Full gene sequencing for KCNJ11, a gene associated with permanent neonatal diabetes, is available at The University of Chicago Genetic Services Laboratory and research on this condition is conducted by several researchers at The University of Chicago.  In 2006, the University of Chicago helped to improve the life of 6-year-old Lilly Jaffe. Through advances in molecular medicine, researchers utilized the Clinical Resource Center (CRC) to treat Lilly for monogenic diabetes with pills instead of insulin. Turning off Lilly’s insulin pump freed her and her family from 10 glucose checks and three to five insulin injections every day. At the time, Lilly was one of the first in the United States to be successfully treated this way.

Monogenic diabetes is a less common type of diabetes that may represent 2 to 3 percent of all people with diabetes, notes Siri Atma Greeley, MD, PhD, Instructor of Pediatrics at the University of Chicago Medical Center. Patients diagnosed with diabetes under a year -- especially under six months of age -- are more likely to have a monogenic cause, and this is most often termed neonatal diabetes. Unlike other types of diabetes, monogenic diabetes is caused by a single mutation in one of a number of possible genes, and it can often be treated with glyburide pills instead of insulin injections – making it a model of personalized medicine.

Greeley notes that about 20 percent of neonatal diabetes patients have problems with speech, coordination, and seizures. Furthermore, an uncertain number seem to experience sleep disturbances. So far, very little is understood about the relationship between the beta cells that make insulin, and neurodevelopment and sleep in these young patients.

With these facts in mind, Greeley and co-investigators Louis Philipson, MD, PhD, Professor of Medicine and Director, Kovler Diabetes Center; Michael Msall, MD, Professor of Pediatrics and Section Chief of Development and Behavioral Pediatrics; and David Gozal, MD, Professor of Pediatrics and Chair of Pediatrics, applied for an ITM pilot award and have been using the funds to study these relationships at the CRC.

To learn how many people have neonatal diabetes and recruit study participants, Greeley developed the online national Neonatal Diabetes Registry (http://NeonatalDiabetes.org), where patients and parents of patients diagnosed with diabetes before they were 12 months old can register. Using this outlet, University of Chicago researchers have already enrolled more than 200 neonatal diabetes patients from around the country and even the world. Patients can send saliva collection kits to University of Chicago through the mail for research-based DNA testing. Selected patients may also choose to travel to Chicago to participate in the related CRC studies. 

So far, more than 15 of these rare cases have completed studies in the CRC. The Registry now also includes more than 50 additional cases of neonatal monogenic diabetes now taking glyburide instead of insulin. The University of Chicago also maintains a registry for patients affected by MODY (maturity onset diabetes of the young), another form of monogenic diabetes. The growing registries have resulted in the collection of well more than 500 DNA samples from patients with either neonatal diabetes or a MODY phenotype.

Currently, Greeley and his team are characterizing the spectrum of neurodevelopmental disabilities that could have resulted from neonatal diabetes gene mutations. Additionally, the CRC protocol includes sleep studies and home wrist activity monitoring to help gauge the possible relationship between sleep and beta cell function in this unique patient population.

“This kind of study could only happen here, at the University of Chicago,” Greeley said. “I’ve been at the right place at the right time.”

By: Jennifer Martin, Writer, Kovler Diabetes Center