She understands that it wasn't her fault that her body turned on itself, that her immune system attacked her insulin-producing islet cells. To quote Caroline, "Diabetes doesn't care how cute you are. Diabetes doesn't care how well you play soccer. Diabetes doesn't care who your friends are or how much your family loves you."
From the outside, her life looks perfectly normal. She plays soccer, swims with friends and goes to ballgames with her family. But in the background is the relentless hum of type 1 diabetes, with vigilant blood sugar surveillance and insulin adjustments.
Her parents, Tom and Michelle Schlehuber, are thankful for the lifesaving medications and technologies that keep their daughter alive, but they pray for the day when Caroline isn't one missed reading away from the emergency room, when her life isn't dominated by glucose meters and insulin pumps.
That day may be closer than they imagined.
The road to discovery is long and riddled with ideas proven wrong. Researchers repeatedly see the most promising ideas fail when subjected to rigorous scientific method. The experience leaves most of them hesitant to use a certain four-letter word — "cure." Instead they use euphemisms like "advancing care" and "better treatments."
But something seems to be stirring among diabetes researchers. One occasionally hears whispers of the word. Some are becoming even bolder with statements like, "It's no longer if we cure diabetes, but when."
The reason for the optimism is that one proven cure already exists. Patients with type 1 diabetes who have received pancreas transplants have seen their disease go away completely. Unfortunately, the transplant requires a lifetime of immunosuppressive drugs whose side effects can be more harmful than diabetes.
The success of transplants shows a cure is possible. But how do we get there without the full transplant? Without the drugs? Researchers are making extraordinary progress toward answering these questions. So much so that many believe the race is on to find a cure. And Mayo Clinic might have the edge.
"I genuinely believe that now is the time for diabetes, and there is a lot going on at Mayo that has major promise," says Stephen J. Russell, M.D., Ph.D., deputy director for translation in Mayo Clinic's Center for Regenerative Medicine. "We know we can turn this new stuff into clinical reality."
Mayo Clinic's Yogish C. Kudva, MBBS, and Ananda Basu, MBBS, M.D., hope to transform life for people like Caroline with a hands-free device called the artificial pancreas.
Functioning just like a biological pancreas, the artificial pancreas uses an abdominal patch that continuously measures blood sugar. A pager-sized pump then delivers exactly the right amount of insulin at exactly the right time. Precision is critical because abnormal blood sugar levels can cause disabling and life-threatening complications such as heart attacks and strokes and damage the nerves, eyes and kidneys.
The artificial pancreas will free people with diabetes from daily preoccupations over finger pricks, blood reads and daily shots. Many people with diabetes have insulin pumps already, but the artificial pancreas represents a sea change because it minimizes patient decision-making.
Looking to the future, Dr. Kudva says, "We're very excited."
Working in partnership with the University of Minnesota, Mayo investigators are developing a novel continuous blood sugar sensor to improve its performance and usability. Mayo investigators are also refining the algorithm that controls insulin delivery so that it can be individualized for each patient.
In an upcoming clinical trial, Mayo researchers will use hard data from humans with type 1 diabetes to predict insulin needs, setting Mayo's efforts apart from other studies that have relied on computer simulations. By next year, Drs. Kudva and Basu hope to test the artificial pancreas in the real world as patients use it for weeks at a time, integrating the device into their daily lives.
The immune system wages war on any virus, bacteria or fungus it considers an invader of the body. As with Caroline's type 1 diabetes, the immune system mistakenly targets the body's own islet cells, compromising the pancreas' ability to monitor blood sugar levels and release insulin.
Mayo Clinic investigator Yasuhiro Ikeda, D.V.M., Ph.D., is investigating a cutting-edge regenerative approach to replace these essential islet cells in the pancreas. Tapping the body's power to heal itself, Dr. Ikeda is working to generate new islets from the diabetic's own skin or blood.
The process extracts cells from the patient and converts them into stem cells. Dr. Ikeda has taken these bioengineered cells — known as induced pluripotent stem (iPS) cells — a step further by inducing them to grow into glucose-responsive, insulin-producing cells in the laboratory. The iPS technology and its promise for humankind have been recognized by the 2012 Nobel Prize in physiology or medicine.
"Our future goal is to make customized islets from iPS cells and then hopefully put them back into the patient," Dr. Ikeda said.
Dr. Ikeda has improved blood sugar levels in diabetic mice for short periods of time using this promising technology. His next steps are to improve the responsiveness of the bioengineered islets to blood sugar fluctuations and increase the amount of insulin they produce. Human trials could start in the next three years.
A problem lingers even if lost islets can be replaced: The patient's body could reject them as the immune system attacks the newly transplanted islets.
In this regard, Dr. Ikeda believes that recent advances in gene therapy hold great promise in preventing the autoimmune response to islets that mark the progression of diabetes.
"If we can suppress autoimmunity, we should be able to suppress the disease," he says.
To reach islets with tremendous precision, Dr. Ikeda uses a mild, nondisease-causing virus called adeno-associated virus (AAV), which travels through the bloodstream to deliver a gene that suppresses the immune system's attack in a localized area.
Dr. Ikeda has already used the gene, called interleukin-10, to prevent the onset of diabetes in diabetes-prone mice. That success drove him to pursue an even more challenging discovery: How do you stop diabetes in its tracks once islet destruction begins?
"Once the immune response kicks in, it's very hard to reverse it," he says.
In pursuit of a landmark discovery, Dr. Ikeda is focused on stopping the progression of diabetes during its so-called "honeymoon" stage. This is the critical period — roughly two years in humans but much shorter in the lab mice Dr. Ikeda is testing — during which the immune system gradually decimates islets in the pancreas.
If diabetes can be stopped early enough, Dr. Ikeda believes a critical mass of islets will be preserved to maintain necessary insulin levels. He hopes clinical trials focused on this approach to gene therapy can start soon.
Another possible treatment for diabetes, called cell therapy, also is aimed at protecting islets from the immune system.
"My hope is we reset the system: that you prevent the cells from killing the islets, the islets repair, and you go on with your life," says Allan B. Dietz, Ph.D., an investigator in Mayo Clinic's Human Cellular Therapy Laboratory, which is integral to Mayo Clinic's regenerative medicine endeavors.
Cell therapy involves the use of mesenchymal stem cells, which can be produced in large quantities from a fat biopsy and implanted back into a patient.
"When you get wounded or have an injury, these are the cells that mediate repair," Dr. Dietz says.
There's a good chance that mesenchymal stem cells can suppress the immune system safely in a targeted area to prevent the destruction of islets while helping islets repair themselves, Dr. Dietz said. He noted that new trials could start soon if funding were available.
Though Caroline's family began praying for a cure the day they learned she had diabetes, they began working toward it almost as soon.
Within months of the diagnosis, the family formed Team Caroline and participated in Juvenile Diabetes Research Foundation's Walk to Cure Diabetes in San Diego. About 15 friends and family members joined in. Over the past six years, their involvement has grown, and last year about 100 people donned bright green shirts and walked with them through Mall of America in Minnesota to raise awareness and funds to support research.
Their goal was $15,000. They exceeded it by more than 20 percent.