血清C肽在2型糖尿病合并非酒精性脂肪性肝病患者肝纤维化进展中的作用

刘佼; 任彩琴; 冯亚莉; 何继瑞

doi:10.3969/j.issn.1001-5256.2021.05.030

血清C肽在2型糖尿病合并非酒精性脂肪性肝病患者肝纤维化进展中的作用

DOI: 10.3969/j.issn.1001-5256.2021.05.030

兰州大学第二医院老年病科，兰州 730000

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：刘佼、任彩琴、冯亚莉负责课题设计，数据收集分析，撰写论文；何继瑞负责审校。

详细信息

作者简介:
刘佼(1995—)，女，主要从事糖尿病及非酒精性脂肪性肝病关系研究

通信作者:
何继瑞，hjrlzys63@163.com

中图分类号: R575.5
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出版历程
- 收稿日期: 2020-10-16
- 录用日期: 2020-11-17
- 出版日期: 2021-05-20

Association between liver fibrosis and C-peptide in patients with type 2 diabetes and nonalcoholic fatty liver disease

Department of Geriatrics, The Second Hospital of Lanzhou University, Lanzhou 730000, China

摘要

摘要: 目的探究血清C肽水平对2型糖尿病(T2DM)合并非酒精性脂肪性肝病(NAFLD)患者肝纤维化进展的影响。方法收集2018年12月—2020年7月就诊于兰州大学第二医院老年病科的484例T2DM患者，依据腹部彩超检查结果，将其分为单纯T2DM组(n=107)及T2DM合并NAFLD组(n=377)，采用NAFLD肝纤维化评分(NFS)将T2DM合并NAFLD组分为3个亚组：排除纤维化亚组(T2DM+F0组，n=136)、不确定亚组(T2DM+F1组，n=146)及纤维化亚组(T2DM+F2组，n=95)，收集纳入人群病史资料及实验室指标。计数资料组间比较采用χ²检验，计量资料两组间比较应用t检验或Mann-Whitney U检验，多组比较使用单因素方差分析或Kruskal-Wallis H检验，logistic回归分析探究促进肝纤维化进展的危险因素，采用受试者工作特征曲线(ROC)分析血清C肽在预测及诊断肝纤维化进展过程的临床价值。结果相比于单纯T2DM组，T2DM合并NAFLD组患者C肽水平明显升高(Z=-6.040，P < 0.001)，T2DM+F2组不仅C肽明显高于T2DM+F1组和T2DM+F0组[2.89(1.84~3.77) vs 1.97(1.12~2.65) vs 1.87(1.25~2.68)，H=36.023，P < 0.001]，高空腹C肽率也显著升高(56.84% vs 23.29% vs 24.27%，χ²=37.583，P < 0.001)。logistic回归分析表明，C肽(OR=1.435，95%CI：1.227~1.678，P < 0.001)是T2DM合并NAFLD患者肝维化的危险因素，ROC曲线也显示C肽对预测该类患者肝纤维化具有重要意义，曲线下面积为0.814，最佳截断值为2.405 ng/ml，灵敏度为64.2%，特异度为89.7%，约登指数为0.539。结论 C肽是T2DM合并NAFLD患者肝纤维化进展的独立危险因素。
- 糖尿病, 2型 /
- 非酒精性脂肪性肝病 /
- C肽
Abstract: Objective To investigate the effect of serum C-peptide level on the progression of liver fibrosis in patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). Methods A total of 484 patients with T2DM who were admitted to Department of Geriatrics, The Second Hospital of Lanzhou University, from December 2018 to July 2020 were enrolled, and according to the results of abdominal ultrasound examination, they were divided into simple T2DM group with 107 patients and T2DM+NAFLD group with 377 patients. According to NAFLD fibrosis score, the patients with T2DM and NAFLD were divided into fibrosis exclusion subgroup (T2DM+F0) with 136 patients, uncertain subgroup (T2DM+F1) with 146 patients, and fibrosis subgroup (T2DM+F2) with 95 patients. Medical history data and laboratory markers were collected. The chi-square test was used for comparison of categorical data; the t-test or the Mann-Whitney U test was used for comparison of continuous data, and a one-way analysis of variance or the Kruskal-Wallis H test was used for comparison between multiple groups; a logistic regression analysis was used to explore the risk factors for the progression of liver fibrosis; the receiver operating characteristic (ROC) curve was used to analyze the clinical value of serum C-peptide in predicting and diagnosing the progression of liver fibrosis. Results Compared with the simple T2DM group, the T2DM+NAFLD group had a significant increase in C-peptide level (Z=-6.040, P < 0.001); compared with the T2DM+F1 and T2DM+F0, the T2DM+F2 had significantly higher C-peptide level [2.89 (1.84-3.77) vs 1.97 (1.12-2.65)/1.87 (1.25-2.68), H=36.023, P < 0.001) and rate of fasting C-peptide (56.84% vs 23.29%/24.27%, χ²=37.583, P < 0.001). The logistic regression analysis showed that C-peptide (OR=1.435, 95% confidence interval: 1.227~1.678, P < 0.001) was a risk factor for liver fibrosis in patients with T2DM and NAFLD, and the ROC curve analysis also showed that C-peptide had great significance in predicting liver fibrosis in such patients, with an area under the ROC curve of 0.814, a sensitivity of 64.2%, a specificity of 89.7%, and a Youden index of 0.539 at the optimal cut-off value of 2.405 ng/ml. Conclusion C-peptide is an independent risk factor for the progression of liver fibrosis in patients with T2DM and NAFLD.
- Diabetes Mellitus, Type 2 /
- Non-alcoholic Fatty Liver Disease /
- C-Peptide

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图 1 血清FCP水平对T2DM合并NAFLD患者肝纤维化的预测价值

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表 1 单纯T2DM组与T2DM合并NAFLD组资料比较

指标	单纯T2DM组(n=107)	合并NAFLD组(n=377)	统计值	P值
男/女(例)	63/44	182/195	χ²=3.748	0.053
年龄(岁)	48.37±7.63	49.33±10.72	t=-0.859	0.391
T2DM病程(年)	3.00(0.94~9.00)	4.00(0.50~9.25)	Z=-0.437	0.662
BMI(kg/m²)	24.52±2.95	26.97±3.67	t=-6.338	< 0.001
AST(U/L)	20.00(16.00~25.00)	23.00(18.00~31.00)	Z=-3.092	< 0.001
ALT(U/L)	25.00(17.00~37.25)	30.50(21.00~48.00)	Z=-3.190	0.001
AST/ALT	0.78(0.61~1.00)	0.77(0.63~0.93)	Z=-0.247	0.805
FPG(mmol/L)	9.50±3.99	10.86±4.62	t=-2.778	0.006
Alb(g/L)	45.51±5.02	45.60±4.70	t=-0.175	0.861
PLT(×10⁹/L)	220.44±81.24	196.53±72.08	t=2.936	0.003
HbA1c(%)	8.47±2.02	9.18±2.22	t=-2.976	0.003
FCP(ng/ml)	1.26(0.80~1.96)	2.10(1.29~2.94)	Z=-6.040	< 0.001
FINS(mU/L)	7.82(4.46~13.77)	14.80(9.41~20.75)	Z=-7.026	< 0.001
HOMA-β	29.79(13.04~70.20)	44.12(23.63~85.58)	Z=-3.076	0.002
UA(μmol/L)	313.88±94.87	345.30±92.95	t=-3.072	0.002
CHO(mmol/L)	4.48±0.88	4.69±1.37	t=-2.189	0.029
TG(mmol/L)	1.80(1.37~2.87)	2.27(1.53~3.45)	Z=-2.656	0.008
HDL(mmol/L)	1.07±0.28	1.07±0.30	t=-0.092	0.926
LDL(mmol/L)	2.77±0.77	2.78±1.12	t=-0.161	0.873
收缩压(mm Hg)	129.95±21.58	134.55±21.11	t=-1.980	0.048
舒张压(mm Hg)	80.88±12.09	84.79±11.98	t=-2.971	0.003

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表 2 T2DM患者发生NAFLD影响因素的logistics回归分析

因素	B值	SE	统计值	OR(95%CI)	P值
FCP	0.623	0.019	27.505	1.865(1.478~2.355)	< 0.001
FINS	0.084	0.016	27.141	1.088(1.054~1.123)	< 0.001
FPG	0.077	0.028	7.463	1.080(1.022~1.141)	0.006
HbA1c	0.159	0.054	8.548	1.173(1.054~1.305)	0.003
UA	0.004	0.001	9.112	1.004 (1.001~1.006)	0.003

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表 3 T2DM合并NAFLD各纤维化亚组资料比较

指标	T2DM+F0组(n=136)	T2DM+F1组(n=146)	T2DM+F2组(n=95)	统计值	P值
男/女(例)	67/69	72/74	43/52	χ²=0.462	0.799
年龄(岁)	42.43±9.49	52.47±8.97¹⁾	54.38±9.79¹⁾	F=58.830	< 0.001
T2DM病程(年)	3.00(0.50~7.75)	4.00(0.33~9.00)	6.00(2.00~12.00)¹⁾²⁾	H=11.799	0.003
BMI(kg/m²)	25.91±3.11	26.63±2.91	28.99±4.56¹⁾²⁾	F=23.178	< 0.001
AST(U/L)	23.00(18.00~30.00)	23.00(18.00~34.00)	23.00(19.00~29.00)	H=0.080	0.961
ALT(U/L)	33.50(23.00~50.00)	30.00(22.00~49.00)	26.00(16.00~40.00)¹⁾	H=12.569	0.002
AST/ALT	0.68(0.56~0.83)	0.77(0.63~0.90)¹⁾	0.91(0.72~1.23)¹⁾²⁾	H=50.741	< 0.001
FPG(mmol/L)	10.64±4.22	10.65±4.24	11.50±5.47	F=1.227	0.294
Alb(g/L)	47.94±4.17	45.51±4.01	42.37±4.43²⁾	F=49.750	< 0.001
PLT(10⁹/L)	264.74±57.73	175.48±38.25¹⁾	127.63±39.78¹⁾²⁾	F=258.378	< 0.001
HbA1c(%)	8.95±2.12	9.46±2.15	9.06±2.42	F=2.078	0.127
FCP(ng/ml)	1.87(1.25~2.68)	1.97(1.12~2.65)	2.89(1.84~3.77)¹⁾²⁾	H=36.023	< 0.001
高FCP率(%)	24.27	23.29	56.84¹⁾²⁾	χ²=37.583	< 0.001
FINS(mU/L)	12.71(8.21~17.09)	15.20(9.12~19.45)	22.15(12.14~29.58)¹⁾²⁾	H=38.885	< 0.001
HOMA-β	38.62(19.71~78.32)	45.74(23.16~81.92)	53.31(25.78~114.32)	H=5.028	0.081
UA(μmol/L)	353.01±87.52	333.38±96.05	352.58±94.71	F=1.970	0.141
CHO(mmol/L)	4.72±1.07	4.86±1.67	4.37±1.78¹⁾	F=3.792	0.023
TG(mmol/L)	2.24(1.50~3.15)	2.30(1.58~4.22)	2.21(1.74~3.51)	H=1.932	0.381
HDL(mmol/L)	1.06±0.29	1.09±0.31	1.08±0.30	F=1.043	0.353
LDL(mmol/L)	2.87±0.90	2.82±1.25	2.60±1.17	F=1.879	0.154
收缩压(mm Hg)	131.26±18.40	134.85±18.64	138.82±26.96¹⁾	F=3.663	0.027
舒张压(mm Hg)	86.18±11.20	83.86±11.37	84.21±13.79	F=1.479	0.229
注：与T2DM+F0组相比，1)P < 0.05；与T2DM+F1组相比，2)P < 0.05。

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表 4 T2DM合并NAFLD肝纤维化进展影响因素的logistic回归分析

因素	B值	SE	统计值	OR(95%CI)	P值
FCP	0.361	0.080	20.143	1.435(1.227~1.678)	< 0.001
FINS	0.059	0.010	32.095	1.061(1.040~1.082)	< 0.001
收缩压	0.013	0.050	8.200	1.013(0.919~1.117)	0.004

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