Objective:To study the relationship between fasting glucose (FPG) and gene polymorphisms of adiponectin (ADIPOQ), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in early pregnancy and insulin resistance in patients with gestational diabetes mellitus (GDM).Methods:Sixty patients diagnosed with GDM within 24 -28 weeks from January 2022 to August 2022 in the Affiliated Hospital of Jining Medical University were selected as the GDM group, and another 60 healthy pregnant women were taken as the normal control group. The fasting insulin (FINS), FPG levels and the homeostatic model assessment insulin resistance index (HOMA-IR) and other clinical data were detected at 8 -12 weeks of pregnancy. Meanwhile, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the polymorphisms of ADIPOQ gene at S0100622 locus, IL-6 gene at S01006318 locus, TNF- α gene at S01009718. Receiver operating characteristics(ROC) curve was used to evaluate the diagnostic performance of FPG combined with polymorphisms of ADIPOQ, IL6 and TNF-α in predicting GDM in early pregnancy.Results:The body mass index (BMI), early pregnancy FPG, mid pregnancy FPG, 75 g oral glucose tolerance test (OGTT) 1 h blood glucose, OGTT 2 h blood glucose, glycosylated hemoglobin (HbA 1c), FINS and HOMA-IR in the GDM group were higher than those in the normal control group: (27.1 ± 2.6) kg/m 2 vs. (25.6 ± 2.5) kg/m 2, (4.7 ± 1.3) mmol/L vs. (4.1 ± 1.5) mmol/L, (5.5 ± 1.3) mmol/L vs. (4.2 ± 1.2) mmol/L, (6.3 ± 1.5) mmol/L vs. (5.5 ± 1.7) mmol/L, (6.0 ± 1.5) mmol/L vs. (5.2 ± 1.4) mmol/L, (5.8 ± 0.7)% vs. (5.2 ± 0.6)%, (6.4 ± 1.1) mU/L vs. (5.2 ± 1.2) mU/L, 1.5 ± 0.6 vs. 1.0 ± 0.7, there were statistical differences ( P<0.05). According to the risk assessment of genotype, the high-risk rate in the GDM group was 88.33% (53/60), while the normal control group was 56.67% (34/60), there was statistical difference ( χ2 = 17.67, P<0.05). In GDM group, the HOMA-IR with ADIPOQ gene S0100622 locus TG genotype was higher than that with TT genotype: 6.58 ± 0.89 vs. 4.98 ± 0.58; the HOMA-IR with IL-6 gene S01006318 locus CG genotype was higher than CC and GG genotype: 8.13 ± 1.31 vs. 6.53 ± 0.81, 4.85 ± 0.54, the HOMA-IR with TNF-αgene S01009718 locus AG genotype was higher than GG genotype: 6.31 ± 1.04 vs. 5.16 ± 0.82, there were statistical differences ( P<0.05). Logistic regression analysis showed that age>35 years, previous diabetes history, BMI, TG genotype at S0100622 locus of ADIPOQ gene, CG genotype at S01006318 locus of IL-6 gene, AG genotype at S01009718 locus TNF- α gene were risk factors for the onset of GDM ( P<0.05). The results of ROC curve analysis showed that the area under the curve (AUC) of FPG for predicting GDM onset was 0.737, with a specificity of 83.50%; FPG combined with ADIPOQ, IL-6, TNF- α genetic risk assessment predicted with AUC of 0.921 and a specificity of 86.80%. Conclusions:ADIPOQ gene TG genotype at S0100622 locus, IL-6 gene CG genotype at S01006318 locus, TNF- α gene AG genotype at the S01009718 locus has a certain correlation with the onset of GDM, which can predict the onset of GDM and is associated with perioperative insulin resistance in patients. Early FPG testing combined with genetic screening has practical clinical guiding significance in reducing adverse pregnancy outcomes for mothers and infants.