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.

Figure 1

Flowchart showing numbers of patients at each step during enrollment. During stage 1, 2,071 patients were screened, 479 were invited into the study based on inclusion criteria, and 274 patients suspected of having monogenic diabetes were enrolled. Twenty-three of the excluded patients in stage 1 were reinvited to join the study during stage 2. In addition to 451 newly screened patients, a total of 474 eligible patients in stage 2 were eligible based on inclusion criteria and were invited. Of these, 90 patients who were suspected of having monogenic diabetes and 143 patients who were not suspected of having monogenic diabetes were enrolled. Overall, 456 patients went through genetic testing, including 313 patients suspected and 143 patients not suspected of having monogenic diabetes. Finally, 38 of the 313 suspected patients tested positive for P/LP variants in eight genes. ¹Total of 1,569 excluded (1,528 did not meet inclusion criteria; 41 unable to assess questionnaire). ²Total of 205 dropped (97 unreachable; 11 declined participation; 50 no showed; 30 assessed to be not suspicious for monogenic diabetes; 17 refused to test). ³Total of 51 assessed to be not suspicious for monogenic diabetes based on lab results and medical history. ⁴Total of 92 dropped (20 unreachable; 23 declined participation; 48 no showed; 1 refused to test). ⁵Total of 149 dropped (111 unreachable; 11 declined participation; 27 no showed).