脂肪组织胰岛素抵抗可预测2型糖尿病合并非酒精性脂肪性肝病患者肝纤维化的严重程度。

Adipose Tissue Insulin Resistance Predicts the Severity of Liver Fibrosis in Patients With Type 2 Diabetes and NAFLD.

作者信息

Kalavalapalli Srilaxmi, Leiva Eddison Godinez, Lomonaco Romina, Chi Xiaofei, Shrestha Sulav, Dillard Rachel, Budd Jeffery, Romero Jessica Portillo, Li Christina, Bril Fernando, Samraj George, Pennington John, Townsend Petra, Orlando Frank, Shetty Shwetha, Mansour Lydia, Silva-Sombra Lorena Rodrigues, Bedossa Pierre, Malaty John, Barb Diana, Gurka Matthew J, Cusi Kenneth

机构信息

Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL 32610, USA.

Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA.

出版信息

J Clin Endocrinol Metab. 2023 Apr 13;108(5):1192-1201. doi: 10.1210/clinem/dgac660.

DOI:10.1210/clinem/dgac660

PMID:36378995

Abstract

CONTEXT

Although type 2 diabetes (T2D) is a risk factor for liver fibrosis in nonalcoholic fatty liver disease (NAFLD), the specific contribution of insulin resistance (IR) relative to other factors is unknown.

OBJECTIVE

Assess the impact on liver fibrosis in NAFLD of adipose tissue (adipose tissue insulin resistance index [adipo-IR]) and liver (Homeostatic Model Assessment of Insulin Resistance [HOMA-IR]) IR in people with T2D and NAFLD.

DESIGN

Participants were screened by elastography in the outpatient clinics for hepatic steatosis and fibrosis, including routine metabolites, cytokeratin-18 (a marker of hepatocyte apoptosis/steatohepatitis), and HOMA-IR/adipo-IR.

SETTING

University ambulatory care practice.

PARTICIPANTS

A total of 483 participants with T2D.

INTERVENTION

Screening for steatosis and fibrosis with elastography.

MAIN OUTCOME MEASURES

Liver steatosis (controlled attenuation parameter), fibrosis (liver stiffness measurement), and measurements of IR (adipo-IR, HOMA-IR) and fibrosis (cytokeratin-18).

RESULTS

Clinically significant liver fibrosis (stage F ≥ 2 = liver stiffness measurement ≥8.0 kPa) was found in 11%, having more features of the metabolic syndrome, lower adiponectin, and higher aspartate aminotransferase (AST), alanine aminotransferase, liver fat, and cytokeratin-18 (P < 0.05-0.01). In multivariable analysis including just clinical variables (model 1), obesity (body mass index [BMI]) had the strongest association with fibrosis (odds ratio, 2.56; CI, 1.87-3.50; P < 0.01). When metabolic measurements and cytokeratin-18 were included (model 2), only BMI, AST, and liver fat remained significant. When fibrosis stage was adjusted for BMI, AST, and steatosis (model 3), only Adipo-IR remained strongly associated with fibrosis (OR, 1.51; CI, 1.05-2.16; P = 0.03), but not BMI, hepatic IR, or steatosis.

CONCLUSIONS

These findings pinpoint to the central role of dysfunctional, insulin-resistant adipose tissue to advanced fibrosis in T2D, beyond simply BMI or steatosis. The clinical implication is that targeting adipose tissue should be the priority of treatment in NAFLD.

摘要

背景

尽管2型糖尿病（T2D）是非酒精性脂肪性肝病（NAFLD）中肝纤维化的一个危险因素，但胰岛素抵抗（IR）相对于其他因素的具体作用尚不清楚。

目的

评估脂肪组织胰岛素抵抗指数（adipo-IR）和肝脏胰岛素抵抗稳态模型评估（HOMA-IR）对T2D和NAFLD患者NAFLD肝纤维化的影响。

设计

在门诊通过弹性成像对参与者进行肝脂肪变性和纤维化筛查，包括常规代谢物、细胞角蛋白-18（肝细胞凋亡/脂肪性肝炎的标志物）以及HOMA-IR/adipo-IR。

地点

大学门诊医疗实践。

参与者

共有483名T2D患者。

干预

用弹性成像筛查脂肪变性和纤维化。

主要观察指标

肝脏脂肪变性（受控衰减参数）、纤维化（肝脏硬度测量）以及IR（adipo-IR、HOMA-IR）和纤维化（细胞角蛋白-18）的测量值。

结果

11%的患者存在临床显著性肝纤维化（F期≥2 = 肝脏硬度测量值≥8.0 kPa），这些患者有更多代谢综合征特征、较低的脂联素水平以及较高的天冬氨酸转氨酶（AST）、丙氨酸转氨酶、肝脏脂肪和细胞角蛋白-18水平（P < 0.05 - 0.01）。在仅包含临床变量的多变量分析（模型1）中，肥胖（体重指数[BMI]）与纤维化的关联最强（比值比，2.56；CI，1.87 - 3.50；P < 0.01）。当纳入代谢测量值和细胞角蛋白-18时（模型2），只有BMI、AST和肝脏脂肪仍然显著。当根据BMI、AST和脂肪变性对纤维化阶段进行调整时（模型3），只有Adipo-IR与纤维化仍有强关联（OR，1.51；CI，1.05 - 2.16；P = 0.03），而BMI、肝脏IR或脂肪变性则不然。