Insight on Diagnosis and Treatment From Over a Decade of Research Through the University of Chicago Monogenic Diabetes Registry

Abstract

Monogenic diabetes is a category of diabetes mellitus caused by a single gene mutation or chromosomal abnormality, usually sub-classified as either neonatal diabetes or maturity-onset diabetes of the young (MODY). Although monogenic diabetes affects up to 3.5% of all patients with diabetes diagnosed before age 30, misdiagnosis and/or improper treatment occurs frequently. The University of Chicago Monogenic Diabetes Registry, established in 2008, offers insight into the diagnosis, treatment, and natural history of individuals known or suspected to have monogenic diabetes. Those interested in participating in the Registry begin by completing a secure web-based registration form found on our website (http://monogenicdiabetes.uchicago.edu/registry/). Participants are then screened for eligibility and consented either by phone, video call, or in person. Relevant medical and family history is collected at baseline and then annually via surveys through our secure Research Electronic Data Capture (REDCap) database. The University of Chicago Monogenic Diabetes Registry has enrolled over 3800 participants from over 2000 families. Participants represent all 50 states and more than 20 different countries. To date, over 1100 participants have a known genetic cause of diabetes. While many Registry participants reported being referred through their diabetes care provider (54%), a large portion also learned about the Registry through web searching (24%), friends/family (18%), or other sources (13%). Around two-thirds of those with a known genetic cause had research-based genetic testing completed rather than clinical testing due to insurance coverage difficulties. Of those who were found to have monogenic diabetes, significant delays in diagnosis were identified, which highlights the need for increased access to clinical genetic testing covered by insurance companies specifically within the United States. Among genes that cause a MODY phenotype, GCK mutations were the most common (59%) followed by HNF1A mutations (28%), while mutations in KCNJ11 were the most common among genes that cause neonatal diabetes (35%) followed by INS (16%). Over the last decade, improvements in data collection for the University of Chicago Monogenic Diabetes Registry have resulted in increased knowledge of the natural history of monogenic diabetes, as well as a better understanding of the most effective treatments. The University of Chicago Monogenic Diabetes Registry serves as a valuable resource that will continue to provide evidence to support improved clinical care and patient outcomes in monogenic diabetes.

Enrollment of underrepresented racial and ethnic groups in the Rare and Atypical Diabetes Network (RADIANT)

“…Site staff helped participants navigate and complete study procedures to help mitigate retention barriers due to limited health literacy or access. Existing studies and registries were leveraged to identify subjects with atypical diabetes for referral to RADIANT including the Monogenic Diabetes Registry at the University of Chicago [13], the Personalized Diabetes Medicine Program at the University of Maryland [14], and the Ketosis-Prone Diabetes Registry at Baylor College of Medicine [15]. Multiple advertisement tools and avenues were used to enhance awareness of RADIANT in the community, among clinicians and potential participants.…”

Monogenic diabetes in children: An underdiagnosed and poorly managed clinical dilemma

“…Monogenic diabetes registries of the University of Chicago revealed GCK mutations in 59% followed by HNF1A mutations in 28%. NDM was commonly caused by mutations in KCNJ11 (35%) and INS (16%)[ 10 ]. Trends in MODY diagnoses show regional variations, such as increased HNF1A -MODY in Northern Europe and predominant GCK -MODY in Southern Europe[ 11 ].…”

Precision diabetes: Lessons learned from maturity‐onset diabetes of the young (MODY)

“…Also, the University of Chicago Monogenic Diabetes Registry serves as a valuable source for patients suspected to have monogenic diabetes including MODY (http://www.monogenicdiabetes.uchicago.edu). This registry established in 2008, enrolled approximately 4,000 participants from 20 different countries with over 1,100 participants with known genetic cause of diabetes 44 .…”