Diagnosis of hepatic glycogenosis in poorly controlled type 1 diabetes mellitus

Abstract

Hepatic glycogenosis (HG) in type 1 diabetes is a underrecognized complication. Mauriac firstly described the syndrome characterized by hepatomegaly with altered liver enzymes, growth impairment, delay puberty and Cushingoid features, during childhood. HG in adulthood is characterized by the liver disorder (with circulating aminotransferase increase) in the presence of poor glycemic control (elevation of glycated hemoglobin, HbA1c levels). The advances in the comprehension of the metabolic pathways driving to the hepatic glycogen deposition point out the role of glucose transporters and insulin mediated activations of glucokinase and glycogen synthase, with inhibition of glucose-6-phosphatase. The differential diagnosis of HG consists in the exclusion of causes of liver damage (infectious, metabolic, obstructive and autoimmune disease). The imaging study (ultrasonography and/or radiological examinations) gives information about the liver alterations (hepatomegaly), but the diagnosis needs to be confirmed by the liver biopsy. The main treatment of HG is the amelioration of glycemic control that is usually accompanied by the reversal of the liver disorder. In selected cases, more aggressive treatment options (transplantation) have been successfully reported.

Keywords: Hepatic glycogenosis, Type 1 diabetes mellitus, Hepatomegaly, Glycogen, Glucose transporters, Insulin, Glucokinase, Glycogen synthase, Glucose-6-phosphatase

Core tip: This review contain an extensive revision of the case reports described in literature; in particular glycemic control (elevation of glycated hemoglobin, HbA1c levels, presence of ketoacidosis and insulin dosage), imaging studies and bioptic findings are summarized and discussed. The pathophysiological mechanisms behind the accumulation of glycogen in hepatocytes in patient with poorly controlled type 1 diabetes mellitus are described in detail.