非酒精性脂肪性肝病的糖尿病和非糖尿病患者存在肠促胰岛素效应受损和空腹高胰高血糖素血症。

Diabetic and nondiabetic patients with nonalcoholic fatty liver disease have an impaired incretin effect and fasting hyperglucagonaemia.

机构信息

Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.

Department of Biomedical Science, NNF Centre for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

J Intern Med. 2016 May;279(5):485-93. doi: 10.1111/joim.12462. Epub 2016 Jan 5.

DOI:10.1111/joim.12462

PMID:26728692

Abstract

OBJECTIVE

We evaluated whether patients with histologically verified nonalcoholic fatty liver disease (NAFLD) have an impaired incretin effect and hyperglucagonaemia.

METHODS

Four groups matched for age, sex and body mass index were studied: (i) 10 patients with normal glucose tolerance and NAFLD; (ii) 10 patients with type 2 diabetes and NAFLD; (iii) eight patients with type 2 diabetes and no liver disease; and (iv) 10 controls. All participants underwent a 50-g oral glucose tolerance test (OGTT) and an isoglycaemic intravenous glucose infusion (IIGI). We determined the incretin effect by relating the beta cell secretory responses during the OGTT and IIGI. Data are presented as medians (interquartile range), and the groups were compared by using the Kruskal-Wallis test.

RESULTS

Controls exhibited a higher incretin effect [55% (43-73%)] compared with the remaining three groups (P < 0.001): 39% (44-71%) in the nondiabetic NAFLD patients, 20% (-5-50%) in NAFLD patients with type 2 diabetes, and 2% (-8-6%) in patients with type 2 diabetes and no liver disease. We found fasting hyperglucagonaemia in NAFLD patients with [7.5 pmol L(-1) (6.8-15 pmol L(-1))] and without diabetes [7.5 pmol L(-1) (5.0-8.0 pmol L(-1))]. Fasting glucagon levels were lower but similar in patients with type 2 diabetes and no liver disease [4.5 pmol L(-1) (3.0-6.0 pmol L(-1))] and controls [3.4 pmol L(-1) (1.8-6.0 pmol L(-1) )]. All groups had similar glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide responses.

CONCLUSIONS

Patients with NAFLD have a reduced incretin effect and fasting hyperglucagonaemia, with the latter occurring independently of glucose (in)tolerance.

摘要

目的

我们评估了组织学证实的非酒精性脂肪性肝病（NAFLD）患者是否存在肠促胰岛素效应受损和高胰高血糖素血症。

方法

我们研究了四组年龄、性别和体重指数相匹配的患者：（i）10 例糖耐量正常和 NAFLD 的患者；（ii）10 例 2 型糖尿病和 NAFLD 的患者；（iii）8 例 2 型糖尿病和无肝病的患者；和（iv）10 例对照者。所有参与者都接受了 50g 口服葡萄糖耐量试验（OGTT）和等血糖静脉葡萄糖输注（IIGI）。我们通过将 OGTT 和 IIGI 期间的胰岛β细胞分泌反应相关联来确定肠促胰岛素效应。数据以中位数（四分位数间距）表示，使用 Kruskal-Wallis 检验比较各组。

结果

对照组表现出更高的肠促胰岛素效应[55%（43-73%）]，与其余三组相比（P<0.001）：2 型糖尿病无 NAFLD 患者为 39%（44-71%），2 型糖尿病合并 NAFLD 患者为 20%（-5-50%），2 型糖尿病且无肝病的患者为 2%（-8-6%）。我们发现，NAFLD 患者的空腹胰高血糖素升高[7.5pmol/L（6.8-15pmol/L）]，无论是否合并糖尿病[7.5pmol/L（5.0-8.0pmol/L）]。2 型糖尿病且无肝病的患者的空腹胰高血糖素水平较低，但与对照组相似[4.5pmol/L（3.0-6.0pmol/L）]和对照组[3.4pmol/L（1.8-6.0pmol/L）]。所有组的胰高血糖素样肽-1 和葡萄糖依赖性胰岛素释放多肽反应相似。