Kovler Diabetes Center’s Monogenic Forum Focuses on Patients

The focus was on patients as researchers and families gathered for last week’s Kovler Diabetes Center Monogenic Diabetes Family Forum.

Louis Philipson, MD, PhD, with IL Gov. Pat Quinn at the  Monogenic Diabetes Family Forum on July 18, 2013.

Louis Philipson, MD, PhD, with IL Gov. Pat Quinn at the Monogenic Diabetes Family Forum on July 18, 2013.

Without the help of patients, said Andrew Hattersley, he never would have made his most important discoveries about monogenic diabetes. It’s a rare form of diabetes caused by genetic mutations that prevent insulin secretion, instead of an errant autoimmune response, as in type 1 diabetes, which destroys insulin-producing beta cells in the pancreas.

“Patients have been central to all advances in monogenic diabetes. We would have found no genes without the help of patients,” he said.

Hattersley, a researcher at Peninsula College at Exeter University in the UK, recently spoke at the Monogenic Diabetes Family Forum, held for the benefit of those very same patients last Thursday and Friday in downtown Chicago. Hosted by the University of Chicago Medicine Kovler Diabetes Center, it was the 2nd gathering of families with genetic forms of diabetes, giving them an opportunity to meet, share their stories, learn from one another’s experiences and mingle with the world’s foremost diabetes researchers.

Illinois Governor Pat Quinn highlighted the conference on Thursday when he signed into law two new bills to support diabetes research. Quinn joined Louis Philipson, MD, PhD, Director of the Kovler Diabetes Center and Tom Cross, Illinois House minority leader and bill sponsor, on stage with patient families to sign the bills.

The first measure created a diabetes awareness license plate for Illinois, funds from which will go to support diabetes research. The second bill requires the Illinois State Diabetes Commission to report on the economic costs of diabetes and provide status of prevention efforts in the state.

Hattersley gave a presentation on his pioneering work at Exeter beginning in 1995, where he helped discover genetic mutations that caused diabetes in children very early in life. Long thought to have the more common type 1 form of the disease, the patients Hattersley was seeing were telling him different stories about how they responded to standard treatments. Some were extremely sensitive to medications; others were able to regulate blood glucose levels on their own, but at a much higher level than non-diabetics.

He told the crowd these personal anecdotes drove him to better understand these differences.

“We have to go on listening to patients, because you know the answers,” he said.

He and collaborators around the world, including the University of Chicago Medicine’s Kenneth Polonsky, MD, dean and executive vice president for medical affairs, and Graeme Bell, PhD, the Louis Block Distinguished Service Professor of Medicine and Human Genetics, eventually characterized a number of such mutations that can impede insulin secretion in the pancreas and can cause diabetes.

One of these is in the genes that control a channel to regulate the flow of potassium ions in and out of the beta cells. In the normal beta cell, glucose metabolism results in increased levels of ATP, a molecule that cells use to store energy. The increase in ATP causes the potassium channel to close. After it closes, potassium ions accumulate within the cell. When they reach a certain level, they trigger the opening of calcium channels. Calcium ions flow in and the cell responds by secreting insulin.

The mutation Hattersley discovered affects the potassium channel, making it less sensitive to the build-up of ATP. The channel remains open, allowing potassium ions to flow in and out rather than accumulate. As a result, insulin secretion is drastically reduced.

The crucial breakthrough for patients with this genetically induced form of diabetes is that a class of drugs known as sulphonylureas—until then used to increase insulin secretion in adult patients with type 2 diabetes—could close this potassium channel and induce the beta cells to secrete insulin normally. Instead of relying on insulin injections or using an insulin pump the rest of their lives, they could simply take a pill instead.

On Friday, Frances Ashcroft, another British scientist from the University of Oxford, spoke about her pioneering work in understanding the mechanisms of the crucial potassium ion channel, which helped lay the groundwork for Hattersley’s work.

“One never expects as a scientist for their work to have an effect on people’s lives,” she said. “It’s extraordinary to be in that position.”

Ashcroft also spoke about the continuing focus on neurological symptoms that sometimes accompany more severe forms of monogenic diabetes. The potassium ion channel is found in many parts of the body in addition to the pancreas, including the brain, heart, smooth muscle and skeletal muscle. Sulphonylureas have been shown to help with neuromuscular symptoms, but Aschcroft said more research is needed into how exactly these drugs induce neurological changes and how best to administer them.

The impact this research has on the lives of patients with these genetic forms of diabetes perhaps has no better spokesperson than 13-year-old Lilly Jaffe, who Philipson and Bell helped diagnose as one of the first children with monogenic neonatal diabetes in the United States to benefit from this new approach in 2006, when she was 6-years-old.

In 2009, Quinn signed another law (also sponsored by Cross) known as “Lilly’s Law,” which established a registry of Illinois children diagnosed with neonatal diabetes before the age of 12 months, to be used by physicians and researchers.

In a speech given on Friday at last week’s forum, Jaffe said, “I now have independence I couldn’t have when I was on insulin.”

She wasn’t speaking just for herself, but for thousands of others around the world freed from a life of insulin injections and constant worries about blood glucose levels by the work of Hattersley, Ashcroft, Philipson, Bell and others.

About Matt Wood (531 Articles)
Matt Wood is a senior science writer and manager of communications at the University of Chicago Medicine & Biological Sciences Division.
%d bloggers like this: