusion takes between 15 to 30 minutes, and is administered into Charlotte’s upper arm. Charlotte received this 14-day set of infusions two times; the second treatment followed 19 months after the first. Charlotte returned to the trial site every 3 months in between the treatments and for 12 months following the second treatment. These visits were to monitor her response to the treatment and included a physical examination, a blood test, and a test to measure her insulin response. Except for a rash between her fingers, which lasted only 1 day, Charlotte has experienced no side effects from the treatment.
When asked about her overall experience in the trial study, Charlotte responded, “It was very cool.” Not the typical response one would expect from an adolescent, but Charlotte has handled her diabetes extremely well from the beginning.
Lilo and Charlotte’s Message: Don’t hesitate. Act quickly.
When it comes to diabetes, Lilo and Charlotte’s message to others is clear and simple: At the first sign of symptoms, do not hesitate; act quickly.
“If you have any suspicions or notice anything wrong with your child, go for a blood test [at your pediatrician’s office] and follow up immediately,” says Lilo. “If this study succeeds in allowing Charlotte to retain the ability to produce some of her own insulin, even for a little while longer than she might have otherwise, it will help to delay, reduce, and possibly even prevent the secondary complications that often accompany type 1 diabetes.” “And make sure you check your blood sugar level regularly,” adds Charlotte.
Lilo has not observed symptoms in other family members, but that does not mean she was going to take chances. The Cunninghams enrolled their two other children, Charlotte’s 16-year-old brother and 19-year-old sister, in a study as well—the TrialNet Natural History Study. This study is screening relatives of people with type 1 diabetes to determine what level of risk these family members have for developing the disease. These studies are being conducted to learn more about the causes and indicators of risk for the development of type 1 diabetes. So far neither one of Charlotte’s siblings appears to be at increased risk. “But if either of them should show signs of the disease, I would enroll them in a clinical trial in a heartbeat,” Lilo says. “We had an incredibly positive experience with Charlotte’s study. We were exposed to so many people who know so much about this disease—we learned so much!” When asked her thoughts on participating in the trial, Charlotte proudly says, “I’m an example of how diabetes research is helping people.”
Since February 2008, Charlotte’s need for injected insulin has increased dramatically. According to Lilo, it is hard to say exactly what is going on. “Charlotte is in the midst of puberty, which could mean her body is requiring more insulin because of hormonal changes,” she says. Nineteen months after her first treatment, Charlotte received her second and final 14-day infusion as part of the trial. The good news is that, even though Charlotte needs more external insulin, tests performed in May 2008 (12 months after Charlotte’s last treatment and nearly 3 years after her initial diagnosis) indicate that she is still producing some insulin. Because her need for external insulin is increasing, Charlotte is exploring the possibility of using an insulin pump, a portable device that injects insulin at programmed intervals. She says she is excited about the prospect of using the pump.
If anything, Charlotte’s life has become more active, rather than less, since being diagnosed with diabetes. Prior to her diagnosis, Charlotte played tennis and basketball. Now she has added surf boarding, lacrosse, and softball to her repertoire of physical activities. “Having diabetes hasn’t really affected me much when I’m doing sports,” she says. “I need to make sure my blood sugar count is okay both before and while I’m playing, but my coaches are very understanding and let me do what I need to do to take care of myself.”
In the meantime, at the time this story was written, Charlotte was preparing to go to summer camp with 70 of her peers, all of whom have diabetes. She has been to the camp twice before and says she likes it a lot. “We meet with meal planners and check our blood sugar regularly, but mostly it’s a regular, fun camp,” Charlotte explained. Like any 13-year-old, Charlotte simply wants to lead as active and normal a life as possible.
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DEPLOY Lifestyle Interventions Delay, Prevent Type 2 Diabetes— Verner Thomas
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At age 61, retired and overweight, Verner Thomas joined the YMCA to try to improve her health. On one of her visits, she was handed a brochure asking if she’d like to participate in something called the “Diabetes Education & Prevention with a Lifestyle Intervention Offered at the YMCA,” or DEPLOY. DEPLOY is testing a diabetes prevention model in which YMCA employees are trained to help people who have risk factors for type 2 diabetes lose weight and increase their physical activity.
With support from NIDDK and in cooperation with the YMCA, the DEPLOY program is building on previous NIDDK-supported research that demonstrated that, in people at high risk, an intensive lifestyle intervention can be an extremely effective means of preventing or delaying the onset of type 2 diabetes.
And Verner is a reaffirmation of those findings.
Prior to involving herself in the program, Verner’s blood sugar and weight strongly indicated that she was at high risk of developing type 2 diabetes within the next 1 to 2 years. Additionally, her cholesterol levels were abnormally high. Today, 2 years after being introduced to the DEPLOY program, Verner exercises regularly, eats a more disciplined diet, and in general is more conscious of the lifestyle that she leads. As a result, she has lost weight, lowered her blood sugar levels, improved her cholesterol levels, and, best of all, has remained diabetes free.
“My daughter is really proud of me,” says Verner. “She says ‘Momma, you look better and feel better. You’re just a much more vibrant person. I want you to keep this up!’”
After speaking with Verner, one gets the feeling that her daughter was preaching to the choir. Ms. Thomas is well aware of the positive changes she’s made in her life as a result of DEPLOY.
Type 2 Diabetes—Reducing the Burden
Diabetes is a chronic, common, and costly disease that is robbing many Americans of good health and quality of life. Type 2 diabetes—once known as adult-onset diabetes, or non-insulin-dependent diabetes mellitus—is the most common form of the disease. It primarily affects adults, but it can develop in childhood and adolescence. Older age, overweight, and inactivity are strong risk factors for type 2 diabetes; heredity plays an important role as well. People with diabetes have blood sugar levels that are above normal. Over the years, high blood sugar damages nerves and blood vessels, leading to serious health complications such as heart disease, stroke, blindness, kidney disease and kidney failure, the need for lower limb amputations, and gum infections.
Ominously, Verner is hardly alone when it comes to being at high risk for type 2 diabetes. People who, like Verner did, have blood sugar levels higher than normal, but not high enough to be classified as diabetes, are considered to have “pre-diabetes.” In addition to 23.6 million Americans who already have type 2 diabetes, the Centers for Disease Control and Prevention estimates that at least another 57 million have pre-diabetes, and thus are at high risk of progressing to type 2 diabetes.
Importantly, there is a window of opportunity to reverse course on the way to developing type 2 diabetes. Spearheaded by the NIDDK, the landmark Diabetes Prevention Program, or DPP, was a clinical trial that showed that in overweight people with pre-diabetes, type 2 diabetes can be prevented or delayed through use of the diabetes medication metformin, or through a lifestyle intervention leading to moderate weight loss through diet and exercise. The immense success of the intensive lifestyle intervention, which showed a 58 percent reduction in risk of developing diabetes, has led to new research studies and programs testing ways to effectively translate these results into interventions that can be widely and effectively implemented to prevent diabetes in those at risk.
Translating DPP with the DEPLOY Program
Verner’s mother had diabetes, as did her grandmother. She has a family history on her father’s side of high blood pressure, as well as a history of obesity on both sides of her family. Verner also understands that, as an African American, she has a 1.8-fold increased risk of developing type 2 diabetes compared to non-Hispanic whites.
“This program (DEPLOY) makes you aware of what you should be doing and what you’re not doing to protect yourself against type 2 diabetes,” says Verner. “It motivated me to take better care of myself—how I eat and exercise….I wasn’t as faithful in my exercising until I got into the program.”
Operating out of local YMCAs, and led by primary investigator Dr. Ronald Ackermann of the Indiana University School of Medicine, DEPLOY takes groups of 8 to 12 people who, like Verner, have pre-diabetes and other risk factors, and puts them through a series of classroom-style meetings that focus on knowledge building and skill development to help them set goals, self-monitor, and problem-solve around their pre-diabetes. Major goals of the program include a 5 to 7 percent reduction in baseline weight, and 150 minutes per week of moderate level physical activity similar to brisk walking. The program is based on the lifestyle intervention that proved so effective at delaying or preventing type 2 diabetes among participants in the DPP.
Verner first started with DEPLOY in January 2006. Since then, in addition to remaining diabetes free, her weight has gone from 219 pounds down to 177, and her blood pressure has gone from 133/90 to 110/72 (normal is 120/80 or lower). Her body mass index (BMI) has also dropped from 33 to 29. BMI is a measure of weight relative to height. A BMI of 30 or more in an adult is considered obese. Verner thus is no longer obese—a significant achievement. She remains determined to get her BMI still lower. But in all categories, including her sugar and cholesterol levels, Verner’s numbers are heading in the right direction. Her fasting blood sugar has fallen from 111 to 90 milligrams per deciliter, meaning she no longer has pre-diabetes—and for that she is grateful.
“I feel healthier and stronger today than I did 2 1/2 years ago,” says Verner. “I’ve gotten a lot of compliments since I lost the weight, and psychologically I feel better. I’m more open, social, and outgoing,” she adds with a satisfying chuckle.
She admits that she also still faces some challenges. “My problem is sweets,” says Verner. “When I’m under stress I fall back on them.” But she says that for the most part she’s been able to keep her sweet tooth under control, as well as the rest of her diet.
To meet their goal of moderate weight loss, participants in DEPLOY are counseled to increase physical activity and to reduce their intake of fat and total calories. The diet and exercise interventions are flexible and sensitive to individual, cultural, and community differences where they are implemented. As part of her diet, Verner eats fish occasionally, and in addition, she says, “I only eat one egg a month. I get my protein from peanut butter, beans, and meat substitutes.”
Looking to the Future
Researchers are making major discoveries in how to predict who will develop type 2 diabetes and its complications; how to personalize individual treatments; and how to use this information to preempt disease onset and development of complications (see box). Public health efforts founded on these discoveries can hopefully help to reduce the burden of type 2 diabetes and its complications in the future. Research programs such as DEPLOY—and the hard work and dedication of the participants—are an important part of making this future real for people at risk for type 2 diabetes.
DEPLOY has a strong fan in Verner: “I’m dedicated to maintaining my regime of eating healthily and exercising regularly,” she says, and she is sure that DEPLOY helped point her in that direction.
The Beneficiary of Decades of Research
Verner Thomas and the millions of other Americans who are either at high risk or already have type 2 diabetes are the beneficiaries of decades of research.
Thirty years ago there were no proven strategies to prevent type 2 diabetes or its complications, and the only treatments, now obsolete, caused dangerously low blood sugar reactions and weight gain in patients.
Today, as a result of research, diabetes is better understood, new and more effective treatments are available, and type 2 diabetes and its complications can be delayed and in some cases, even prevented. For example:
Researchers now know that obesity is a strong risk factor for type 2 diabetes, and have a new understanding of the molecular links between obesity and insulin resistance, a condition that prevents the body from effectively using insulin.
Risk factors other than obesity have been identified and can be targeted.
Newly-identified diabetes genes will enhance researchers’ ability to identify and intervene in those at risk.
Based on clinical research demonstrating the health benefits of early detection and therapy, Medicare now covers testing for diabetes.
New drug development has been aided by an NIH-supported clinical trial that validated an indicator, called hemoglobin A1c, that reflects average blood sugar control over a 2 to 3 month period.
New oral medications that target the specific metabolic abnormalities of type 2 diabetes are available.
The Diabetes Prevention Program (DPP) demonstrated that type 2 diabetes can be prevented or delayed in those at risk. The benefits of the DPP were seen in all ages, all racial and ethnic groups, in women with history of gestational diabetes, and in people with diabetes risk genes.
The landmark DPP findings are being actively disseminated to the public by the National Diabetes Education Program.
Kidney disease resulting from diabetes can now be detected earlier by standardized blood tests to estimate kidney function and monitor urine protein excretion.
With timely laser surgery and appropriate follow-up care, people with advanced eye disease related to diabetes can reduce their risk of blindness by 90 percent.
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Bariatric Surgery—Weighing the Pros and Cons—Mariah Watts
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By the time she was 16 years old, Mariah Watts was five-feet eight-inches tall, suffered from sleep apnea, had pre-diabetes—and weighed over 350 pounds. In addition to being unable to breathe well while sleeping (sleep apnea) and facing a high risk for type 2 diabetes, she also had a difficult time with many ordinary activities, such as sitting in seats at school. “I was always so self conscious,” says the now 17-year-old who struggled with being overweight for many years, as well as with some of the serious health conditions that accompany obesity. “I wouldn’t wish this on anybody,” she says.
In January, 2008, Mariah underwent bariatric surgery, an operation that promotes weight loss. Seven months later, Mariah was down to 234 pounds, no longer had trouble breathing or sleeping, and no longer had pre-diabetes. Both she and her family are delighted with these results. “The surgery has changed Mariah’s attitude and given her a whole new lease on life,” says her mother, Mazie.
Although bariatric surgery can have dramatic health benefits, researchers caution that it also carries substantial risks.
Today, Mariah is voluntarily participating in the Teen Longitudinal Assessment of Bariatric Surgery, Teen-LABS, an observational study supported by the NIDDK to help determine if bariatric surgery is an appropriate treatment option for extremely overweight teens. Mariah enrolled in the study just before her surgery, enabling researchers to assess her health and quality of life in great detail both before and after the surgery, for comparison. Teen-LABS is being conducted at several medical centers in the U.S. and is led by Dr. Thomas Inge, a pediatric surgeon at the Cincinnati Children’s Hospital Medical Center.
Although bariatric surgery is not a common procedure in adolescents, its use has been increasing in clinical practice as a treatment for very severe obesity in this age group. Thus, the NIDDK is supporting the Teen-LABS study to collect health outcome data on adolescents who were already planning to have bariatric surgery, so as to evaluate its risks and benefits. (NIDDK does not pay for the surgery.) With these data, future adolescent patients, their parents, and health care teams will be able to make more informed, evidence-based decisions.
Bariatric Surgery and Adolescents
Bariatric surgery promotes substantial weight loss by restricting food intake and, in some cases, decreasing the amount of calories and nutrients the body absorbs. This surgery can also reduce the risk for—and in some cases even reverse—type 2 diabetes, a devastating disease.
However, the surgery also comes with substantial risks. Early complications may include bleeding, infection, leaks from the site where the intestines are sewn together (in certain operations), and blood clots in the legs that can progress to the lungs and heart. Later complications may include malnutrition, especially in patients who do not take their prescribed vitamins and minerals, hernias, and other health problems.
Therefore, recommended criteria for accepting an adolescent as a candidate for bariatric surgery are more stringent than for adults. Teens considered for this surgery have extreme obesity (as defined by body mass index, a measure of weight relative to height). Many of the adolescents who have enrolled in Teen-LABS so far have weighed 300 or 400 pounds, or more. Additionally, the teens who are candidates for this surgery have serious weight-related health problems, such as sleep apnea, type 2 diabetes, or other conditions. Furthermore, they must have tried other approaches to lose weight, without success.
In addition, experts recommend that potential adolescent patients and their parents should be evaluated to see whether they are emotionally prepared for the operation and the lifestyle changes they will need to make. A teen must be motivated and have strong family support, because the fact is bariatric surgery is not an easy way out to control weight. Even after surgery, patients will have to continue follow-up with health care professionals throughout their lives—and they will need to maintain a lifetime of healthy habits, including eating less food and exercising regularly.
Mariah says she is committed to making those life-long changes.
A Family Decision
A number of factors contribute to obesity. These include environmental and behavioral factors as well as genetic susceptibility. In Mariah’s case, as in most obese individuals, the exact contribution of each is not known. “My father, his sisters and their children are all big people,” says Mariah’s mother. In addition, she says Mariah struggled with eating as a child. “I ate constantly,” adds Mariah. “I’d get full and 30 minutes later would want to eat again.”
By age 11, Mariah weighed between 230 and 250 pounds and started dieting. She went to nutritionists and tried different types of diets. But nothing seemed to work. As time passed, Mazie observed her daughter becoming increasingly depressed and lethargic. “I started taking her to doctors and dieticians,” says Mazie. “It was painful to watch her go through all of this.”
Finally, as a last resort, Mazie encouraged her daughter to consider bariatric surgery. Mariah, desperate to lose weight, was agreeable to the idea—and did her homework. Mariah researched the procedure so thoroughly over the internet “that I could have done the surgery myself,” she adds with a smile.
There are several types of bariatric surgery. Mariah underwent the Roux-en-Y gastric bypass version. This surgery limits Mariah’s food intake because it reduced her stomach to the size of a small pouch. It also decreases the absorption of calories and nutrients by preventing food from contacting most of the stomach and the upper part of her small intestine. The surgery changes the digestive tract so that food is routed directly from the small stomach pouch to a lower part of the small intestine.
According to Mariah, the worst thing about having had the surgery is the fact that she sometimes will eat more than her post-surgery digestive tract can handle, leaving her feeling weak, dizzy, and sweaty. “It’s horrible. It feels like you’re dying,” she says, adding that the feeling lasts for about 25 or 30 minutes. She also adds that she’s been learning how to restrict her eating habits further. “When I go to a restaurant now, I know what to eat and what not to eat,” says Mariah. And in general, she says she’s eating much healthier.
As a result, she has much more energy than she had before. “Before the surgery I used to come home from school, lay around, sleep or watch TV,” says Mariah. “Now I find something physical to do every day. My little sister likes when I jump on the trampoline with her. This summer I swam in the family pool all the time and really enjoyed it. And when my friends come over, we go for walks; stuff I didn’t do before.”
“Mariah is an entirely different person,” says her mother. “She’s dating for the first time. Life is just more normal. I just see so much joy in her.”
Participating in the Teen-LABS Study
Shortly after Mariah and her parents decided to go forward with the surgery, Mariah’s parents encouraged her to take part in the Teen-LABS study. “The study was something new to us,” says Mazie. “We had never experienced anything like this, but we thought it was important for us to get involved so that other parents and their teenage children could make more informed decisions about whether or not to have this type of surgery.” Mariah agrees.
The Teen-LABS study began in 2007 and is based on the related LABS study, which is assessing risks and benefits of bariatric surgery in adults and is also supported by NIDDK. Over the span of 5 years, Teen-LABS will collect data on teens like Mariah, who had bariatric surgery as adolescents, and will compare this information with data from adult participants in the LABS study who had bariatric surgery as adults, after having been obese since their teen years. Teen-LABS and LABS researchers are collecting information on the pre-operative and 2-year post-operative status of adolescent and adult participants, including measuring body composition, body fat, cardiovascular disease risks, sleep apnea episodes, diabetes indicators, depressive symptoms, quality of life, eating habits, and nutritional status. Additionally, the investigators are storing serum and plasma (components of blood), urine, and genetic samples for future studies.
What would Mariah tell other teens and their families who are considering bariatric surgery? “They need to do their homework first,” she says. This homework will become more informative in the future with new data, thanks to her participation in Teen-LABS, along with the other study volunteers. “And,” Mariah adds, “they need to commit to eating better and exercising more.”
For additional information about bariatric surgery:
Bariatric Surgery for Severe Obesity (NIDDK publication)—
For more information on the Teen-LABS study—
As part of its multifaceted research portfolio on the causes, prevention, and treatment of obesity, the NIDDK additionally encourages research to understand how bariatric surgery has its effects. Certain bariatric surgical procedures are associated with remission of diabetes soon after surgery, even before substantial weight loss has occurred. Through increased understanding of potential mechanisms by which alterations in the gut reduce risk for or ameliorate type 2 diabetes in obese individuals, researchers may be able to improve surgical and nonsurgical therapies for obesity-related health conditions.
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Vascular Access—A Major Component To Treating Kidney Failure with Hemodialysis—James Willingham
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To listen to the lilt and laughter in James Willingham’s voice one would be hard-pressed to believe that this 66-year-old was diagnosed with kidney failure, referred to as end-stage renal disease (ESRD), 5 years ago while in the hospital for congestive heart failure and cardiac asthma, and that he has been undergoing hemodialysis treatments three times a week ever since.
“I was in the hospital being treated for my heart and asthma conditions when they checked my kidneys and found that they were functioning at only 10 to 15 percent of normal. They immediately put me on dialysis,” says James. Dialysis is a treatment for kidney failure; the dialysis machine cleanses the blood—a vital process that would normally be done by working kidneys. Patients with ESRD need either dialysis or a kidney transplant to live.
A couple of months after his ESRD diagnosis, James was asked if he would like to take part in one of the clinical studies being conducted by the Dialysis Access Consortium, or DAC, sponsored by the NIDDK. The DAC Study was testing the impact of anti-clotting reagents in preventing early failure in “vascular access,” which is required for dialysis. A vascular access is the site on the body where blood is removed and returned during dialysis treatments.
James responded in the affirmative. “I figured that even if I couldn’t help myself, maybe I could help someone else” as a result of participating in the study.
According to James, there’s been a long history of high blood pressure and type 2 diabetes in his family. Yet, none of his four siblings has ESRD. However, three of his first cousins, the children of his mother’s sister, are on dialysis as well.
James has known that he’s had high blood pressure since his high school days. He’s not sure exactly when, but later in life he was also diagnosed with type 2 diabetes. “When I was young I never took it seriously, never treated it,” he says. But by around age 50, it caught up with him, eventually resulting in his kidney failure. He began taking steps to improve his health. He no longer needs to take insulin for his diabetes. “I control it mostly by diet,” he says. He also walks 2 to 3 miles a week.
“I have my good days and bad,” says James, “but if I exercise a bit, and don’t go overboard with what I eat and drink, I can live a pretty good life on dialysis.”
Dialysis and the Importance of Good Vascular Access
When renal failure occurs, the kidneys lose their capacity to remove bodily waste from the blood. Hemodialysis is a method for removing waste products such as urea and creatinine, as well as extra water from the blood when the kidneys are no longer functioning properly.
An important first step before starting regular hemodialysis sessions is preparing a vascular access on the body that will be used at each dialysis session for inserting a needle and tubing, through which blood is circulated out of the body, to the dialysis machine for cleansing, and then back into the body. The vascular access site is usually placed in the forearm or the upper arm. To maximize the amount of blood cleansed during hemodialysis treatments, the vascular access should allow continuous high volumes of blood flow. For easier and more efficient removal and replacement of blood with fewer complications, the access should be prepared weeks or months before dialysis is required.
Because James’ kidney disease was diagnosed at such a late stage, he needed dialysis immediately. Consequently, physicians temporarily outfitted him with a traditional catheter in his chest. Catheters are not ideal for permanent vascular access because they can clog, become infected, and cause narrowing of the veins in which they are placed. But if hemodialysis needs to start quickly, as it did in James’ case, a catheter will work for several weeks or even months while a more permanent, surgically created access has time to develop. In this situation the catheter was left in James’ chest for an entire year, as no infections or any other complications developed.
Types of Vascular Access
In addition to traditional catheters, which are recommended only for temporary use, the two other types of vascular access are arteriovenous fistulas (AV fistulas) and arteriovenous grafts (AV grafts).
A properly functioning AV fistula is considered the best long-term vascular access for hemodialysis because it provides adequate blood flow, lasts a long time, and has a lower complication rate than other types of access. A fistula is an opening or connection between any two parts of the body that are usually separate—for example, a hole in the tissue that normally separates the bladder from the bowel. While most kinds of fistulas are a problem, an AV fistula is useful for hemodialysis patients because it causes the vein to grow larger and stronger for easy access to the blood system.
A surgeon creates an AV fistula by connecting an artery directly to a vein. Usually placed in the forearm, the vein of a new AV fistula will grow thicker after 3-6 months so that it can take repeated needle insertions and allow blood to flow quickly to the dialyzer. Once AV fistulas are working well for dialysis treatments, they tend to last longer than other types of dialysis access like catheters and AV grafts. A good fistula can function up to 10 years or longer.
Because James has smaller, weaker veins that wouldn’t develop properly into a fistula, he was given an AV graft, a vascular access that connects an artery to a vein using a synthetic tube, or graft, implanted under the skin in his arm. The graft becomes an artificial vein that can be used repeatedly for needle placement and blood access during hemodialysis. A graft doesn’t need to develop as a fistula does, so it can be used sooner after placement, often within 2 to 3 weeks.
Compared with properly formed fistulas, however, grafts tend to have more problems with clotting and infection and need replacement sooner. However, a well-cared-for graft can function for several years. Fortunately, that was James’ case.
The Dialysis Access Consortium (DAC) Study
The NIDDK established the Dialysis Access Consortium, which consists of seven primary clinical centers and a data coordinating center, to undertake interventional clinical trials to improve outcomes in dialysis patients who received either a fistula or a graft.
Two randomized placebo-controlled clinical trials were designed. The first trial evaluated the effects of the antiplatelet agent clopidogrel (Plavix®) on prevention of early AV fistula failure. The AV fistula trial ended in 2007 and revealed that clopidogrel did not improve the likelihood that an AV fistula would develop into a useable fistula for dialysis. The second clinical trial, which James participated in, focused on AV grafts for dialysis access. The AV graft trial studied a drug that combines dipyridamole with aspirin, and had the goal of preventing the narrowing of the vascular access in hemodialysis patients with grafts.
James, who says he is grateful for having been able to take part in the study, took his medication every day, twice a day; once in the morning and once in the evening, and reports having had no complications with his graft.
“The study was a very good experience for me,” James says. “I had help monitoring the graft to make sure it was open and that my blood pressure was good. And my outpatient dialysis nurse was terrific. She took very good care of me, talked with me and told me how I was doing every step of the way.” He says he did his part by keeping the graft clean and not picking up heavy objects with the grafted arm.
Dialysis is not the most pleasant of processes. “I’ve been on dialysis every Monday, Wednesday, and Friday morning for 5 years now, and each session lasts about 4 hours. That’s a long time to sit in that chair. And it’s very painful. It’s a 16-gauge needle, about the size of a plastic coffee stirrer that they stick in you. And you don’t want the needle to come out or you have a problem.” So to be able to maintain a free-flowing, uninfected vascular access without complications is a real plus for patients like James.
The AV graft trial that James was in ended early in 2008, and the results will soon be made public. From James’ perspective, he believes in the process. “It is studies like these that help people like me,” he says, with that lively, friendly tone in his voice that he employs so well.
Hope through Further Research
To improve the quality of life of patients with end-stage renal disease, the NIDDK currently supports additional clinical and basic science research efforts. For example, the Frequent Hemodialysis Network is conducting two clinical trials: the Daily Trial is comparing conventional hemodialysis (2.5 hours, 3 days per week) to more frequent hemodialysis (1.5 - 2.75 hours, 6 days a week) and the Nocturnal Trial is comparing home conventional hemodialysis delivered 3 days per week to nocturnal home hemodialysis given 6 times per week. Another example of NIDDK-supported efforts for patients with ESRD is a new consortium that will pursue studies to understand the high rate of AV fistula failure seen in many patients that have an AV fistula placed for dialysis access. The NIDDK is also supporting the Chronic Renal Insufficiency Cohort (CRIC) to better understand how chronic kidney disease progresses to ESRD. Another effort supported by NIDDK is the Animal Models of Diabetic Complications Consortium, which has the goal of improving or creating animal models of human diabetes complications, including diabetic kidney disease. Diabetic kidney disease is currently the leading cause of ESRD in the U.S. The animal models will help scientists to elucidate the causes of kidney disease and develop prevention and treatment approaches. Finally, the NIDDK distributes science-based information on dialysis and other aspects of kidney disease to patients, health care providers, and the general public through its National Kidney and Urologic Diseases Information Clearinghouse (http://kidney.niddk.nih.gov/) and its National Kidney Disease Education Program
The Dialysis Access Consortium Arteriovenous Graft study was carried out at seven NIDDK-funded research sites: Boston University (Dr. Laura Dember); Duke University (Dr. Arthur Greenberg); the University of Iowa (Dr. Bradley Dixon); the University of Maine (Dr. Jonathan Himmelfarb); the University of Texas, Southwestern (Dr. Miguel Vazquez); the University of Alabama (Dr. Michael Allon); and Washington University in St. Louis (Dr. James Delmez). The Data Coordinating Center was located at the Cleveland Clinic (Dr. Gerald Beck). Three satellite sites were supported by NIDDK and five satellite sites were supported by industry.
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