First-trimester lipid- and glucose-derived indices for predicting gestational diabetes mellitus: development of a combined model in a single-center retrospective cohort.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with substantial maternal and neonatal morbidity. Early identification of women at risk remains a clinical priority. This study aimed to develop and evaluate a simple first-trimester risk prediction model for subsequent GDM using fasting triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and glucose-derived indices (TyG, TG/HDL-C, and Lipid-IR). METHODS: This single-center retrospective cohort included 679 pregnant women with first-trimester fasting lipid and glucose measurements. Of these, 342 developed GDM (diagnosed at 24–28 weeks using a two-step approach and Carpenter–Coustan criteria), and 337 remained normoglycemic. Baseline demographic, anthropometric, laboratory, and obstetric/neonatal variables were compared. TyG was calculated as ln[(fasting triglycerides (mg/dL) × fasting glucose (mg/dL)) / 2], TG/HDL-C as TG (mg/dL) divided by HDL-C (mg/dL), and Lipid-IR as ln(2 × TG (mg/dL) + total cholesterol (mg/dL)). Independent predictors were identified through multivariable logistic regression. Receiver operating characteristic (ROC) analysis evaluated discriminative ability and optimal cut-off points using Youden’s J statistic. RESULTS: Compared with controls, women who developed GDM were older and had higher pre-pregnancy and current body weights, body mass index (BMI), and waist circumference (all p ≤ 0.003). They also exhibited higher fasting glucose, HbA1c, insulin, TG, total cholesterol, and liver enzyme levels, and lower HDL-C concentrations (all p ≤ 0.03). Cesarean delivery was more frequent among women with GDM (58% vs. 32%; p = 0.001), with higher birth weights and lower 5-minute Apgar scores. In multivariable models, Lipid-IR (OR 1.85), TG/HDL-C (OR 2.12), and TyG (OR 1.63) were independently associated with GDM (all p < 0.001). Discrimination was strong, with AUCs of 0.88 for TyG, 0.82 for Lipid-IR, and 0.79 for TG/HDL-C; combining all three indices increased the AUC to 0.92 (sensitivity 89%, specificity 85%). CONCLUSION: In this single-center retrospective cohort, first-trimester lipid–glucose indices—particularly the TyG index were strongly associated with subsequent GDM, and a combined model showed good discrimination for risk stratification. External validation and assessment of clinical impact are required before routine clinical implementation. CLINICAL TRIAL NUMBER: Not applicable. CLINICAL IMPLICATION: Simple lipid–glucose–derived indices can be incorporated into early prenatal screening to identify women at high risk for GDM, enabling early risk stratification and intensified follow-up prior to OGTT, rather than treatment initiation.