Abstract
OBJECTIVE: To implement, disseminate, and evaluate a sustainable method for identifying, diagnosing, and promoting individualized therapy for monogenic diabetes. RESEARCH DESIGN AND METHODS: Patients were recruited into the implementation study through a screening questionnaire completed in the waiting room or through the patient portal, physician recognition, or self-referral. Patients suspected of having monogenic diabetes based on the processing of their questionnaire and other data through an algorithm underwent next-generation sequencing for 40 genes implicated in monogenic diabetes and related conditions. RESULTS: Three hundred thirteen probands with suspected monogenic diabetes (but most diagnosed with type 2 diabetes) were enrolled from October 2014 to January 2019. Sequencing identified 38 individuals with monogenic diabetes, with most variants found in GCK or HNF1A. Positivity rates for ascertainment methods were 3.1% for clinic screening, 5.3% for electronic health record portal screening, 16.5% for physician recognition, and 32.4% for self-referral. The algorithmic criterion of non-type 1 diabetes before age 30 years had an overall positivity rate of 15.0%. CONCLUSIONS: We successfully modeled the efficient incorporation of monogenic diabetes diagnosis into the diabetes care setting, using multiple strategies to screen and identify a subpopulation with a 12.1% prevalence of monogenic diabetes by molecular testing. Self-referral was particularly efficient (32% prevalence), suggesting that educating the lay public in addition to clinicians may be the most effective way to increase the diagnosis rate in monogenic diabetes. Scaling up this model will assure access to diagnosis and customized treatment among those with monogenic diabetes and, more broadly, access to personalized medicine across disease areas.