血清SFRP5、HSP60和Nesfatin-1水平预测妊娠期糖尿病发病的价值

The predictive value of serum SFRP5, HSP60 and Nesfatin-1 levels for the onset of gestational diabetes mellitus

摘要

目的 探索血清分泌型卷曲相关蛋白5(SFRP5)、热休克蛋白60(HSP60)和摄食抑制因子-1(Nesfatin-1)水平对妊娠期糖尿病(GDM)发病的影响。方法 选取2022年1月至2023年6月期间于我院首次就诊并建档分娩的100例GDM患者作为病例组,并进一步分为孕早期组(n=20)、孕中期组(n=40)、孕晚期组(n=40);另选取同期于我院建档分娩的糖耐量正常孕妇40例作为对照组.采用酶联免疫吸附法(ELISA)检测血清SFRP5、HSP60、Nesfatin-1水平.采用Pearson相关分析各指标间的相关性;采用多因素Logistic回归分析影响GDM发病的因素;通过受试者工作特征(ROC)曲线评估各指标对GDM的预测价值。结果 GDM组血清SFRP5水平低于对照组,HSP60、Nesfatin-1水平高于对照组(t值分别为8.761、7.045、7.571,均P<0.05);GDM组空腹血糖(FPG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、糖化血红蛋白(HbA1c)水平均显著高于对照组(t值为15.702、8.312、18.963、2.741,均P<0.05);孕早期组、孕中期组、孕晚期组血清SFRP5水平依次降低(F值为48.711,均P<0.05),血清HSP60、Nesfatin-1水平依次升高(F值为分别为47.097、46.482,均P<0.05);GDM组血清SFRP5水平与FPG、FINS、HOMA-IR、HbA1c呈负相关(r值的范围为-0.511~-0.418,P<0.05),HSP60、Nesfatin-1水平与上述指标呈正相关(r值的范围分别为0.436~0.512、0.412~0.481,P<0.05);血清SFRP5是影响GDM发病的保护因素(OR值及95%CI为0.531(0.416~0.677)),HSP60、Nesfatin-1、FPG、FINS、HOMA-IR、HbA1c均是影响GDM发病的危险因素(OR值及95%CI分别为1.628(1.259~2.105)、2.317(1.810~2.966)、3.208(2.147~4.794)、2.414(1.754~3.323)、3.104(2.295~4.198)、2.415(1.622~3.595);血清SFRP5、HSP60、Nesfatin-1水平及三者联合预测GDM发病的曲线下面积(AUC)分别为0.863、0.858、0.855及0.967,三者联合显著优于单独预测(均P<0.05)。结论 血清HSP60、Nesfatin-1水平升高、SFRP5水平降低与GDM发病有关,均是影响GDM发病的因素,三者联合预测GDM发病的效能更佳.

Abstract

Objective To investigate the association of serum levels of secreted frizzled-related protein 5 (SFRP5), heat shock protein 60 (HSP60), and Nesfatin-1 with the onset of gestational diabetes mellitus (GDM). Methods A total of 100 GDM patients who underwent their first prenatal visit and delivered at Cangzhou People's Hospital between January 2022 and June 2023 were enrolled as the case group, further stratified into first-trimester (n=20), second-trimester (n=40), and third-trimester (n=40) subgroups. Additionally, 40 pregnant women with normal glucose tolerance were selected as the control group. Serum levels of SFRP5, HSP60, and Nesfatin-1 were measured using enzyme-linked immunosorbent assay (ELISA). Pearson correlation analysis was used to assess correlations between indicators; multivariate logistic regression analysis was employed to identify factors influencing GDM onset; and receiver operating characteristic (ROC) curves were utilized to evaluate the predictive value of each indicator for GDM. Results Compared with the control group, the GDM group exhibited significantly lower serum SFRP5 levels but higher HSP60 and Nesfatin-1 levels (t=8.761, 7.045 and 7.571, respectively, all P<0.05), along with elevated fasting plasma glucose (FPG), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), and glycosylated hemoglobin (HbA1c) (t=15.702, 8.312, 18.963 and 2.741, all P<0.05). Within the GDM cohort, serum SFRP5 progressively declined across gestational trimesters (F=48.711, P<0.05), whereas HSP60 and Nesfatin-1 increased (F=47.097 and 46.482, both P<0.05). Negative correlations were observed between SFRP5 and FPG/FINS/HOMA-IR/HbA1c (r=-0.511 to -0.418, P<0.05), while HSP60 and Nesfatin-1 showed positive correlations with these metabolic parameters (r=0.436-0.512 and 0.412-0.481, P<0.05). Multivariate analysis confirmed SFRP5 as a protective factor (OR=0.531, 95%CI: 0.416-0.677), with HSP60, Nesfatin-1, FPG, FINS, HOMA-IR, and HbA1c identified as risk factors [OR (95%CI): 1.628 (1.259-2.105), 2.317 (1.810-2.966), 3.208 (2.147-4.794), 2.414 (1.754-3.323), 3.104 (2.295-4.198), 2.415 (1.622-3.595)]. ROC analysis demonstrated the area under the curve (AUC) values of 0.863 (SFRP5), 0.858 (HSP60), 0.855 (Nesfatin-1), and 0.967 (combined model), with the combined model significantly outperforming individual biomarkers (all P<0.05). Conclusion Elevated serum HSP60 and Nesfatin-1 levels and decreased SFRP5 levels are associated with GDM onset and serve as influencing factors. The combination of these three biomarkers demonstrates superior predictive efficacy for GDM.

关键词

妊娠期糖尿病 / 分泌型卷曲相关蛋白5 / 热休克蛋白60 / 摄食抑制因子-1 / 预测价值

Key words

gestational diabetes mellitus / secreted frizzled related protein 5 / heat shock protein 60 / nesfatin-1 / predictive value

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基金资助

河北省卫生健康委员会资助项目(20241713)