The University of Chicago Medicine established and maintains the Western Hemisphere’s largest registry for patients with monogenic forms of diabetes. The registry represents a unique partnership between nearly 3,500 participants and UChicago Medicine researchers who are pursuing critical research on the genetic causes, diagnosis and treatment of MODY diabetes, neonatal/congenital diabetes, and rare syndromic forms of diabetes.
Up to five percent of all diabetes cases may have an underlying monogenic cause, but are most often misdiagnosed as the more common type 1 or type 2 diabetes. Importantly, uncovering a molecular genetic cause can have significant clinical implications, including major differences in treatment, better understanding of other possible manifestations, and proper diagnosis of family members.
The Monogenic Diabetes Registry was established by UChicago Medicine’s Louis Philipson, MD, PhD, who serves as the American Diabetes Association’s president for medicine and science, and Siri Atma Greeley, MD, PhD, an internationally renowned expert in monogenic diabetes who serves as the registry’s principal investigator. Philipson is also director of the Kovler Diabetes Center, UChicago Medicine's comprehensive center for innovative diabetes research and highly individualized patient care.
“Our registry serves as a resource for thousands of physicians and patients across the country who want to learn more about monogenic diabetes, and our research that is shaping national standards of care,” says Ronald Cohen, MD, chief of pediatric endocrinology at UChicago Medicine Comer Children’s Hospital. “We know that early and accurate diagnosis — followed by individualized treatment — is key to controlling diabetes and avoiding future developmental issues.”
We know that early and accurate diagnosis — followed by individualized treatment — is key to controlling diabetes and avoiding future developmental issues.
Ronald Cohen, MD
Among the many ongoing research projects being conducted through the registry, Greeley is currently working with the University of Wisconsin-Madison’s newborn screening lab to study the feasibility of including congenital diabetes in newborn screening programs. Congenital diabetes describes a group of rare (one in 100,000 births) but treatable forms of diabetes, which often have a delayed diagnosis because the cardinal signs (polyuria and polydipsia) are difficult to recognize in infants. Preliminary data show dried blood-spot samples may detect elevated glucose levels within the first few days of life. The study also will assess the clinical consequences of a delayed diagnosis, including neurodevelopmental disability.
Greeley and Michelle Lemelman, MD, are studying the neurodevelopmental outcomes of a group of patients with neonatal or congenital diabetes caused by mutations in the KCNJ11 gene. This gene encodes the ATP-sensitive potassium (KATP) channel found in insulin-secreting pancreatic beta cells. Patients can usually be treated very effectively with oral sulfonylurea pills instead of insulin injections. Ongoing studies at UChicago Medicine have shown that children with KATP-related diabetes have a spectrum of neurodevelopmental disabilities. Greeley and Lemelman are taking this a step further to learn the extent to which these disabilities are related to glycemic dysfunction during brain development.
In other research funded by the American Diabetes Association, Greeley is studying patients diagnosed with non-KATP-related diabetes in the first year of life to determine the neurodevelopmental consequences of high and low blood sugars in infancy. He will also assess measures of the patients’ clinical diabetes control and quality of life to determine their relationship to genetic diagnosis and treatment history.
With funding from the National Institute of Diabetes and Digestive and Kidney Diseases, UChicago Medicine is partnering with several institutions to create a center for the identification and study of individuals with rare and atypical diabetes mellitus (U54). By analyzing these patients’ phenotypic and genotypic defects, the group also hopes to gain insights into more common, heterogeneous forms of type 2 diabetes.
“This is a transformative opportunity to increase our understanding of diabetes and to develop a community resource to advance research through collection and dissemination of data and samples for access by the broader research community,” Greeley says.
Comer Children’s now has a pediatric endocrinologist focused on the care of patients with thyroid abnormalities and thyroid cancer. Michelle Lemelman, MD, who completed her residency and fellowship at UChicago Medicine, will be responsible for the development of a new thyroid clinic that focuses on early detection and treatment for children.
“Little is known about treatment and management of thyroid cancer in children, so current guidelines are based largely on our experience with adults,” Lemelman says. “My hope is that, over time, we can help create revised standards of care for the diagnosis and treatment of children based on our experience with a larger group of pediatric thyroid patients.”