Can HbA1c combined with fasting plasma glucose help to assess priority for GCK-MODY vs HNF1A-MODY genetic testing?

GCK-MODY and HNF1A-MODY are the most common subtypes of Maturity Onset Diabetes of the Young (MODY) [1–3]. HNF1A-MODY mutation carriers may respond to sulfonylureas, while GCK-MODY does not necessitate therapy; therefore, molecular diagnosis is instrumental to guide therapeutic decision. In many laboratories next generation sequencing is not available yet, and genetic testing of common MODY genes is performed using Sanger DNA sequencing. Thus, establishing which gene has to be screened first is mainly based on clinician expertise. Though HNF1A mutation carriers are frequently diagnosed with overt diabetes, both GCK-MODY and HNF1A-MODY can present with impaired fasting glucose (IFG). In the latter case, oral glucose tolerance test (OGTT) may help to distinguishbetween the two types [4]; however, a less expensive and time-consuming test would be preferable. GCK-MODY is usually considered in pediatric patients negative to type 1 diabetes (T1D)-related autoantibodies and stable, mild fasting hyperglycaemia (100–150 mg/dl). In addition, an HbA1c ≥ 6% (42 mmol/mol) [5] or ≤ 7.6% (60 mmol/mol) [2] has been utilized as criterium to select candidates for GCK genetic testing. In this study, we wanted to evaluate the usefulness of HbA1c combined with fasting glucose (FPG) < 150 mg/dl to prioritize sequencing between the two genes. Ninety-nine cases with GCK-MODY and with HNF1A-MODY confirmed by genetic testing were selected among patients attending Italian pediatric diabetes centers.