Hepatic glycogenosis: An underdiagnosed complication of diabetes mellitus?

Abstract

Hepatic glycogenosis (HG) is characterized by excessive glycogen accumulation in hepatocytes and represents a hepatic complication of diabetes that particularly occurs in patients with longstanding poorly controlled type 1 diabetes (T1D). HG has been reported to be a very rare disease, although it is believed to be extremely underdiagnosed because it is not possible to distinguish it from non-alcoholic fatty liver disease (NAFLD) unless a liver biopsy is performed. In contrast to HG, NAFLD is characterized by liver fat accumulation and is the more likely diagnosis for patients with type 2 diabetes and metabolic syndrome. The pathogenesis of HG involves the concomitant presence of insulin and excess glucose, which increases glycogen storage in the liver. HG is characterized by a transient elevation in liver transaminases and hepatomegaly. Differentiating between these two conditions is of the utmost importance because HG is a benign disease that is potentially reversible by improving glycemic control, whereas NAFLD can progress to cirrhosis. Therefore, HG should be suspected when liver dysfunction occurs in patients with poorly controlled T1D. The aim of this article is to review the epidemiology, clinical characteristics, pathogenesis and histology of HG.

Keywords: Diabetes mellitus; Hepatic complications; Hepatic glycogenosis; Non-alcoholic fatty liver disease; Type 1 diabetes.

Figure 1

Pathogenesis of hepatic glycogenosis. Glucose from the blood enters hepatocytes by facilitated diffusion independent of insulin and is converted into glycogen via glucose-6-phosphate. Glycogen synthesis depends on insulin and glucose (modified from Munns et al[12]). GLUT2: Glucose transporter 2.

Figure 2

Liver biopsy, haematoxylin and eosin staining. The hepatocytes are swollen with pale cytoplasm and accentuation of the cell membranes. Sinusoids appear compressed by the swollen hepatocytes. Glycogen nuclei are present (black arrow).

Figure 3

Liver biopsy, periodic acid-Schiff staining. A: Periodic acid-Schiff (PAS) demonstrates abundant cytoplasmic deposits. An intense reaction is also found in the nucleus; B: The hepatocyte cytoplasm is not stained with PAS after diastase treatment confirming the present of glycogen.