Approach to the Patient with MODY-Monogenic Diabetes.
Maturity-onset diabetes of the young, or MODY-monogenic diabetes, is a not-so-rare collection of inherited disorders of non-autoimmune diabetes mellitus that remains insufficiently diagnosed despite increasing awareness. These diagnoses are important to efficiently and accurately diagnose, given the clinical implications of syndromic features, cost-effective treatment regimen and the potential impact on multiple family members. Proper recognition of the clinical manifestations, family history, and cost-effective lab and genetic testing provide the diagnosis. All patients must undergo a thorough history, physical examination, multi-generation family history, lab evaluation (HbA1c, glutamic acid decarboxylase antibodies (GADA), islet antigen 2 antibodies (IA-2A), and Zinc Transporter 8 antibodies (ZnT8)). The presence of clinical features with 3 (or more) negative antibodies is indicative of MODY-monogenic diabetes, and is followed by genetic testing. Molecular genetic testing should be performed before attempting specific treatments in most cases. Additional testing that is helpful in determining the risk of MODY-monogenic diabetes is the MODY clinical risk calculator (> 25% PPV suggestive of MODY) and 2-hour post-prandial (after largest meal of day) urinary C-peptide to creatinine ratio (with a > 0.2 nmol/mmol to distinguish HNF1A- or 4A-MODY from Type 1 Diabetes) 1,2. Treatment, as well monitoring for microvascular and macrovascular complications is determined by the specific variant that is identified. In addition to the diagnostic approach, this article will highlight recent therapeutic advancements when patients no longer respond to first line therapy (historically sulfonylurea treatment in many variants).