Liver Glycogen Accumulation in Unstable Diabetes

Abstract

Two patients who had severe unstable diabetes mellitus with frequent hypoglycemic episodes and who required soluble insulin for control are described. Both developed hepatomegaly. Quantitative and qualitative studies of liver glycogen and its related enzymes were performed. The liver glycogen content was high (8 per cent) but its molecular structure was virtually normal. Both the [3-amylolysis limit and the phosphorylase activity appeared to be lower than normal but did not approach the levels associated with glycogen storage disorders. The values of the other enzymes tested were normal. Therefore it appears that the elevated liver glycogen levels seen in some patients with brittle diabetes mellitus are not the result of enzyme deficiency but are secondary to wide fluctuations in blood sugar and frequent doses of soluble insulin. DIABETES 17:13-16, January, 1968.

Effects of Short-Term Improvement of Insulin Treatment and Glycemia on Hepatic Glycogen Metabolism in Type 1 Diabetes

“…Although older studies using the biopsy technique reported increased glycogen deposition in such patients (25,26), the observed reduction by ~29% in peak liver glycogen content is in accordance with the only other study performed in type 1 diabetic patients under near-physiological conditions of mixed meal ingestion (7).…”

Hepatic glycogenosis: Reversible hepatomegaly in type 1 diabetes

“…At presentation, our three cases had anorexia, nausea, abdominal pain, tender hepatomegaly and elevated liver transaminase concentrations. This has been described in association with hepatic glycogen accumulation and unstable diabetes 4,12,16 . With improved glycaemic control, almost complete physical and biochemical recovery occurs within 14 days, 4,12,16 as was seen in our patients.…”

“…Glycogenosis is the hepatic response to poor glycaemic control in children, adolescence and adults with type 1 diabetes, while NASH is the more likely diagnosis in adults with type 2 diabetes 4 . While first described in association with acute ketoacidosis or recurrent hypoglycaemia, 11–13 it has since been appreciated that hepatic glucogenosis is also seen in unstable diabetes without acute ketoacidosis or hypoglycaemia 6 . Hepatic glycogenosis is a benign disease with little chance of progression to fibrosis 4 .…”

“…Hepatic glycogenosis is a benign disease with little chance of progression to fibrosis 4 . It is readily treatable by improvement of glycaemic control 4,8,12 . The natural history of NASH remains controversial, 8 with up to 50% of adult patients developing progressive fibrosis and 15% developing cirrhosis 14 …”

Hepatic Glycogen Metabolism in Type 1 Diabetes After Long-Term Near Normoglycemia

“…In conclusion, combined longand short-term intensified insulin substitution normalizes rates of hepatic glycogen synthesis but not the contribution of gluconeogenesis to glycogen synthesis in type 1 diabetes. Diabetes 51:49 -54, 2002 E arly studies on glycogen metabolism in type 1 diabetic patients using liver biopsies revealed controversial results, reporting either increased or decreased liver glycogen concentrations (1)(2)(3)(4). When liver glycogen was continuously measured with 13 C nuclear magnetic resonance (NMR) spectroscopy, it became clear that under physiologic conditions of mixed meal ingestion, poorly controlled type 1 diabetic patients indeed exhibit a defect of net liver glycogen synthesis that accumulates throughout the day and is most pronounced after dinner (5).…”