Abstract:
The association between chronic HCV infection and type 2 diabetes mellitus (T2DM) has been established; however, there is limited research on β-cell function particularly in the pre-diabetic population. Here, we evaluated indices of β-cell function and insulin sensitivity across the spectrum from normal glucose tolerance to T2DM in individuals with and without chronic hepatitis C (CHC), and the effects of antiviral treatments on these variables. A total of 153 non-cirrhotic, non-fibrotic CHC patients with a BMI <25 were enrolled in the study. Among them, 119 were successfully treated with either direct acting antiviral (DAA) drugs or pegylated interferon/ribavirin (IFN/RBV) anti-HCV therapy. Fasting state- and oral glucose tolerance test (OGTT)-derived indexes were used to evaluate β-cell function and insulin sensitivity. Among all subjects, 19 (13%) had T2DM and 21% exhibited pre-diabetes including 8% isolated impaired fasting glucose (IFG) and 13% combined IFG and impaired glucose tolerance (IGT). Early and total insulin secretion adjusted for the degree of insulin resistance were decreased in pre-diabetic CHC patients compared to HCV-uninfected individuals. Viral eradication through DAA or IFN/RBV therapy demonstrated positive impacts on insulin sensitivity and β-cell function in CHC patients who achieved sustained virologic response (SVR), regardless of fasting or OGTT state. These findings emphasize the role of HCV in the development of β-cell dysfunction, while also suggesting that viral eradication can improve insulin secretion, reverse insulin resistance, and ameliorate glycemic control. These results have important implications for managing pre-diabetic CHC patients and could prevent diabetes-related clinical manifestations and complications.
摘要:
慢性HCV感染与2型糖尿病(T2DM)之间的关联已经建立;然而,对β细胞功能的研究有限,特别是在糖尿病前期人群中。这里,我们评估了有或没有慢性丙型肝炎(CHC)的个体从正常糖耐量到T2DM的β细胞功能和胰岛素敏感性指标,以及抗病毒治疗对这些变量的影响。总共153例非肝硬化,BMI<25的非纤维化CHC患者纳入研究.其中,用直接作用抗病毒(DAA)药物或聚乙二醇化干扰素/利巴韦林(IFN/RBV)抗HCV治疗成功治疗了119例。空腹状态和口服葡萄糖耐量试验(OGTT)衍生指标用于评估β细胞功能和胰岛素敏感性。在所有科目中,19(13%)患有T2DM,21%表现出糖尿病前期,包括8%的空腹血糖受损(IFG)和13%的IFG和糖耐量受损(IGT)。与未感染HCV的个体相比,糖尿病前期CHC患者根据胰岛素抵抗程度调整后的早期和总胰岛素分泌降低。通过DAA或IFN/RBV治疗根除病毒显示对实现持续病毒学应答(SVR)的CHC患者的胰岛素敏感性和β细胞功能有积极影响。无论禁食或OGTT状态。这些发现强调了HCV在β细胞功能障碍发展中的作用,同时也表明根除病毒可以改善胰岛素分泌,逆转胰岛素抵抗,并改善血糖控制。这些结果对管理糖尿病前期CHC患者具有重要意义,并可以预防糖尿病相关的临床表现和并发症。