摘要目的: 探讨达格列净辅助治疗妊娠期糖尿病(GDM)患者对其血糖水平、胰岛功能、Toll样受体-4(TLR4)/细胞核因子κB(NF-κB)信号通路的影响。方法: 选取本院2021年5月~2023年2月就诊的GDM患者126例,采用随机数字表法分为对照组(n=63)、研究组(n=63)。对照组给予二甲双胍治疗,研究组在对照组基础上给予达格列净。比较两组治疗前、治疗4周后血糖、糖化血红蛋白(HbA1c)、胰岛功能指标、氧化-炎症指标[丙二醛(MDA)、白介素-12(IL-12)、超氧化物歧化酶(SOD)、肿瘤坏死因子-α(TNF-α)]、病情相关指标[尿微量蛋白(mA1b)、尿酸(UA)、总胆红素(TBIL)]、TLR4/NF-κB信号通路相关因子[Toll样受体4(TLR4)、细胞内抑制性蛋白κB(IκB)、核因子-κB(NF-κB) mRNA]。比较两组母婴结局及安全性。结果: 研究组治疗后FPG[(4.21±0.53)mmol/L VS(5.87±0.86)mmol/L]、2hPG[(5.17±1.02)mmol/L VS (7.98±1.26)mmol/L]、HbA1c[(4.33±0.76)% VS (5.86±1.02)%]水平低于对照组(P＜0.05);研究组治疗后FINS水平[(60.35±7.63)mIU/L VS (72.94±8.52)mIU/L]、HOMA-IR[(1.28±0.35) VS (1.94±0.41)]低于对照组,HOMA-β[(50.49±4.58) VS (42.83±3.95)]高于对照组(P＜0.05);研究组治疗后血清MDA、IL-12、TNF-α水平低于对照组,SOD水平高于对照组(P＜0.05);研究组治疗后mA1b、UA水平低于对照组,TBIL水平高于对照组(P＜0.05);研究组治疗后TLR4[(0.37±0.10)VS (0.95±0.31)]、NF-κB[(0.40±0.12)VS (0.91±0.30)]mRNA水平低于对照组,IκB mRNA水平[(1.73±0.33)VS (1.18±0.31)]高于对照组(P＜0.05);研究组不良母婴结局发生率低于对照组[4.76% VS 15.87%](P＜0.05);治疗期间两组均未发生明显不良反应。结论: 达格列净辅助治疗GDM患者,可有效改善血糖、胰岛功能,抑制氧化-炎症反应,控制病情进展,改善不良母婴结局,且具有一定安全性,其疗效机制可能与抑制TLR4/NF-κB信号通路活化有关。
Abstract：Objective: To investigate the effects of dagliprazin adjuvant therapy on blood glucose level, islet function and toll-like receptor-4 (TLR4)/nuclear factor κB (NF-κB) signaling pathway in patients with gestational diabetes mellitus (GDM). Methods: A total of 126 GDM patients visited the hospital from May 2021 to February 2023 were randomized 1∶1 to metformin treatment (control group) or dagliprazin + metformin (study group). Blood glucose, glycated hemoglobin (HbA1c), islet function index and oxygen-inflammation index including malondialdehyde (MDA), interleukin-12 (IL-12), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), disease-related indicators including urinary microprotein (mA1b), uric acid (UA), total bilirubin (TBIL), TLR4/NF-κB signaling pathway related factors including TLR4, intracellular inhibitory protein κB (IκB), NF-κB mRNA were compared between the two groups before treatment and 4 weeks after treatment. The outcome and safety of the two groups were assessed. Results: The levels of FPG [(4.21±0.53) mmol/L VS (5.87±0.86) mmol/L], 2hPG [(5.17±1.02) mmol/L VS (7.98±1.26) mmoL/L], and HbA1c [(4.33±0.76)% VS (5.86±1.02)%] in the study group after treatment were lower than those in the control group (P<0.05). After treatment, the FINS level [(60.35±7.63) mIU/L VS (72.94±8.52) mIU/L] and HOMA-IR [(1.28±0.35) VS (1.94±0.41)] in the study group were lower than those in the control group, while the HOMA-β [(50.49±4.58) VS (42.83±3.95)] was higher than that in the control group (P<0.05). After treatment, the levels of serum MDA, IL-12, and TNF-α in the study group were lower than those in the control group, while the level of SOD was higher than that in the control group (P<0.05). After treatment, the levels of mA1b and UA in the study group were lower than those in the control group, while the level of TBIL was higher than that in the control group (P<0.05). After treatment, the mRNA levels of TLR4 [(0.37±0.10) VS (0.95±0.31)] and NF-κB [(0.40±0.12) VS (0.91±0.30)] in the study group were lower than those in the control group, while the mRNA level of IκB [(1.73±0.33) VS (1.18±0.31)] was higher than that in the control group (P<0.05). The incidence of adverse maternal and infant outcomes in the study group was lower than that in the control group [4.76% vs 15.87%] (P<0.05). No significant adverse reactions occurred in both groups during the treatment period. Conclusion: Dagliprazin adjuvant therapy in patients with GDM can effectively improve blood glucose and islet function, inhibit oxidation-inflammation response, control disease progression, and improve adverse maternal and infant outcomes, with certain safety, and its therapeutic mechanism may be related to inhibiting the activation of TLR4/NF-κB signaling pathway.
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2025, Vol. 31 
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