毒理性
胰岛素在典型治疗剂量下与血清酶水平升高或临床上明显的肝损伤无关。然而，在控制不佳的1型糖尿病患者中，使用胰岛素可能导致一种称为糖原病或糖原性肝病的临床综合征，表现为不同程度的肝肿大、腹痛和血清转氨酶升高。血清ALT和AST水平从正常到正常上限的20到30倍不等。碱性磷酸酶和胆红素水平略有升高或正常。血清葡萄糖和糖化血红蛋白A1c水平始终升高，而且随着血糖控制的改善，肝脏和代谢异常会迅速缓解。与肝肿大、生长迟缓、青春期延迟和库欣样面容在儿童中相关的糖原病的严重形式被称为莫里阿克综合征。在治疗高剂量静脉葡萄糖期间胰岛素过量患者中也会发生血清酶升高的糖原病（案例1）。在接受短期高剂量糖皮质激素治疗的患者中也有报道糖原病。
糖原病的诊断可以通过肝活检确认，典型的表现为肝细胞略肿胀，胞浆苍白，细胞膜明显，用周期性酸希夫（PAS）染色显示胞浆内糖原积聚。CT成像通常显示肝脏增大和密度增高，与通常导致密度减低的肝脂肪变性形成对比。这种情况可能会复发，伴随反复的高血糖发作，但似乎不会导致慢性肝损伤、纤维化或肝硬化。因此，血清酶升高是由于明显的高血糖和间歇性或高水平胰岛素的组合，而不是由于固有的肝毒性或对胰岛素的特应性反应。该综合征最常见于控制不佳的1型糖尿病的儿童或年轻人。
可能性评分：A[H]（已知肝损伤的原因，但只有在高剂量或间歇性剂量给药并且存在高血糖的情况下才会发生）。
Insulin in typical therapeutic doses is not associated with serum enzyme elevations or with episodes of clinically apparent liver injury. However, use of insulin in poorly controlled type 1 diabetes can result in a clinical syndrome known as glycogenosis or glycogenic hepatopathy, marked by varying degrees of hepatomegaly, abdominal pain and serum aminotransferase elevations. Serum ALT and AST levels range from normal to 20 to 30 times the upper limit or normal. Alkaline phosphatase and bilirubin levels are minimally increased or normal. Serum glucose and hemoglobin A1c levels are invariably elevated, and the liver and metabolic abnormalities resolve rapidly with better glycemic control. A severe form of glycogenosis associated with hepatomegaly, growth retardation, delayed puberty and Cushingoid facies in children is known as Mauriac syndrome. Glycogenosis with serum enzyme elevations can also occur in patients with insulin overdose during treatment with high doses of intravenous glucose (Case 1). Glycogenosis has also been reported in patients recieving short-term, high-dose corticosteroids..
The diagnosis of glycogenosis can be confirmed by liver biopsy which typically shows slightly swollen hepatocytes with pale cytoplasm and accentuated cell membranes, which with periodic acid Schiff (PAS) staining demonstrates intracytoplasmic accumulation of glycogen. Imaging by CT usually shows an enlarged and hyper-dense liver in contrast to hepatic steatosis which generally causes a hypo-dense pattern. The condition can be relapsing, accompanying repeated episodes of hyperglycemia, but it does not appear to result in chronic liver injury, fibrosis or cirrhosis. Thus, the serum enzyme elevations are due to the combination of marked hyperglycemia and intermittent or high levels of insulin and not to intrinsic hepatotoxicity or an idiosyncratic reaction to insulin. The syndrome occurs most commonly in children or young adults with poorly controlled type 1 diabetes.
Likelihood score: A[H] (known cause of liver injury, but only when administered in high or intermittent doses and in the presence of hyperglycemia).
来源:LiverTox
