Chatila R, West A B
Department of Internal Medicine, Yale University, New Haven, Connecticut, USA.
Medicine (Baltimore). 1996 Nov;75(6):327-33. doi: 10.1097/00005792-199611000-00003.
In adults with diabetes mellitus, hepatomegaly and abnormalities of liver enzymes occur as a consequence of hepatocellular glycogen accumulation, as has been well described in children. During periods of hyperglycemia glucose freely enters the hepatocytes driving glycogen synthesis, which is augmented further by administration of insulin to supraphysiologic levels. The accumulation of excessive amounts of glycogen in the hepatocytes is a function of intermittent episodes of hyperglycemia and hypoglycemia and the use of excessive insulin. Hepatic glycogenosis occurs in patients with poorly controlled insulin-dependent type I or type II diabetes. The clinical manifestations of this phenomenon may include abdominal pain and obstructive symptoms such as early satiety, nausea, and vomiting. Ascites has rarely been reported. The typical biochemical findings are mildly to moderately elevated aminotransferases, with or without mild elevations of alkaline phosphatase. Liver synthetic function is usually normal. All these abnormalities, including the hepatomegaly, are readily reversible with sustained euglycemic control. The other major cause of hepatomegaly in patients with diabetes is steatosis. This is a function of the body habitus and state of insulin resistance rather than glycemic control. However, the distinction between steatosis and glycogenosis is important: whereas steatosis may progress to fibrosis and cirrhosis, glycogenosis does not, but reflects the need for better diabetic control. Glycogenosis and steatosis cannot be distinguished reliably on ultrasound examination. The histology, however, is definitive. In glycogenosis, as in primary glycogen storage diseases, there is excess glycogen in the cytoplasm, and often also in the nucleus, of hepatocytes. The hepatocytes throughout the lobule appear pale and swollen with clearly defined cell boundaries. Ultrastructural examination reveals cytoplasmic glycogen in clumps displacing organelles to the periphery of the cell, and there is little if any steatosis. We have shown that hepatomegaly due to glycogenosis in adults with diabetes is similar in all respects to the condition seen in children. As in children, liver enzyme abnormalities are unreliable in predicting the presence or the extent of glycogenosis. Hepatic glycogenosis can occur at any age, and therefore should be included in the differential diagnosis of hepatomegaly in all insulin-requiring diabetics.
在成年糖尿病患者中，肝细胞糖原蓄积会导致肝肿大和肝酶异常，这在儿童中已有详尽描述。在高血糖期间，葡萄糖可自由进入肝细胞，促使糖原合成，而将胰岛素剂量提升至超生理水平会进一步增强糖原合成。肝细胞中过量糖原的蓄积是高血糖和低血糖间歇性发作以及过量使用胰岛素的结果。肝糖原贮积症发生于胰岛素依赖型Ⅰ型或Ⅱ型糖尿病控制不佳的患者。这一现象的临床表现可能包括腹痛以及诸如早饱、恶心和呕吐等梗阻症状。腹水鲜有报道。典型的生化检查结果是转氨酶轻度至中度升高，碱性磷酸酶可有或无轻度升高。肝脏合成功能通常正常。所有这些异常，包括肝肿大，在持续血糖正常控制后都很容易逆转。糖尿病患者肝肿大的另一个主要原因是脂肪变性。这取决于身体体型和胰岛素抵抗状态，而非血糖控制情况。然而，区分脂肪变性和糖原贮积症很重要：脂肪变性可能进展为纤维化和肝硬化，而糖原贮积症不会，但反映了需要更好地控制糖尿病。在超声检查中无法可靠地区分糖原贮积症和脂肪变性。然而，组织学检查具有决定性意义。在糖原贮积症中，如同原发性糖原贮积病一样，肝细胞的细胞质中存在过量糖原，细胞核中往往也有。整个小叶的肝细胞看起来苍白且肿胀，细胞边界清晰。超微结构检查显示细胞质中的糖原聚集成团，将细胞器挤向细胞周边，几乎没有脂肪变性。我们已经表明，成年糖尿病患者因糖原贮积症导致的肝肿大在各方面都与儿童所见情况相似。与儿童一样，肝酶异常在预测糖原贮积症的存在或程度方面并不可靠。肝糖原贮积症可发生于任何年龄，因此在所有需要胰岛素治疗的糖尿病患者肝肿大的鉴别诊断中都应考虑到。
