Associations of estimated glucose disposal rate with liver steatosis and fibrosis
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摘要:目的
探讨预估葡萄糖处理率(eGDR)与代谢功能障碍相关肝脏脂肪变性和肝纤维化的相关性, 并分析这种关联性在不同人群特征中的差异。
方法纳入2017—2020年美国国家健康与营养调查(NHANES)数据库中10 549例参与振动控制瞬时弹性成像技术(VCTE)检查的参与者为研究对象。通过腰围、高血压和糖化血红蛋白(HbA1c)计算eGDR。以受控衰减参数(CAP)≥248 dB/m作为肝脏脂肪变性诊断标准，以肝脏硬度(LSM)≥8.2 kPa作为肝纤维化的判定标准。采用多因素Logistic回归分析评估eGDR与肝脏脂肪变性和肝纤维化的关系，并进行亚组分析和交互作用检验。
结果调整混杂因素后, eGDR水平与肝脏脂肪变性和肝纤维化风险均呈显著负相关。将研究对象按eGDR水平三分位数(Q1、Q2、Q3)分为Q1组、Q2组和Q3组。与Q1组相比, Q2组和Q3组肝脏脂肪变性的风险比分别为0.485(95% CI: 0.394~0.597)和0.286(95% CI: 0.239~0.343), 差异均有统计学意义(P < 0.001);肝纤维化风险比分别为0.457(95% CI: 0.363~0.576)和0.162(95% CI: 0.100~0.263), 差异均有统计学意义(P < 0.001)。亚组分析结果显示, eGDR与肝脏脂肪变性的负相关性在不同年龄和吸烟状态人群中存在差异，交互作用检验差异有统计学意义(P交互 < 0.001);eGDR与肝纤维化的负相关性在不同体力活动人群中的交互作用检验中差异有统计学意义(P交互 < 0.001)。eGDR水平与肝脏脂肪变性和肝纤维化的相关性保持稳定(P交互>0.05)。
结论eGDR水平与肝脏脂肪变性和肝纤维化风险密切相关，可作为评估肝脏代谢异常的有效指标。这一发现为肝脏脂肪变性和肝纤维化早期筛查、风险分层和预后评估提供了新思路。
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关键词:
- 肝脏脂肪变性 /
- 肝纤维化 /
- 预估葡萄糖处理率 /
- 代谢功能障碍 /
- 肝脏硬度 /
- 葡萄糖耐量异常 /
- 振动控制瞬时弹性成像技术 /
- 代谢功能障碍相关脂肪性肝病
Abstract:ObjectiveTo investigate the association of estimated glucose disposal rate (eGDR) with metabolic dysfunction-associated liver steatosis and fibrosis, and to analyze the difference of the association in different population.
MethodsA total of 10, 549 participants from 2017 to 2020 in National Health and Nutrition Examination Survey (NHANES) database who underwent vibration-controlled transient elastography (VCTE) were included. eGDR was calculated based on waist circumference, hypertension, and glycated hemoglobin (HbA1c). The controlled attenuation parameter (CAP) ≥ 248 dB/m was used as diagnostic criterion for liver steatosis, and liver stiffness measurement (LSM) ≥ 8.2 kPa was used as criterion for liver fibrosis. Multivariable Logistic regression analysis was conducted to assess the relationship between eGDR and liver steatosis and fibrosis, with subgroup analysis and interaction tests performed.
ResultsAfter adjusting for confounding factors, eGDR level was significantly negatively associated with the risks of both liver steatosis and fibrosis. The participants were divided into tertiles based on eGDR levels (Q1, Q2, Q3). Compared with the Q1 group, the risk ratios for liver steatosis in the Q2 and Q3 groups were 0.485 (95%CI, 0.394 to 0.597) and 0.286 (95%CI, 0.239 to 0.343), respectively(P < 0.001); the risk ratios for liver fibrosis were 0.457 (95%CI, 0.363 to 0.576) and 0.162 (95%CI, 0.100 to 0.263), respectively (P < 0.001). Subgroup analysis showed that the negative association between eGDR and liver steatosis differed among populations of different ages and smoking statuses, with statistically significant differences in interaction tests (P for interaction < 0.001); similarly, the negative association between eGDR and liver fibrosis differed among populations with different levels of physical activity, with statistically significant differences in interaction tests (P for interaction < 0.001). The associations of eGDR levels with liver steatosis and fibrosis remained stable (P for interaction>0.05).
ConclusioneGDR levels are closely associated with the risks of liver steatosis and fibrosis and can serve as an effective indicator for assessing liver metabolic abnormalities. This finding provides new insights into early screening, risk stratification, and prognosis assessment for liver steatosis and fibrosis.
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表 1 研究对象基线资料比较(Mean±SD)[n(%)]
项目 分类 总体(n=10 549) Q1组(n=3 533) Q2组(n=3 522) Q3组(n=3 494) P 年龄/岁 47.74±17.00 56.25±15.05 49.22±16.73 39.94±15.06 < 0.001 20~ < 40岁 3 280(31.09) 415(16.57) 990(32.60) 1 875(55.38) < 0.001 40~ < 60岁 3 570(35.60) 1 181(37.07) 1 297(39.12) 1 092(31.50) 60~80岁 3 699(27.80) 1 937(46.36) 1 235(28.28) 527(13.11) 性别 女 5 342(50.66) 1 622(43.92) 1 750(49.88) 1 970(56.51) < 0.001 男 5 207(49.34) 1 911(56.08) 1 772(50.12) 1 524(43.49) 种族 非西班牙裔白人 3 767(63.92) 1 345(67.19) 1 289(62.78) 1 133(62.37) < 0.001 非西班牙裔黑人 2 547(10.54) 1 091(13.22) 775(10.03) 681(8.92) 墨西哥裔美国人 1 361(8.76) 390(6.63) 505(10.36) 466(9.03) 其他西班牙裔 1 061(7.06) 321(5.50) 333(6.57) 407(8.69) 其他种族 1 813(9.72) 386(7.46) 620(10.25) 807(11.00) 教育水平 高中以下 1 863(10.05) 691(11.25) 621(10.42) 551(8.81) < 0.001 高中 2 523(26.80) 878(28.27) 911(29.57) 734(23.32) 大学肄业 3 502(30.90) 1 230(34.91) 1 175(30.41) 1 097(28.24) 大学及以上 2 661(32.25) 734(25.56) 815(29.60) 1 112(39.63) 婚姻状况 未婚 4 668(41.67) 1 541(38.10) 1 533(40.20) 1 594(45.67) 0.001 已婚 5 881(58.33) 1 992(61.90) 1 989(59.80) 1 900(54.33) 吸烟状况 从不吸烟 6 194(58.08) 1 847(52.30) 2 019(56.30) 2 328(64.04) < 0.001 有吸烟史 2 517(25.73) 1 144(34.36) 825(24.73) 548(19.95) 现在吸烟 1 838(16.18) 542(13.34) 678(18.97) 618(16.01) 饮酒情况 不饮酒 978(6.86) 280(6.50) 374(7.32) 324(6.74) 0.576 饮酒 9 571(93.14) 3 253(93.50) 3 148(92.68) 3 170(93.26) 体力活动 剧烈体力活动 2 660(30.05) 499(15.52) 788(28.22) 1 373(42.77) < 0.001 中等体力活动 2 553(26.39) 920(29.57) 904(26.74) 729(23.65) 无体力活动 5 336(43.56) 2 114(54.91) 1 830(45.04) 1 392(33.58) BMI/(kg/m2) 29.74±7.13 35.06±7.20 30.77±6.18 24.78±3.65 < 0.001 腰围/cm 100.76±17.23 115.91±14.43 103.60±13.61 86.71±8.88 < 0.001 身高/cm 168.18±9.98 169.42±10.40 167.98±10.13 167.39±9.41 < 0.001 空腹血糖/(mmol/L) 6.09±1.75 7.08±2.66 5.95±1.25 5.52±0.65 < 0.001 胰岛素/(μIU/mL) 13.45±19.51 21.53±32.36 13.44±11.87 7.74±5.34 < 0.001 HbA1c/% 5.66±0.92 6.21±1.30 5.62±0.69 5.28±0.36 < 0.001 ALT/(U/L) 22.69±15.94 25.91±17.11 23.83±17.02 19.25±13.15 < 0.001 AST/(U/L) 21.60±11.29 22.36±10.46 21.72±11.94 20.93±11.31 0.005 GGT/(IU/L) 29.08±37.93 36.93±43.27 29.82±33.92 22.40±35.48 < 0.001 Cr/(μmol/L) 77.71±30.04 83.17±43.29 77.26±26.88 73.90±16.43 < 0.001 UA/(μmol/L) 318.81±84.88 353.35±87.42 320.85±81.69 290.51±74.84 < 0.001 BUN/(mg/mL) 14.88±5.21 16.38±6.23 14.87±5.04 13.72±4.09 < 0.001 TG/(mg/mL) 112.07±97.21 135.36±97.23 123.36±121.95 86.28±61.93 < 0.001 TC/(mg/mL) 188.48±40.25 187.90±41.61 193.24±40.30 184.90±38.72 < 0.001 HDL/(mg/mL) 53.52±15.48 48.46±13.38 53.09±15.89 57.79±15.41 < 0.001 hs-CRP/(mg/L) 3.70±7.11 5.31±8.35 3.81±7.39 2.37±5.35 < 0.001 HOMA-IR 3.96±7.42 7.14±12.63 3.68±3.98 1.93±1.47 < 0.001 LSM/kPa 5.79±4.87 7.30±6.82 5.67±4.60 4.73±2.32 < 0.001 CAP/(dB/m) 265.16±62.84 307.44±57.28 270.88±57.67 227.79±46.83 < 0.001 eGDR/[mg/(kg·min)] 7.66±2.78 4.13±1.33 7.59±0.97 10.44±0.84 < 0.001 糖尿病 否 8 386(84.80) 2 025(62.70) 2 974(88.73) 3 387(98.48) < 0.001 是 2 163(15.20) 1 508(37.30) 548(11.27) 107(1.52) 高血压 否 5 807(61.70) 198(7.02) 2 115(66.13) 3 494(100.00) < 0.001 是 4 742(38.30) 3 335(92.98) 1 407(33.87) 0 心血管疾病 否 9 540(92.22) 2 902(84.24) 3 232(92.76) 3 406(97.89) < 0.001 是 1 009(7.78) 631(15.76) 290(7.24) 88(2.11) 慢性肾脏病 否 8 692(86.22) 2 455(73.74) 2 980(88.37) 3 257(93.99) < 0.001 是 1 857(13.78) 1 078(26.26) 542(11.63) 237(6.01) 肿瘤 否 9 535(89.72) 3 071(86.64) 3 141(87.61) 3 323(93.87) < 0.001 是 1 014(10.28) 462(13.36) 381(12.39) 171(6.13) 肝脂肪变性 否 4 269(42.90) 605(14.62) 1 307(36.17) 2 357(70.35) < 0.001 是 6 280(57.10) 2 928(85.38) 2 215(63.83) 1 137(29.65) 肝纤维化 否 9 530(91.33) 2 866(80.81) 3 239(92.51) 3 425(98.42) < 0.001 是 1 019(8.67) 667(19.19) 283(7.49) 69(1.58) 空腹子样本权重通过加权算法进行统计分析; 计数资料采用未加权频数和加权百分比表示。BMI: 体质量指数;
WBC: 白细胞; RBC: 红细胞; Hb: 血红蛋白; PLT: 血小板; HbA1c: 糖化血红蛋白; ALT: 谷丙转氨酶;
AST: 谷草转氨酶; GGT: 谷酰转肽酶; Cr: 肌酐; UA: 尿酸; BUN: 尿素; TG: 甘油三酯; TC: 总胆固醇; HDL: 高密度脂蛋白;
hs-CRP: 超敏C反应蛋白; HOMA-IR: 胰岛素抵抗; LSM: 肝脏硬度; CAP: 受控衰减参数; eGDR: 估算葡萄糖处理率。
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表 2 eGDR与肝脏脂肪变性和肝纤维化的关系
模型 分类 肝脏脂肪变性 肝纤维化 OR(95% CI) P OR(95% CI) P 模型1 eGDR 0.623(0.605~0.643) < 0.001 0.666(0.640~0.693) < 0.001 Q1 参照 — 参照 — Q2 0.301(0.252~0.359) < 0.001 0.331(0.275~0.398) < 0.001 Q3 0.076(0.064~0.091) < 0.001 0.067(0.043~0.103) < 0.001 模型2 eGDR 0.762(0.743~0.781) < 0.001 0.721(0.684~0.761) < 0.001 Q1 参照 — 参照 — Q2 0.500(0.401~0.622) < 0.001 0.424(0.342~0.527) < 0.001 Q3 0.298(0.249~0.358) < 0.001 0.151(0.094~0.243) < 0.001 模型3 eGDR 0.753(0.735~0.772) < 0.001 0.733(0.695~0.773) < 0.001 Q1 参照 — 参照 — Q2 0.485(0.394~0.597) < 0.001 0.457(0.363~0.576) < 0.001 Q3 0.286(0.239~0.343) < 0.001 0.162(0.100~0.263) < 0.001
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表 3 eGDR与肝脏脂肪变性关系的亚组分析
项目 分类 Q2 Q3 P趋势 P交互 OR(95%CI) P OR(95%CI) P 年龄 20~ < 40岁 0.259(0.182~0.370) < 0.001 0.126(0.091~0.174) < 0.001 < 0.001 < 0.001 40~ < 60岁 0.474(0.378~0.594) < 0.001 0.334(0.228~0.490) < 0.001 < 0.001 60~80岁 0.599(0.430~0.835) 0.004 0.379(0.293~0.489) < 0.001 < 0.001 性别 女 0.482(0.355~0.653) < 0.001 0.258(0.164~0.406) < 0.001 < 0.001 0.892 男 0.445(0.306~0.646) < 0.001 0.263(0.173~0.400) < 0.001 < 0.001 种族 非西班牙裔白人 0.452(0.328~0.622) < 0.001 0.251(0.194~0.324) < 0.001 < 0.001 0.790 非西班牙裔黑人 0.532(0.360~0.786) 0.003 0.217(0.131~0.358) < 0.001 < 0.001 墨西哥裔美国人 0.407(0.188~0.883) 0.027 0.244(0.117~0.510) 0.001 < 0.001 其他西班牙裔 0.411(0.272~0.620) < 0.001 0.234(0.136~0.402) < 0.001 < 0.001 其他种族 0.483(0.287~0.813) 0.008 0.287(0.173~0.478) < 0.001 < 0.001 教育水平 高中以下 0.627(0.392~1.002) 0.051 0.239(0.139~0.410) < 0.001 < 0.001 0.198 高中毕业生 0.449(0.327~0.617) < 0.001 0.302(0.224~0.407) < 0.001 < 0.001 大学肄业 0.373(0.259~0.537) < 0.001 0.186(0.129~0.267) < 0.001 < 0.001 大学及以上 0.512(0.313~0.837) 0.010 0.299(0.228~0.393) < 0.001 < 0.001 婚姻状况 未婚 0.560(0.417~0.753) < 0.001 0.277(0.192~0.400) < 0.001 < 0.001 0.299 已婚 0.398(0.269~0.588) < 0.001 0.232(0.164~0.328) < 0.001 < 0.001 吸烟状况 从不吸烟 0.637(0.457~0.887) 0.010 0.426(0.267~0.679) 0.001 < 0.001 0.044 有吸烟史 0.358(0.257~0.498) < 0.001 0.199(0.141~0.280) < 0.001 < 0.001 吸烟 0.584(0.342~0.997) 0.049 0.245(0.128~0.468) < 0.001 < 0.001 饮酒情况 不饮酒 0.512(0.253~1.034) 0.061 0.314(0.150~0.659) 0.004 0.004 0.835 饮酒 0.457(0.369~0.566) < 0.001 0.246(0.204~0.296) < 0.001 < 0.001 体力活动 剧烈体力活动 0.363(0.207~0.638) 0.001 0.173(0.101~0.295) < 0.001 < 0.001 0.793 中等体力活动 0.523(0.429~0.637) < 0.001 0.260(0.207~0.327) < 0.001 < 0.001 无体力活动 0.433(0.258~0.727) 0.003 0.303(0.176~0.521) < 0.001 < 0.001 体质量指数分类 正常 0.225(0.080~0.632) 0.007 0.132(0.051~0.340) < 0.001 < 0.001 0.077 超重 0.454(0.312~0.658) < 0.001 0.308(0.225~0.422) < 0.001 < 0.001 肥胖 0.423(0.311~0.574) < 0.001 0.158(0.097~0.257) < 0.001 < 0.001
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表 4 eGDR与肝纤维化关系的亚组分析
项目 分类 Q2 Q3 P趋势 P交互 OR(95%CI) P OR(95%CI) P 年龄 20~ < 40岁 0.459(0.293~0.720) 0.002 0.112(0.056~0.226) < 0.001 < 0.001 0.057 40~ < 60岁 0.404(0.256~0.639) < 0.001 0.201(0.083~0.489) 0.001 < 0.001 60~80岁 0.643(0.440~0.941) 0.025 0.418(0.202~0.863) 0.021 0.008 性别 女性 0.331(0.224~0.488) < 0.001 0.076(0.023~0.253) < 0.001 < 0.001 0.052 男性 0.587(0.445~0.774) < 0.001 0.285(0.199~0.408) < 0.001 < 0.001 种族 非西班牙裔白人 0.433(0.311~0.603) < 0.001 0.188(0.094~0.375) < 0.001 < 0.001 0.135 非西班牙裔黑人 0.455(0.251~0.827) 0.012 0.337(0.182~0.624) 0.001 < 0.001 墨西哥裔美国人 0.580(0.278~1.214) 0.133 0.156(0.049~0.499) 0.005 0.008 其他西班牙裔 0.722(0.428~1.219) 0.209 0.110(0.038~0.319) < 0.001 < 0.001 其他种族 0.405(0.219~0.748) 0.006 0.089(0.033~0.242) < 0.001 < 0.001 教育水平 高中以下 0.459(0.249~0.845) 0.015 0.236(0.089~0.624) 0.006 0.003 0.059 高中毕业生 0.480(0.329~0.700) < 0.001 0.131(0.073~0.236) < 0.001 < 0.001 大学肄业 0.298(0.195~0.454) < 0.001 0.096(0.058~0.159) < 0.001 < 0.001 大学及以上 0.820(0.413~1.629) 0.553 0.328(0.110~0.978) 0.046 0.048 婚姻状况 未婚 0.572(0.368~0.887) 0.015 0.275(0.093~0.808) 0.022 0.008 0.359 已婚 0.412(0.298~0.569) < 0.001 0.120(0.075~0.191) < 0.001 < 0.001 吸烟状况 从不吸烟 0.586(0.375~0.916) 0.021 0.141(0.056~0.353) < 0.001 < 0.001 0.459 有吸烟史 0.418(0.287~0.607) < 0.001 0.172(0.092~0.322) < 0.001 < 0.001 吸烟 0.447(0.203~0.985) 0.046 0.173(0.046~0.649) 0.012 0.012 饮酒情况 不饮酒 0.301(0.131~0.694) 0.007 0.199(0.029~1.355) 0.094 0.035 0.752 饮酒 0.473(0.364~0.615) < 0.001 0.169(0.104~0.275) < 0.001 < 0.001 体力活动 剧烈体力活动 0.287(0.178~0.462) < 0.001 0.034(0.011~0.109) < 0.001 < 0.001 0.011 中等体力活动 0.480(0.333~0.691) < 0.001 0.178(0.077~0.412) < 0.001 < 0.001 无体力活动 0.718(0.374~1.381) 0.303 0.339(0.145~0.796) 0.016 0.027 体质量指数分类 正常 0.570(0.155~2.087) 0.376 0.388(0.094~1.605) 0.179 0.129 0.070 超重 0.844(0.470~1.517) 0.552 0.366(0.142~0.941) 0.038 0.020 肥胖 0.407(0.303~0.545) < 0.001 0.037(0.010~0.136) < 0.001 < 0.001
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