Evaluation of Type 2 Diabetes Like Subtypes in Gestational Diabetes

Introduction: Gestational diabetes mellitus (GDM) is a condition characterized by glucose intolerance that is first identified during pregnancy and typically resolves after childbirth. This condition can lead to various complications, both prenatal and postnatal, including type 2 diabetes (T2D). However, not all women with GDM progress to T2D, and the molecular mechanisms underlying this heterogeneity remain poorly understood. Here, we hypothesized that GDM participants could be clustered into T2D-like subtypes. Methods: To derive T2D-like subtypes, we applied K-means clustering to GDM participants using the predefined T2D subtype cluster centers established in the QPHI cohort. Differential methylation analysis was performed, and the top-ranked sites were used for further analysis. Additionally, we estimated system-specific age acceleration and its association with subtype-specific complications. Results: Our study demonstrated the effectiveness of the novel clustering approach, originally developed for T2D, in GDM. Additionally, the exploratory analysis of the top-ranked CpG sites suggested potential subtype-related methylation patterns. The identified pathways also suggested overlapping molecular mechanisms underlying both GDM and T2D. Conclusion: These findings support the feasibility of classifying GDM into T2D-like clinical subtypes and suggest potential epigenetic differences that warrant validation in larger longitudinal cohorts.