Prevalence of Maturity-Onset Diabetes of the Young Among Women with Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is routinely screened for during pregnancy to prevent complications in both mother and newborn. However, a subset of women diagnosed with GDM may, in fact, have Maturity-Onset Diabetes of the Young (MODY), a monogenic form of diabetes. Although GDM and MODY both manifest as disorders of glucose metabolism, they differ significantly in terms of management and follow-up. MODY diagnosis is confirmed through genetic testing, and predictive tools have been developed to estimate the likelihood of MODY in individuals with diabetes. This study aims to evaluate the prevalence of MODY among women diagnosed with GDM (WwGDM) and assess the utility of the MODY Probability Calculator (MPC). WwGDM based on a positive screening test in the first or second trimester and negative islet autoantibodies were recruited from the Diabetology Center of the Faculty Hospital Královské Vinohrady between October 2021 and April 2024. The probability of MODY was assessed in each participant using the MPC. Genetic testing included sequencing of the glucokinase gene followed by next-generation sequencing of 63 genes associated with beta-cell disorders. Additionally, data on the newborns of participating mothers were collected. Of 172 WwGDM, 82 met the inclusion criteria and agreed to participate in the study. Although 66/82 (80.5%) had a predicted MODY probability of 75.5% based on the MPC, no pathogenic variants were identified. Two women carried variants of uncertain significance, in the RFX6 and ONECUT1 genes, respectively. Most newborns were delivered at term and experienced an uncomplicated postnatal course. Neonatal hypoglycemia, defined as blood glucose levels below 2.2 mmol/L, occurred in 3.8% of cases. Birth weight exceeded 4,000 g in 5.1% of neonates, while 2.6% had a birth weight below 2,500 g. Comprehensive molecular genetic testing for MODY and beta-cell dysfunction in an unselected cohort of Czech WwGDM revealed no pathogenic alterations. The MPC was not a suitable tool for identifying MODY among WwGDM.