肝脂肪变性和胰岛素抵抗而非脂肪性肝炎促进非酒精性脂肪性肝病中的致动脉粥样硬化血脂异常。

Hepatic Steatosis and Insulin Resistance, But Not Steatohepatitis, Promote Atherogenic Dyslipidemia in NAFLD.

作者信息

Bril Fernando, Sninsky John J, Baca Arthur M, Superko H Robert, Portillo Sanchez Paola, Biernacki Diane, Maximos Maryann, Lomonaco Romina, Orsak Beverly, Suman Amitabh, Weber Michelle H, McPhaul Michael J, Cusi Kenneth

机构信息

Divisions of Endocrinology, Diabetes, and Metabolism (F.B., P.P.S., D.B., R.L., K.C.), Gastroenterology, Hepatology, and Nutrition (A.S.), and Pathology (M.H.W.), and Pediatric Gastroenterology, Hepatology, and Nutrition (M.M.), University of Florida, Gainesville, Florida 32610; Malcom Randall Veterans Affairs Medical Center (F.B., P.P.S., D.B., R.L., A.S., M.H.W., K.C.), Gainesville, Florida 32608; Quest Diagnostics (J.J.S., A.M.B., M.J.M.), San Juan Capistrano, California 92675; Cholesterol, Genetic, and Heart Disease Institute (H.R.S.), San Mateo, California 94402; Division of Diabetes (B.O., K.C.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.

出版信息

J Clin Endocrinol Metab. 2016 Feb;101(2):644-52. doi: 10.1210/jc.2015-3111. Epub 2015 Dec 16.

DOI:10.1210/jc.2015-3111

PMID:26672634

Abstract

CONTEXT

Patients with nonalcoholic fatty liver disease (NAFLD) are at increased risk of cardiovascular disease, and atherogenic lipoproteins may play an important role.

OBJECTIVE

The objective of the study was to determine the contribution of the severity of steatohepatitis to atherogenic dyslipidemia in patients with NAFLD.

DESIGN

This was a cross-sectional study.

SETTING

The study was conducted at a university hospital.

PATIENTS

Patients were recruited from outpatient clinics or from the general population (n = 188).

INTERVENTIONS

Measurement of hepatic triglyceride content by magnetic resonance spectroscopy, histology (liver biopsy), metabolic profile by means of an oral glucose tolerance test, and lipoprotein analyses were performed.

OUTCOMES

Outcomes measured included standard lipids, lipoprotein subfraction analysis (apolipoprotein B/A1 levels, low-density lipoprotein (LDL) particle size/phenotype, and LDL/high-density lipoprotein subfractions), and insulin resistance.

RESULTS

Patients with NAFLD had severe insulin resistance, especially at the level of the adipose tissue, when compared with patients without NAFLD. Despite small differences in triglycerides and high-density lipoprotein-cholesterol, patients with NAFLD had a significantly higher plasma apolipoprotein B to apolipoprotein A1 ratio (0.66 ± 0.02 vs 0.58 ± 0.02, P = .01) and smaller LDL particle size (216.2 ± 0.7 vs 219.4 ± 1.1 Å, P = .01). Of note, these differences between patients with/without NAFLD were independent of the presence of obesity. Severity of steatohepatitis did not significantly influence the lipoprotein profile. Worse atherogenic dyslipidemia was best predicted by the degree of liver fat accumulation and adipose tissue and systemic insulin resistance.

CONCLUSIONS

NAFLD was associated with a worse atherogenic lipoprotein profile, regardless of similar body mass index and other clinical parameters. We speculate that this lipoprotein profile is driven mostly by liver fat content and insulin resistance and appears not to be worsened by obesity or the severity of liver disease (nonalcoholic steatohepatitis).

摘要

背景

非酒精性脂肪性肝病（NAFLD）患者患心血管疾病的风险增加，致动脉粥样硬化脂蛋白可能起重要作用。

目的

本研究的目的是确定脂肪性肝炎的严重程度对NAFLD患者致动脉粥样硬化血脂异常的影响。

设计

这是一项横断面研究。

地点

该研究在一家大学医院进行。

患者

患者从门诊诊所或普通人群中招募（n = 188）。

干预措施

通过磁共振波谱法测量肝脏甘油三酯含量、组织学检查（肝活检）、口服葡萄糖耐量试验评估代谢状况以及进行脂蛋白分析。

结果

与无NAFLD的患者相比，NAFLD患者存在严重的胰岛素抵抗，尤其是在脂肪组织水平。尽管甘油三酯和高密度脂蛋白胆固醇存在细微差异，但NAFLD患者的血浆载脂蛋白B与载脂蛋白A1比值显著更高（0.66±0.02对0.58±0.02，P = 0.01），低密度脂蛋白颗粒尺寸更小（216.2±0.7对219.4±1.1 Å，P = 0.01）。值得注意的是，有/无NAFLD患者之间的这些差异与肥胖的存在无关。脂肪性肝炎的严重程度并未显著影响脂蛋白谱。肝脏脂肪堆积程度、脂肪组织和全身胰岛素抵抗最能预测致动脉粥样硬化血脂异常的严重程度。