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

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). 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. 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%). 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. Not applicable. 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. Early lipid–glucose indices predict gestational diabetes: First-trimester TyG index, TG/HDL-C ratio, and Lipid-IR were identified as independent predictors of gestational diabetes mellitus (GDM). Strong predictive accuracy of the TyG index: The TyG index achieved the highest discriminative performance (AUC = 0.88; sensitivity 85%; specificity 82%). Combined model provides superior performance: Integration of TyG, TG/HDL-C, and Lipid-IR indices enhanced diagnostic accuracy (AUC = 0.92; sensitivity 89%; specificity 85%). Feasibility in routine prenatal care: These indices can be automatically calculated from standard first-trimester lipid and glucose tests, allowing pre-OGTT risk stratification. Clinical implications: Early identification of at-risk women may enable timely lifestyle interventions, reducing macrosomia and adverse obstetric outcomes. • TyG index, TG/HDL-C ratio, and Lipid-IR were all independently associated with GDM. • TyG showed the strongest individual predictive ability (AUC 0.88). • The combined model of all three indices achieved AUC 0.92, outperforming individual parameters. Gestational diabetes mellitus (GDM) remains a major cause of maternal and neonatal morbidity. Early detection before the oral glucose tolerance test (OGTT) may improve outcomes. Retrospective cohort of 679 pregnant women (342 GDM, 337 controls) with first-trimester fasting lipid and glucose data.