Role of Genetics in Maturity-Onset Diabetes of the Young and Personalized Diabetes Care , explores review

The review carried out by Sung-Hoon Kim, Division of Endocrinology & Metabolism, Department of Medicine, Cheil General Hospital & Women's Healthcare Center, Dankook University College of Medicine, Seoul, Korea, provides an overview of recent updates on MODY in the literature with a focus on studies conducted in Korea.

MODY is a monogenic condition passed down in an autosomal dominant pattern, primarily caused by defects in pancreatic β-cell function. Patients often develop symptoms during adolescence or early adulthood. However, MODY is frequently misdiagnosed as either type 1 or type 2 diabetes, leading to unnecessary or inappropriate treatments.

To date, researchers have identified 13 MODY subtypes, each linked to mutations in specific genes such as HNF1A, GCK, HNF4A, and HNF1B. These mutations result in varying clinical presentations—from mild fasting hyperglycemia in GCK-MODY, which often requires no treatment, to progressive β-cell failure in HNF1A-MODY, which responds well to sulfonylureas instead of insulin.

The review, published in the Diabetes & Metabolism Journal, highlights the variability of MODY gene prevalence across populations. In Europe, HNF1A and GCK mutations dominate, whereas Asian populations, including Korean and Japanese groups, show lower detection rates of known MODY genes. This suggests the presence of undiscovered MODY-causing genes in these regions, pointing to the need for further genetic research and broader testing panels.

Genetic diagnosis not only enables personalized treatment but also allows predictive testing for asymptomatic family members. With advancements in next-generation sequencing, detecting known and novel MODY mutations has become more feasible and cost-effective.

Importantly, the review emphasizes the role of MODY as a model for precision medicine in diabetes care. A timely and accurate diagnosis can help clinicians choose targeted therapies and avoid unnecessary insulin use, particularly in patients with subtypes like HNF1A- or HNF4A-MODY. Moreover, identifying MODY has prognostic value and can guide management during pregnancy and long-term follow-up.

However, the lack of awareness and diagnostic challenges mean many MODY cases remain undetected. The authors call for the establishment of national MODY registries and structured diagnostic approaches to improve early identification and treatment outcomes.

"MODY, a monogenic form of diabetes accounting for 1–2% of cases, holds key insights into diabetes pathogenesis. Its clinical variability stems from genetic heterogeneity and advances in molecular genetics now allow for tailored treatments by subtype—showcasing personalized medicine," the authors concluded.

"Early and accurate diagnosis benefits both patients and families by guiding therapy and prognosis. However, most MODY cases remain undiagnosed due to diagnostic challenges. A nationwide registry and systematic strategies are crucial for improving detection and management.

Reference:

Kim SH. Maturity-Onset Diabetes of the Young: What Do Clinicians Need to Know?. Diabetes Metab J. 2015;39(6):468-477.