TyG相关指数、25(OH)D与T2DM合并MAFLD患者的相关性研究

肖泊杉1, 盛佳曦1, 王冰玉1, 贺舒靖1, 张肖1, 刘聪辉1, 齐亚娟2, 吴乃君1

【作者机构】 1华北理工大学附属医院内分泌与代谢病科; 2华北理工大学基础医学院
【分 类 号】 R587.1
【基    金】 河北省医学科学研究课题(20260636) 河北省自然科学基金资助项目(H2022209087)。
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TyG相关指数、25(OH)D与T2DM合并MAFLD患者的相关性研究

TyG相关指数、25(OH)D与T2DM合并MAFLD患者的相关性研究

肖泊杉1 盛佳曦1 王冰玉1 贺舒靖1 张 肖1 刘聪辉1 齐亚娟2 吴乃君1

1.华北理工大学附属医院内分泌与代谢病科,河北唐山 063210;2.华北理工大学基础医学院,河北唐山 063210

[摘要] 目的 探讨甘油三酯-葡萄糖(TyG)相关指数、25-羟基维生素D[25(OH)D]与2型糖尿病(T2DM)合并代谢相关脂肪性肝病(MAFLD)的关系,分析T2DM合并MAFLD的影响因素,为T2DM合并MAFLD患者的早期筛查及预防提供参考依据。 方法 选取2024年12月至2025年6月于华北理工大学附属医院住院的274例T2DM合并MAFLD患者为病例组,选取同期171例T2DM未合并MAFLD的患者为对照组。收集两组临床资料,分析T2DM合并MAFLD的影响因素,受试者操作特征曲线评估TyG相关指数对T2DM合并MAFLD预测价值。 结果 两组年龄、体质量指数(BMI)、舒张压、病程、冠心病病史、高血压病史、TyG-BMI、TyG-腰围(TyG-WC)、TyG-腰臀比(TyG-WHR)、TyG-腰高比(TyG-WHtR)、TyG指数、25(OH)D、天门冬氨酸转氨酶、丙氨酸转氨酶、γ-谷氨酰转肽酶、总胆红素、间接胆红素、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇、甘油三酯、白蛋白(Alb)、血尿素、血尿酸、空腹血糖、餐后2 h血糖、空腹胰岛素、餐后2 h胰岛素、空腹C肽、餐后2 h C肽、糖化血红蛋白比较,差异有统计学意义(P<0.05)。Alb、HDL-C、TyG-WC、TyG-BMI、TyG-WHtR、TyG-WHR、25(OH)D是T2DM合并MAFLD的影响因素(P<0.05)。TyG-WHtR预测T2DM合并MAFLD的曲线下面积为0.768、TyG-WC为0.766、TyG-WHR为0.764、TyG-BMI为0.762。 结论 TyG-WHtR对T2DM合并MAFLD具有一定的预测价值。

[关键词] 2型糖尿病;代谢相关脂肪性肝病;甘油三酯葡萄糖指数;25-羟基维生素D

2型糖尿病(type 2 diabetes mellitus,T2DM)与代谢相关脂肪性肝病(metabolic associated fatty liver disease,MAFLD)是代谢综合征的核心组成部分[1-2];二者共存加重胰岛素抵抗(insulin resistance,IR)与代谢紊乱,增加患者心血管疾病的发生风险[3]。IR是T2DM和MAFLD的共同病理基础[4-5];因其评估“金标准”操作复杂,亟须寻找简便可靠的替代指标预测T2DM合并MAFLD患者。

甘油三酯-葡萄糖(triglyceride-glucose,TyG)指数是评估IR的简便替代指标[6]。为更全面评估代谢风险,研究者将TyG指数与肥胖指标结合,衍生出TyG-体质量指数(TyG-body mass index,TyG-BMI)、TyG-腰围(TyG-waist circumference,TyG-WC)、TyG-腰臀比(TyG -waist-to-hip ratio,TyG-WHR)和TyG-腰高比(TyG-waist-to-height ratio,TyG-WHtR)等复合指标。研究发现,TyG-BMI在识别男性内脏肥胖方面的表现优于传统TyG指数[7];TyG-WHtR在成人MASLD发病风险预测中更具优势[8]。此外,25羟基维生素D[25 hydroxyvitamin D,25(OH)D]缺乏与IR、慢性炎症相关,可能参与T2DM及MAFLD的发生、发展,而肥胖状态可能降低生物利用率,使其作用机制更为复杂[9-10]。然而,TyG相关指数、25(OH)D在T2DM合并MAFLD患者中的联合研究较为缺乏。故本研究旨在探讨TyG相关指数与25(OH)D在T2DM合并MAFLD患者中的相关性,比较TyG相关指数对T2DM合并MAFLD的预测价值。

1 资料与方法

1.1 一般资料

采用病例对照研究的样本量计算公式,N=2PQZα+Zβ2/(P1-P02N为样本量;当α=0.05和β=0.10时Zα=1.96、Zβ=1.28;P1是病例组某个因素的暴露率,P0是对照组该因素的暴露率;本研究P0=0.50,P1=0.75,计算得P=0.625,Q=0.375,得出病例组及对照组的基础样本量约为80例。在基础样本量的基础上增加10%~20%的样本量,总样本量为176~192例。为确保研究结论稳健、提升模型稳定性,本研究确立扩大样本量的收集策略,最终共纳入445例患者。

选取2024年12月至2025年6月于华北理工大学附属医院住院的274例T2DM合并MAFLD患者为病例组,选取同期171例T2DM未合并MAFLD的患者为对照组。本研究经华北理工大学附属医院临床医学研究伦理委员会批准(20241226028)。

1.1.1 诊断标准

1.1.1.1 T2DM 诊断符合《中国2型糖尿病防治指南(2020年版)》[11]相关标准,具有典型高血糖症状且满足以下任一条件:随机血糖 ≥11.1 mmol/L、空腹血糖(fasting plasma glucose, FPG) ≥7.0 mmol/L、口服葡萄糖耐量试验2 h血糖 ≥11.1 mmol/L或糖化血红蛋白(glycosylated hemoglobinA1c,HbA1c) ≥6.5%。若无典型症状,则需在不同日重复检测以确诊(随机血糖除外)。

1.1.1.2 MAFLD 脂肪肝诊断依据超声表现:①肝区近场回声弥漫性增强,远场回声逐渐衰减;②肝内管道结构显示不清;③肝脏轻度至中度肿大,边缘角圆钝;④肝内血流信号减少但走行正常;具备第①项及第②~④项中任意一项即可诊断脂肪肝。进一步结合代谢状态,符合以下三类标准之一可确诊为MAFLD:①超重或肥胖;②T2DM;③存在至少两项代谢风险异常,包括:a.男性腰围 ≥90 cm,女性腰围 ≥80 cm;b.血压 ≥130/85 mmHg(1 mmHg=0.133 kPa)或接受降压治疗;c.甘油三酯(triglyceride,TG) ≥1.7 mmol/L或正在接受降脂治疗;d.男性高密度脂蛋白胆固醇(highdensity lipoprotein cholesterol,HDL-C)<1.0 mmol/L,女性<1.3 mmol/L[12]

1.1.2 纳入标准

病例组:①年龄 ≥18岁;②同时符合T2DM和MAFLD诊断。对照组:①年龄 ≥18岁;②符合T2DM诊断。

1.1.3 排除标准

①患有其他类型糖尿病及急性并发症;②大量饮酒;③有以下任意一项肝病病史:药物诱发的脂肪肝、自身免疫性肝病、病毒性肝炎、酒精性肝炎、肝硬化、肝癌等;④近期低脂饮食,使用影响糖脂代谢、肝功能药物,长期服用激素、维生素D及钙剂。

1.2 研究方法

1.2.1 收集临床资料

收集患者一般临床资料,包括性别、年龄、病程、WC、臀围、BMI、收缩压、舒张压、吸烟史、饮酒史、冠心病病史、高血压病史、用药史;实验室检验指标,包括FPG、空腹胰岛素(fasting insulin,FINS)、空腹C肽(fasting C-peptide,FCP),餐后2 h血糖(2-hour postprandial plasma glucose,2hPG)、餐后2 h胰岛素(2-hour postprandial insulin,2hINS)、餐后2 h C肽(2-hour postprandial C-peptide,2hCP)、HbA1c、总胆固醇(total cholesterol,TC)、TG、低密度脂蛋白胆固醇(lowdensity lipoprotein cholesterin,LDL-C)、HDL-C、丙氨酸转氨酶(alanine aminotransferase,ALT)、天冬氨酸转氨酶(aspartate transaminase,AST)、γ-谷氨酰转肽酶(gamma-glutamyl transferase,GGT)、总胆红素(total bilirubin,TBil)、直接胆红素(direct bilirubin,DBil)、间接胆红素(indirect bilirubin,IBil)、白蛋白(Albumin,Alb)、血尿酸(serum uric acid,SUA)、血尿素(blood urea,Urea)、血肌酐(serum creatinine,Scr)。

1.2.2 25(OH)D测定

统一使用罗氏诊断产品(上海)有限公司生产的25(OH)D检测试剂盒,由华北理工大学附属医院核医学科专业检验医师严格按说明书方法经罗氏全自动电化学发光免疫分析仪(型号:Cobas e601)进行测定。

1.2.3 相关计算公式

BMI=体重(kg)/身高(m)2,WHR=WC(cm)/臀围(cm), WHtR=WC(cm)/身高(cm),TyG=In[TG(mg/dl)× FPG(mg/dl)/2],TyG-BMI=TyG×BMI,TyG-WC=TyG× WC,TyG-WHR=TyG×WHR,TyG-WHtR=TyG×WHtR。

1.3 统计学方法

采用SPSS 27.0统计学软件进行数据分析。符合正态分布的计量资料用均数±标准差表示,比较采用t检验;不符合正态分布的计量资料采用中位数(M)和四分位数(P25P75)表示,比较采用秩和检验。计数资料用例数(百分率)[例(%)]表示,比较采用χ2检验。影响因素采用logistic回归模型,采用逐步向前回归法分析;受试者操作特征(receiver operating characteristic,ROC)曲线评估TyG相关指数预测T2DM合并MAFLD的价值。对于存在的少量缺失的变量,本研究采用完整病例分析进行处理。以P<0.05为差异有统计学意义。

2 结果

2.1 两组基线资料比较

两组年龄、BMI、舒张压、病程、冠心病病史、高血压病史、TyG-BMI、TyG-WC、TyG-WHR、TyG-WHtR、TyG指数、25(OH)D、AST、ALT、GGT、TBil、IBil、HDL-C、LDL-C、TG、Alb、Urea、SUA、FPG、2hPG、FINS、2hINS、FCP、2hCP、HbA1c比较,差异有统计学意义(P<0.05)。见表1。

表1 两组基线资料比较

项目病例组(274例)对照组(171例)χ2/t/Z值P值性别[例(%)]0.2020.653男135(49.27)88(51.46)女139(50.73)83(48.54)年龄(岁,xˉ±s)55.94±12.4259.78±11.753.2430.001 BMI(kg/m2,xˉ±s)27.14±3.4224.50±3.557.824<0.001收缩压(mmHg,xˉ±s)140.15±16.75137.47±16.611.6460.101舒张压(mmHg,xˉ±s)87.99±11.8883.10±10.844.369<0.001病程(年,xˉ±s)7.71±6.9011.49±8.814.766<0.001家族史[例(%)]143(52.19)75(43.86)2.9240.087吸烟史[例(%)]84(30.66)43(25.15)1.5680.211饮酒史[例(%)]66(24.09)39(22.81)0.0960.757冠心病病史[例(%)]41(14.96)47(27.49)10.406<0.001高血压病史[例(%)]145(52.92)74(43.27)3.9190.048服用降压药[例(%)]119(43.43)60(35.09)3.0480.081服用降脂药[例(%)]48(17.52)38(22.22)1.4940.222服用降糖药[例(%)]180(65.93)108(63.16)0.3560.551 TyG-BMI(xˉ±s)263.47±42.74222.83±41.169.896<0.001 TyG-WC(xˉ±s)954.96±125.68831.65±118.4410.293<0.001 TyG-WHR(xˉ±s)9.29±0.948.37±0.9010.151<0.001 TyG-WHtR(xˉ±s)5.72±0.715.02±0.6810.272<0.001 TyG指数(xˉ±s)9.69±0.799.07±0.807.968<0.00125(OH)D(ng/ml,xˉ±s)16.14±6.0718.12±8.432.6680.008 AST[U/L,M(P25,P75)]20.00(16.00,28.00)18.00(15.00,22.00)4.292<0.001 ALT[U/L,M(P25,P75)]25.00(17.00,40.00)18.00(13.00,23.00)6.553<0.001 GGT[U/L,M(P25,P75)]33.00(23.00,51.30)22.00(16.00,32.00)7.259<0.001 TBil(μmol/L,xˉ±s)14.73±6.3313.53±5.771.9970.046

续表1

项目病例组(274例)对照组(171例)χ2/t/Z值P值DBil[μmol/L,M(P25,P75)]3.70(2.84,5.22)3.60(2.70,4.71)0.5970.553 IBil(μmol/L,xˉ±s)10.54±4.399.60±3.982.2830.023 TC(mmol/L,xˉ±s)5.12±1.194.93±1.311.5590.122 HDL-C[mmol/L,M(P25,P75)]1.05(0.91,1.33)1.16(1.04,1.40)4.325<0.001 LDL-C(mmol/L,xˉ±s)3.42±0.963.22±1.022.1590.031 TG[mmol/L,M(P25,P75)]1.93(1.32,3.01)1.27(0.94,1.92)7.123<0.001 Alb(g/L,xˉ±s)44.83±3.0343.18±3.974.659<0.001 Urea[mmol/L,M(P25,P75)]5.58(4.65,6.70)6.18(5.26,7.31)3.373<0.001 Scr[μmol/L,M(P25,P75)]61.00(52.80,74.00)65.00(52.00,79.00)1.4060.160 SUA(μmol/L,xˉ±s)331.71±92.62301.15±83.493.514<0.001 FPG(mmol/L,xˉ±s)10.37±3.638.89±3.904.073<0.0012hPG(mmol/L,xˉ±s)14.30±5.1212.26±4.654.229<0.001 FINS[μIU/L,M(P25,P75)]11.09(6.73,16.91)6.07(3.30,11.84)6.048<0.0012hINS[μIU/L,M(P25,P75)]32.79(17.94,55.12)18.93(11.42,40.90)4.621<0.001 FCP(ng/ml,xˉ±s)3.01±1.432.04±1.297.191<0.0012hCP(ng/ml,xˉ±s)6.41±3.484.63±3.445.275<0.001 HbA1c(%,xˉ±s)8.95±1.948.40±2.042.8580.004

注 BMI:体质量指数;TyG:甘油三酯-葡萄糖;WC:腰围;WHR:腰臀比;WHtR:腰高比;25(OH)D:25-羟基维生素D;AST:天冬氨酸转氨酶;ALT:丙氨酸转氨酶;GGT:γ-谷氨酰转肽酶;TBil:总胆红素;DBil:直接胆红素;IBil:间接胆红素;TC:总胆固醇;HDL-C:高密度脂蛋白胆固醇;LDL-C:低密度脂蛋白胆固醇;TG:甘油三酯;Alb:白蛋白;Urea:血尿素;Scr:血肌酐;SUA:血尿酸;FPG:空腹血糖;2hPG:餐后2 h血糖;FINS:空腹胰岛素;2hINS:餐后2 h胰岛素;FCP:空腹C肽;2hCP:餐后2 h C肽;HbA1c:糖化血红蛋白。

2.2 T2DM合并MAFLD的影响因素分析

以T2DM患者是否合并MAFLD为因变量(是=1,否=0),以表1中差异有统计学意义(P<0.05)的变量为自变量。多重共线性检验结果显示,各变量方差膨胀因子(variance inflation factor,VIF)均<5,不存在共线性。logistic回归分析结果显示,Alb、HDL-C、TyG-WC、TyG-BMI、TyG-WHtR、TyG-WHR、25(OH)D是T2DM合并MAFLD的影响因素(P<0.05)。见表2。

表2 T2DM合并MAFLD影响因素的logistic回归分析结果

项目βS.E.Waldχ2P值OR值95%CIVIF Alb0.1450.04112.196<0.0011.1561.066~1.2541.192 HDL-C-1.3730.4808.1680.0040.2530.099~0.6501.11625(OH)D-0.0390.0147.9320.0050.9620.936~0.9881.121 TyG-BMI0.0250.00367.551<0.0011.0261.020~1.0324.956 TyG-WC0.0090.00170.785<0.0011.0091.007~1.0114.576 TyG-WHR1.1550.13968.914<0.0013.1732.416~4.1674.653 TyG-WHtR1.5100.17971.349<0.0014.5253.188~6.4234.702

注 T2DM:2型糖尿病;MAFLD:代谢相关脂肪性肝病;Alb:白蛋白;HDL-C:高密度脂蛋白胆固醇;25(OH)D:25-羟基维生素D;TyG:甘油三酯-葡萄糖;BMI:体质量指数;WC:腰围;WHR:腰臀比;WHtR:腰高比;VIF:方差膨胀因子。

2.3 TyG相关指数对T2DM合并MAFLD患者的预测效能

TyG-WHtR预测T2DM合并MAFLD的曲线下面积(area under the curve,AUC)为0.768、TyG-WC为0.766、TyG-WHR为0.764、TyG-BMI为0.762。见图1、表3。

图1 TyG相关指数预测T2DM合并MAFLD患者的ROC曲线

表3 TyG相关指数对T2DM合并MAFLD的预测价值

项目AUC约登指数灵敏度(%)特异度(%)95%CI TyG-BMI0.7620.38986.952.00.715~0.808 TyG-WC0.7660.38676.662.00.721~0.812 TyG-WHR0.7640.40769.371.30.719~0.809 TyG-WHtR0.7680.39065.373.70.723~0.812

注 TyG:甘油三酯-葡萄糖;T2DM:2型糖尿病;MAFLD:代谢相关脂肪性肝病;BMI:体质量指数;WC:腰围;WHR:腰臀比;WHtR:腰高比。

3 讨论

本研究结果显示,病例组TyG指数、TyG-WC、TyG-BMI、TyG-WHR、TyG-WHtR高于对照组,25(OH)D水平低与对照组;logistic回归分析结果显示,TyG-WC、TyG-BMI、TyG-WHtR、TyG-WHR、25(OH)D是T2DM合并MAFLD的影响因素(P<0.05)。ROC曲线结果显示,TyG-WHtR预测T2DM合并MAFLD的AUC为0.768、TyG-WC为0.766、TyG-WHR为0.764、TyG-BMI为0.762。

TyG指数反映全身IR状态,IR是T2DM合并MAFLD的核心病理基础,IR与慢性低度炎症有关,导致代谢和心血管疾病的发展[13]。葡萄糖和脂肪酸氧化增强会产生活性氧[14];可能导致氧化应激、损害组织,加重代谢并发症[15-16]。MAFLD与内脏脂肪(visceral adipose tissue,VAT)的过度堆积密切相关。腹部肥胖中,内脏脂肪较皮下脂肪更易释放游离脂肪酸和炎症因子[17]。TyG-WC和TyG-BMI虽然纳入肥胖指标,但WC无法区分皮下脂肪与内脏脂肪,BMI则无法反映体脂分布;而WHtR经腰围与身高比值校正个体体型差异,优于WC和BMI。研究表明,身材矮小与IR和T2DM风险增加相关[18]。身高与糖尿病风险的关联机制尚未完全阐明,现有研究支持身高较高者往往胰岛素敏感性与β细胞功能更佳的观点,这可能与其肝脏脂肪沉积较少有关[19]。因此,将身高和WC结合起来的指标可能更综合地反映代谢风险。

VAT过度堆积可诱发IR,VAT分泌大量游离脂肪酸、促炎性细胞因子,抑制胰岛素受体底物-1酪氨酸磷酸化,阻断PI3K/Akt信号通路,从而降低葡萄糖转运蛋白4的转运效率[20]。肝脏糖异生与从头脂质合成被异常激活,推动MAFLD进展[21-22]。25(OH)D缺乏则导致维生素D受体(vitamin D receptor,VDR)的激活不足,削弱其在多器官中的保护作用[23-24]。在肝脏中,VDR的抗炎、抗氧化和抗纤维化作用减弱,减弱对糖异生和从头脂质合成的抑制[25-26]。25(OH)D通过激活VDR,抑制NF-κB等促炎信号通路,降低肿瘤坏死因子-α、白细胞介素-6等炎症因子水平,从而减轻脂肪组织的慢性炎症[27]。在脂代谢层面,25(OH)D上调PPARα等信号通路,加速游离脂肪酸(free fatty acid,FFA)的β-氧化,减少内脏脂肪沉积及肝脏FFA输入。PPARα是调节脂质代谢的重要通路,可能成为治疗MAFLD的关键靶点[28]。动物研究显示,维生素D可通过增强PPARα表达改善肝脂肪变性[29]。因此,TyG指数升高和25(OH)D水平降低与T2DM合并MAFLD的发生密切相关。

综上所述,TyG-WHtR、25(OH)D与T2DM患者发生MAFLD相关,可用于早期识别风险;二者简便、经济无创,值得临床推广。但是,本研究存在一定的局限性:本研究为单中心横断面研究,样本量较小,可能存在选择偏倚,结果外推性受限,且无法推断因果关系,未来仍需开展大样本量、多中心、前瞻性研究予以证实。

利益冲突声明:本文所有作者均声明不存在利益冲突。

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Study on the correlation between TyG-related indices, 25(OH)D and T2DM patients complicated with MAFLD

XIAO Boshan1 SHENG Jiaxi1 WANG Bingyu1 HE Shujing1 ZHANG Xiao1 LIU Conghui1 QI Yajuan2 WU Naijun1

1.Department of Endocrinology and Metabolic Diseases, North China University of Science and Technology Affiliated Hospital, Hebei Province, Tangshan 063210, China; 2.School of Basic Medicine, North China University of Science and Technology, Hebei Province, Tangshan 063210, China

[Abstract] Objective To explore the relationship between triglyceride-glucose (TyG)-related indices, 25-hydroxyvitamin D [25(OH)D] and type 2 diabetes mellitus (T2DM) complicated with metabolic associated fatty liver disease(MAFLD), and to analyzed the influencing factors of T2DM complicated with MAFLD, providing a reference basis for the early screening and prevention of T2DM patients complicated with MAFLD. Methods A total of 274 T2DM patients complicated with MAFLD who were hospitalized in the North China University of Science and Technology Affiliated Hospital from December 2024 to June 2025 were collected as case group, and 171 T2DM patients without MAFLD during the same period were selected as control group. The clinical data of two groups were collected, the influencing factors of T2DM complicated with MAFLD was analyzed, and the receiver operating characteristic curve was used to evaluate the predictive value of TyG-related indices for T2DM complicated with MAFLD. Results There were statistically significant differences between two groups in age, body mass index (BMI), diastolic blood pressure, disease duration, history of coronary heart disease, history of hypertension, TyG-BMI, TyG-waist circumference (TyG-WC), TyG-waist-to-hip ratio(TyG-WHR), TyG-waist-to-height ratio (TyG-WHtR), TyG index, 25 (OH) D, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, total bilirubin,indirect bilirubin, high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol, triglycerides,albumin (Alb), blood urea, serum uric acid, fasting plasma glucose, 2-hour postprandial plasma glucose, fasting insulin, 2-hour postprandial insulin, fasting C-peptide, 2-hour postprandial C-peptide, glycated hemoglobin (P<0.05). Alb, HDL-C, TyG-WC, TyG-BMI, TyG-WHtR, TyG-WHR,25(OH)D were the influencing factors for the T2DM complicated with MAFLD (P<0.05). The area under the curve of TyG-WHtR was 0.768, the TyG-WC was 0.766, the TyG-WHR was 0.764, and the TyG-BMI was 0.762. Conclusion TyG-WHtR has certain predictive value for T2DM complicated with MAFLD.

[Key words] Type 2 diabetes mellitus; Metabolic associated fatty liver disease; Triglyceride-glucose indices; 25-hydroxyvitamin D

[中图分类号] R587.1

[文献标识码] A

[文章编号] 1673-7210(2026)07(a)-0056-06

DOI:10.20047/j.issn1673-7210.25100159

[基金项目] 河北省医学科学研究课题(20260636);河北省自然科学基金资助项目(H2022209087)。

[作者简介] 肖泊杉(2000.6-),女,硕士;研究方向:内分泌与代谢病学。

[通讯作者] 吴乃君(1973.9-),女,博士,主任医师;研究方向:内分泌与代谢病学。

(收稿日期:2025-10-07)

(修回日期:2026-01-25)

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