甲状腺激素水平与非酒精性脂肪性肝病发生的关系

田甜; 胡文炜; 李雪; 吴杰; 张丹; 李长政

doi:10.3969/j.issn.1001-5256.2021.10.020

甲状腺激素水平与非酒精性脂肪性肝病发生的关系

DOI: 10.3969/j.issn.1001-5256.2021.10.020

中国人民解放军火箭军特色医学中心消化内科，北京 100088

基金项目:

北京市科技计划课题 (Z1511000040150070)

详细信息

通信作者:
李长政，licz007@aliyun.com

中图分类号: R575.5
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出版历程
- 收稿日期: 2021-03-24
- 录用日期: 2021-05-20
- 出版日期: 2021-10-20

Association between thyroxine level and nonalcoholic fatty liver disease

Department of Gastroenterology, PLA Rocket Forces Characteristic Medical Center, Beijing 100088, China

Research funding:

Project of Beijing Science and Technology Program (Z1511000040150070)

摘要

摘要: 目的探讨甲状腺激素水平与非酒精性脂肪性肝病(NAFLD)发生的关系。方法回顾性分析2015年7月—2019年4月在中国人民解放军火箭军特色医学中心体检人群3289例临床资料，根据病史及甲状腺功能分为亚临床甲状腺功能减退组(n=210)及甲状腺功能正常组(n=3079)。将甲状腺功能正常组根据腹部彩超结果分为NAFLD组(n=516)及非NAFLD组(n=2563)；根据BMI划分为非肥胖亚组(BMI＜25 kg/m²)、肥胖亚组(BMI≥25 kg/m²)；根据年龄划分为老年组(≥60岁)、中青年组(＜60岁)。对甲状腺功能正常组进行不同年龄层、不同体型亚组分型。收集性别、年龄、BMI、血压、腰围、空腹血糖、尿酸、总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白、游离三碘甲状腺原氨酸、游离甲状腺素、三碘甲状腺原氨酸、甲状腺素、促甲状腺激素指标。符合正态分布的计量资料2组间比较采用两独立样本t检验，非正态分布的计量资料2组间比较采用Mann-Whitney U检验，计数资料2组间比较采用χ²检验，危险因素分析采用多因素logistic回归分析，应用受试者工作特征曲线(ROC曲线)分析所观察指标预测NAFLD发生的临界值。结果亚临床甲状腺功能减退组NAFLD患病率高于甲状腺功能正常组(22.38% vs 16.76%，χ²=4.380，P=0.036)，亚临床甲状腺功能减退组NAFLD患者促甲状腺激素水平高于非NAFLD患者(Z=-1.994, P=0.046)。甲状腺功能正常组甲状腺各参数水平在NAFLD组与非NAFLD组间差异无统计学意义(P值均＞0.05)，但进行年龄、体型分层后，肥胖-中青年亚组中，男性、低游离甲状腺素、空腹血糖、甘油三酯是NAFLD发生的独立危险因素(比值比分别为4.729、0.067、1.814、1.717，P值分别为0.003、0.010、0.011、0.014)。游离甲状腺素、空腹血糖、甘油三酯预测NAFLD的临界值分别为1.123 ng/dL、5.15 mmol/L、1.02 mmol/L，联合预测ROC曲线下面积为0.832。结论亚临床甲状腺功能减退人群NAFLD患病率高；甲状腺素水平在正常范围内时，低游离甲状腺素水平与中青年肥胖人群NAFLD的发生有关。
- 甲状腺素 /
- 非酒精性脂肪性肝病 /
- 危险因素
Abstract: Objective To investigate the association between thyroxine level and nonalcoholic fatty liver disease (NAFLD). Methods A retrospective analysis was performed for 3289 subjects who underwent physical examination in PLA Rocket Force Characteristic Medical Center from July 2015 to April 2019, and according to medical history and thyroid function, they were divided into subclinical hypothyroidism group with 210 subjects and normal thyroid function group with 3079 subjects. According to the results of abdominal color Doppler ultrasound, the normal thyroid function group was divided into NAFLD group with 516 subjects and non-NAFLD group with 2563 subjects; according to body mass index (BMI), the normal thyroid function group was divided into non-obese group (BMI < 25 kg/m²) and obese group (BMI ≥25 kg/m²); according to the age, the normal thyroid function group was divided into elderly group (age ≥60 years) and young and middle-aged group (age < 60 years). The normal thyroid function group was typed based on age and body type. Related data were collected, including sex, age, BMI, blood pressure, waist circumference, fasting blood glucose, uric acid, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, free triiodothyronine, free thyroxine, triiodothyronine, thyroxine, and thyroid stimulating hormone (TSH). The two-independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test used for comparison of categorical data between two groups. A multivariate logistic regression analysis was used to investigate risk factors, and the receiver operator characteristic (ROC) curve was used to analyze the cut-off values of related indices in predicting NAFLD. Results The subclinical hypothyroidism group had a higher prevalence rate of NAFLD than the normal thyroid function group (22.38% vs 16.76%, χ²=4.380, P=0.036), and in the subclinical hypothyroidism group, the NAFLD patients had a higher level of TSH than the non-NAFLD patients(Z=-1.994, P=0.046). In the subclinical hypothyroidism group, there were no significant differences in thyroid parameters between the NAFLD group and the non-NAFLD group (all P > 0.05); after stratification based on age and body type, in the obese-young and middle-aged subgroup, male sex, low free thyroxine, fasting blood glucose, and triglyceride were independent risk factors for NAFLD (odds ratio=4.729, 0.067, 1.814, and 1.717, P=0.003, 0.010, 0.011, and 0.014). The cut-off values of free thyroxine, fasting blood glucose, and triglyceride were 1.123 ng/dL, 5.15 mmol/L, and 1.02 mmol/L, respectively, in predicting NAFLD, and the area under the ROC curve was 0.832 for combined prediction. Conclusion There is a high prevalence rate of NAFLD in the population with subclinical hypothyroidism, and when thyroid function is within the normal range, low free thyroxine is associated with the onset of NAFLD in the young and middle-aged obese people.
- Thyroxine /
- Non-Alcoholic Fatty Liver Disease /
- Risk Factors

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图 1 中青年-肥胖组NAFLD诊断的ROC曲线

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表 1 亚临床甲状腺功能减退组患者甲状腺功能比较

指标	NAFLD患者(n=47)	非NAFLD患者(n=163)	统计值	P值
FT3(pg/mL)	3.11(2.84~3.31)	2.98(2.80~3.16)	Z=-1.469	0.142
FT4(ng/dL)	1.16±0.15	1.12±0.13	t=1.708	0.089
T3(ng/mL)	1.06±0.20	1.07±0.17	t=-0.054	0.957
T4(μg/dL)	7.30±1.54	7.51±1.34	t=-0.912	0.363
TSH(μIU/mL)	5.74(4.81~7.58)	5.19(4.77~6.01)	Z=-1.994	0.046

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表 2 正常范围内甲状腺功能各参数与NAFLD关系的多因素分析

因素	B值	SE	Wald χ²	P值	OR	95%CI
FT3(pg/mL)	0.087	0.899	0.009	0.922	1.091	0.188~6.351
FT4(ng/dL)	2.504	1.752	2.043	0.153	12.234	0.395~379.377
T3(ng/mL)	1.435	1.743	0.678	0.410	4.202	0.138~127.896
T4(μg/dL)	-0.012	0.181	0.004	0.947	0.988	0.693~1.408
TSH(μIU/mL)	-0.062	0.206	0.089	0.765	0.940	0.628~1.408
BMI(kg/m²)	0.094	0.117	0.650	0.420	1.099	0.874~1.382
舒张压(mmHg)	0.027	0.018	2.145	0.143	1.027	0.991~1.065
腰围(cm)	0.110	0.029	13.937	＜0.001	1.116	1.054~1.183
空腹血糖(mmol/L)	0.155	0.111	1.968	0.161	1.168	0.940~1.451
尿酸(μmol/L)	0.008	0.003	9.051	0.003	1.008	1.003~1.014
总胆固醇(mmol/L)	-0.377	0.193	3.805	0.051	0.686	0.469~1.002
常量	-19.565	3.721	27.647	0.000	0.000

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表 3 中青年-肥胖组NAFLD单因素分析

因素	脂肪肝(n=182)	非脂肪肝(n=212)	统计值	P值
FT3(pg/mL)	3.23±0.31	3.09±0.33	t=-4.707	＜0.001
FT4(ng/dL)	1.20(1.10~1.29)	1.15(1.06~1.26)	Z=-2.546	0.011
T3(ng/mL)	1.10(1.00~1.22)	1.06(0.97~1.18)	Z=-2.132	0.033
T4(μg/dL)	7.60(6.60~8.50)	7.44(6.66~8.41)	Z=-0.126	0.900
TSH(μIU/mL)	2.02(1.52~2.64)	1.91(1.39~2.96)	Z=-0.827	0.408
空腹血糖(mmol/L)	5.40(5.10~5.90)	5.10(4.80~5.40)	Z=-6.174	＜0.001
尿酸(μmol/L)	337.00(281.00~414.00)	280.00(245.00~327.00)	Z=-7.681	＜0.001
总胆固醇(mmol/L)	4.95(4.39~5.49)	4.72(4.14~5.11)	Z=-3.317	0.001
甘油三酯(mmol/L)	1.57(1.15~2.20)	0.95(0.77~1.38)	Z=-8.592	＜0.001
高密度脂蛋白(mmol/L)	1.10(0.96~1.26)	1.28(1.13~1.48)	Z=-6.975	＜0.001
低密度脂蛋白(mmol/L)	3.26±0.74	2.92±0.75	t=-4.407	＜0.001
BMI(kg/m²)	27.77(26.25~29.46)	26.26(25.41~27.34)	Z=-6.374	＜0.001
收缩压(mmHg)	129(120~138)	118(109~128)	Z=-7.208	＜0.001
舒张压(mmHg)	80(74~87)	72(66~77)	Z=-8.202	＜0.001
腰围(cm)	90(83~96)	81(77~86)	Z=-9.787	＜0.001
男/女(例)	98/84	25/187	χ²=80.656	＜0.001

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表 4 中青年-非肥胖组NAFLD相关因素单因素分析

因素	脂肪肝(n=113)	非脂肪肝(n=2166)	统计值	P值
FT3(pg/mL)	3.15(2.99~3.42)	3.01(2.83~3.19)	Z=-6.379	＜0.001
FT4(ng/dL)	1.19(1.12~1.28)	1.16(1.08~1.25)	Z=-3.264	0.001
T3(ng/mL)	1.08(0.95~1.19)	1.02(0.94~1.12)	Z=-3.095	0.002
T4(μg/dL)	7.40(6.41~8.30)	7.50(6.79~8.30)	Z=-0.799	0.424
TSH(μIU/mL)	1.76(1.25~2.53)	1.92(1.39~2.57)	Z=-1.170	0.242
空腹血糖(mmol/L)	5.30(4.95~5.60)	4.90(4.70~5.20)	Z=-7.439	＜0.001
尿酸(μmol/L)	307.00(252.00~358.00)	249.00(218.00~284.00)	Z=-8.449	＜0.001
总胆固醇(mmol/L)	4.77(4.22~5.27)	4.42(3.96~5.28)	Z=-4.102	＜0.001
甘油三酯(mmol/L)	1.26(0.94~2.01)	0.76(0.61~0.97)	Z=-11.207	＜0.001
高密度脂蛋白(mmol/L)	1.24(1.03~1.40)	1.49(1.30~1.68)	Z=-8.657	＜0.001
低密度脂蛋白(mmol/L)	3.03(2.49~3.62)	2.55(2.17~3.02)	Z=-6.100	＜0.001
BMI(kg/m²)	23.88(22.94~24.30)	20.45(19.20~22.06)	Z=-13.619	＜0.001
收缩压(mmHg)	117(109~129)	108(100~116)	Z=-7.753	＜0.001
舒张压(mmHg)	72(66~81)	66(61~72)	Z=-7.016	＜0.001
腰围(cm)	79(74~85)	68(64~72)	Z=-13.923	＜0.001
男/女(例)	62/51	76/2090	χ2=497.978	＜0.001

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表 5 老年-非肥胖组NAFLD相关因素单因素分析

因素	脂肪肝(n=88)	非脂肪肝(n=128)	统计值	P值
FT3(pg/mL)	3.10±0.32	2.98±0.28	t=2.929	0.004
FT4(ng/dL)	1.21(1.12~1.31)	1.16(1.11~1.25)	Z=-2.533	0.011
T3(ng/mL)	1.10(0.97~1.24)	1.07(0.97~1.19)	Z=-1.065	0.287
T4(μg/dL)	8.22±1.51	8.06±1.38	t=0.829	0.408
TSH(μIU/mL)	1.72(1.25~2.37)	1.98(1.32~2.77)	Z=-1.827	0.068
空腹血糖(mmol/L)	5.60(5.20~6.35)	5.40(5.12~5.90)	Z=-2.004	0.045
尿酸(μmol/L)	333.36±68.32	286.63±65.38	t=5.068	＜0.001
总胆固醇(mmol/L)	4.68(4.04~5.41)	5.17(4.61~5.67)	Z=-3.018	0.003
甘油三酯(mmol/L)	1.28(0.93~1.78)	1.19(0.95~1.62)	Z=-0.620	0.535
高密度脂蛋白(mmol/L)	1.28±0.34	1.53±0.42	t=-4.638	＜0.001
低密度脂蛋白(mmol/L)	2.99±0.97	3.22±0.91	t=-1.929	0.055
BMI(kg/m²)	23.08(22.18~24.29)	21.66(20.11~23.31)	Z=-4.947	＜0.001
收缩压(mmHg)	132(124~141)	128(116~141)	Z=-1.801	0.072
舒张压(mmHg)	76±10	74±10	t=2.014	0.045
腰围(cm)	84(79~89)	74(70~81)	Z=-7.432	＜0.001
男/女(例)	70/18	39/89	χ2=50.244	＜0.001

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表 6 老年-肥胖组NAFLD相关因素单因素分析

因素	脂肪肝(n=133)	非脂肪肝(n=57)	统计值	P值
FT3(pg/mL)	3.14±0.32	2.98±0.29	t=-3.370	0.001
FT4(ng/dL)	1.20±0.16	1.19±0.14	t=-0.722	0.471
T3(ng/mL)	1.14±0.15	1.12±1.17	t=-0.786	0.433
T4(μg/dL)	8.13±1.44	8.05±1.39	t=-0.321	0.748
TSH(μIU/mL)	1.84(1.33~2.40)	1.93(1.33~1.73)	Z=-0.204	0.838
空腹血糖(mmol/L)	5.80(5.40~6.45)	6.00(5.30~6.60)	Z=-0.958	0.338
尿酸(μmol/L)	359.31±81.90	309.26±77.12	t=-3.926	＜0.001
总胆固醇(mmol/L)	4.65(4.17~5.30)	4.71(4.11~5.42)	Z=-0.315	0.753
甘油三酯(mmol/L)	1.45(1.10~1.94)	1.43(1.11~1.94)	Z=-0.178	0.858
高密度脂蛋白(mmol/L)	1.13(1.01~1.30)	1.25(1.07~1.52)	Z=-2.764	0.006
低密度脂蛋白(mmol/L)	3.00(2.42~3.52)	2.96(2.51~3.76)	Z=-0.396	0.692
BMI(kg/m²)	27.10(26.03~28.49)	26.99(25.68~29.78)	Z=-0.404	0.686
收缩压(mmHg)	144(130~153)	148(133~160)	Z=-1.565	0.118
舒张压(mmHg)	81±10	77±11	t=-2.263	0.025
腰围(cm)	93±8	89±8	t=-3.368	0.001
男/女(例)	100/33	16/41	χ2=37.253	＜0.001

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表 7 中青年-肥胖组NAFLD多因素分析

因素	B值	SE	Wald χ²	P值	OR	95%CI
FT3	0.926	0.554	2.798	0.094	2.525	0.853~7.473
FT4	-2.705	1.055	6.578	0.010	0.067	0.008~0.528
T3	-0.375	0.976	0.147	0.701	0.687	0.101~4.659
空腹血糖	0.595	0.235	6.396	0.011	1.814	1.143~2.877
尿酸	0.004	0.002	2.332	0.127	1.004	0.999~1.008
甘油三酯	0.540	0.597	0.602	0.014	1.717	1.116~2.640
高密度脂蛋白	-0.463	0.088	1.179	0.438	0.629	0.195~2.028
BMI	0.096	0.021	2.723	0.278	1.101	0.926~1.309
收缩压	0.018	0.030	0.014	0.255	1.018	0.987~1.049
舒张压	0.034	0.523	8.823	0.099	1.035	0.994~1.077
腰围	0.003	2.942	17.025	0.907	1.004	0.946~1.064
男性	1.554	0.554	2.798	0.003	4.729	1.696~13.183
常数	-12.139	1.055	6.578	0.000	0.000

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表 8 中青年-非肥胖组NAFLD相关多因素分析

因素	B值	SE	Wald χ²	P值	OR	95%CI
FT3	0.720	0.492	2.140	0.143	2.053	0.783~5.384
FT4	0.442	0.934	0.224	0.636	1.556	0.250~9.695
T3	-0.516	0.834	0.383	0.536	0.597	0.116~3.061
空腹血糖	0.093	0.117	0.630	0.427	1.097	0.872~1.380
尿酸	0.000	0.002	0.045	0.832	1.000	0.996~1.005
甘油三酯	1.047	0.221	22.386	＜0.001	2.850	1.847~4.399
高密度脂蛋白	0.000	0.449	0.000	0.999	1.000	0.414~2.412
BMI	0.664	0.107	38.516	＜0.001	1.942	1.575~2.395
收缩压	0.022	0.014	2.621	0.105	1.023	0.995~1.051
舒张压	-0.014	0.020	0.476	0.490	0.986	0.949~1.025
腰围	0.020	0.029	0.458	0.499	1.020	0.963~1.081
男性	1.366	0.446	9.367	0.002	3.919	1.634~9.396
常数	-25.026	2.884	75.321	0.000	0.000

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表 9 老年-非肥胖组NAFLD相关多因素分析

因素	B值	SE	Wald χ²	P值	OR	95%CI
FT3	0.458	0.628	0.532	0.466	1.581	0.462~5.417
FT4	1.930	1.418	1.852	0.174	6.890	0.428~111.055
空腹血糖	0.159	0.119	1.790	0.181	1.173	0.929~1.481
尿酸	0.007	0.003	5.733	0.017	1.007	1.001~1.012
总胆固醇	-0.225	0.204	1.211	0.271	0.799	0.536~1.192
高密度脂蛋白	-0.354	0.543	0.425	0.514	0.702	0.242~2.035
舒张压	0.021	0.019	1.234	0.267	1.021	0.984~1.059
BMI	0.144	0.124	1.351	0.245	1.155	0.906~1.474
腰围	0.063	0.037	2.865	0.091	1.065	0.990~1.145
男性	0.948	0.493	3.702	0.054	2.580	0.983~6.775
常数	-15.844	4.054	15.277	0.000	0.000

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表 10 老年-肥胖组NAFLD相关多因素分析

因素	B值	SE	Wald χ²	P值	OR	95%CI
FT3	0.946	0.641	2.178	0.140	2.575	0.733~9.045
尿酸	0.007	0.003	6.980	0.008	1.007	1.002~1.013
高密度脂蛋白	-0.218	0.681	0.102	0.749	0.804	0.212~3.056
腰围	0.010	0.024	0.187	0.666	1.010	0.965~1.058
舒张压	0.012	0.017	0.456	0.499	1.012	0.978~1.047
男性	1.526	0.438	12.149	＜0.001	4.601	1.950~10.853
常数	-6.843	3.462	3.908	0.048	0.001

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参考文献(25)

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