[1]方德刚a,肖清华b,杨 柳a,等.2 型糖尿病并发非酒精性脂肪性肝炎患者血清脂质组学分析及诊断价值研究[J].现代检验医学杂志,2023,38(03):159-164.[doi:10.3969/j.issn.1671-7414.2023.03.029]
 FANG De-ganga,XIAO Qing-huab,YANG Liua,et al.Serum Lipomics Analysis and Diagnostic Value of Type 2 Diabetes Patients with Nonalcoholic Steatohepatitis[J].Journal of Modern Laboratory Medicine,2023,38(03):159-164.[doi:10.3969/j.issn.1671-7414.2023.03.029]
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2 型糖尿病并发非酒精性脂肪性肝炎患者血清脂质组学分析及诊断价值研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年03期
页码:
159-164
栏目:
论著
出版日期:
2023-05-15

文章信息/Info

Title:
Serum Lipomics Analysis and Diagnostic Value of Type 2 Diabetes Patients with Nonalcoholic Steatohepatitis
文章编号:
1671-7414(2023)03-159-06
作者:
方德刚a肖清华b杨 柳a张晶晶a曹 珂a易林娜a
(中国人民解放军联勤保障部队第九二一医院a. 门诊;b. 肝病科,长沙410003)
Author(s):
FANG De-gangaXIAO Qing-huabYANG LiuaZHANG Jing-jingaCAO Kea YI Lin-naa
(a. Department of Outpatien; b. Department of Hepatology, No. 921 Hospital, Joint Logistics Support Force of the Chinese People’s Liberation Army,Changsha 410003, China)
关键词:
2 型糖尿病非酒精性脂肪性肝炎脂质组学血清标志物
分类号:
R587.2;R446.112
DOI:
10.3969/j.issn.1671-7414.2023.03.029
文献标志码:
A
摘要:
目的 探讨2 型糖尿病(T2DM)并发非酒精性脂肪性肝炎(nonalcoholic steatohepatitis, NASH)患者血清脂质组学分析及诊断价值。方法 选取2018 年4 月~ 2020 年4 月中国人民解放军联勤保障部队第九二一医院收治的80 例T2DM 并发非酒精性脂肪性肝病(nonalcoholic fatty liver disease, NAFLD)患者,根据肝活检结果分组,其中T2DM 并发NASH 患者38 例(NASH 组),并发非酒精性单纯性脂肪肝(NAFL)患者42 例(NAFL 组)。采用超高效液相色谱- 串联质谱法(UPLC-MS/MS) 进行血清脂质组学分析,并比较其检测结果,同时采用Logistic 逐步回归分析及受试者工作特征(ROC)曲线对T2DM 发生NASH 的潜在血清标志物进行筛选。结果 与NAFL 组比较,NASH 组碱性磷酸酶(ALP)(98.79±29.65 U/L vs 82.94±18.66U/L)、天冬氨酸氨基转移酶(AST)(32.12±13.64 U/L vs 21.33±15.51U/L)、γ- 谷氨酰基转肽酶(GGT)(86.87±24.38 U/L vs 45.06±15.22U/L)、晨起空腹血糖(FPG)(10.20±3.15mmol/L vs 7.72±1.79mmol/L)明显升高,差异具有统计学意义(t=4.176~33.168,均P<0.05);脂质学分析NASH 组磷脂酰胆碱(PC)(38∶3),PC(35∶4),PC(36∶1)a,PC(36∶1)b,PC(44∶5)、磷脂酰乙醇胺(PE)(34∶1)c,PE(34∶1)d,PE(36∶2),PE(38∶1),PE(39∶1),磷脂酰丝氨酸(PS)(33∶0)、三酰甘油(TG)(52∶1)、TG(54∶2)、鞘磷脂(SM)(37∶1),SM(39∶1),SM(40∶1)、葡萄糖神经酰胺(GlcCer)(40∶2)和棕榈酰苯丙氨酸水平均明显高于NAFL 组(VIP=1.275 ~ 3.176,均P <0.05);NASH 组PC(38∶5),PC(38∶6),TG(52∶4),TG(54∶4),TG(54∶5),TG(57∶6),TG(58∶4)和TG(60∶6)水平明显低于NAFL 组(VIP=1.086 ~ 3.086,均P <0.05);Logistic 逐步回归分析显示:PC(36∶1)a 和PE(38∶1)升高是T2DM患者进展为NASH的危险因素(P<0.05);PC(36∶1)a 和PE(38 ∶ 1)ROC 曲线下面积分别为0.814,0.792,敏感度分别为94.28%,94.86%,特异度分别为77.65%,76.31%,均高于GGT,AST 和ALT。结论 T2DM 并发NASH 患者,出现变化的主要脂质是甘油磷脂、鞘脂和TG,其中PC(36∶1),PE(38∶1)可能成为诊断NASH 的潜在血清标志物。
Abstract:
Objective To investigate the value of serum lipoomics analysis and diagnosis in type 2 diabetes mellitus (T2DM) patients with nonalcoholic steatohepatitis (NASH).Methods 80 patients with T2DM combined with nonalcoholic fatty liver disease (NAFLD) admitted to the 921st Hospital, Joint Logistics Support Force of the Chinese People’s Liberation Army from April 2018 to April 2020, and grouped on the liver biopsy results. Among them, 38 patients with T2DM combined with NASH (NASH group), and 42 patients with non-alcoholic simple fatty liver disease (NAFL)(NAFL group).The serum lipids were analyzed by ultra-high performance liquid chromatography-mass spectrometry and the detection results were compared. At the same time, the potential serum markers of NASH in T2DM were screened by logistic stepwise regression analysis and subject working characteristics (ROC). Results Compared with NAFL group, in NASH group, ALP (98.79 ± 29.65 U/L vs 82.94 ± 18.66 U/L),AST (32.12 ± 13.64 U/L vs 21.33 ± 15.51 U/L),γ- GGT (86.87 ± 24.38 U/L vs 45.06 ± 15.22U/L) and FPG (10.20 ± 3.15 mmol/L vs 7.72 ± 1.79 mmol/L) increased significantly in the morning, with significant difference (t=4.176 ~ 33.168, all P<0.05). Lipographic analysis of NASH group phosphatidylcholine (PC) (38 ∶3), PC (35 ∶4),PC(36∶1)a, PC (36∶1)b, PC (44∶5), phosphatidylethanolamine (PE) (34∶1)c, PE (34∶1)d, PE (36∶2), PE (38∶1), PE (39∶1), phosphatidylserine (PS) (33 ∶ 0), triacylglycerol (TG) (52∶1), TG (54∶2), sphingomyelin (SM) (37∶1), SM (39∶1), SM (40∶1). The levels of glucose ceramide (GlcCer) (40∶2) and palmitoyl phenylalanine were significantly higher than those in NAFL group (VIP=1.275 ~ 3.176, all P<0.05). The levels of PC (38∶5), PC (38∶6), TG (52∶4), TG (54∶4), TG (54∶5), TG (57∶6), TG (58∶4) and TG (60∶6) in NASH group were significantly lower than those in NAFL group (VIP=1.086 ~ 3.086, all P <0.05). Logistic stepwise regression analysis showed that the increase of PC (36∶1)a and PE (38∶1) was a risk factor for T2DM patients to develop NASH (P<0.05). The area under ROC curve of PC(36∶1)a and PE (38∶1) were 0.814 and 0.792, the sensitivity were 94.28% and 94.86%, and the specificity were 77.65% and 76.31%, respectively, higher than GGT, AST, ALT. Conclusion In T2DM patients with NASH, the main lipid changes were glycerophospholipid, sphingolipid and TG. PC (36∶1) and PE (38 ∶ 1) may become potential serum markers for the diagnosis of NASH.

参考文献/References:

[1] 张凯, 李全双, 程星.2 型糖尿病患者血清低清蛋白 水平对糖化清蛋白检测结果的影响[J]. 现代检验医 学杂志, 2020, 35(4): 126-129. ZHANG Kai, LI Quanshuang, CHENG Xing. Effect of serum low albumin level on the detection of glycosylated albumin in patients with type 2 diabetes mellitus[J]. Journal of Modern Laboratory Medicine,2020, 35(4): 126-129.
[2] COTTER T G, RINELLA M. Nonalcoholic fatty liver disease 2020: the state of the disease[J]. Gastroenterology, 2020, 158(7): 1851-1864.
[3] 何丽婷, 艾竹, 向之明. 人体成分分析技术在评估 非酒精性脂肪肝中的应用价值[J]. 现代医院, 2019,19(8): 1157-1160, 1165. HE Liting, AI Zhu, XIANG Zhiming. Application value of human body composition analysis technology in the evaluation of nonalcoholic fatty liver disease [J]. Modern Hospitals, 2019, 19(8): 1157-1160, 1165.
[4] 覃俊媛, 李梦婷, 杨雪, 等.赶黄草总黄酮对非酒精 性脂肪肝小鼠肝功能和脂质代谢的影响[J]. 成都中 医药大学学报, 2017, 40(4): 33-36. QIN Junyuan, LI Mengting, YANG Xue, et al. Effects of total flavonoids of penthorum chinense pursh on liver function and lipid metabolism for non-alcoholic fatty liver disease in mice [J]. Journal of Chengdu University of Traditional Chinese Medicine, 2017, 40(4): 33-36.
[5] 于娜, 杨泽宇, 吕学燕. 酒精性脂肪肝代谢因子研究 进展[J]. 江苏科技信息: 学术研究, 2018, 35(27): 46-48. YU Na, YANG Zeyu, L? Xueyan. Research progress of alcoholic fatty liver disease metabolic factors [J]. Jiangsu Science & Technology Information, 2018,35(27): 46-48.
[6] 佟之复, 张见麟. 糖尿病诊断标准[J]. 疾病监测,1999, 14(1): 27-31. TONG Zhifu, ZHANG Jianlin. Diagnostic criteria for diabetes[J]. Disease Surveillance, 1999, 14(1): 27-31.
[7] 中华医学会肝脏病学分会脂肪肝和酒精性肝病学 组. 非酒精性脂肪性肝病诊疗指南(2010 年1 月修 订)[J] . 中华内科杂志,2010,49( 3 ): 275-278. The Chinese National Workshop on Fatty Liver and Alcoholic Liver disease for the Chinese Liver Disease Association. Guidelines for management of nonalcoholic fatty liver disease(Revised in January 2010)[J]. Chinese Journal of Internal Medicine, 2010,49(3): 275-278.
[8] GODINEZ-LEIVA E, BRIL F. Nonalcoholic fatty liver disease (NAFLD) for primary care providers: beyond the liver[J]. Current Hypertension Reviews, 2021,17(2): 94-111.
[9] HA N B , LE R H , TRINH S , et al. Sa1613 Clinical characteristics and long-term outcomes in patients with nonalcoholic fatty liver disease (NAFLD) among the spectrum of obesity: A long-term longitudinal study[J]. Gastroenterology, 2019, 156(6):S-1253.
[10] 石小举, 郑倩倩, 牛俊奇, 等. 脂质组学在原发性肝 癌中的研究进展[J]. 中华肝脏病杂志, 2019, 27(10): 809-812. SHI Xiaoju, ZHENG Qianqian, NIU Junqi, et al. Research progress of lipolipomics in primary hepatocellular carcinoma[J]. Chinese Journal of Hepatology, 2019, 27(10): 809-812.
[11] 杨琴, 曾祥士, 代东伶.儿童非酒精性脂肪性肝病 相关的脂质代谢基因变异及生物学信息分析[J]. 中 华实用儿科临床杂志, 2019, 34(19): 1458-1461. YANG Qin, ZENG Xiangshi, DAI Dongling. Genetic variation and biological information analysis of lipid metabolism associated with non-alcoholic fatty liver disease in children[J]. Chinese Journal of Applied Clinical Pediatrics, 2019, 34(19): 1458-1461.
[12] YOUNOSSI Z M. Non-alcoholic fatty liver disease – A global public health perspective[J]. Journal of Hepatology, 2019, 70(3): 531-544.
[13] 韩静, 苏胜偶, 李亚伟, 等.老年2 型糖尿病合并非 酒精性脂肪肝血清nesfatin-1 变化及其影响因素[J]. 临床输血与检验, 2017, 19(2): 158-162. HAN Jing, SU Shengou, LI Yawei, et al. The relationship between serum nesfatin-1 level and lnsulin resistance in patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease[J]. Journal of Clinical Transfusion and Laboratory Medicine, 2017, 19(2): 158-162.
[14] 路晓茅, 张洁, 邸阜生.2 型糖尿病单纯性脂肪肝与 非酒精性脂肪性肝炎患者血清脂质组学的变化[J]. 中华糖尿病杂志, 2020, 12(1): 41-47. LU Xiaomao, ZHANG Jie, DI Fusheng. Serum lipidomics in type 2 diabetes mellitus patients with simple fatty liver or nonalcoholic steatohepatitis[J]. Chinese Journal of Diabetes Mellitus, 2020, 12(1): 41- 47.
[15] 李昊翔, 徐梦娇, 袁婧, 等.2 型糖尿病合并非酒精 性脂肪肝患者血清白脂素浓度变化及其影响因素 [J]. 江苏大学学报(医学版), 2019, 29(1): 62-66. LI Haoxiang, XU Mengjiao, YUAN Jing, et al. Changes of serum leucolipin concentration and its influencing factors in patients with type 2 diabetes mellitus complicated with nonalcoholic fatty liver[J]. Journal of Jiangsu University(Medicine Edition), 2019, 29(1): 62-66.
[16] 阮雄中, 陈压西. 代谢性炎症与非酒精性脂肪性 肝病的发生与发展[J]. 中华消化杂志, 2020, 40(9): 581-584. RUAN Xiongzhong, CHEN Yaxi. Metabolic inflammation and the development of non-alcoholic fatty liver disease[J]. Chinese Journal of Digestion,2020, 40(9): 581-584.
[17] 陈冲, 丁世华, 吴东海, 等.塞来昔布对非酒精性脂 肪肝小鼠模型的肝脏脂质堆积及Akt 磷酸化水平的 影响[J]. 现代消化及介入诊疗, 2019, 24(12): 1412- 1416. CHEN Chong, DING Shihua, WU Donghai, et al. Effect of Celecoxib on lipid accumulation and Akt phosphorylation in non-alcoholic fatty liver of mice[J]. Modern Digestion & Intervention, 2019, 24(12): 1412- 1416.
[18] 曾钗明, 陈建康, 李兴华, 等. 慢性乙型肝炎合并非 酒精性脂肪肝的临床和实验室特征[J]. 中国医学创 新, 2019, 16(35): 136-141. ZENG Chaiming, CHEN Jiankang, LI Xinghua, et al. Clinical and laboratory characteristics of chronic hepatitis B complicated with nonalcoholic fatty liver disease[J]. Medical Innovation of China, 2019, 16(35): 136-141.
[19] 关阳, 陈金军, 邓红. 非酒精性脂肪性肝病患者人 体脂肪成分指标的变化[J]. 实用肝脏病杂志, 2018,21(2): 229-232. GUAN Yang, CHEN Jinjun, DENG Hong. Body compositions in patients with nonalcoholic fatty liver disease[J]. Journal of Practical Hepatology, 2018,21(2): 229-232.
[20] 杨蕊旭, 胡春秀, 宓余强, 等. 非酒精性脂肪性肝病 患者血清脂质组学研究[J]. 中华肝脏病杂志, 2017,25(2): 122-127. YANG Ruixu, HU Chunxiu, MI Yuqiang, et al. A serum lipidomic study of patients with non-alcoholic fatty liver disease[J]. Chinese Journal of Hepatology, 2017,25(2): 122-127.

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备注/Memo

备注/Memo:
作者简介:方德刚(1967-),男,本科,副主任医师,研究方向:门诊管理及健康管理,E-mail: degang921@163.com。
更新日期/Last Update: 2023-05-15