Diseases are rarely turned off like a light switch. As satisfying as it is to explain a biological mechanism at the genetic or cellular level, extrapolating those discoveries to a human level requires the mind to make difficult leaps of scale. What’s more, even when a basic science finding is effectively translated into clinical treatment, that success is almost always partial and variable.
So with all that realism holding expectations in check, it’s even more powerful when a treatment makes a dramatic, practically overnight difference in a patient. Such stories are few and far between – and yet at the downtown Gleacher Center last week, there were dozens on display as part of the first Celebrating the Miracles family forum put on by the University of Chicago Kovler Diabetes Center.
“It’s really a rare, rare opportunity as a scientist,” said Siri Atma Greeley, instructor of pediatrics at the University of Chicago, “because not only do you get to make some discoveries that might elucidate a molecular pathway for our intellectual curiosity, but you get to see the actual real life impact and benefit to the people right in front of you who are telling these wonderful stories. It’s beautiful from a professional and personal level.”
The miracles of the conference’s name were the young monogenic diabetes patients gifted a unique alternative to a lifetime of insulin treatment. Due to a mutation in a potassium channel that controls the natural secretion of insulin, the patients were diagnosed with diabetes as early as days after their birth. Their parents were told that their son or daughter would likely have to be on insulin – delivered by injection or pump – for the rest of their lives.
But in 2004, British scientist Andrew Hattersley discovered a mutation that caused some of these early-onset diabetes cases. In 2006, he determined that such diabetes cases could be treated with sulfonylurea drugs – cheap oral medication originally designed for people with type 2 diabetes. Later that year, 6-year-old Lilly Jaffe was treated by Louis Philipson of the University of Chicago and became one of the first Americans to be switched from insulin to the pills, a story that was publicized in the Chicago Tribune and other media outlets.
As Lilly’s story spread around the country and world, more and more eligible cases were brought to the attention of Medical Center physicians. Last week, many of those patients and their families traveled to Chicago from as far away as Alaska and Venezuela to share their stories and learn about the latest monogenic diabetes research.
There was Ethan Sabala from Cleveland, who suffered from diabetes along with his father, grandmother, uncles and cousins. When his son Owen was born, Ethan and his wife, Maria, tested him with Ethan’s blood-sugar kit as soon as he showed the telltale signs of hyperglycemia, finding his glucose to be nearly four times the normal level. Owen was diagnosed with monogenic diabetes – and his father was found to have the same mutation. Together, father and son “transitioned” last year to the drug glyburide, and both have been insulin-free with stable blood sugar since.
“Originally I just did it because I wanted to see if there were any side effects or adverse reactions, to see what he’d be feeling,” Ethan said. “It was just a good side effect that my numbers improved too.”
As one of only 100-some American families with a child being treated this way for monogenic diabetes, the Sabalas were excited to swap stories with other parents in a series of small breakout sessions. There, parents discussed their child’s sleep habits on the medication, what happened when they accidentally gave them a higher dose, and methods of tricking toddlers into taking their pills (marshmallows, gumdrops, and raisins). Greeley, who led two sessions on everyday clinical management, said that the discussions were as interesting to the doctors as they were to the parents.
“It’s like we’re in a laboratory; we’re learning as they are learning,” Greeley said.
“At the moment, any trial is a trial of one patient at a time,” said Sian Ellard, a researcher from Hattersley’s laboratory who spoke at the conference about continued research into new mutations.
For some of the parents, one of the challenges was trying to understand what their 2-year-olds and 3-year-olds were feeling on the drug or off it. For those concerns, the input of Michael Bubos, 18, and Emily Mayhugh, 20, was invaluable. Both Michael and Emily were diagnosed within weeks of their birth with diabetes; both endured years of injections and the wearing of an uncomfortable pump. But after transitioning to glyburide a couple of years ago, both Michael and Emily could tell the parents of young diabetic children exactly what they wanted to hear: that they now felt like normal young adults.
“It was a world of difference,” said Michael, who runs varsity track and cross-country for his high school in Valparaiso, Indiana. “It’s been four years, and I’m starting to get to the point where I’m starting to forget all the insulin dependency. I’ve kind of started taking it more for granted, but I’ve felt great.”
“I feel liberated, truly. It’s liberating to not have to carry my pump around every day,” said Emily, of Williamsport, Virginia. “I remember the first thing I did when I was fully off insulin; I said “Mom, I want some dresses.” I could never wear them because I didn’t have a place to put my pump.”
For the younger kids, the educational process was more hands-on. In the childcare room, they learned a game where one kid played the role of glucose, and another performed as insulin and chased glucose around a table. As another group of kids closed off a “potassium channel” (a tube through which they dropped blocks), the glucose slowed down and was caught by the insulin.
One of those children, Ethan Vartanian from Yorba Linda, California, was put on glyburide by his doctors in 2008 after his mother, Kristen, found Lilly Jaffe’s story on the internet. Steve Vartanian, Ethan’s father, said that the family felt “blessed” by the treatment, and about the potential for their son to experience the simplicity of a normal, insulin-free life.
“I have goosebumps just thinking about the future,” Vartanian said. “Everything’s bright. That means a lot. You get to look at someone like Emily, and she’s in college, and fast forward to Ethan being in college. So there’s no reason for them not to have what they want in life and that’s awesome. He won’t know any difference. He’ll just know this is what I take, these pills.”