Hepatic glycogenosis: An underdiagnosed complication of diabetes mellitus?

Julián, María Teresa; Alonso, Núria; Ojanguren, Isabel; Pizarro, Eduarda; Ballestar, Enric; Puig-Domingo, Manel

doi:10.4239/wjd.v6.i2.321

Cited by 32 publications

(32 citation statements)

References 34 publications

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“…In some cases, this can lead to a glycogen overload, resulting in liver damage. Hepatic glycogenosis or hepatomegaly is a glycogen overload disorder [58]. 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.…”

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

137

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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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

137

120

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“…GS activity often becomes dysregulated in steatosis, exacerbating the already existing dysglycemia (12,17,18). Recent reports have shown that hepatic overexpression of the G-regulatory subunits of PP1 increased hepatic glycogen accumulation, protected mice from fasting hypoglycemia, and accelerated postprandial blood glucose clearance in mice fed a chow diet or an HFD or in rats with streptozotocininduced diabetes (15,19,20).…”

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confidence: 99%

Hepatic Overexpression of CD36 Improves Glycogen Homeostasis and Attenuates High-Fat Diet-Induced Hepatic Steatosis and Insulin Resistance

Garbacz

Miller

et al. 2016

Molecular and Cellular Biology

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The common complications in obesity and type 2 diabetes include hepatic steatosis and disruption of glucose-glycogen homeostasis, leading to hyperglycemia. Fatty acid translocase (FAT/CD36), whose expression is inducible in obesity, is known for its function in fatty acid uptake. Previous work by us and others suggested that CD36 plays an important role in hepatic lipid homeostasis, but the results have been conflicting and the mechanisms were not well understood. In this study, by using CD36-overexpressing transgenic (CD36Tg) mice, we uncovered a surprising function of CD36 in regulating glycogen homeostasis. Overexpression of CD36 promoted glycogen synthesis, and as a result, CD36Tg mice were protected from fasting hypoglycemia. When challenged with a high-fat diet (HFD), CD36Tg mice showed unexpected attenuation of hepatic steatosis, increased very low-density lipoprotein (VLDL) secretion, and improved glucose tolerance and insulin sensitivity. The HFD-fed CD36Tg mice also showed decreased levels of proinflammatory hepatic prostaglandins and 20-hydroxyeicosatetraenoic acid (20-HETE), a potent vasoconstrictive and proinflammatory arachidonic acid metabolite. We propose that CD36 functions as a protective metabolic sensor in the liver under lipid overload and metabolic stress. CD36 may be explored as a valuable therapeutic target for the management of metabolic syndrome. Individuals with metabolic syndrome or type 2 diabetes are susceptible to nonalcoholic fatty liver disease (1) and disruption of hepatic glucose and glycogen homeostasis (2). Hepatic steatosis is defined as an excess accumulation of fat in hepatocytes. Previous reports suggested that fatty acid translocase (FAT/CD36) plays an important role in hepatic lipid homeostasis (3-6). CD36 is a multiligand class B scavenger receptor with high affinity for lipids and lipid-containing ligands. CD36 is known for its lipid uptake function in macrophages, skeletal muscle, and the heart. However, the role of CD36 in hepatic lipid metabolism is still not well understood, and the available evidence is often conflicting, partly due to the lack of a reliable in vivo liver-specific gain-of-function model to specifically evaluate the function of CD36 in the liver.The basal expression of CD36 in the liver is low; however, it is highly inducible by a high-fat diet (HFD) (3). The hepatic expression of CD36 is under the transcriptional control of the nuclear receptors: liver X receptor (LXR), pregnane X receptor (PXR), peroxisome proliferator-activated receptors (PPARs), and the aryl hydrocarbon receptor (AhR) (4). Some studies have suggested that hepatic CD36, by functioning as a fatty acid transporter, has a role in the pathogenesis of hepatic steatosis (3), obesity (7, 8), and age-related hepatic steatosis (5). Furthermore, we and others reported that induction of CD36 was a common factor in fatty liver following the activation of LXR and PXR (6, 9). On the other hand, recent reports suggested that CD36 signaling might actually be beneficial in preventing fatty live...

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“…However, the key clinical features are hepatomegaly and a mild to moderate increase in transaminases, although in some cases, the transaminase levels can be dramatically elevated, up to 30 times the upper limit of normal (10). As in case 3, and in to a lesser extends in case 2, very high transaminase levels in the range of acute hepatitis has been reported in patients with GH (4,11).…”

Section: Discussionmentioning

confidence: 98%

Glycogenic hepatopathy in young adults: a case series

Silva¹,

Marques²,

Cardoso³

et al. 2016

Rev Esp Enferm Dig

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Glycogenic hepatopathy is a rare and underecognized complication in long-standing poorly controlled type 1 diabetes mellitus patients. This is a distinct entity from other causes of hepatomegaly and elevated liver enzymes in diabetics, such as nonalcoholic fatty liver disease. Glycogenic hepatopathy is characterized by the combination of poorly controlled diabetes, acute liver injury with marked elevation in serum aminotransferases, and the characteristic histological features on liver biopsy. It is important to distinguish this entity as it has the potential for resolution following improved glycemic control.In this report, we describe four cases of adult patients presenting elevated serum transaminases and hepatomegaly with a history of poorly controlled type I diabetes mellitus. One of the patients had also elevated amylase and lipase in the serum, without clinical or imagiologic evidence of acute pancreatitis. Liver biopsy was performed in all patients and revealed glycogenic hepatopathy. Clinician's awareness of glycogenic hepatopathy should prevent diagnostic delay or misdiagnosis and will provide better insight and management for this condition.

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Hepatic glycogenosis: An underdiagnosed complication of diabetes mellitus?

Cited by 32 publications

References 34 publications

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

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

Hepatic Overexpression of CD36 Improves Glycogen Homeostasis and Attenuates High-Fat Diet-Induced Hepatic Steatosis and Insulin Resistance

Glycogenic hepatopathy in young adults: a case series

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