Objective To analyze the interactive effect of potassium inward rectifier channel protein subunit 11 (KCNJ11) gene polymorphism and triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) on efficacy of lifestyle intervention in patients with newly diagnosed gestational diabetes mellitus (GDM).

Methods A total of 192 patients with newly diagnosed GDM were selected as the study subjects and divided into qualified group and non-achievement group based on their glycemic control status after lifestyle intervention. Baseline data, KCNJ11 gene polymorphism and TG/HDL-C were compared between the two groups. Multicollinearity diagnosis was performed to screen variables, and factors influencing the glycemic control rate after lifestyle intervention in newly diagnosed GDM were analyzed. The interactive effect of KCNJ11 gene polymorphism and TG/HDL-C on post-intervention glycemic control and their predictive value for glycemic control were evaluated.

Results Statistically significant differences were observed in the distribution of KCNJ11 gene polymorphisms and TG/HDL-C between the two groups (P < 0.05). The AG and GG genotypes, as well as a high TG/HDL-C, were independently associated with suboptimal glycemic control (P < 0.05). KCNJ11 gene polymorphism and TG/HDL-C exhibited an additive interactive effect on glycemic control, and their combined predictive accuracy for glycemic control, as indicated by the area under the curve (AUC), was 0.841, which was superior to their individual predictive performance (P < 0.05).

Conclusion KCNJ11 gene polymorphism and TG/HDL-C interactively influence the efficacy of lifestyle intervention in newly diagnosed GDM, suggesting that the KCNJ11 gene may be involved in the regulation of β-cell function. Their combined detection holds favorable predictive value for glycemic control rate and can provide a reference for clinical stratified management.