血清GGT、ALT对2型糖尿病早期诊断价值的初步探讨

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申春梅, 王龙武, 王妹芳. 血清GGT、ALT对2型糖尿病早期诊断价值的初步探讨. 25(5): 349-351
SHEN Chunmei, WANG Longwu, WANG Meifang. Preliminary investigation on the value of serum GGT and ALT for the early diagnosis of type 2 diabetes mellitus. Labratory Medicine, 25(5): 349-351 复制到剪切板

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《检验医学》编辑部

血清GGT、ALT对2型糖尿病早期诊断价值的初步探讨

申春梅, 王龙武, 王妹芳

复旦大学附属上海市第五人民医院检验科,上海 200240

作者简介：申春梅,女,1979年生,硕士,技师,主要从事分子生物学检验工作。

摘要

目的

探讨血清γ-谷氨酰基转移酶(GGT)、丙氨酸氨基转移酶(ALT)对2型糖尿病早期诊断的临床应用价值。

方法

采用Roche Modular全自动生化分析仪及配套试剂检测200例2型糖尿病患者(男、女各100例)及200名正常对照者的血清葡萄糖(Glu)、GGT和ALT水平,并进行统计分析。

结果

2型糖尿病患者男性及女性的Glu、GGT水平与对照组比较,差异均有统计学意义( P<0.05),而ALT则无差异;男性和女性2型糖尿病患者中GGT浓度超出参考区间的百分率分别是13%和16%,明显高于对照组。

结论

GGT对于2型糖尿病的早期诊断有一定意义。

关键词: γ-谷氨酰基转移酶; 丙氨酸氨基转移酶; 2型糖尿病

中图分类号:Q555 文献标志码:A 文章编号:1673-8640(2010)05-0349-03

Preliminary investigation on the value of serum GGT and ALT for the early diagnosis of type 2 diabetes mellitus

SHEN Chunmei, WANG Longwu, WANG Meifang

Department of Clinical Laboratory, Shanghai Fifth People's Hospital , Fudan University ,Shanghai 200240,China

Abstract

Objective

To investigate the clinical application value of serum gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) for the early diagnosis of type 2 diabetes mellitus.

Methods

200 patients with type 2 diabetes mellitus were enrolled in experiment group(100 males and 100 females). 200 healthy subjects were enrolled as control group. The levels of serum glucose (Glu), GGT and ALT of patients and healthy subjects were detected by Roche Modular automatic biochemistry analyzer system and the results were analyzed statistically.

Results

The difference of serum Glu and GGT between experiment group and control group had statistical significance( P<0.05). There was no difference of ALT between experiment group and control group. The abnormality rates of GGT among male and female patients with type 2 diabetes mellitus were 13% and 16% respectively, which were higher than those in control group.

Conclusions

GGT may be a marker for the early diagnosis of type 2 diabetes mellitus.

Keyword: Gamma-glutamyltransferase; Alanine aminotransferase; Type 2 diabetes mellitus

Show Figures

肝酶谱长期以来被认为是肝胆功能紊乱的指标, 其中丙氨酸氨基转移酶(ALT)是反映肝损伤较为敏感的指标, 而γ -谷氨酰基转移酶(GGT)多被用作酒精性肝损伤的指标。目前国外开展的研究表明GGT 或ALT是2型糖尿病的一个独立预测因素^[1~3], Lee等^[4]的研究提示血清GGT在其生理范围内浓度的增加可作为糖尿病发生的一个敏感和早期的生物学标记。我们旨在探讨2型糖尿病患者血清GGT、 ALT的变化, 为研究2型糖尿病的早期诊断提供参考依据。

材料和方法

一、仪器和试剂

Roche Modular4P全自动生化分析仪及Roche原装试剂(批号:血糖为696778-01; GGT为606451-01; ALT为600455-01); 校准品为Roche cfas(批号:180124-01); 室内质控品为Beckman公司产品(批号:L1为M802291, L3为 M802293)。

二、研究对象

2型糖尿病组为2007至2009年间复旦大学附属上海市第五人民医院诊治的2型糖尿病患者共200例, 男、女各100例, 年龄48~90岁。剔除慢性病毒性肝炎、自身免疫性肝病、药物性肝病和其他遗传性疾病所致的肝病和大量饮酒者。正常对照组为同期在复旦大学附属上海市第五人民医院参加体检的人员200名, 男、女各100名, 年龄50~86岁, 根据体检结论剔除有明确心、脑血管、内分泌等疾病和各种肝病患者。

三、2型糖尿病诊断标准

1. 出现糖尿病症状, 随机血浆葡萄糖(Glu)浓度≥ 11.1 mmol/L(200 mg/dL)。

2. 空腹血浆Glu(FPG)浓度≥ 7.0 mmol/L(126 mg/dL), 空腹指至少8 h内无含热量食物的摄入。

3. 口服Glu耐量试验(OGTT) 2 h血浆Glu浓度≥ 11.1 mmol/L(200 mg/dL)。试验应按世界卫生组织(WHO)的要求进行, 受试者服用的糖量相当于溶于水的75 g无水Glu。

四、方法

用普通真空采血管采取2型糖尿病组及正常对照组受试者清晨空腹静脉血3 mL, 待血液凝固后, 3 500 r/min(离心半径为15 cm)离心10 min, 分离血清, 并于2 h内完成Glu、GGT和ALT水平的检测。当日样本测定前进行质控品测定, 结果在控时再进行样本测定, 并同时加带质控品。2次质控结果均在控时, 视当日样本测定结果有效。本实验室GGT参考区间为5~58 U/L, 将GGT浓度分为6个水平进行分析, 分别为5~19、20~29、30~39、40~49、50~58、> 58 U/L。

五、统计学方法

2型糖尿病组GGT 和ALT数据呈偏态分布, 用中位数(范围)表示, 采用非参数检验。Glu数据呈正态分布, 用 $\begin{matrix} \bar{x} \end{matrix}$ ± s表示, 采用t检验。率的比较采用Fisher确切概率法。用SPSS 13.0统计学软件分析数据, P< 0.05为差异有统计学意义。

结果

一、男性和女性2型糖尿病组及正常对照组中的各项指标见表1。男性及女性的Glu和GGT水平在2型糖尿病组和对照组之间差异均有统计学意义(P< 0.05), ALT在2组之间差异均无统计学意义(P> 0.05)。

二、2型糖尿病组及正常对照组各GGT水平的例数见表2。女性2型糖尿病组中30~39、40~49、50~58及> 58 U/L 4个浓度水平的例数均多于正常对照组; 男性2型糖尿病组中40~49、50~58及> 58U/L 3个浓度水平的例数多于正常对照组。男性和女性2型糖尿病组中GGT浓度超出参考区间的百分率分别是13%和16%, 明显高于正常对照组(P< 0.05)。

表1 2型糖尿病组和正常对照组Glu、GGT和ALT水平比较

表2 男性及女性2型糖尿病组和正常对照组GGT浓度分布情况

讨论

本研究从横断面比较了2型糖尿病组和对照组GGT及ALT的水平, 研究结果提示2型糖尿病患者血清GGT水平明显高于正常对照组, 而ALT在2组之间无差异。但其他一些研究提示ALT和 GGT均是2型糖尿病的预测因素, 但ALT的预测作用低于GGT^{[1, 5]}。一项对尼日利亚2型糖尿病患者的研究结果也提示GGT和ALT显著增高较为常见^[6]。本研究结果与以上文献的差异一方面可能与ALT没有潜在抗氧化功能有关, 另外可能与国外的相关研究多为流行病学的前瞻性研究, 其选择的人数较多、追踪时间较长有关。Lee等^[4]的研究提示血清GGT在其生理范围内浓度的增加可作为糖尿病发生的一个敏感和早期的生物学标记, 结合表2数据考虑在后续的研究中开展对GGT水平较高但未超出参考区间的部分人群进行随访, 进一步探讨GGT在2型糖尿病早期诊断的价值。

2型糖尿病患者血清GGT浓度增高可能与体内发生氧化应激有关, 高血糖、高血脂导致在代谢过程中线粒体产生大量活性氧, 其可损坏线粒体功能, 引起氧化应激反应。活性氧作为一种信号分子, 能够激活很多细胞内应激通路, 导致胰岛素抵抗、β 细胞损伤和β 细胞分泌缺陷^[7]。现在, 氧化应激被认为是造成糖尿病及其并发症、肺纤维化、癫痫、高血压、动脉粥样硬化、癌症、肾病变和帕金森症等疾病的重要原因。GGT属氧化还原酶类, 是细胞内抗氧化的重要成分, 位于多数细胞的外表面并且传递谷胱甘肽的摄取。GGT升高很可能是体内氧化应激的一项指标, 提示可能存在氧自由基活性等对多种细胞的损伤。虽然GGT长期以来被认为是一个肝胆功能紊乱以及酒精性肝损伤的指标, 但国外一些研究表明血清 GGT水平增高是代谢综合征, 特别是糖耐量受损或糖尿病的独立预测因素^[8]。因此GGT有望成为组织损伤的预示性指标, 其临床价值不仅仅限于肝胆疾病。

通过本研究及相关文献可提示GGT可能会成为一个预测2型糖尿病的辅助指标, 其检测方便, 费用低廉, 对于监测糖尿病高危人群及中老年人群中2型糖尿病的发生和发展有一定意义。

The authors have declared that no competing interests exist.

参考文献

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[1]	Vozarova B, Stefan N, Lindsay RS, et al. High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes[J]. Diabetes, 2002, 51(6): 1889-1895. [本文引用:2] [JCR: 7.895]
[2]	Kim CH, Park JY, Lee KU, et al. Association of serum gamma-glutamyltransferase and alanine aminotrans-ferase activities with risk of type 2 diabetes mellitus independent of fatty liver[J]. Diabetes Metab Res Rev, 2009, 25(1): 64-69. [本文引用:1]
[3]	Sato KK, Hayashi T, Nakamura Y, et al. Liver enzymes compared with alcohol consumption in predicting the risk of type 2 diabetes: the Kansai healthcare study[J]. Diabetes Care, 2008, 31(6): 1230-1236. [本文引用:1] [JCR: 7.735]
[4]	Lee DH, Ha MH, Kim JH, et al. Gamma-glutamyl transferase and diabetes—a 4 year follow-up study[J]. Diabetologia, 2003, 46(3): 359-364. [本文引用:2] [JCR: 6.487]
[5]	Nannipieri M, Gonzales C, Baldi S, et al. Liver enzymes, the metabolic syndrome, and incident diabetes: the Mexico City diabetes study[J]. Diabetes Care, 2005, 28(7): 1757-1762. [本文引用:1] [JCR: 7.735]
[6]	Balogun WO, Adeleye JO, Akinlade KS, et al. Fre-quent occurrence of high gamma-glutamyl transferase and alanine amino transferase among Nigerian patients with type 2 diabetes[J]. Afr J Med Med Sci, 2008, 37(2): 177-183. [本文引用:1]
[7]	Fridlyand LE, Philipson LH. Reactive species and early manifestation of insulin resistance in type 2 diabetes[J]. Diabetes Obes Metab. 2006, 8(2): 136-145. [本文引用:1] [JCR: 5.181]
[8]	Meisinger C, Löwel H, Heier M, et al. Serum gamma-glutamyltransferase and risk of type 2 diabetes mellitus in men and women from the general population[J]. J Intern Med, 2005 , 258(6): 527-535. [本文引用:1] [JCR: 6.455]

2002

7.895

0.0

... 目前国外开展的研究表明GGT 或ALT是2型糖尿病的一个独立预测因素^[1~3],Lee等^[4]的研究提示血清GGT在其生理范围内浓度的增加可作为糖尿病发生的一个敏感和早期的生物学标记 ...

... 但其他一些研究提示ALT和 GGT均是2型糖尿病的预测因素,但ALT的预测作用低于GGT^[1,5] ...

2009

0.0

. 2009, 25(1):64-69

Association of serum γ-glutamyltransferase and alanine aminotransferase activities with risk of type 2 diabetes mellitus independent of fatty liver

Chul-Hee Kim 1 ,Joong-Yeol Park 2 ,Ki-Up Lee 2 ,Jin-Ho Kim 3 andHong-Kyu Kim 3,*

1 Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea 2 Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea 3 Health Promotion Center, Asan Medical Center, Seoul, South Korea * Health Promotion Center, Asan Medical Center, 388-1 Poongnap-dong, Songpa-gu, Seoul 138-736, South Korea.

> Background Although elevated serum concentrations of γ-glutamyltrans- ferase (GGT) or alanine aminotransferase (ALT) have been associated with type 2 diabetes mellitus, it is unclear whether each is an independent predictor of type 2 diabetes or merely a surrogate marker for fatty liver or hepatic injury.

2008

7.735

0.0

2003

6.487

0.0

. 2003, 46(3):359-364 DOI:10.1007/s00125-003-1036-5

Gamma-glutamyl transferase and diabetes#cod#x02014;a 4 year follow-up study

1.Department of Preventive Medicine, College of Medicine, Kosin University, 34 Amnam-dong, Suh-gu, Pusan, Korea 602-702, , , 2.Health Care Center, Pohang Steel Company, Pohang, Korea, , , 3.Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA, , , 4.Department of Laboratory Medicine and Division of Epidemiology, School of Public Health, University of Minnesota, Minnesota, USA, , , 5.Institute for Nutrition Research, University of Oslo, Oslo, Norway, , , 6.Division of Epidemiology, School of Public Health, University of Minnesota, Minnesota, USA, , ,

Aims/Hypothesis. Gamma-glutamyltransferase (GGT) is located on the external surface of most cells and mediates the uptake of gluthathione, an important component of intracellular antioxidant defenses. An increase in GGT concentration has been regarded as a marker of alcohol consumption or liver disease. However, more subtle gradations in GGT could be informative because its expression is enhanced by oxidative stress and it could be released by several conditions inducing cellular stress. Recently, serum GGT concentrations have been associated with many cardiovascular disease risk factors or components of the insulin resistance syndrome. We did a prospective study with the hypothesis that serum GGT is a predictor of incident diabetes.

... Lee等^[4]的研究提示血清GGT在其生理范围内浓度的增加可作为糖尿病发生的一个敏感和早期的生物学标记,结合表2数据考虑在后续的研究中开展对GGT水平较高但未超出参考区间的部分人群进行随访,进一步探讨GGT在2型糖尿病早期诊断的价值 ...

2005

7.735

0.0

... 但其他一些研究提示ALT和 GGT均是2型糖尿病的预测因素,但ALT的预测作用低于GGT^[1,5] ...

2008

0.0

... 一项对尼日利亚2型糖尿病患者的研究结果也提示GGT和ALT显著增高较为常见^[6] ...

2006

5.181

0.0

. 2006, 8(2):136-145

Reactive species and early manifestation of insulin resistance in type 2 diabetes

L. E. Fridlyand andL. H. Philipson *

Department of Medicine, University of Chicago, Chicago, IL, USA * *Louis H. Philipson, Department of Medicine, MC-1027, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA. E-mail: l-philipson@uchicago.edu

> The early stages of type 2 diabetes mellitus are characterized by the development of insulin resistance (IRe) in muscle cells and adipocytes with the concomitant loss of β-cell compensation. We have extensively reviewed the literature related to metabolic and signalling pathways of reactive oxygen species (ROS) in regard to the coordinated development of oxidative stress and IRe. We considered the hypothesis that oxidative stress leads to IRe in muscle cells and adipocytes, but found that the data are more consistent with the hypothesis that the cellular mechanisms that protect against oxidative stress per se are capable of creating an ROS-dependent insulin-resistant state. Furthermore, ROS-induced mitochondrial dysfunction can lead to disruptions of lipid metabolism, increasing the intracellular lipid content, and, in addition, contribute to lipid-dependent IRe in myocytes. Together, these two ROS-activated pathways to IRe can contribute to a global state of profound resistance to insulin action. Therapeutic strategies should, therefore, be directed towards reducing insulin resistance without an increase in ROS production or concentration. Pharmacological or other approaches to IRe that result in the activation of mitochondrial biogenesis in particular could be highly beneficial in the prevention or treatment of both insulin resistance and type 2 diabetes.

... 细胞分泌缺陷^[7] ...

2005

6.455

0.0

. 2005, 258(6):527-535

Serum γ-glutamyltransferase and risk of type 2 diabetes mellitus in men and women from the general population

C. MEISINGER 1,2 ,H. LÖWEL 2 ,M. HEIER 1,2 ,A. SCHNEIDER 2 ,B. THORAND 2 andFOR THE KORA STUDY GROUP 1

1 From the Central Hospital of Augsburg, MONICA/KORA Myocardial Infarction Registry, Augsburg; 2 GSF National Research Center for Environment and Health, Institute of Epidemiology, Neuherberg; Germany * C. Meisinger MD, MPH, Central Hospital of Augsburg, MONICA/KORA Myocardial Infarction Registry, Stenglinstr. 2, D-86156 Augsburg, Germany. (fax: 0049/821/400-2838; e-mail: christa.meisinger@gsf.de ).

> Objectives. To examine gender-specific associations between γ -glutamyltransferase (GGT) and incident type 2 diabetes mellitus in a representative population-based sample in Germany.

... 虽然GGT长期以来被认为是一个肝胆功能紊乱以及酒精性肝损伤的指标,但国外一些研究表明血清 GGT水平增高是代谢综合征,特别是糖耐量受损或糖尿病的独立预测因素^[8] ...