Model for Integration of Monogenic Diabetes Diagnosis Into Routine Care: The Personalized Diabetes Medicine Program

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.

Enrollment of underrepresented racial and ethnic groups in the Rare and Atypical Diabetes Network (RADIANT)

“…Site staff helped participants navigate and complete study procedures to help mitigate retention barriers due to limited health literacy or access. Existing studies and registries were leveraged to identify subjects with atypical diabetes for referral to RADIANT including the Monogenic Diabetes Registry at the University of Chicago [13], the Personalized Diabetes Medicine Program at the University of Maryland [14], and the Ketosis-Prone Diabetes Registry at Baylor College of Medicine [15]. Multiple advertisement tools and avenues were used to enhance awareness of RADIANT in the community, among clinicians and potential participants.…”

Overburden of rare ALMS1 deleterious variants in Chinese early‐onset type 2 diabetes with severe insulin resistance

“…Specifically, certain patients with HNF1B or WFS1 pathogenic mutations do not present with typical extrapancreatic features; instead, they only exhibit glycaemic impairment. 30,31 In the previous studies, 32,33 although ALMS1 has been included in the monogenic diabetes genes list, the characteristics of patients with variants were not further explored.…”

The Etiological Diagnosis of Diabetes: Still a Challenge for the Clinician

“…One should note that the majority of MgDs are revealed in adults, with a phenotype that may suggest T2D, and these patients are usually followed by general practitioners who may not be well informed about MgD. A recent study showed that self-referral by the patients was the most efficient way to increase the diagnosis rate of MgD [112], underlying the potential for educating patients with diabetes on this topic.…”