Diagnosis of hepatic glycogenosis in poorly controlled type 1 diabetes mellitus

Giordano, Stefania; Martocchia, Antonio; Toussan, Lavinia; Stefanelli, Manuela; Pastore, Francesca; Devito, Antonio Cosimo; Risicato, Marcello G; Ruco, Luigi; Falaschi, P.

doi:10.4239/wjd.v5.i6.882

Cited by 35 publications

(38 citation statements)

References 55 publications

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“…Glycogenic hepatopathy is an underrecognized and uncommon complication of poorly controlled DM type 1 manifested by hepatomegaly, abdominal pain, nausea and vomiting, elevated serum transaminases, and elevated plasma lactate levels [ 9 , 10 ].…”

Section: Discussionmentioning

confidence: 99%

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A Rare Case of Persistent Lactic Acidosis in the ICU: Glycogenic Hepatopathy and Mauriac Syndrome

Deemer

Alvarez

2016

Case Reports in Critical Care

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Mauriac syndrome is a rare disorder that can present with the single feature of glycogenic hepatopathy in children and adults with poorly controlled diabetes mellitus. An often underrecognized finding of glycogenic hepatopathy is lactic acidosis and hyperlactatemia. Primary treatment of glycogenic hepatopathy is improved long-term blood glucose control. Resolution of symptoms and hepatomegaly will occur with improvement in hemoglobin A1C. We present here a case of a young adult female presenting to the intensive care unit with Mauriac syndrome. This case demonstrates exacerbation of lactic acidosis in a patient with glycogenic hepatopathy treated for diabetic ketoacidosis with high dose insulin and dextrose.

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Section: Discussionmentioning

confidence: 99%

“…Large amounts of insulin drive glycogen synthesis and decrease gluconeogenesis and glycogenolysis. Further insulin administration and hyperglycemia facilitate further glycogen synthesis, which creates congested hepatocytes resulting in storage overload [ 10 , 11 ].…”

Section: Discussionmentioning

confidence: 99%

A Rare Case of Persistent Lactic Acidosis in the ICU: Glycogenic Hepatopathy and Mauriac Syndrome

Deemer

Alvarez

2016

Case Reports in Critical Care

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“…Repeated ketoacidosis episodes accompanied by high blood glucose levels increase the risk of glycogen overload in the liver, as DKA is often treated with insulin administration. A high percentage of cases of hepatomegaly has been reported in patients who presented with DKA [59]. Diabetic patients, both type 1 and type 2, show an elevation in their liver enzymes that in most cases associated with non-alcoholic fatty liver disease (NAFLD) [60, 61].…”

Section: Dka Oxidative Stress and Diabetic Co-morbiditiesmentioning

confidence: 99%

Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes

Marie

Jain

2016

Free Radical Biology and Medicine

138

120

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Diets that boost ketone production are increasingly used for treating several neurological disorders. Elevation in ketones in most cases is considered favorable, as they provide energy and are efficient in fueling the body’s energy needs. Despite all the benefits from ketones, the above normal elevation in the concentration of ketones in the circulation tend to illicit various pathological complications by activating injurious pathways leading to cellular damage. Recent literature demonstrates a plausible link between elevated levels of circulating ketones and oxidative stress, linking hyperketonemia to innumerable morbid conditions. Ketone bodies are produced by the oxidation of fatty acids in the liver as a source of alternative energy that generally occurs in glucose limiting conditions. Regulation of ketogenesis and ketolysis plays an important role in dictating ketone concentrations in the blood. Hyperketonemia is a condition with elevated blood levels of acetoacetate (AA), 3-β-hydroxybutyrate (BHB), and acetone. Several physiological and pathological triggers, such as fasting, ketogenic diet, and diabetes cause an accumulation and elevation of circulating ketones. Complications of the brain, kidney, liver, and microvasculature were found to be elevated in diabetic patients who had elevated ketones compared to those diabetics with normal ketone levels. This review summarizes the mechanisms by which hyperketonemia and ketoacidosis cause an increase in redox imbalance and thereby increasing the risk of morbidity and mortality in patients.

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“…Frequent episodes of ketosis significantly increased the risk of hepatic glycogen overload in diabetic patients [34]. On the other hand hepatic infarction was also reported to be associated with ketonemia [35].…”

Section: Discussionmentioning

confidence: 99%

Role of Hyperketonemia in Inducing Oxidative Stress and Cellular Damage in Cultured Hepatocytes and Type 1 Diabetic Rat Liver

Marie¹,

Jain

2015

Cell Physiol Biochem

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Background/Aims: Type 1 diabetic (T1D) patients have a higher incidence of liver disease. T1D patients frequently experience elevated plasma ketone levels along with hyperglycemia. However, no study has examined whether hyperketonemia per se has any role in excess liver damage in T1D. This study investigates the hypothesis that hyperketonemia can induce oxidative stress and cellular dysfunction. Methods: STZ treated diabetic rats, FL83B hepatocytes, and GCLC knocked down (GSH deficient) hepatocytes were used. Results: The blood levels of ALT and AST, biomarkers of liver damage, and ketones were elevated in T1D rats. An increase in NOX4 and ROS along with a reduction in GSH and GCLC levels was observed in T1D rat livers in comparison to those seen in non-diabetic control or type 2 diabetic rats. MCP-1 and ICAM-1 were also elevated in T1D rat livers and ketone treated hepatocytes. Macrophage markers CCR2 and CD11A that interact with MCP-1, and ICAM-1 respectively, were also elevated in the T1D liver, indicating macrophage infiltration. Additionally, activated macrophages increased hepatocyte damage with ketone treatment, which was similar to that seen in GCLC knockdown hepatocytes without ketones. Conclusion: Hyperketonemia per se can induce macrophage mediated damage to hepatocytes and the liver, caused by GSH depletion and oxidative stress up regulation in T1D.

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Diagnosis of hepatic glycogenosis in poorly controlled type 1 diabetes mellitus

Cited by 35 publications

References 55 publications

A Rare Case of Persistent Lactic Acidosis in the ICU: Glycogenic Hepatopathy and Mauriac Syndrome

A Rare Case of Persistent Lactic Acidosis in the ICU: Glycogenic Hepatopathy and Mauriac Syndrome

Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes

Role of Hyperketonemia in Inducing Oxidative Stress and Cellular Damage in Cultured Hepatocytes and Type 1 Diabetic Rat Liver

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