Research Information System
Journal of the Endocrine Society, vol.9, no.8, 2025 (ESCI)
Context Rare monogenic conditions that predispose to diabetes can be misdiagnosed due to phenotypic overlap with more common conditions. Misdiagnosis can lead to ineffective, over-, or under-treatment. Specific genetic mechanisms can direct more precise treatment and facilitate clinical trial options. Recognition of characteristics of these conditions is necessary to facilitate high-yield referrals to genetics providers in order to improve diagnosis and treatment. Objective Highlight clinical characteristics and diagnostic outcomes of patients undergoing genetics evaluation through a multidisciplinary Atypical Diabetes Program. Design, Setting, and Patients Retrospective cohort review was completed for 87 patients referred to genetics from endocrinologists associated with the multidisciplinary Atypical Diabetes Program at a tertiary academic medical center between September 2019 and October 2022. Main Outcome Measure Description of clinical characteristics of patients with a diagnostic or uncertain clinical genetic test result, as well as proportion of patients with these results. Results Six patients (8.8%) had a pathogenic variant confirming diagnosis of lipodystrophy (4), monogenic diabetes (1), or monogenic obesity (1). Fifteen (22.0%) had a variant of uncertain significance, 5 of which correlated with their clinical features. As a result of genetics evaluation, all with a confirmed diagnosis had more precise treatment implemented and/or the opportunity to enroll in a clinical trial. Conclusion Identification of rare genetic conditions predisposing to diabetes, enabled here through multidisciplinary genetics and endocrinology collaboration as part of the Atypical Diabetes Program, ultimately improves patient care. Endocrinologist attention to clinical features of these conditions is key to inform referral for genetics evaluation and testing.