Tackling Diabetes

Written by Carole Bartoo

Last April, 13-year-old Luke Mitchell had a routine well-child checkup at his pediatrician’s office in Nashville. The visit ended up being anything but routine. Instead of hearing that everything was OK and being sent on his way, he was diagnosed with type 1 diabetes.

The news, which would alter Luke’s life forever, was shocking. There was no family history of the disease and his symptoms, increased thirst and urination, had been subtle.

Luke’s identical twin brother, Grant, was quickly tested and found not to have the disease – yet – but the boys’ doctor was concerned. The next day, the whole family was sent to the Children’s Diabetes Program at the Vanderbilt Eskind Diabetes Clinic.

As Luke was instructed on the use of blood sugar tests and insulin injections to manage his disease, Grant was given a unique opportunity: testing to pinpoint his risk for developing the disease and an opportunity to participate in a new wave of research that is yielding some of the most tantalizing evidence in decades for possible prevention of type 1 diabetes.

The whole Mitchell family was offered the chance to participate in the Type 1 Diabetes TrialNet; a research network, funded by the National Institutes of Health (NIH), that is charged with finding ways to prevent, delay or even reverse the progression of type 1 diabetes. They accepted the offer without hesitation.

Research is critical because the rates of juvenile, or type 1, diabetes are mysteriously rising.

A 2007 study from the University of Colorado at Denver in the journal Diabetes Care found the incidence of type 1 diabetes in youth younger than 17 was increasing by nearly 3 percent every year. The fastest rate of increase was among children under age 4. This evidence is echoed in clinics all over the world, including in Middle Tennessee.

“It’s definitely more prevalent than it used to be. The rates are growing, especially among white, non-Hispanic young people. But what is really troubling is the early onset,” said Bill Russell, M.D., director of the clinic and the Ian M. Burr Division of Pediatric Endocrinology and Diabetes at Vanderbilt and principal investigator for Vanderbilt’s TrialNet center.

Unlike type 2 diabetes, which disproportionally affects African-Americans and Hispanics and is strongly linked with obesity, type 1 diabetes is an autoimmune disease, in which the body’s immune system turns on its own cells. In this case, the insulin-producing beta cells in the pancreas are destroyed rapidly, possibly triggered by environmental agents in people with a genetic predisposition. Also unlike type 2 diabetes, type 1 cannot be reversed through diet and exercise.

To succeed in prevention studies, the disease must be caught in its earliest stages, or even before it starts.  This means the 18 TrialNet centers around the world must screen tens of thousands of people within families where at least one person has type 1 diabetes. Close family members of people with diabetes are 10 times more likely than normal to get the disease, making them excellent participants. Twins of people with diabetes have a 60 percent risk, so they are ideal.

So Grant Mitchell entered the study. Within days, he found out his risk was actually much higher than average. A special blood test turned up several antibodies that strongly suggest he will develop the disease – probably sooner rather than later. Grant is now also enrolled in one of TrialNet’s prevention studies: to test the effectiveness of oral insulin in delaying the onset of diabetes.

This is a frightening time for the Mitchell family, but Russell says he is gratified that young people like Grant – who are at such high risk for diabetes – can now choose to do something about it; even if it is just choosing to participate in research.

Since the discovery of insulin in 1922, tremendous advancements have been made in controlling the disease and delaying devastating side effects, such as kidney failure, blindness and amputation. But still, no cure is in sight. Once type 1 diabetes develops, it is permanent.

“That’s why this new knowledge about the increase in development of type 1 diabetes in the youngest is so important. The longer you have the disease, the more damage can be done.

Puberty accelerates damage so that in some cases neuropathy (loss of sensation) can begin in adolescence,” said Russell, adding that it’s harder to control diabetes in a very young child who cannot understand the importance of testing and treatment.

As any parent can tell you, what you learn in the first days of a child being diagnosed with diabetes can be overwhelming.

“As a mother I was emotional, with all the glucose numbers, carb counting and injections that were to become part of our life and his life forevermore. I was thinking of it as a death sentence, but (Vanderbilt endocrinologist) Dr. Ravi Mathew shrugged and said it is just an inconvenience. That helped me get through this first year,” Sara recalled.

But what if diabetes could be prevented? Scientists say a cure may be remote, but prevention is getting tantalizingly close. There is particular interest in a critical window of time – the time between the triggering of the autoimmune response and the most destructive, initial phases of the disease. It can be a narrow window, perhaps a matter of months, especially in the very young. But within this time frame, research results are enticing.

TrialNet research is testing a number of medicines administered to people who have antibodies against the insulin molecule, but don’t yet have the disease. Early results indicate the onset of type 1 diabetes can be delayed by four or more years. It is preliminary, but it is the best news Russell says he has heard in years. Even a delay of two years appears to have a telescoping effect, preserving good health for many years later on.

For Luke Mitchell, the window of opportunity for prevention trials has passed. One year he was fine, and the next, he had full-blown diabetes and was no longer a good candidate for the studies. But through TrialNet, Grant was caught before he developed even the earliest signs of disease. He is within that magic window.

Russell reminds families to remain realistic about this early stage of research. “We might not prevent Grant from
ultimately developing diabetes, but what we can learn from him right now is very valuable,” he said.

The commitment is a big one for families who choose to participate in TrialNet. Every day, Grant must take a capsule that contains either insulin or a placebo. He and his family must return to the clinic every six months for testing. Both parents submitted blood tests, and that’s where their direct participation ends, but 6-year-old sibling, Mia, will continue to be screened annually.

When the Mitchells return for clinic visits at the Monroe Carell Jr. Children’s Hospital at Vanderbilt, it’s usually a family affair, but on a visit in February, Mia and her father stayed home.

Grant sat in a recliner watching sports on TV, arm extended as a research nurse prepared him for a blood draw and four-hour glucose tolerance test. Sara sat behind Grant while Luke leaned in the doorway of the clinic room to watch his brother.

“He’s my best friend,” Luke said with great appreciation. He said he and Grant often dress alike and have many of the same interests. The boys even pulled a switch one April Fool’s Day in fourth grade as a prank. Both are in basketball and track right now, and each says his favorite sport is whatever is in season.

But diabetes is a permanent lifestyle change for the twins, and it has become a major difference between the two.
“I go to my locker right before lunch to do my blood test and my shot,” Luke explains.

“I didn’t even know you did that,” said Grant with surprise. “I knew he had to go do testing sometime, but I wasn’t exactly sure when.”

Sara Mitchell says participating in TrialNet has offered her a sense of control, and is kind of an equalizer for her sons.
“Since Grant has joined TrialNet, it has been nice because we now get to remind him to take his ‘insulin’ (the study pill) too. Luke doesn’t feel singled out as much,” Sara said.

“I would never have thought about doing something like this before Luke got diabetes,” Grant says. “This won’t hurt me, and it might help so other people don’t have to do (insulin injections) every day. I know that’s hard.”

Sara says the past year has been difficult, but she is proud of her children. “I think it has been great to see this side of medicine, and this side of our children.”