非肥胖多囊卵巢综合征患者胰岛素抵抗的危险因素及Nomogram预测模型构建

Risk factors of insulin resistance in non obese patients with polycystic ovary syndrome and construction of Nomogram prediction model

目的 分析非肥胖多囊卵巢综合征(PCOS)患者胰岛素抵抗的危险因素及Nomogram预测模型构建。方法 收集2018年6月—2020年8月浙江中医药大学附属湖州中医院收治的PCOS患者100例,根据患者是否发生胰岛素抵抗分为抵抗组及未抵抗组,同期选择于该院查体中心查体的健康人群40例为对照组,采集PCOS患者入院24 h内的空腹静脉血5 ml,采集对照组于查体时的空腹静脉血5 ml,采用放射免疫法检测所有患者血清黄体生成素(LH)、泌乳素(PRL)、卵泡刺激素(FSH)及雌二醇(E2)水平,采用酶联免疫吸附法检测患者血清血管内皮生长因子(VEGF)、内皮抑素(ES)、脂肪特异性丝氨酸蛋白酶抑制剂(Vaspin)及25-羟维生素D水平。采用Pearson线性相关分析各因子水平变化的相关性,采用多因素logistics回归分析非肥胖PCOS患者发生胰岛素抵抗的影响因素,采用ROC曲线分析各指标在非肥胖PCOS患者发生胰岛素抵抗预测中的价值。结果 非抵抗组及抵抗组患者血清LH水平明显高于对照组,抵抗组患者血清LH水平明显低于非抵抗组(P<0.01)。非抵抗组及抵抗组患者血清VEGF、ES及Vaspin水平明显高于对照组,25-(OH)D水平明显低于对照组;抵抗组患者血清VEGF、ES及Vaspin水平明显高于非抵抗组,25-(OH)D水平明显低于非抵抗组(P<0.01)。采用Pearson线性相关分析得出,VEGF、ES、Vaspin与HOMA-IR呈明显正相关(均P<0.05);25-(OH)D、LH与HOMA-IR呈明显负相关(均P<0.05)。采用多因素logistics回归分析得知,VEGF、ES、Vaspin、25-(OH)D及LH均是非肥胖PCOS患者发生胰岛素抵抗的独立影响因素(均P<0.05)。ROC曲线分析得出,VEGF预测非肥胖PCOS患者发生胰岛素抵抗的曲线下面积(AUC)为0.861;ES预测非肥胖PCOS患者发生胰岛素抵抗的AUC为0.809;25-(OH)D预测非肥胖PCOS患者发生胰岛素抵抗的AUC为0.837;Vaspin预测非肥胖PCOS患者发生胰岛素抵抗的AUC为0.715;LH预测非肥胖PCOS患者发生胰岛素抵抗的AUC为0.681。对Nomogram准确性进行验证,结果显示该列线图对判断非肥胖PCOS患者发生胰岛素抵抗的C-index值为0.651。结论 VEGF、ES、Vaspin、25-(OH)D及LH均是影响非肥胖多囊卵巢综合征发生胰岛素抵抗的独立影响因素,据此建立预测模型对非肥胖PCOS患者胰岛素抵抗发生风险具有较高准确性。

Objective To analyze the risk factors of insulin resistance in non obese patients with polycystic ovary syndrome(PCOS) and construct Nomogram prediction model.Methods 100 cases of PCOS patients in Huzhou Hospital Affiliated to Zhejiang University of traditional Chinese Medicine from 2018 to 2020 were collected, and they were divided into resistance group and non resistance group according to whether the patients had insulin resistance.At the same time, 40 healthy people in the physical examination center of our hospital were selected as the control group.5 ml of fasting venous blood was collected from PCOS patients within 24 h after admission, and 5 ml of fasting venous blood was collected in the control group during physical examination Serum luteinizing hormone(LH),prolactin(PRL),follicle stimulating hormone(FSH) and estradiol(E_(2)) levels were detected in all patients.The serum levels of vascular endothelial growth factor(VEGF),endostatin(ES),fat specific serine protease inhibitor(Vaspin) and 25 hydroxyvitamin D [25-(OH)D] were detected by enzyme-linked immunosorbent assay.Pearson linear correlation was used to analyze the correlation between the changes of each factor level.Multivariate logistic regression analysis was used to analyze the influencing factors of insulin resistance in non obese PCOS patients.ROC curve was used to analyze the value of each index in the diagnosis of insulin resistance in non obese PCOS patients.Results the serum LH level in the non resistance group and the resistance group was significantly higher than that in the control group, and the serum LH level in the resistance group was significantly lower than that in the non resistance group(P<0.01).The serum levels of VEGF,ES and vaspin in the non resistance group and the resistance group were significantly higher than those in the control group, and the 25-(OH)D level was significantly lower than that in the control group;the serum VEGF,ES and vaspin levels in the resistance group were significantly higher than those in the non resistance group, and the 25-(OH)D level was significantly lower than that in the non resistance group(P<0.01).Pearson linear correlation analysis showed that VEGF,ES,vaspin were significantly positively correlated with HOMA-IR(P<0.05);25-(OH)D,LH were significantly negatively correlated with HOMA-IR(P<0.05).Multivariate logistic regression analysis showed that VEGF,ES,vaspin, 25-(OH)D and LH were independent risk factors for insulin resistance in non obese PCOS patients(all P<0.05).ROC curve analysis showed that the AUC of VEGF diagnosis of insulin resistance in non obese PCOS patients was 0.861;the AUC of ES diagnosis of insulin resistance in non obese PCOS patients was 0.809;the AUC of 25-(OH)D diagnosis of insulin resistance in non obese PCOS patients was 0.837;the AUC of vaspin in the diagnosis of non obese PCOS patients with insulin resistance was 0.715;The AUC of insulin resistance in non obese PCOS patients diagnosed by LH was 0.681.The accuracy of nomogram was verified.The results showed that the c-index value of nomogram was 0.695 for judging insulin resistance in non obese PCOS patients.Conclusion VEGF,ES,vaspin, 25-(OH)D and LH are the independent influencing factors, and the establishment of a prediction model has high accuracy for the risk of insulin resistance in non obese PCOS patients.