Monogenic diabetes: the impact of making the right diagnosis.

PURPOSE OF REVIEW: Monogenic forms of diabetes have received increased attention and genetic testing is more widely available; however, many patients are still misdiagnosed as having type 1 (T1D) or type 2 diabetes. This review will address updates to monogenic diabetes prevalence, identification, treatment, and genetic testing. RECENT FINDINGS: The creation of a T1D genetic risk score and the use of noninvasive urinary C-peptide creatinine ratios have provided new tools to aid in the discrimination of possible monogenic diabetes from likely T1D. Early, high-dose sulfonylurea treatment in infants with a KCNJ11 or ABCC8 mutation continues to be well tolerated and effective. As the field moves towards more comprehensive genetic testing methods, there is an increased opportunity to identify novel genetic causes. Genetic testing results continue to allow for personalized treatment but should provide patient information at an appropriate health literacy level. SUMMARY: Although there have been clinical and genetic advances in monogenic diabetes, patients are still misdiagnosed. Improved insurance coverage of genetic testing is needed. The majority of data on monogenic diabetes has been collected from Caucasian populations, therefore, research studies should endeavor to include broader ethnic and racial diversity to provide comprehensive information for all populations.

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

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.