Lecube Albert, Hernández Cristina, Genescà Joan, Simó Rafael
Diabetes Research Unit. Endocrinology Division, Institut de Recerca, Hospital Universitari Vall d'Hebron, Pg. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Diabetes Care. 2006 May;29(5):1096-101. doi: 10.2337/diacare.2951096.
The purpose of this study was to explore the initial pathogenic mechanisms of diabetes associated with hepatitis C virus (HCV) infection.
Insulin resistance, proinflammatory cytokines, and beta-cell function were evaluated in a case-control study. A total of 28 consecutive nondiabetic patients with chronic hepatitis C were included in the study (anti-HCV+). Fourteen patients with chronic hepatitis other than HCV infection served as the control group (anti-HCV-). Both groups were closely matched by the main clinical variables associated with insulin resistance and the degree of liver fibrosis. In addition, there were no differences between groups regarding hepatic insulin extraction measured by calculating the ratio between C-peptide and insulin. Serum levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha, soluble TNF receptor [sTNFR] 1, soluble TNFR2, and interleukin-6) were measured by enzyme-linked immunosorbent assay. Insulin resistance (homeostasis model assessment [HOMA] of insulin resistance [HOMA-IR]) and insulin secretion at baseline (HOMA-beta) and after various stimulus (oral glucose tolerance test, standard food intake, and intravenous glucagon) were determined by previously validated mathematic indexes.
HOMA-IR was higher in anti-HCV+ than in anti-HCV- patients (4.35 +/- 2.27 vs. 2.58 +/- 1.74; P = 0.01). All the proinflammatory cytokines analyzed were significantly higher in anti-HCV+ patients than in anti-HCV- patients. In addition, sTNFR1 and sTNFR2 were directly correlated to HOMA-IR. HOMA-beta as well as insulin and C-peptide responses after the intravenous glucagon test were significantly higher in anti-HCV+ patients than in anti-HC- patients.
Insulin resistance mediated by proinflammatory cytokines, but not a deficit in insulin secretion, could be the primary pathogenic mechanism involved in the development of diabetes associated with HCV infection.
本研究旨在探讨丙型肝炎病毒（HCV）感染相关糖尿病的初始致病机制。
在一项病例对照研究中评估胰岛素抵抗、促炎细胞因子和β细胞功能。共有28例连续的非糖尿病慢性丙型肝炎患者纳入研究（抗HCV阳性）。14例非HCV感染的慢性肝炎患者作为对照组（抗HCV阴性）。两组在与胰岛素抵抗相关的主要临床变量和肝纤维化程度方面进行了密切匹配。此外，通过计算C肽与胰岛素的比值测量的肝脏胰岛素摄取在两组之间没有差异。采用酶联免疫吸附测定法测量促炎细胞因子（肿瘤坏死因子[TNF]-α、可溶性TNF受体[sTNFR]1、可溶性TNFR2和白细胞介素-6）的血清水平。通过先前验证的数学指标确定胰岛素抵抗（胰岛素抵抗稳态模型评估[HOMA-IR]）以及基线时（HOMA-β）和各种刺激后（口服葡萄糖耐量试验、标准食物摄入和静脉注射胰高血糖素）的胰岛素分泌。
抗HCV阳性患者的HOMA-IR高于抗HCV阴性患者（4.35±2.27对2.58±1.74；P = 0.01）。抗HCV阳性患者中分析的所有促炎细胞因子均显著高于抗HCV阴性患者。此外，sTNFR1和sTNFR2与HOMA-IR直接相关。抗HCV阳性患者静脉注射胰高血糖素试验后的HOMA-β以及胰岛素和C肽反应显著高于抗HCV阴性患者。
促炎细胞因子介导的胰岛素抵抗而非胰岛素分泌不足可能是HCV感染相关糖尿病发生发展的主要致病机制。
