Relationship Between Disease Severity, Hyperinsulinemia, and Impaired Insulin Clearance in Patients With Nonalcoholic Steatohepatitis
Relationship Between Disease Severity, Hyperinsulinemia, and Impaired Insulin Clearance in Patients With Nonalcoholic Steatohepatitis
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DOI：
10.1002/hep.26988
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发表时间：
2014-06-01
期刊：
影响因子：
13.5
通讯作者：
Cusi, Kenneth
中科院分区：
文献类型：
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作者：
Bril, Fernando;Lomonaco, Romina;Cusi, Kenneth
高胰岛素血症被认为在非酒精性脂肪性肝炎（NASH）和相关心血管风险的发病机制中起关键作用。然而，胰岛素清除率对高胰岛素血症的相对贡献及其与肝组织学的关系尚未得到仔细评估。为了检验这一点，我们招募了190名患者（32名无非酒精性脂肪肝[NAFLD]，36名单纯性脂肪变性[SS]，122名活检证实的NASH）。通过口服葡萄糖耐量试验估计胰岛素分泌和肝脏胰岛素清除率，而在正常血糖胰岛素钳夹期间测量外周胰岛素敏感性和全身胰岛素清除率。进行肝活检以评估组织学（分级/分期）。与SS患者相比，NASH患者的肝脏胰岛素敏感性相似，但脂肪组织胰岛素抵抗更严重，高胰岛素血症更严重。SS和NASH患者有相似的减少30%（P
Hyperinsulinemia is believed to play a key role in the pathogenesis of nonalcoholic steatohepatitis (NASH) and associated cardiovascular risk. However, the relative contribution of insulin clearance to hyperinsulinemia and its relationship to liver histology have not been carefully evaluated before. To examine this, we enrolled 190 patients (32 without nonalcoholic fatty liver disease [NAFLD], 36 with simple steatosis [SS], and 122 with biopsy-proven NASH). Insulin secretion and hepatic insulin clearance were estimated by means of an oral glucose tolerance test, whereas peripheral insulin sensitivity and whole-body insulin clearance were measured during a euglycemic insulin clamp. A liver biopsy was performed to assess histology (grade/stage). Patients with NASH had similar hepatic insulin sensitivity, compared to patients with SS, but more severe adipose tissue insulin resistance and worse hyperinsulinemia. Patients with SS and NASH had a similar similar to 30% reduction (P