谷氨酸和尿液α1G微球蛋白水平与GDM患者肾损伤及妊娠结局的关联

Association of glutamic acid and urinary α1G microglobulin levels with kidney injury and pregnancy outcomes in patients with GDM

摘要

目的 探讨妊娠期糖尿病(GDM)患者血清谷氨酸(Glu)、尿液α1G微球蛋白(α1GMG)水平与早期肾损伤及妊娠结局的相关性。方法 选择2021年7月至2023年7月于宜宾市第二人民医院收治的106例GDM孕妇为GDM组,根据患者是否发生早期肾损伤分为损伤组和未损伤组,另选择同期产前检查健康的孕妇102例作为对照组,检测患者及健康孕妇血清Glu及尿液α1GMG。根据GDM患者的妊娠结局分为妊娠结局不良组和妊娠结局良好组,检测尿微量白蛋白(U-mAlb)、血清尿素(Urea)、尿酸(UA)、血肌酐(Scr)、β2G微球蛋白(β2GMG)水平。采用pearson法分析血清Glu、尿液α1GMG水平与肾功能指标的相关性,采用受试者工作特征曲线(ROC)分析血清Glu、尿液α1GMG对不良妊娠结局的预测价值。结果 GDM组较对照组血清Glu和尿液α1GMG水平均升高(t=20.052、31.426,P<0.001),损伤组较未损伤组血清Glu、尿液α1GMG水平及肾功能指标均升高(t=9.122、7.501、21.568、2.875、7.525、8.715、7.089,P<0.05)。在发生异位妊娠、先兆流产、宫内发育受限的GDM患者中,血清Glu和尿液α1GMG高表达患者比例高于低表达患者比例(χ²=6.362、7.102、5.754、6.278、4.624、8.820,P<0.05)。妊娠结局不良组较妊娠结局良好组血清Glu和尿液α1GMG水平均升高(t=6.802、7.054,P<0.001)。血清Glu、尿液α1GMG及联合预测患者发生不良妊娠结局的曲线下面积分别为0.883、0.855、0.961,二者联合优于单独预测价值(Z=2.453、2.981,P<0.05)。结论 GDM患者的血清Glu和尿液α1GMG水平均与早期肾损伤和妊娠结局有关。

Abstract

Objective To investigate the correlation between serum glutamic acid (Glu) and urinary α1G microglobulin (α1GMG) levels with early kidney injury and pregnancy outcomes in patients with gestational diabetes mellitus (GDM). Methods A total of 106 pregnant women diagnosed with GDM at Yibin Second People's Hospital from July 2021 to July 2023 were included as the GDM group. These patients were further divided into a kidney injury group and a non-injury group based on the presence of early kidney injury. Additionally, 102 healthy pregnant women undergoing prenatal check-ups during the same period were selected as the control group. Serum Glu and urinary α1GMG levels were measured in all participants. GDM patients were also categorized into a poor pregnancy outcome group and a favorable pregnancy outcome group, and their urinary microalbumin (U-mAlb), serum urea (Urea), uric acid (UA), serum creatinine (Scr), and β2G microglobulin (β2GMG) levels were assessed. The Pearson method was used to analyze the correlation between serum Glu, urinary α1GMG, and renal function indicators. The receiver operating characteristic (ROC) curve was employed to assess the predictive value of serum Glu and urinary α1GMG for adverse pregnancy outcomes. Results Compared to the control group, the GDM group showed significantly higher serum Glu and urinary α1GMG levels (t=20.052 and 31.426, respectively, P<0.001). The kidney injury group exhibited higher serum Glu, urinary α1GMG levels, and renal function indicators than the non-injury group (t=9.122, 7.501, 21.568, 2.875, 7.525, 8.715 and 7.089, respectively, P<0.05). Among GDM patients with ectopic pregnancy, threatened miscarriage, or intrauterine growth restriction, the proportion of patients with high Glu and α1GMG expression was significantly higher than that of those with low expression (χ²=6.362, 7.102, 5.754, 6.278, 4.624 and 8.820, respectively, P<0.05). The poor pregnancy outcome group had significantly higher serum Glu and urinary α1GMG levels compared to the favorable outcome group (t=6.802 and 7.054, respectively, P<0.001). The area under the curve (AUC) for predicting adverse pregnancy outcomes was 0.883 for serum Glu, 0.855 for urinary α1GMG, and 0.961 for their combined prediction, with the combined prediction showing superior accuracy compared to individual markers (Z=2.453 and 2.981, respectively, P<0.05). Conclusion Serum Glu and urinary α1GMG levels are associated with early kidney injury and pregnancy outcomes in GDM patients.

关键词

妊娠期糖尿病 / 谷氨酸 / α1G微球蛋白 / 早期肾损伤 / 妊娠结局

Key words

gestational diabetes mellitus / glutamic acid / α1G microglobulin / early renal injury / pregnancy outcome

参考文献

[1] Wang Q Y, You L H, Xiang L L, et al. Current progress in metabolomics of gestational diabetes mellitus[J]. World J Diabetes, 2021, 12(8): 1164-1186.

[2] Popova P V, Pustozerov E A, Tkachuk A S, et al. Improving nutrition for the prevention of gestational diabetes: current status and perspectives[J]. World J Diabetes, 2021, 12(9): 1494-1506.

[3] 卢春生, 梁旭森, 谢芳, 等. ADP、Glu及HbA1c联合检测在糖尿病诊断中的价值[J]. 中国医疗器械信息, 2021, 27(19): 151-152.

[4] 焦翔, 张继东. 胱抑素C及α1G微球蛋白检测对糖尿病肾病诊断作用[J]. 中国社区医师, 2021, 37(22): 92-93.

[5] 中华医学会妇产科学分会产科学组, 中华医学会围产医学分会妊娠合并糖尿病协作组. 妊娠合并糖尿病诊治指南(2014)[J]. 中华妇产科杂志, 2014, 49(8): 561-569.

[6] 计静, 魏君香, 米阳, 等. 妊娠期糖尿病不良妊娠结局相关危险因素分析[J]. 中国妇幼健康研究, 2021, 32(11): 1574-1578.

[7] Lu W, Hu C. Molecular biomarkers for gestational diabetes mellitus and postpartum diabetes[J]. Chin Med J (Engl), 2022, 135(16): 1940-1951.

[8] Ren L L, Mao T, Meng P, et al. Glutamine addiction and therapeutic strategies in pancreatic cancer[J]. World J Gastrointest Oncol, 2023, 15(11): 1852-1863.

[9] Perego C, Cairano E S D, Galli A, et al. Autoantibodies against the glial glutamate transporter GLT1/EAAT2 in Type 1 diabetes mellitus-clues to novel immunological and non-immunological therapies[J]. Pharmacol Res, 2022, 177: 106130.

[10] 余茜琼, 王志卫, 黄昌伟. 胰岛素自身抗体与C肽、谷氨酸脱羧酶抗体在鉴别诊断成人隐匿性自身免疫性糖尿病中的临床意义[J]. 糖尿病新世界, 2023, 26(21): 48-50, 54.

[11] 陆文茜. 妊娠期糖尿病的代谢组学研究[D]. 广东: 南方医科大学, 2021.

[12] Saini N, Virdee M, Helfrich K K, et al. Global metabolomic profiling reveals hepatic biosignatures that reflect the unique metabolic needs of late-term mother and fetus[J]. Metabolomics, 2021, 17(2): 23.

[13] Ostermann M, Summers J, Lei K, et al. Micronutrients in critically ill patients with severe acute kidney injury-a prospective study[J]. Sci Rep, 2020, 10(1): 1505.

[14] Diboun I, Ramanjaneya M, Majeed Y, et al. Metabolic profiling of pre-gestational and gestational diabetes mellitus identifies novel predictors of pre-term delivery[J]. J Transl Med, 2020, 18(1): 366.

[15] Jin L, Niu C, Ni Y. Correlation between peripheral blood α1G-MG, DNMT1 expression, and the severity of diabetic nephropathy renal pathological damage[J]. Medicine (Baltimore), 2023, 102(42): e35409.

[16] Zhou Y, Zhang Y, Chen J, et al. Diagnostic value of α1G-MG and URBP in early diabetic renal impairment[J]. Front Physiol, 2023, 14: 1173982.

[17] Fan X, Ye W, Ma J, et al. Metabolic differences between unilateral and bilateral renal stones and their association with markers of kidney injury[J]. J Urol, 2022, 207(1): 144-151.

[18] 郭慧, 靳建伟, 李梦霞. 尿微量白蛋白α1G微球蛋白N-乙酰-β-D-葡萄糖苷酶及血清胱抑素C的联合检测在妊娠期糖尿病患者早期肾功能损伤诊断中的价值分析[J]. 山西医药杂志, 2021, 50(17): 2564-2566.

[19] 颜红梅, 夏姣, 唐云琳, 等. 妊娠期糖尿病孕妇血清TRF、LN、α1G-MG预测早期肾损伤价值[J]. 中国计划生育学杂志, 2022, 30(5): 1123-1127.