1551-P: Optimizing MODY Detection in a Pediatric Diabetes Population

Abstract

Maturity-onset diabetes of the young (MODY) is under-diagnosed or misdiagnosed as type 1 diabetes (T1D) or type 2 diabetes (T2D), in part due to lack of systematic genetic testing. We aimed to define patient characteristics that could guide the decision to conduct genetic testing for MODY diagnosis in racially/ethnically diverse youth with diabetes. In our electronic health record-based Diabetes Registry, we found 4,752 cases carrying a diagnosis of T1D (78.3%), T2D (20.4%) or MODY (1.3%) seen within the past 3 years. We then screened the Diabetes Registry in an agnostic manner for likely MODY cases (“Study Cohort”) based on: (1) diagnosis of diabetes at age <25 y, (2) family history of diabetes in 3-consecutive generations, (3) absent islet autoantibodies (Ab) except GAD65 Ab. We collected data on their clinical and biochemical characteristics, and results of MODY testing if available. In the Study Cohort (n=350, 7.4% of the Diabetes Registry), 62.3% were female; 57% Hispanic, 13.8% non-Hispanic white, 26.4% non-Hispanic black and 2.9% other. 4.6% had previously received a diagnosis of MODY, 16.6% T1D and 78.8% T2D. Frequency of MODY diagnosis was 3.5 times higher in the Study Cohort than in the Diabetes Registry (p<0.001). At diabetes diagnosis, mean age was 13 y (± 3.2) and HbA1c 9.8% (± 2.6). To further refine characteristics of potential MODY, we performed cluster analysis on the Study Cohort using variables commonly used to establish diabetes type at diagnosis: age, BMI-z score, glucose, C-peptide, HbA1c and islet Ab. The cluster with the highest rate of prior MODY diagnosis (25%) had the lowest age at onset (10.9 ± 2.5 y), BMI-z (0.5 ± 0.9), C-peptide (1.5 ± 1.2 ng/mL) and acanthosis nigricans frequency (12.5%) (all p<0.05). Furthermore, in this cluster, molecular confirmation rate was 75% in those patients who had undergone genetic testing (1/3 of the cluster). The patient characteristics defined by this stepwise approach expands and enhances accurate MODY diagnosis and improves the yield of genetic testing for MODY. Disclosure M. Tosur: None. A.K. Refaey: None. D. Guffey: None. A. Balasubramanyam: None. M.J. Redondo: None. Funding Mike Hogg Fund