e: katie@katiescarlettbrandt.com

Lilly Jaffe is not keen on publicity. A petite girl with long, brown hair and big, brown eyes, Lilly can beam a broad smile when she’s happy—and lose it in an instant when she becomes the focus of too much attention.

This aversion may exist because for her entire life—six whole years so far—she’s been followed by an entourage that includes, at alternating times, her mother, father, the school nurse, a blood glucose gauge and insulin shots. It’s all for her benefit, of course, and necessary for children like Lilly with Type 1 diabetes, but a lot of constant and concentrated attention for one little girl nonetheless.

Until a couple of months ago, meals in the Jaffe household involved math to calculate Lilly’s carbs and compute her insulin needs. Play dates always included mom who would suspend games to draw Lilly’s blood for glucose checks. Family outings were never completely worry-free because Lilly’s blood sugar levels could rise or fall to dangerous highs or lows unexpectedly. And at school, time between lessons or lunch meant visits to the nurse.

And then Lilly’s life changed.

Initially the idea of change worried Lilly, and she resisted. Diagnosed when she was just a month old, Lilly’s life revolved around insulin shots or her pump: a pager-size device attached by a tiny catheter into her hip that delivered constant, low doses of insulin into her body.

But Lou Philipson, a University of Chicago endocrinologist, suggested this summer that Lilly’s specific type of diabetes might be controlled with pills instead of pump.

Lilly didn’t immediately embrace the idea. “She found comfort and security in that pump,” said Laurie Jaffe, Lilly's mom. But where Lilly found apprehension in the new treatment, her parents saw hope instead.

Michael Jaffe, Lilly’s dad, had heard Philipson speak about the relatively unrecognized treatment at a presentation for the Chicago chapter of the Juvenile Diabetes Research Foundation. Afterward, Michael approached Philipson and described his daughter’s case, which led to Lilly having her genes tested. One spit sample and a couple weeks later, Philipson and his Chicago colleague, geneticist Graeme Bell, announced that one of the two particular strands of Lilly’s genes involved in her insulin secretion showed a mutation.

She was a perfect monogenic diabetic candidate for oral drug treatment.

Diagnosis and discovery

The oral drugs that the doctors proposed belonged to a family called sulfonylureas. Since the 1970s, Type 2 diabetics have used those same drugs to help manage the disease, but nobody realized that the drugs also could play a major role in Lilly’s type of diabetes. Even British scientist Andrew Hattersley didn’t realize what he was
on to when, three years ago, he began researching potassium channels in infants diagnosed with diabetes before 6 months of age.

On Aug. 3, 2006, the New England Journal of Medicine published Hattersley’s findings and scientists around the world began to see that treatment—though not a total cure—was possible through these drugs. “To date we have examined over 280 patients diagnosed before 6 months of age and found over 140 patients with this type of diabetes,” he said.

When Lilly’s doctor diagnosed her six years ago, nobody saw this coming. Laurie had taken Lilly for her well-baby one-month check up.The doctor looked her over, pronounced her as perfect a baby as could be and left the room while Laurie bundled Lilly and herself into their jackets. But before they left, the doctor returned, and Laurie could read the concern creasing his face. Lilly’s urine sample showed high levels of glucose, meaning her body either wasn’t producing or wasn’t using insulin the way nature intended in order to break down sugars.

Since that day, Laurie said, “We’ve always believed in our hearts that there would be a cure someday, but we thought it would be 15 years down the line.”

Sleeping cells

Only 2,000 to 2,500 people in the United States have the same type of diabetes as Lilly, scientists estimate. It occurs in some infants diagnosed with Type 1 diabetes before 6 months of age and, in very rare instances, between 6 and 12 months.

In typical Type 1 diabetes, the immune system, for some reason, attacks and destroys the pancreas’s beta cells responsible for making insulin. Type 1 diabetics like Lilly, (about 1 in 200,000 live births), have a normal number of insulin-secreting cells, but, Philipson said, “for all intents and purposes, the cells have been
asleep for [their] entire lives.”

They “sleep” because the ions responsible for waking them up never do. In a fully functional beta cell, glucose metabolism leads to increased amounts of ATP, an energy-storing molecule in the cell. The increases in ATP cause the potassium channels along the cell’s wall to close. Because they’re closed, potassium ions
build up within the cell, and when those reach a certain level, they prompt the calcium channels—also along the cell’s wall—to open. As the calcium ions enter, they alert the cell that it’s time to begin insulin secretion.

The mutation in diabetes cases like Lilly’s happens in one of two possible genes, either KCNJ11 or ABCC8, and affects the potassium channel. Chicago’s Deborah Edidin, Lilly’s pediatric endocrinologist, suspected Lilly had a mutation, but it was Jaffe and Philipson’s chance meeting that put the transition in motion.

Lilly’s KATP channels are less sensitive to ATP build-up and there-fore don’t close and keep the potassium ions from exiting. So the potassium ions don’t accumulate, the calcium ions never surge in signaling the cell to secrete insulin, and Lilly’s insulin levels remain unreadable.

When Bell tested Lilly’s DNA for the mutation, he looked at KCNJ11 first, where mutations are more common. “It’s absolutely critical to test DNA first because if you just take people off insulin, they could become very ill or even die,” Philipson said. The test for mutations in the KCNJ11 gene costs $10, and for the ABCC8 gene, which is much larger, the test costs about $200.

Because of those cases, scientists aren’t positive that the sulfonylureas will prove effective for Lilly’s entire lifetime. However, Philipson said, even if it only works for 10 or 20 years, medical research may catch up with her. The field has advanced with such speed in the past few decades that virtually everyone who has contributed to the research of ion channels and sulfonylureas in insulin secretion—people from England, Japan, the United States and elsewhere—is still alive, so continued advancement is highly likely.

And already molecular medicine has progressed to a point where, if or when Lilly decides to have children of her own, scientists likely will be able to test the DNA in her eggs to see which ones are capable of producing babies without diabetes. Such knowledge carries with it both tremendous promise and ethical considerations.

“It’s becoming more and more common to link genetics with health, but it’s not always good,” Philipson said of genetic testing that can indicate whether patients are
prone to certain disorders, such as stomach, prostate or breast cancers. “Do we want to know?” Philipson poses. “Do we want the insurance companies to know?”

...to read more, click here
(downloads pdf)