Ty-G指数、LAP及血脂比分别对PCOS患者
Ty-G index, LAP and lipid ratios in PCOS patients
合并代谢综合征的预测价值探讨
Study on the predictive value of metabolic syndrome
目的：评估Ty-G指数（Triglyceride-Glucose）、脂质蓄积产物（Lipid Accumulation Product，LAP）及血脂比与PCOS患者发生MetS风险的关系；进一步探讨Ty-G指数、LAP及血脂比分别对PCOS患者发生MetS的预测价值；找到PCOS患者中可以早期预测MetS发生的可靠标生物志物。
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### Objective:
1. Evaluate the association between Ty-G index (Triglyceride-Glucose), Lipid Accumulation Product (LAP), and blood lipid ratio with the risk of MetS in PCOS patients.
2. Further explore the predictive value of Ty-G index, LAP, and blood lipid ratio for the development of MetS in PCOS patients.
3. Identify reliable biomarkers for early prediction of MetS in PCOS patients.
方法：本研究共纳入134例PCOS患者。根据2009年国际多协会联合声明诊断MetS标准，将134例PCOS患者分为合并MetS组51例和未合并MetS组83例。收集所有患者的临床资料及生化指标。采用Logistic回归分析，确定Ty-G指数、LAP及血脂比与MetS发病风险的关系，并进一步将Ty-G指数与LAP分层处理，阐明其对MetS发病风险的影响。通过受试者工作特征曲线下面积评估Ty-G指数、LAP及血脂比分别对PCOS患者发生MetS的预测效能。
Methods: This study included 134 patients with PCOS. According to the 2009 International Multi-Association Consensus Statement for the diagnosis of MetS, the 134 patients with PCOS were divided into a MetS 合併組 (n=51) and a non-MetS 合併組 (n=83). Clinical data and biochemical indicators were collected from all patients. Logistic regression analysis was used to determine the relationship between Ty-G index, LAP, and lipid ratio and the risk of MetS development. Furthermore, Ty-G index and LAP were stratified to elucidate their effects on the risk of MetS development. The predictive efficacy of Ty-G index, LAP, and lipid ratio for the occurrence of MetS in PCOS patients was evaluated by the area under the receiver operating characteristic curve (AUC).
结果：134例PCOS患者中MetS的发生率为38%。二元 Logistic回归分析显示，在调整混杂因素后，Ty-G指数、LAP及血脂比均为PCOS患者发生MetS的独立危险因素（P＜0.05）。为进一步验证结果的可靠性，将Ty-G指数及LAP划分为三分位数，作为分类变量进行分析。结果表明与PCOS患者Ty-G指数的T1组（最低三分位）相比， T3组（最高三分位）PCOS患者发生MetS的风险显著升高（P趋势＜0.05）。同样在PCOS患者中，LAP的T3组（最高三分位）发生MetS的风险比T1组（最低三分位）增加了634.72倍（P趋势＜0.05）。ROC曲线表明三者均可以良好的预测PCOS患者中MetS的发生。其中Ty-G指数的预测价值最高，其截断值为8.70。
Results: The incidence of MetS in 134 PCOS patients was 38%. Binary Logistic regression analysis showed that Ty-G index, LAP, and blood lipid ratio were independent risk factors for MetS in PCOS patients after adjusting for confounding factors (P＜0.05). To further verify the reliability of the results, Ty-G index and LAP were divided into tertiles as categorical variables for analysis. The results showed that compared with the T1 group (lowest tertile) of Ty-G index in PCOS patients, the risk of MetS in the T3 group (highest tertile) of PCOS patients was significantly increased (Ptrend＜0.05). Similarly, in PCOS patients, the risk of MetS in the T3 group (highest tertile) of LAP increased by 634.72 times compared with the T1 group (lowest tertile) (Ptrend＜0.05). ROC curve showed that all three indicators could well predict the occurrence of MetS in PCOS patients. Among them, Ty-G index had the highest prediction value, with a cut-off value of 8.70.
结论：Ty-G指数、LAP、TG/HDL-C、TC/HDL-C及LDL-C/HDL-C是新颖的临床生物标志物，可早期预测PCOS患者中MetS的发生。
Conclusion: Ty-G index, LAP, TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C are novel clinical biomarkers for early prediction of MetS occurrence in PCOS patients.
背景
Background
多囊卵巢综合征（polycystic ovary syndrome，PCOS）又称之为Stein-Leventhal综合征，是由Stein和Leventhal于1935年首次提出。全球流行病调查显示PCOS在育龄期女性的发病率为5%-10%[1]。越来越多的研究表明，PCOS是一种复杂的多基因疾病，具有显著的表观遗传倾向，并易受环境因素影响，包括饮食和生活方式因素[2]。PCOS还会导致其他长期健康风险、代谢并发症及心理问题，比如II型糖尿病（type 2 diabetes，T2DM）、心血管疾病（cardiovascular disease，CVD）、子宫内膜癌、代谢综合征、静脉血栓风险及焦虑等[3, 4]。
## Translated Text:
Polycystic ovary syndrome (PCOS), also known as Stein-Leventhal syndrome, was first reported by Stein and Leventhal in 1935. Global epidemiological studies show that the prevalence of PCOS in women of reproductive age is 5%-10% [1]. Growing evidence suggests that PCOS is a complex, polygenic disease with a significant epigenetic predisposition and susceptibility to environmental factors, including dietary and lifestyle factors [2]. PCOS can also lead to other long-term health risks, metabolic complications, and psychological problems, such as type 2 diabetes (T2DM), cardiovascular disease (CVD), endometrial cancer, metabolic syndrome, venous thromboembolism risk, and anxiety [3, 4].
代谢综合征(Metabolic Syndrome，MetS) 是一组以腹型肥胖、空腹血糖受损、高血压、血脂异常为特征的的代谢紊乱症候群。其发病机制复杂，涉及IR、脂代谢紊乱、慢性炎症、遗传与环境因素等多个方面，其中IR是代谢综合征发生的核心特征[5]。有研究表明与年龄匹配的正常育龄期女性相比，患有PCOS女性MetS的患病率增加近11倍[6]。在PCOS患者中，MetS的存在可能会进一步增加现有的代谢紊乱风险。
Metabolic syndrome (MetS) is a group of metabolic disorders characterized by abdominal obesity, impaired fasting glucose, hypertension, and dyslipidemia. Its pathogenesis is complex, involving insulin resistance (IR), lipid metabolism disorders, chronic inflammation, and genetic and environmental factors. Among them, IR is the core feature of metabolic syndrome[5]. Studies have shown that the prevalence of MetS is nearly 11 times higher in women with PCOS than in age-matched normal reproductive-aged women[6]. In PCOS patients, the presence of MetS may further increase the existing risk of metabolic disorders.
脂质蓄积指数（Lipid Accumlation Product，LAP）是一种新的肥胖相关指标，用来衡量脂肪在腹部蓄积程度，可解释为内脏脂肪堆积[7]。许多研究表明LAP与MetS、CVD、DM2及高血压密切相关，且对于预测IR、CVD、MetS等疾病的发生风险是既准确又简单的指标[8-10]。甘油三酯-葡萄糖指数（Triglyceride-Glucose，Ty-G）早期是由南美专家引入，旨在评估社区IR。IR虽然不是诊断MetS的重要组成成分，但在MetS的病理生理中有着至关重要的作用。有研究表明Ty-G指数比HOMA-IR在评估IR方面更有价值[11]。而Ty-G指数具有简单、方便、成本低、准确等优点，被认为是一种新的IR生物标志物。总胆固醇（Total Cholesterol，TC）/高密度脂蛋白胆固醇（High density lipoprotein，HDL-C）比值、低密度脂蛋白胆固醇（Low density lipoprotein，LDL-C）/HDL-C比值和TG/HDL-C比值等可以反映不同脂质成分在体内的平衡情况，对评估心血管健康和代谢状态具有一定的临床意义。在MetS中，血脂比值往往偏高，而高TC/HDL-C比值和TG/HDL-C比值通常被认为是心血管疾病和代谢综合征的危险因素，与胰岛素抵抗、炎症反应和内皮功能障碍等密切相关[12]。在全球范围内，代谢综合征已成为了重大公共卫生问题，对人类的身心健康造成严重的威胁。因此，本研究通过对PCOS患者的研究，旨在评估LAP、Ty-G指数及血脂比与PCOS患者发生代谢综合征风险的相关性，进一步探讨和比较LAP、Ty-G指数及血脂比分别识别和预测PCOS患者发生代谢综合征的能力。
The lipid accumulation product (LAP) is a new obesity-related indicator used to measure the degree of fat accumulation in the abdomen, which can be explained as visceral fat accumulation [7]. Many studies have shown that LAP is closely related to MetS, CVD, DM2 and hypertension, and it is a simple and accurate indicator for predicting the risk of diseases such as IR, CVD and MetS [8-10]. The Triglyceride-Glucose Index (Ty-G) was introduced by South American experts early to assess community IR. Although IR is not an important component of MetS diagnosis, it plays a crucial role in the pathophysiology of MetS. Some studies have shown that Ty-G index is more valuable than HOMA-IR in evaluating IR [11]. The Ty-G index has advantages such as simplicity, convenience, low cost and accuracy, and is considered a new IR biomarker. Total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio, low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio and TG/HDL-C ratio can reflect the balance of different lipid components in the body, which is of clinical significance for evaluating cardiovascular health and metabolic status. In MetS, blood lipid ratios tend to be high, and high TC/HDL-C and TG/HDL-C ratios are generally considered risk factors for cardiovascular disease and metabolic syndrome, and are closely related to insulin resistance, inflammatory response and endothelial dysfunction [12]. Metabolic syndrome has become a major public health issue worldwide, posing a serious threat to human physical and mental health. Therefore, this study aims to assess the correlation between LAP, Ty-G index and blood lipid ratio and the risk of metabolic syndrome in PCOS patients, and further explore and compare the ability of LAP, Ty-G index and blood lipid ratio to identify and predict metabolic syndrome in PCOS patients.
材料与方法
Materials and Methods
研究对象
Study subjects
本研究已通过延安大学附属医院伦理委员会审查与批准。回顾性分析2022年01月至2024年01月在延安大学附属医院妇科门诊及生殖医学门诊就诊并确诊为PCOS患者。 采取符合2018年我国卫生部发布的PCOS诊断卫生行业标准[13]：（1）必要条件：月经稀发、闭经或不规则子宫出血；（2）符合下列2项中的1项，即可诊断为疑似PCOS：①高雄激素血症或高雄激素的临床表现，②超声表现为卵巢呈多囊样改变(一侧或双侧卵巢直径2～9mm的卵泡≥12个，和（或）卵巢体积≥10ml)；（3）诊断为疑似PCOS后逐一排除其他可能引起高雄激素和排卵异常的疾病，方可确定诊断为PCOS。
This study was approved by the Ethics Committee of the Affiliated Hospital of Yan'an University. A retrospective analysis was conducted on patients diagnosed with PCOS who visited the Gynecology Clinic and the Reproductive Medicine Clinic of the Affiliated Hospital of Yan'an University from January 2022 to January 2024.
The diagnostic criteria for PCOS were in accordance with the 2018 PCOS Diagnostic Hygiene Industry Standard issued by the Ministry of Health of China [13]: (1) Necessary conditions: oligomenorrhea, amenorrhea, or irregular uterine bleeding; (2) Meeting 1 of the following 2 items can be diagnosed as suspected PCOS: ① Hyperandrogenemia or clinical manifestations of hyperandrogenism, ② Ultrasound showing polycystic changes in the ovaries (≥12 follicles with a diameter of 2-9 mm in one or both ovaries, and/or ovarian volume ≥10 ml); (3) After being diagnosed as suspected PCOS, other diseases that may cause hyperandrogenism and ovulation disorders are excluded one by one to confirm the diagnosis of PCOS.
MetS诊断标准：符合2009年国际多协会联合声明的统一标准[14]：以下5项条件中满足3项或以上：（1）亚洲女性WC≥80cm；(2)甘油三酯水平升高≥ 150 mg/dL（1.7 mmol/L）或针对这种脂质异常的特异性治疗；（3）低浓度HDL-C水平，HDL-C（女性） <50 mg/dL （1.29 mmol/L）或特定药物治疗；（4）收缩压≥130mmHg或舒张压≥85mmHg，或既往诊断高血压病；（5）空腹血糖浓度≥100mg/dL（5.6mmol/L）或既往诊断为糖尿病。
The Diagnostic Criteria for MetS:
According to the 2009 International Joint Statement of Multiple Societies, the following five criteria are met with 3 or more:
1. WC ≥ 80 cm for Asian women;
2. Elevated triglyceride levels ≥ 150 mg/dL (1.7 mmol/L) or specific treatment for this lipid abnormality;
3. Low HDL-C levels, HDL-C (women) <50 mg/dL (1.29 mmol/L) or specific medication treatment;
4. Systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 85 mmHg, or previously diagnosed hypertension;
5. Fasting blood glucose concentration ≥ 100 mg/dL (5.6 mmol/L) or previously diagnosed diabetes.
1.2 研究方法
1.2 Methodology
1.2.1 分组
1.2.1 Grouping
根据2009年国际多协会联合声明诊断MetS标准，将134例PCOS患者分为合并代谢综合征组和未合并代谢综合征组，其中合并MetS组51例；未合并MetS组83例。
Based on the diagnostic criteria of MetS according to the 2009 International Joint Association Declaration, 134 patients with PCOS were divided into a metabolic syndrome group and a non-metabolic syndrome group, including 51 cases in the MetS group and 83 cases in the non-MetS group.
1.2.2 临床资料收集
1.2.2 Clinical data collection
收集所有PCOS患者的身高（m）、体重（kg）、腰围（cm）、血压等一般资料。
Collect general information such as height (m), weight (kg), waist circumference (cm), and blood pressure of all PCOS patients.
采集受试者月经周期或撤退性出血后2-4天晨起的空腹静脉血。化验其生化指标包括：卵泡刺激素（FSH）、黄体生成素（LH）、雌二醇(E2 )、孕酮(P）、睾酮(T)、抗缪勒管激素（AMH）、空腹血糖（FBG）、空腹胰岛素(FINS)、TG、TC、HDL-C、LDL-C
Collect fasting venous blood from the subjects in the morning 2-4 days after the menstrual cycle or withdrawal bleeding. Analyze the following biochemical indicators: follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone (P), testosterone (T), anti-Müllerian hormone (AMH), fasting blood glucose (FBG), fasting insulin (FINS), TG, TC, HDL-C, LDL-C
1.2.3 相关指数计算公式
## 1.2.3 Related index calculation formula<br>
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体质量指数[BMI=体重（kg）/身高^2（m2）]
Body mass index[BMI=weight(kg)/height^2(m2)]
稳态模型胰岛素抵抗指数=[ FPG(mmol／L)×FINS(mIU／L)／22.5]
Homeostasis Model Assessment of Insulin Resistance Index = [ FPG(mmol/L) × FINS(mIU/L) / 22.5 ]
脂质蓄积产物（Lipid Accumulation Product，LAP）计算：根据kahn提出的计算公式[34]：LAP（女）=[WC(cm)-58] ×TG(mmol/L)
## Lipid Accumulation Product (LAP) Calculation:
# Based on the calculation formula proposed by Kahn [34]: #
## LAP (female) = [WC(cm) - 58] × TG(mmol/L)
甘油三脂-葡萄糖指数(Triglyceride-Glucose，Ty-G)计算公式:
Triglyceride-Glucose Index (Ty-G) calculation formula:
Ty-G= Ln [TG(mg/dl)×FBG（mg/dl）/2]
Ty-G = Ln [TG (mg/dl) × FBG (mg/dl) / 2]
1.3统计学方法
### 1.3 Statistical method
使用Microsoft Excel建立数据库，应用SPSS 26.0统计软件进行统计学分析。计量资料先进行正态性检验和方差齐性检验，对于服从正态分布及方差齐的数据用均数±标准差（x±s）描述；组间比较采用两独立样本t检验。对于不服从正态分布则采用两独立样本秩和检验，数据采用中位数[M(P25，P75)]描述。计数资料用百分率表示，组间比较采用卡方检验。各指标间相关关系采用Spearman相关分析；采用logistic回归分析PCOS患者合并MetS的危险因素；采用受试者工作特征曲线分析及曲线下面积比较Ty-G、LAP、血脂比预测和诊断PCOS患者合并代谢综合征的价值，并确定最佳预测指标及临界值。P<0.05为差异有统计学意义。
A database was established using Microsoft Excel, and SPSS 26.0 statistical software was used for statistical analysis. Quantitative data were first tested for normality and homogeneity of variance. Data that followed a normal distribution and had homogeneity of variance were described using mean ± standard deviation (x±s). Two independent sample t-tests were used for group comparisons. For data that did not follow a normal distribution, two independent sample rank-sum tests were used, and data were described using medians [M(P25, P75)]. Categorical data were expressed as percentages, and group comparisons were performed using chi-square tests. Spearman correlation analysis was used to assess the correlation between indicators. Logistic regression analysis was used to analyze the risk factors for MetS in PCOS patients, and receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) comparison were used to analyze the value of Ty-G, LAP, and lipid ratio in predicting and diagnosing metabolic syndrome in PCOS patients. The optimal prediction indicators and cut-off values were determined. P<0.05 was considered statistically significant.
结果
Results
PCOS及PCOS合并MetS患者中诊断MetS各组分患病率
Prevalence of MetS components in PCOS and PCOS with MetS patients
在PCOS患者中WC≥80cm的患病率为85.07%（114/134）；TG≥1.70mmol/L的患病率为32.84%（44/134）；HDL-C＜1.29mmol/L的患病率为50.00%（67/134）；高血压（收缩压≥130mmHg或者舒张压≥85mmHg）的患病率为17.91%（24/134）；空腹血糖受损（FBG≥5.60mmHg）的患病率为19.40%（26/134）。在PCOS合并MetS患者中诊断MetS各项诊断指标的异常发生率分别为：腹型肥胖98.04%（50/51）；高密度脂蛋白水平降低82.35%（42/51）；甘油三酯水平升高78.43%(40/51)；高血压37.25%（19/51）；空腹血糖受损 37.25%（19/51）。见表1。
In PCOS patients, the prevalence of WC≥80cm was 85.07% (114/134); the prevalence of TG≥1.70mmol/L was 32.84% (44/134); the prevalence of HDL-C＜1.29mmol/L was 50.00% (67/134); the prevalence of hypertension (systolic blood pressure ≥130mmHg or diastolic blood pressure ≥85mmHg) was 17.91% (24/134); the prevalence of impaired fasting glucose (FBG≥5.60mmHg) was 19.40% (26/134). In PCOS patients with MetS, the prevalence of abnormal MetS diagnostic indicators was: abdominal obesity 98.04% (50/51); decreased high-density lipoprotein levels 82.35% (42/51); elevated triglyceride levels 78.43% (40/51); hypertension 37.25% (19/51); impaired fasting glucose 37.25% (19/51). See Table 1.
表1 PCOS及PCOS合并MetS患者中MetS各组分患病率[n(%)]
Table 1 Prevalence of Mets components in women with PCOS and PCOS combined with MetS [n(%)]
MetS成分 | PCOS合并MetS组（n=51） | 未合并MetS组（n=83） | 合计 （n=134） |
WC≥80cm | 50（98.04） | 64（77.11） | 114（85.07） |
TG≥1.70mmol/L | 40（78.43） | 4（4.82） | 44（32.84） |
HDL-C＜1.29mmol/L | 42（82.35） | 25（30.12） | 67（50.00） |
SBP≥130mmHg或DBP≥85mmHg | 19（37.25） | 5（6.02） | 24（17.91） |
FBG≥5.60mmHg | 19（37.25） | 7（8.43） | 26（19.40） |
PCOS患者合并MetS组与未合并MetS组一般临床资料及生化指标比较
Comparison of General Clinical Data and Biochemical Indicators Between PCOS Patients with MetS and PCOS Patients Without MetS
本研纳入134例PCOS患者中，合并MetS患者51例，未合并MetS患者83例。其中PCOS合并MetS组和未合并MetS组患者的年龄中位数均为28.00岁，两组之间年龄的比较，差异无统计学意义（P＜0.05）。在PCOS患者合并MetS组中体重、BMI、腰围、FBG、FINS、HOMA-IR、TG、TC、TG/HDL-C、TC/HDL-C、LDL-C/HDL-C、LAP、Ty-G指数、LH/FSH及T水平均显著高于未合并MetS组（P＜0.05）。而HDL-C水平显著低于未合并MetS组（P＜0.05）。两组之间身高、收缩压、舒张压、血清LDL-C、LH、FSH、E2、P、PRL及AMH水平等方面的比较差异无统计学意义（P＞0.05）。见表2。
## Translated Text:
Among the 134 patients with PCOS included in this study, 51 had MetS and 83 did not. The median age of the patients in the PCOS with MetS group and the PCOS without MetS group was 28.00 years, and there was no statistically significant difference in age between the two groups (P<0.05). In the PCOS with MetS group, the weight, BMI, waist circumference, FBG, FINS, HOMA-IR, TG, TC, TG/HDL-C, TC/HDL-C, LDL-C/HDL-C, LAP, Ty-G index, LH/FSH and T levels were all significantly higher than those in the PCOS without MetS group (P<0.05). However, the HDL-C level was significantly lower than that in the PCOS without MetS group (P<0.05). There were no statistically significant differences between the two groups in height, systolic blood pressure, diastolic blood pressure, serum LDL-C, LH, FSH, E2, P, PRL and AMH levels (P>0.05). See Table 2.
表2 PCOS患者合并MetS组与未合并MetS组一般临床资料及生化指标比较
Table 2 Comparison of general clinical data and biochemical indices between PCOS patients with and without MetS
指标 | PCOS合并MetS组 （n=51） | 未合并MetS组 （n=83） | t/z | P | |
年龄（岁） | 28.00(25.00，32.00) | 28.00（25.00，31.00） | -0.301 | 0.763 | |
身高（m) | 1.63(1.59，1.65) | 1.62（1.58，1.66） | 0.837 | 0.402 | |
体重（kg） | 72.50（63.50，77.50） | 63.00（53.00，70.00） | -4.150 | ＜0.001 | |
BMI（kg/m2） | 27.39（24.46，30.00） | 24.03（20.83，27.15） | -4.225 | ＜0.001 | |
腰围（cm） | 98.00（88.00，102.00） | 86.00（81.00，96.00） | -4.649 | ＜0.001 | |
收缩压（mmHg） | 120.00（110.00，127.00） | 115.00（109.00，122.00） | -1.721 | 0.085 | |
舒张压（mmHg） | 77.02±8.59 | 74.76±6.50 | -1.617 | 0.110 | |
FBG(mmol/L) | 5.44(5.09，6.00) | 5.06(4.76，5.34) | -4.235 | ＜0.001 | |
FINS (mU/L) | 20.57(16.50，29.67) | 10.70(6.72，17.93) | -5.222 | ＜0.001 | |
HOMA-IR | 4.81（3.80，7.57） | 2.52(1.54，4.05) | -5.565 | ＜0.001 | |
TG(mmol/L) | 2.10（1.74，3.41） | 1.04(0.79，1.27) | -8.458 | ＜0.001 | |
TC(mmol/L) | 4.63±0.74 | 4.260.83 | -2.543 | 0.012 | |
HDL-C(mmol/L) | 1.14（0.96，1.26） | 1.42(1.25，1.68) | -5.674 | ＜0.001 | |
LDL-C(mmol/L) | 2.67±0.64 | 2.480.71 | -1.518 | 0.132 | |
TC/HDL-C | 4.17(3.40，4.88) | 2.85(2.24，3.57) | -6.138 | ＜0.001 | |
TG/HDL-C | 3.94(3.22，7.46) | 1.71(1.09，2.26) | -8.278 | ＜0.001 | |
LDL-C/HDL-C | 2.36(1.95，2.79) | 1.66(1.22，2.29) | -4.770 | ＜0.001 | |
LAP | 82.99(55.44，126.54) | 27.83(19.92，45.51) | -8.301 | ＜0.001 | |
Ty-G指数 | 9.13(8.91，9.57) | 8.34(8.02，8.58) | -8.931 | ＜0.001 | |
LH（IU/L） | 8.78(4.92，11.78) | 6.73(4.65，10.50) | -1.164 | 0.244 | |
FSH（IU/L） | 5.36(4.33，7.00) | 6.19(5.23，7.20) | -1.957 | 0.058 | |
LH/FSH | 1.56(1.01，2.28) | 1.02(0.85，1.77) | -2.481 | 0.013 | |
T(nmol/L) | 1.27(0.85，1.68) | 0.96(0.69，1.25) | -2.837 | 0.005 | |
E2(pmol/L) | 168.90(123.60，247.30) | 166.80(138.30，166.80) | -0.172 | 0.864 | |
P(nmol/L) | 0.67(0.37，1.00) | 0.69(0.58，1.21) | -2.495 | 0.070 | |
PRL(uIU/ml) | 254.05(167.30，399.40) | 232.61(172.00，339.00) | -0.211 | 0.833 | |
AMH(ng/mL) | 6.72（4.23，9.14） | 5.81（3.95，7.49） | -1.159 | 0.246 | |
Ty-G指数、LAP及血脂比与MetS发病的相关性
## Ty-G Index, LAP, and Blood Lipid Ratio as Indicators of MetS Risk
通过Logistic回归分析，对Ty-G指数、LAP及血脂比与PCOS合并MetS发病风险进行相关性分析。模型1在未调整任何变量的情况下，TG/HDL-C、TC/HDL-C、LDL-C/HDL-C、Ty-G指数及LAP与PCOS合并MetS的发病风险增加相关（P＜0.05）；模型2对年龄、BMI、WC、SBP、DBP、HOMA-IR、LH/FSH、T、TC调整后，TG/HDL-C、TC/HDL-C、LDL-C/HDL-C、Ty-G指数及LAP仍与PCOS合并MetS的发病风险增加相关（P＜0.05）。见表3
## Logistic Regression Analysis of the Relationship between Ty-G Index, LAP, Lipid Ratio and the Risk of PCOS Combined with MetS
Logistic regression analysis was used to explore the correlation between the Ty-G index, LAP, lipid ratio and the risk of PCOS combined with MetS.
**Model 1:** Without adjusting for any variables, TG/HDL-C, TC/HDL-C, LDL-C/HDL-C, Ty-G index, and LAP were all associated with an increased risk of PCOS combined with MetS (P < 0.05).
**Model 2:** After adjusting for age, BMI, WC, SBP, DBP, HOMA-IR, LH/FSH, T, and TC, TG/HDL-C, TC/HDL-C, LDL-C/HDL-C, Ty-G index, and LAP remained significantly associated with an increased risk of PCOS combined with MetS (P < 0.05).
See Table 3..
表3 血脂比、Ty-G指数及LAP与MetS发病的相关性Logistic回归分析
Table 3 Logistic Regression Analysis on the Correlation of Lipid Ratio, Ty-G Index, and LAP with MetS Onset
指标 | 模型1 | 模型2 | ||||
β值 | P值 | OR（95%CI） | β值 | P值 | OR（95%CI） | |
TG/HDL-C | 1.61 | ＜0.001 | 5.00（2.77，9.02） | 2.30 | ＜0.001 | 9.99（3.66，27.31） |
TC/HDL-C | 1.19 | ＜0.001 | 3.30（2.11，5.16） | 1.35 | ＜0.001 | 3.84（2.05，7.17） |
LDL-C/HDL-C | 1.15 | ＜0.001 | 3.17（1.83，5.49） | 1.02 | 0.007 | 2.78（1.32，5.85） |
Ty-G | 7.65 | ＜0.001 | 3.32（3.04，4.6）* | 11.79 | ＜0.001 | 5.12（2.54，7.70）* |
LAP | 0.09 | ＜0.001 | 1.09（1.06，1.13） | 0.20 | ＜0.001 | 1.23（1.12，1.32） |
注：模型1：未调整任何因素；模型2：调整年龄、BMI、WC、SBP、DBP、HOMA-IR、LH/FSH、T、TC；
Note: Model 1: no adjustments made; Model 2: adjustments made for age, BMI, WC, SBP, DBP, HOMA-IR, LH/FSH, T, TC
*Ty-G指数OR值（对数变换）
*Ty-G index OR value (log-transformed)
PCOS患者中Ty-G指数三分位与MetS发病的相关性
The association of tertile Ty-G index with MetS development in PCOS patients
为了验证Ty-G指数增加PCOS患者发生MetS风险的可靠性，进一步将
## In order to verify the reliability of Ty-G index in increasing the risk of MetS in PCOS patients, further..
Ty-G指数按三分位分组，作为一个分类变量进行处理。结果表明PCOS患者
The Ty-G index was treated as a categorical variable by dividing it into tertiles.
The results showed that PCOS patients
Ty-G指数的T3组(最高三分位)发生MetS的风险比T1组（最低三分位）显著增加（P趋势＜0.05）。见表4。
The risk of MetS in the T3 group (highest tertile) of Ty-G index was significantly increased compared with the T1 group (lowest tertile) (P for trend < 0.05). See Table 4.
表4 PCOS患者中Ty-G指数三分位与MetS发病的相关性
Table 4. Correlation between Ty-G index tertiles and prevalence of MetS in PCOS patients
指标 | 模型1 | 模型2 |
OR（95%CI） | OR（95%CI） | |
Ty-G指数 | 3.32（3.04，4.60）* | 5.12（2.54，7.70）* |
Ty-G三分组 | ||
T1 | 1 | 1 |
T2 | 13.83（1.70，112.33） | 32.19（2.45，423.01） |
T3 | 429.00（45.98，4002.83） | 2070.95（84.64，50674.72） |
P趋势 | ＜0.001 | ＜0.001 |
注：模型1：未调整任何因素；模型2：调整年龄、BMI、WC、SBP、DBP、HOMA-IR、LH/FSH、T、TC；
Note: Model 1: No factors adjusted; Model 2: Age, BMI, WC, SBP, DBP, HOMA-IR, LH/FSH, T, TC adjusted;
*Ty-G指数OR值（对数变换）
*Ty-G Index OR value (logarithmic transformation)
PCOS患者中LAP与MetS发病的相关性
## The Correlation Between Laparoscopic Findings and Metabolic Syndrome in Patients with PCOS
将 LAP作为一个分类变量进行处理，分为三分位来验证结果的可靠性及稳定性。结果表明在PCOS患者中，LAP的T3组（最高三分位）发生MetS的风险比T1组（最低三分位）增加了634.72倍（P趋势＜0.05）。见表5
The LAP is treated as a categorical variable, and it is divided into three quantiles to verify the reliability and stability of the results. The results showed that in PCOS patients, the risk of MetS in the T3 group (the highest quantile) of LAP was 634.72 times higher than that in the T1 group (the lowest quantile) (Ptrend < 0.05). Refer to Table 5.
表5 PCOS患者中LAP三分位与MetS发病的相关性
Table 5 Correlation of LAP tertiles with the incidence of MetS in PCOS patients
指标 | 模型1 | 模型2 |
OR（95%CI） | OR（95%CI） | |
LAP | 1.09（1.06，1.13） | 1.23（1.12，1.32） |
LAP三分组 | ||
T1 | 1 | 1 |
T2 | 18.87（2.48，159.08） | 26.22（2.58，266.22） |
T3 | 198.00（23.65，1657.84） | 635.72（40.93，9874.26） |
P趋势 | ＜0.001 | ＜0.001 |
注：模型1：未调整任何因素；模型2：调整年龄、BMI、WC、SBP、DBP、HOMA-IR、LH/FSH、T、TC；
Note: Model 1: no adjustments made; Model 2: adjustments made for age, BMI, WC, SBP, DBP, HOMA-IR, LH/FSH, T, TC
预测PCOS患者发生MetS的最佳指标及截断值
Predicting the best indicators and cut-off values for MetS in patients with PCOS
为了比较各指标对PCOS患者发生MetS的预测价值。分别以HOMA-IR、TG、Ty-G指数、LAP、TG/HDL-C、TC/HDL-C、LDL-C/HDL-C为自变量，以是否合并MetS为结局变量，绘制ROC曲线。从图1及表6可得出HOMA-IR、TG、Ty-G指数、LAP、TG/HDL-C、TC/HDL-C、LDL-C/HDL-C的ROC曲线下面积（AUC）均大于0.5，其中Ty-G指数曲线下面积最大，为0.960；其次TG、LAP、TG/HDL-C、TC/HDL-C、IR、LDL-C/HDL-C的AUC分别为0.936、0.928、0.927、0.817、0.787、0.746。根据ROC曲线分析及约登指数，发现Ty-G指数是PCOS患者发生MetS的最佳预测指标，其截断值为8.70，敏感性和特异性分别为92.20%和88.00%。
To compare the predictive value of various indicators for MetS in PCOS patients, ROC curves were drawn with HOMA-IR, TG, Ty-G index, LAP, TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C as independent variables and MetS as the outcome variable. As shown in Figure 1 and Table 6, the areas under the ROC curve (AUC) for HOMA-IR, TG, Ty-G index, LAP, TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C were all greater than 0.5. Among them, the Ty-G index curve had the largest AUC, which was 0.960. The AUCs for TG, LAP, TG/HDL-C, TC/HDL-C, IR, and LDL-C/HDL-C were 0.936, 0.928, 0.927, 0.817, 0.787, and 0.746, respectively. Based on the ROC curve analysis and Youden's index, it was found that the Ty-G index was the best predictor for MetS in PCOS patients, with a cut-off value of 8.70, a sensitivity of 92.20%, and a specificity of 88.00%.
图1 各指标在PCOS患者中对MetS发病预测价值的ROC曲线
Figure 1: ROC curves of various indicators for the prediction of MetS in PCOS patients
表6 各指标对PCOS患者发生MetS的预测评估
Table 6 Predictive Evaluation of Each Indicator for the Occurrence of MetS in PCOS Patients
观察指标 | 曲线下面积 | 敏感度 （%） | 特异度 （%） | 最佳截断值 | 约登指数 |
HOMA-IR | 0.787 | 78.40 | 72.30 | 3.71 | 50.70 |
Ty-G指数 | 0.960 | 92.20 | 88.00 | 8.70 | 80.10 |
LAP | 0.928 | 96.10 | 74.70 | 45.28 | 70.80 |
LDL-C/HDL-C | 0.746 | 80.40 | 65.10 | 1.94 | 45.50 |
TG/HDL-C | 0.927 | 94.10 | 79.50 | 2.49 | 73.60 |
TC/HDL-C | 0.816 | 94.10 | 62.70 | 3.08 | 56.80 |
TG | 0.936 | 86.30 | 91.60 | 1.65 | 77.80 |
讨论
Discussion
PCOS病理生理机制复杂，到目前为止尚未完全明确[15]。多项证据表明这种内分泌失调的病因与环境、遗传、发育等密切相关。但人们普遍认为高雄激素血症和胰岛素抵抗是PCOS发生的主要病理生理，且二者在PCOS相关的生殖及代谢紊乱发展中起着重要的作用[16]。代谢综合征的核心特征是IR、内脏肥胖、动脉粥样硬化性血脂异常和内皮功能障碍[5]。这些疾病相互关联，并具有共同的介质、通路和病理生理机制。临床上常用MetS来识别发生CVD、T2DM的高危患者。而IR、脂质代谢紊乱及慢性炎症等是PCOS与MetS之间共同的病理生理机制，这些因素可能导致PCOS患者更容易发生MetS。有研究表明与正常育龄期女性相比，PCOS患者发生MetS的风险明显升高[17]。据报道，全球PCOS合并MetS的发生率为47.3%[18]。yang[19]等人研究发现PCOS患者中MetS的发生率为32.5%；而非PCOS患者中MetS的发生率为9.2%。在本研究中PCOS合并MetS发生率为38.00%。本研究结果与上述学者研究结果均不一致。这可能与遗传因素、地理环境、种族、研究人群的选择、样本量及选取MetS诊断标准不同有关。本研究将PCOS患者进一步按年龄分层后分析，发现PCOS患者合并MetS的发生率在年龄上并无差异。我们猜想导致这一现象的原因可能是随着社会发展的进步，人们的生活节奏较快，其学习压力及生活压力的增加，导致人们饮食结构的改变，其发病率在各个年龄阶段均有一定上升趋势。但是显而易见，PCOS患者中MetS的发生愈来愈年轻化。所以对患有PCOS的年轻女性应早期和定期进行MetS的筛查。
PCOS has a complex pathophysiology that is not fully understood to date [15]. Multiple lines of evidence suggest that the pathogenesis of this endocrine disorder is closely related to the environment, genetics, and development. However, it is widely believed that hyperandrogenism and insulin resistance are the main pathophysiological mechanisms of PCOS, and both play an important role in the development of reproductive and metabolic disorders associated with PCOS [16]. The core features of metabolic syndrome are IR, visceral obesity, atherosclerotic dyslipidemia, and endothelial dysfunction [5]. These diseases are interconnected and share common mediators, pathways, and pathophysiological mechanisms. MetS is clinically used to identify patients at high risk for CVD and T2DM. IR, lipid metabolism disorders, and chronic inflammation are common pathophysiological mechanisms between PCOS and MetS, and these factors may make PCOS patients more susceptible to MetS. Studies have shown that the risk of MetS in PCOS patients is significantly higher compared to normal women of childbearing age [17]. The reported global prevalence of MetS in PCOS is 47.3% [18]. Yang et al. [19] found a prevalence of MetS of 32.5% in PCOS patients, compared to 9.2% in non-PCOS patients. In this study, the prevalence of MetS in PCOS was 38.00%. The results of this study are inconsistent with those of the aforementioned scholars. This may be related to differences in genetic factors, geographical environment, ethnicity, selection of study populations, sample size, and the chosen MetS diagnostic criteria. After further stratification of PCOS patients by age, this study found no difference in the prevalence of MetS in PCOS patients across age groups. We speculate that the reason for this phenomenon may be that with the progress of social development, people's pace of life is faster, and the increase in their learning and life pressures leads to changes in their dietary structure, resulting in a certain upward trend in the incidence rate in all age groups. However, it is clear that the occurrence of MetS in PCOS patients is becoming younger. Therefore, young women with PCOS should be screened for MetS early and regularly.
中心性肥胖是诊断MetS的主要成分之一。而在PCOS患者中大约有40%-60%的患者表现为肥胖，且大多以腹型肥胖为主[20]。肥胖是由机体遗传与环境等多种因素共同作用产生的一种慢性代谢性疾病，主要表现为体内脂肪过度蓄积或分布异常。肥胖在PCOS和MetS的疾病发展中均扮演着重要的角色，肥胖可进一步加重PCOS患者的临床症状及IR，而IR可影响脂肪细胞的代谢，导致体重进一步增加，形成恶性循环。在本研究中发现随着BMI的升高，PCOS患者MetS的发生率也逐渐递增。所以临床上对于超重或肥胖的的PCOS患者早期进行代谢状况的筛查，同时进行体重管理，对于预防PCOS患者发生远期心血管疾病及T2DM的发生有着重要意义。
Central obesity is one of the main components of the diagnosis of MetS. Among PCOS patients, about 40%-60% are obese, and most of them are mainly abdominal obesity [20]. Obesity is a chronic metabolic disease caused by the combined effects of genetic, environmental and other factors, mainly manifested as excessive accumulation or abnormal distribution of fat in the body. Obesity plays an important role in the development of PCOS and MetS. Obesity can further aggravate the clinical symptoms and IR of PCOS patients, while IR can affect the metabolism of fat cells, leading to further weight gain, forming a vicious cycle. This study found that with the increase of BMI, the incidence of MetS in PCOS patients also increased gradually. Therefore, it is of great significance for the prevention of long-term cardiovascular diseases and T2DM in PCOS patients to screen for metabolic status in overweight or obese PCOS patients early and carry out weight management at the same time,
血脂异常在PCOS患者中很常见，其主要特征表现为HDL-C水平的降低和TG水平的升高[21]。在本研究中，PCOS患者TG水平升高的发生率为32.84%；HDL-C水平降低的发生率为50.00%，且与未合并MetS的患者相比，合并MetS患者的TG、TC水平显著升高，HDL-C水平显著降低。血脂异常同样也是MetS发生的重要影响因素。一项流行病学研究的证据表明，低HDL-C和高TG水平的同时发生是冠心病的强危险因素，也是患者发生冠脉事件机率最高的危险因素，其中HDL-C每增加1mg/dl，CVD的风险就会降低2%-3%[22]。所以对于任何年龄阶段的PCOS患者均应常规行血脂化验检查，包括LDL-C、TG、HDL-C以及非HDL-C。早期筛查出血脂异常的患者，并进行生活方式干预或者药物治疗，使血脂水平尤其LDL-C达到正常水平，预防远期并发症的发生。
Blood lipid abnormalities are very common in patients with PCOS, with main feature is decreased HDL-C level and elevated TG level [21]. In this study, the incidence of elevated TG levels in PCOS patients was 32.84%, the incidence of decreased HDL-C levels was 50.00%, and the levels of TG, TC were significantly higher and the level of HDL-C was significantly lower in patients who had MetS than in patients who did not have MetS. Dyslipidemia is also an important factor affecting the occurrence of MetS. Evidence from epidemiological studies suggests that the simultaneous occurrence of low HDL-C and high TG levels is a strong risk factor for coronary heart disease, which is also the risk factor with the highest probability of coronary events in patients. Every 1 mg/dl increase in HDL-C, CVD risk decreases by 2%-3% [22]. Therefore, routine blood lipid tests should be performed for PCOS patients at any age, including LDL-C, TG, HDL-C, and non-HDL-C. Early screening for patients with dyslipidemia and lifestyle interventions or drug therapy, especially to bring LDL-C levels to normal levels, can prevent the occurrence of long-term complications.
众多学者在寻找PCOS人群中筛查MetS的可靠标志物，例如:Ty-G指数、LAP、内脏肥胖指数 （VAI）、血脂比、ApoB/ApoA1 比值等[23-25]。Ty-G指数是一种新的代谢指标，早期旨在评估社区IR。IR不仅是PCOS发生的核心环节，也是MetS发病的主要原因。IR会增加PCOS患者发生MetS的风险，而合并MetS的PCOS患者更容易出现高雄激素血症、血脂异常和其他代谢紊乱[26, 27]。所以找到早期可预测MetS发生的可靠指标至关重要。多项研究表明Ty-G指数是糖尿病、CVD、高血压、急性冠脉综合征等疾病发生的危险因素，且对于这些疾病的发生有较好的预测价值[28-30]。Yang等人研究结果表明Ty-G指数与MetS患病率成正相关，且是PCOS患者发生MetS的独立危险因素，当截断值为8.65时可良好的预测PCOS患者中MetS的发生。Aslan等人研究Ty-G指数与TG/HDL-C分别预测国际肥胖青少年代谢综合征的发生，发现当Ty-G指数＞8.50时可很好的预测MetS的发生，且效果优于TG/HDL-C[31]。本研究通过回顾性横断面研究评估Ty-G指数、LAP、TG/LDL-C、TC/HDL-C、LDL-C/HDL-C对PCOS患者发生MetS的预测价值，并研究出新的MetS诊断模型。ROC曲线表明以上指标均是预测MetS发生的有效指标，其中Ty-G指数有较高的诊断及预测价值，其截断值为8.70，特异性为88%。而预测MetS敏感性最高的指标是LAP，为96.1%。
Many scholars are searching for reliable markers to screen for MetS in PCOS population, such as: Ty-G index, LAP, visceral adiposity index (VAI), blood lipid ratio, ApoB/ApoA1 ratio, etc. [23-25] Ty-G index is a new metabolic index, which was originally designed to evaluate community IR. IR is not only the core link of PCOS, but also the main cause of MetS. IR will increase the risk of MetS in PCOS patients, while PCOS patients with MetS are more likely to have hyperandrogenism, dyslipidemia and other metabolic disorders [26, 27]. Therefore, it is essential to find reliable indicators that can predict the occurrence of MetS early. Many studies have shown that Ty-G index is a risk factor for the occurrence of diseases such as diabetes, CVD, hypertension, and acute coronary syndrome, and it has a good predictive value for the occurrence of these diseases [28-30]. Yang et al.'s study results showed that Ty-G index was positively correlated with the prevalence of MetS, and it was an independent risk factor for MetS in PCOS patients. When the cutoff value was 8.65, it could well predict the occurrence of MetS in PCOS patients. Aslan et al. studied the ability of Ty-G index and TG/HDL-C to predict the occurrence of metabolic syndrome in international obese adolescents, and found that when Ty-G index＞8.50, it could well predict the occurrence of MetS, and the effect was better than TG/HDL-C [31]. This study retrospectively evaluated the predictive value of Ty-G index, LAP, TG/LDL-C, TC/HDL-C, LDL-C/HDL-C for the occurrence of MetS in PCOS patients, and developed a new MetS diagnosis model. ROC curve showed that all the above indicators were effective indicators for predicting the occurrence of MetS, among which Ty-G index had higher diagnostic and predictive value, and its cutoff value was 8.70, with specificity of 88%. The indicator with the highest sensitivity for predicting MetS was LAP, at 96.1%.
LAP是21世纪由国外学者Kahn提出，是一种新的肥胖相关指标。越来越多的研究结果表明LAP与MetS、糖尿病及高血压等疾病的发生密切相关[9, 32]。国内学者研究LAP在普通人群中识别MetS的能力和预测价值，发现LAP比中国传统肥胖指标如腰围、臀围、腰臀等能更好的预测MetS的发生[33]。本研究通过Logistic回归分析表明LAP是PCOS患者发生MetS的危险因素。且在PCOS患者中，LAP的T3组（最高三分位）发生MetS的风险比T1组（最低三分位）增加了634.72倍（P趋势＜0.05）。但目前关于LAP预测PCOS患者发生MetS的参考区间尚无统一定论，这可能归因于许多因素，如生活方式、饮食习惯、种族、研究人群的选择、样本量及MetS诊断标准等。本研究虽然未进一步探讨LAP与MetS各指标间的相关性，但根据ROC曲线结果表明LAP可作为PCOS患者筛查MetS的可靠标志物。
## LAP: A Predictive Biomarker for MetS in PCOS Patients
LAP (Lipid Accumulation Product), a novel obesity-related indicator proposed by foreign scholar Kahn in the 21st century, has been increasingly recognized for its close association with the development of MetS, diabetes, and hypertension [9, 32]. Studies on the ability of LAP to identify MetS and its predictive value in the general population have shown that LAP is superior to traditional Chinese obesity indicators such as waist circumference, hip circumference, and waist-to-hip ratio in predicting the occurrence of MetS [33]. This study, through Logistic regression analysis, demonstrated that LAP is a risk factor for MetS in PCOS patients. Moreover, in PCOS patients, the T3 group (highest tertile) with LAP had a 634.72-fold increased risk of developing MetS compared to the T1 group (lowest tertile) (P trend < 0.05). However, there is currently no consensus on the reference range for LAP predicting MetS in PCOS patients, which may be attributed to various factors such as lifestyle, dietary habits, ethnicity, selection of study population, sample size, and MetS diagnostic criteria. Although this study did not further explore the correlation between LAP and individual MetS indicators, the ROC curve results suggest that LAP can serve as a reliable marker for screening MetS in PCOS patients.
综上所述，在PCOS患者中MetS的发生率较高，且愈来愈年轻化。肥胖、Ty-G指数及LAP可增加PCOS患者MetS的发病风险。所以临床上对于超重和肥胖的患者要严格进行体重管理，预防MetS及远期并发症的发生。本研究发现Ty-G指数预测PCOS患者发生MetS的效能较强。Ty-G指数是在甘油三酯和空腹血糖的基础上获得，这表明对于PCOS患者无论任何年龄段均应该监测血糖、血脂，并及时进行临床干预是防止PCOS患者发生MetS的重要手段。
In conclusion, the prevalence of MetS in PCOS patients is high and becoming younger. Obesity, Ty-G index, and LAP can increase the risk of MetS in PCOS patients. Therefore, strict weight management should be implemented for overweight and obese patients in clinical practice to prevent the occurrence of MetS and long-term complications. This study found that the Ty-G index is a strong predictor of MetS in PCOS patients. The Ty-G index is obtained based on triglycerides and fasting blood glucose, which suggests that monitoring blood glucose and blood lipids should be performed in PCOS patients regardless of their age, and timely clinical intervention is an important means to prevent the occurrence of MetS in PCOS patients.
参考文献
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