Development and validation of a multivariable genotype-informed gestational diabetes prediction algorithm for clinical use in the Mexican population: insights into susceptibility mechanisms

Introduction: Gestational diabetes mellitus (GDM) is underdiagnosed in Mexico. Early GDM risk stratification through prediction modeling is expected to improve preventative care. We developed a GDM risk assessment model that integrates both genetic and clinical variables.

Research design and methods: Data from pregnant Mexican women enrolled in the 'Cuido mi Embarazo' (CME) cohort were used for development (107 cases, 469 controls) and data from the 'Mónica Pretelini Sáenz' Maternal Perinatal Hospital (HMPMPS) cohort were used for external validation (32 cases, 199 controls). A 2-hour oral glucose tolerance test (OGTT) with 75 g glucose performed at 24-28 gestational weeks was used to diagnose GDM. A total of 114 single-nucleotide polymorphisms (SNPs) with reported predictive power were selected for evaluation. Blood samples collected during the OGTT were used for SNP analysis. The CME cohort was randomly divided into training (70% of the cohort) and testing datasets (30% of the cohort). The training dataset was divided into 10 groups, 9 to build the predictive model and 1 for validation. The model was further validated using the testing dataset and the HMPMPS cohort.

Results: Nineteen attributes (14 SNPs and 5 clinical variables) were significantly associated with the outcome; 11 SNPs and 4 clinical variables were included in the GDM prediction regression model and applied to the training dataset. The algorithm was highly predictive, with an area under the curve (AUC) of 0.7507, 79% sensitivity, and 71% specificity and adequately powered to discriminate between cases and controls. On further validation, the training dataset and HMPMPS cohort had AUCs of 0.8256 and 0.8001, respectively.

Conclusions: We developed a predictive model using both genetic and clinical factors to identify Mexican women at risk of developing GDM. These findings may contribute to a greater understanding of metabolic functions that underlie elevated GDM risk and support personalized patient recommendations.