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Tessa Tonleu J, Reyes NA, Hillerson ND, Horton WB. Improvement of Glycogenic Hepatopathy With Minimal Corresponding Improvement of Glycemic Control in a Person With Type 1 Diabetes: Case Report and Literature Review. AACE Clin Case Rep 2025; 11:113-116. [PMID: 40201471 PMCID: PMC11973649 DOI: 10.1016/j.aace.2024.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Revised: 11/25/2024] [Accepted: 12/12/2024] [Indexed: 04/10/2025] Open
Abstract
Background/Objective Glycogenic hepatopathy is characterized by diffuse glycogen accumulation in hepatocytes that leads to hepatomegaly and elevated transaminases. Notably, the condition is reversible as improving glycemic control has been shown to resolve glycogenic hepatopathy and provide symptomatic relief. Case Report A 30-year-old female with longstanding and poorly-controlled type 1 diabetes presented to her primary care physician for a routine follow-up visit. Routine lab work demonstrated hyperglycemia and elevated liver enzymes (alkaline phosphatase of 180 U/L, aspartate aminotransferase of 111 U/L, and alanine aminotransferase of 101 U/L). At laboratory reassessment 3 weeks later, liver function tests remained elevated and hepatic ultrasound was unrevealing. She was referred to gastroenterology for further evaluation and laboratory tests for viral and autoimmune hepatitis were negative while magnetic resonance imaging of the abdomen was unremarkable. Given the nondiagnostic work-up, liver biopsy was performed and pathology was consistent with glycogenic hepatopathy. She was referred to Endocrinology for improved glycemic control; however, liver enzymes normalized over the next several months despite minimal improvement in glycemic control. She was eventually transitioned to a closed-loop automated insulin delivery system and started dulaglutide for management of obesity. Subsequent A1c values significantly improved and liver enzymes remained within normal limits. Discussion This case raises awareness of an under recognized complication of type 1 diabetes and challenges conventional thinking about factors leading to its resolution. Conclusion Further investigation into the underlying pathophysiology of glycogenic hepatopathy is needed.
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Affiliation(s)
- Joselyn Tessa Tonleu
- Division of Endocrinology and Metabolism, University of Virginia School of Medicine, Charlottesville, Virginia
| | - Nicolas A. Reyes
- Division of Endocrinology and Metabolism, University of Virginia School of Medicine, Charlottesville, Virginia
| | - Natalie D. Hillerson
- Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia
| | - William B. Horton
- Division of Endocrinology and Metabolism, University of Virginia School of Medicine, Charlottesville, Virginia
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Suzuki T, Orime K, Akamatsu R, Akiyama T, Yamakawa T, Terauchi Y. Type 1 Diabetes Mellitus with Diabetic Ketoacidosis Presenting with Transient Severe Fatty Liver and Subsequent Liver Dysfunction. Intern Med 2024; 63:3339-3344. [PMID: 38719597 PMCID: PMC11729162 DOI: 10.2169/internalmedicine.3488-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 03/19/2024] [Indexed: 12/17/2024] Open
Abstract
Patients often present with severe fatty liver (FL) due to insulin deficiency at the onset of diabetic ketoacidosis (DKA). On the other hand, glycogenic hepatopathy (GH) is a possible cause of liver dysfunction in patients with DKA. We herein report a case of type 1 diabetes mellitus with severe FL at the onset of DKA, who demonstrated subsequent marked liver dysfunction after achieving an improvement of FL. As liver dysfunction persisted even after the FL improved, GH was suspected to be the cause of liver dysfunction. FL and GH have different prognoses and should therefore be differentiated using imaging studies and biopsies.
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Affiliation(s)
- Takayuki Suzuki
- Department of Endocrinology and Diabetes, Yokohama City University Medical Center, Japan
| | - Kazuki Orime
- Department of Endocrinology and Diabetes, Yokohama City University Medical Center, Japan
| | - Ryoichi Akamatsu
- Department of Endocrinology and Diabetes, Yokohama City University Medical Center, Japan
| | - Tomoaki Akiyama
- Department of Endocrinology and Diabetes, Yokohama City University Medical Center, Japan
| | - Tadashi Yamakawa
- Department of Endocrinology and Diabetes, Yokohama City University Medical Center, Japan
| | - Yasuo Terauchi
- Department of Endocrinology and Metabolism, Yokohama City University School of Medicine, Japan
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3
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Bian C, He X, Wang Q, Zheng Z, Zhang Y, Xiong H, Li Y, Zhao M, Li J. Biochemical Toxicological Study of Insulin Overdose in Rats: A Forensic Perspective. TOXICS 2023; 12:17. [PMID: 38250973 PMCID: PMC10819875 DOI: 10.3390/toxics12010017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 12/17/2023] [Accepted: 12/22/2023] [Indexed: 01/23/2024]
Abstract
Due to nonspecific pathological changes and the rapid degradation of insulin in postmortem blood samples, the identification of the cause of death during insulin overdose has always been a difficulty in forensic medicine. At present, there is a lack of studies on the toxicological changes and related mechanisms of an insulin overdose, and the specific molecular markers of insulin overdose are still unclear. In this study, an animal model of insulin overdose was established, and 24 SD rats were randomly divided into a control group, insulin overdose group, and a recovery group (n = 8). We detected the biochemical changes and analyzed the toxicological mechanism of an insulin overdose. The results showed that after insulin overdose, the rats developed irregular convulsions, Eclampsia, Opisthotonos, and other symptoms. The levels of glucose, glycogen, and C-peptide in the body decreased significantly, while the levels of lactate, insulin, and glucagon increased significantly. The decrease in plasma K+ was accompanied by the increase in skeletal muscle K+. The PI3K-AKT signaling pathway was significantly activated in skeletal muscle, and the translocation of GLUT4/Na+-K+-ATPase to sarcolemma was significantly increased. Rare glycogenic hepatopathy occurred in the recovery group after insulin overdose. Our study showed that insulin overdose also plays a role in skeletal muscle cells, mainly through the PI3K-Akt signaling pathway. Therefore, the detection of signaling pathway proteins of the skeletal muscle cell membrane GLUT4 and Na+-K+-ATPase has a certain auxiliary diagnostic value for forensic insulin overdose identification. Glycogen detection in the liver and skeletal muscle is important for the diagnosis of insulin overdose, but it still needs to be differentiated from other causes of death. Skeletal muscle has great potential for insulin detection, and the ratio of insulin to the C-peptide (I:C) can determine whether an exogenous insulin overdose is present.
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Affiliation(s)
- Cunhao Bian
- Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; (C.B.); (X.H.); (Q.W.); (Z.Z.); (Y.Z.); (H.X.); (Y.L.); (M.Z.)
- Chongqing Engineering Research Center of Criminal Investigation Technology, Chongqing 400016, China
- Chongqing Key Laboratory of Forensic Medicine, Chongqing 400016, China
| | - Xin He
- Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; (C.B.); (X.H.); (Q.W.); (Z.Z.); (Y.Z.); (H.X.); (Y.L.); (M.Z.)
- Chongqing Engineering Research Center of Criminal Investigation Technology, Chongqing 400016, China
- Chongqing Key Laboratory of Forensic Medicine, Chongqing 400016, China
| | - Qi Wang
- Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; (C.B.); (X.H.); (Q.W.); (Z.Z.); (Y.Z.); (H.X.); (Y.L.); (M.Z.)
- Chongqing Engineering Research Center of Criminal Investigation Technology, Chongqing 400016, China
- Chongqing Key Laboratory of Forensic Medicine, Chongqing 400016, China
| | - Zhe Zheng
- Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; (C.B.); (X.H.); (Q.W.); (Z.Z.); (Y.Z.); (H.X.); (Y.L.); (M.Z.)
- Chongqing Engineering Research Center of Criminal Investigation Technology, Chongqing 400016, China
- Chongqing Key Laboratory of Forensic Medicine, Chongqing 400016, China
| | - Yongtai Zhang
- Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; (C.B.); (X.H.); (Q.W.); (Z.Z.); (Y.Z.); (H.X.); (Y.L.); (M.Z.)
- Chongqing Engineering Research Center of Criminal Investigation Technology, Chongqing 400016, China
- Chongqing Key Laboratory of Forensic Medicine, Chongqing 400016, China
| | - Hongli Xiong
- Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; (C.B.); (X.H.); (Q.W.); (Z.Z.); (Y.Z.); (H.X.); (Y.L.); (M.Z.)
- Chongqing Engineering Research Center of Criminal Investigation Technology, Chongqing 400016, China
- Chongqing Key Laboratory of Forensic Medicine, Chongqing 400016, China
| | - Yongguo Li
- Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; (C.B.); (X.H.); (Q.W.); (Z.Z.); (Y.Z.); (H.X.); (Y.L.); (M.Z.)
- Chongqing Engineering Research Center of Criminal Investigation Technology, Chongqing 400016, China
- Chongqing Key Laboratory of Forensic Medicine, Chongqing 400016, China
| | - Mingzhu Zhao
- Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; (C.B.); (X.H.); (Q.W.); (Z.Z.); (Y.Z.); (H.X.); (Y.L.); (M.Z.)
- Chongqing Engineering Research Center of Criminal Investigation Technology, Chongqing 400016, China
- Chongqing Key Laboratory of Forensic Medicine, Chongqing 400016, China
| | - Jianbo Li
- Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; (C.B.); (X.H.); (Q.W.); (Z.Z.); (Y.Z.); (H.X.); (Y.L.); (M.Z.)
- Chongqing Engineering Research Center of Criminal Investigation Technology, Chongqing 400016, China
- Chongqing Key Laboratory of Forensic Medicine, Chongqing 400016, China
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Singh Y, Gurung S, Gogtay M. Glycogen hepatopathy in type-1 diabetes mellitus: A case report. World J Hepatol 2022; 14:471-478. [PMID: 35317186 PMCID: PMC8891674 DOI: 10.4254/wjh.v14.i2.471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 11/19/2021] [Accepted: 01/11/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND It has been studied that fluctuating glucose levels may superimpose glycated hemoglobin in determining the risk for diabetes mellitus (DM) complications. While non-alcoholic steatohepatitis (NASH) remains a predominant cause of elevated transaminases in Type 2 DM due to a strong underplay of metabolic syndrome, Type 1 DM can contrastingly affect the liver in a direct, benign, and reversible manner, causing Glycogen hepatopathy (GH) - with a good prognosis. CASE SUMMARY A 50-year-old female with history of poorly controlled type 1 DM, status post cholecystectomy several years ago, and obesity presented with nausea, vomiting, and abdominal pain. Her vitals at the time of admission were stable. On physical examination, she had diffuse abdominal tenderness. Her finger-stick glucose was 612 mg/dL with elevated ketones and low bicarbonate. Her labs revealed abnormal liver studies: AST 1460 U/L, ALP: 682 U/L, ALP: 569 U/L, total bilirubin: 0.3mg/dL, normal total protein, albumin, and prothrombin time/ international normalized ratio (PT/INR). A magnetic resonance cholangiopancreatography (MRCP) demonstrated mild intra and extra-hepatic biliary ductal dilation without evidence of choledocholithiasis. She subsequently underwent a diagnostic ERCP which showed a moderately dilated CBD, for which a stent was placed. Studies for viral hepatitis, Wilson's Disease, alpha-1-antitrypsin, and iron panel came back normal. Due to waxing and waning transaminases during the hospital course, a liver biopsy was eventually done, revealing slightly enlarged hepatocytes that were PAS-positive, suggestive of glycogenic hepatopathy. With treatment of hyperglycemia and ensuing strict glycemic control, her transaminases improved, and she was discharged. CONCLUSION With a negative hepatocellular and cholestatic work-up, our patient likely had GH, a close differential for NASH but a poorly recognized entity. GH, first described in 1930 as a component of Mauriac syndrome, is believed to be due to glucose and insulin levels fluctuation. Dual echo magnetic resonance imaging sequencing and computed tomography scans of the liver are helpful to differentiate GH from NASH. Still, liver biopsy remains the gold standard for diagnosis. Biopsy predominantly shows intra-cellular glycogen deposition, with minimal or no steatosis or inflammation. As GH is reversible with good glycemic control, it should be one of the differentials in patients with brittle diabetes and elevated transaminases. GH, however, can cause a dramatic elevation in transaminases (50-1600 IU/L) alongside hepatomegaly and abdominal pain that would raise concern for acute liver injury leading to exhaustive work-up, as was in our patient above. Fluctuation in transaminases is predominantly seen during hyperglycemic episodes, and proper glycemic control is the mainstay of the treatment.
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Affiliation(s)
- Yuvaraj Singh
- Internal Medicine, Saint Vincent Hospital, Worcester, MA 01604, United States.
| | - Susant Gurung
- Internal Medicine, Saint Vincent Hospital, Worcester, MA 01604, United States
| | - Maya Gogtay
- Internal Medicine, Saint Vincent Hospital, Worcester, MA 01604, United States
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5
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Mertens J, De Block C, Spinhoven M, Driessen A, Francque SM, Kwanten WJ. Hepatopathy Associated With Type 1 Diabetes: Distinguishing Non-alcoholic Fatty Liver Disease From Glycogenic Hepatopathy. Front Pharmacol 2021; 12:768576. [PMID: 34759828 PMCID: PMC8573337 DOI: 10.3389/fphar.2021.768576] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 10/06/2021] [Indexed: 12/14/2022] Open
Abstract
Autoimmune destruction of pancreatic β-cells results in the permanent loss of insulin production in type 1 diabetes (T1D). The daily necessity to inject exogenous insulin to treat hyperglycemia leads to a relative portal vein insulin deficiency and potentiates hypoglycemia which can induce weight gain, while daily fluctuations of blood sugar levels affect the hepatic glycogen storage and overall metabolic control. These, among others, fundamental characteristics of T1D are associated with the development of two distinct, but in part clinically similar hepatopathies, namely non-alcoholic fatty liver disease (NAFLD) and glycogen hepatopathy (GlyH). Recent studies suggest that NAFLD may be increasingly common in T1D because more people with T1D present with overweight and/or obesity, linked to the metabolic syndrome. GlyH is a rare but underdiagnosed complication hallmarked by extremely brittle metabolic control in, often young, individuals with T1D. Both hepatopathies share clinical similarities, troubling both diagnosis and differentiation. Since NAFLD is increasingly associated with cardiovascular and chronic kidney disease, whereas GlyH is considered self-limiting, awareness and differentiation between both condition is important in clinical care. The exact pathogenesis of both hepatopathies remains obscure, hence licensed pharmaceutical therapy is lacking and general awareness amongst physicians is low. This article aims to review the factors potentially contributing to fatty liver disease or glycogen storage disruption in T1D. It ends with a proposal for clinicians to approach patients with T1D and potential hepatopathy.
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Affiliation(s)
- Jonathan Mertens
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium.,Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Edegem, Belgium.,Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Wilrijk, Belgium
| | - Christophe De Block
- Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Edegem, Belgium.,Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Wilrijk, Belgium
| | - Maarten Spinhoven
- Department of Radiology, Antwerp University Hospital, Edegem, Belgium
| | - Ann Driessen
- Department of Pathology, Antwerp University Hospital, Antwerp, Belgium.,CORE, Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium
| | - Sven M Francque
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium.,Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Wilrijk, Belgium
| | - Wilhelmus J Kwanten
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium.,Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Wilrijk, Belgium
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6
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Hepatocellular Glycogen Accumulation in the Setting of Poorly Controlled Type 1 Diabetes Mellitus: Case Report and Review of the Literature. Case Reports Hepatol 2020; 2020:9368348. [PMID: 32128265 PMCID: PMC7048907 DOI: 10.1155/2020/9368348] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Accepted: 01/22/2020] [Indexed: 02/06/2023] Open
Abstract
Glycogenic hepatopathy (GH) is the accumulation of glycogen in the hepatocytes and represents a rare complication in patients with diabetes mellitus (DM), most commonly type 1 DM. We present a case of a 23-year-old woman with a medical history of poorly controlled type 1 DM and gastroesophageal reflux disease (GERD) who presented with progressively worsening right-sided abdominal pain. Diagnostic workup resulted in a liver biopsy with hepatocytes that stained heavily for glycogen with no evidence of fibrosis or steatohepatitis. A diagnosis of glycogenic hepatopathy was made, and an aggressive glucose control regimen was implemented leading to resolution of symptoms and improvement in AST, ALT, and ALP. In addition to presenting this rare case, we offer a review of literature and draw important distinctions between glycogenic hepatopathy and other differential diagnoses with the aim of assisting providers in the diagnostic workup and treatment of glycogenic hepatopathy.
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7
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Stender S, Zaha VG, Malloy CR, Sudderth J, DeBerardinis RJ, Park JM. Assessment of Rapid Hepatic Glycogen Synthesis in Humans Using Dynamic 13C Magnetic Resonance Spectroscopy. Hepatol Commun 2020; 4:425-433. [PMID: 32140658 PMCID: PMC7049683 DOI: 10.1002/hep4.1458] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 11/19/2019] [Indexed: 01/04/2023] Open
Abstract
Carbon-13 magnetic resonance spectroscopy (MRS) following oral intake of 13C-labeled glucose is the gold standard for imaging glycogen metabolism in humans. However, the temporal resolution of previous studies has been >13 minutes. Here, we describe a high-sensitivity 13C MRS method for imaging hepatic glycogen synthesis with a temporal resolution of 1 minute or less. Nuclear magnetic resonance spectra were acquired from the liver of 3 healthy volunteers, using a 13C clamshell radiofrequency transmit and paddle-shaped array receive coils in a 3 Tesla magnetic resonance imaging system. Following a 15-minute baseline 13C MRS scan of the liver, [1-13C]-glucose was ingested and 13C MRS data were acquired for an additional 1-3 hours. Dynamic change of the hepatic glycogen synthesis level was analyzed by reconstructing the acquired MRS data with temporal resolutions of 30 seconds to 15 minutes. Plasma levels of 13C-labeled glucose and lactate were measured using gas chromatography-mass spectrometry. While not detected at baseline 13C MRS, [1-13C]-labeled α-glucose and β-glucose and glycogen peaks accumulated rapidly, beginning as early as ~2 minutes after oral administration of [1-13C]-glucose. The [1-13C]-glucose signals peaked at ~5 minutes, whereas [1-13C]-glycogen peaked at ~25 minutes after [1-13C]-glucose ingestion; both signals declined toward baseline levels over the next 1-3 hours. Plasma levels of 13C-glucose and 13C-lactate rose gradually, and approximately 20% of all plasma glucose and 5% of plasma lactate were 13C-labeled by 2 hours after ingestion. Conclusion: We observed rapid accumulation of hepatic [1-13C]-glycogen following orally administered [1-13C]-glucose, using a dynamic 13C MRS method with a temporal resolution of 1 minute or less. Commercially available technology allows high temporal resolution studies of glycogen metabolism in the human liver.
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Affiliation(s)
- Stefan Stender
- Department of Molecular Genetics University of Texas Southwestern Medical Center Dallas TX.,Department of Clinical Biochemistry Rigshospitalet Copenhagen Denmark
| | - Vlad G Zaha
- Advanced Imaging Research Center University of Texas Southwestern Medical Center Dallas TX.,Department of Internal Medicine University of Texas Southwestern Medical Center Dallas TX
| | - Craig R Malloy
- Advanced Imaging Research Center University of Texas Southwestern Medical Center Dallas TX.,Department of Internal Medicine University of Texas Southwestern Medical Center Dallas TX
| | - Jessica Sudderth
- Howard Hughes Medical Institute and Children's Medical Center Research Institute University of Texas Southwestern Medical Center Dallas TX
| | - Ralph J DeBerardinis
- Howard Hughes Medical Institute and Children's Medical Center Research Institute University of Texas Southwestern Medical Center Dallas TX
| | - Jae Mo Park
- Advanced Imaging Research Center University of Texas Southwestern Medical Center Dallas TX.,Department of Radiology University of Texas Southwestern Medical Center Dallas TX.,Department of Electrical and Computer Engineering University of Texas at Dallas Richardson TX
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Lui DTW, Woo YC, Chow WS, Lee CH, Lee ACH, Leung EKH, Tan KCB, Lam KSL, Lam JKY. Glycogenic hepatopathy as an unusual etiology of deranged liver function in a patient with type 1 diabetes: A case report. Medicine (Baltimore) 2019; 98:e15296. [PMID: 31027093 PMCID: PMC6831370 DOI: 10.1097/md.0000000000015296] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
RATIONALE Deranged liver function is a common finding among patients with diabetes mellitus. We report a case of liver biopsy-proven glycogenic hepatopathy (GH) in a patient with long-standing poorly controlled type 1 diabetes (DM1), presented with recurrent transaminitis. PATIENT CONCERNS A 28-year-old Chinese woman was noted to have deranged liver function with transaminases elevated to more than 15 times the upper limit of normal. DIAGNOSIS She had underlying long-standing poorly controlled DM1. Blood tests including hepatitis serology and autoimmune panel were negative. Liver biopsy confirmed the diagnosis of GH, showing an increase in glycogen deposition with intact liver parenchymal architecture, and no inflammation or significant fibrosis. INTERVENTIONS Her glycemic control was optimized. OUTCOMES Her transaminase levels normalized upon subsequent follow-up with improved glycemic control. LESSONS GH is suspected when transaminase flare occurs in patients with poorly controlled DM1, usually with exaggerated hemoglobin A1c levels, especially after drug-induced, viral, autoimmune and metabolic liver diseases are excluded. The gold standard of diagnosis is liver biopsy. When diagnosis of GH is ascertained, the mainstay of treatment is to optimize glycemic control. Typically, the transaminases may become normal within days to months after improvement of glycemic control. Compared to non-alcoholic fatty liver disease, GH is associated with favorable prognosis and runs a benign course, making this differentiation clinically important.
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Hamed AE, Elwan N, Naguib M, Elwakil R, Esmat G, El Kassas M, Abd-Elsalam S, Moussa S. Diabetes Association with Liver Diseases: An Overview for Clinicians. Endocr Metab Immune Disord Drug Targets 2019; 19:274-280. [PMID: 30444204 DOI: 10.2174/1871530318666181116111945] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 09/24/2018] [Accepted: 10/04/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND There is a strong association between liver diseases and diabetes (DM) which is higher than expected by a correlation between two very common diseases. Liver diseases may occur as a result of diabetes, and the reverse is true as well. AIM To review the etiology of this association between liver diseases and diabetes and how to diagnose it. METHODS Studies that identified this association between liver diseases and diabetes and how to diagnose it was reviewed. RESULTS This association can be divided into the following categories: liver disease related to diabetes (Diabetic hepatopathy), hepatogenous diabetes (HD), and liver diseases that occur in conjunction with Diabetes mellitus. Two hours after glucose loading is the best screening test for HD. HbA1c may neither be suitable for diagnosis nor monitoring of diabetes that links liver disease. CONCLUSION NAFLD, hepatogenous diabetes, glycogenic hepatopathy and diabetic hepatosclerosis are the most important association between liver diseases and diabetes. The criteria for the diagnosis of diabetes associating liver disease are the same for primary diabetes. Two hours post glucose load is the best screening test for HD due to the fact that fasting glucose can be normal early in the disease. The tool used for diabetes monitoring depends on stage and severity of liver condition.
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Affiliation(s)
| | - Nadia Elwan
- Faculty of Medicine, Tanta University, Tanta, Egypt
| | | | - Reda Elwakil
- Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Gamal Esmat
- Faculty of Medicine, Cairo University, Cairo, Egypt
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10
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Hamed AE, Elsahar M, Elwan NM, El-Nakeep S, Naguib M, Soliman HH, Ahmed Aboubakr A, AbdelMaqsod A, Sedrak H, Assaad SN, Elwakil R, Esmat G, Salh S, Mostafa T, Mogawer S, Sadek SE, Saber MM, Ezelarab H, Mahmoud AA, Sultan S, El Kassas M, Kamal E, ElSayed NM, Moussa S. Managing diabetes and liver disease association. Arab J Gastroenterol 2018; 19:166-179. [PMID: 30420265 DOI: 10.1016/j.ajg.2018.08.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 08/26/2018] [Indexed: 02/05/2023]
Abstract
There is strong association between liver diseases and diabetes (DM) which is higher than expected by a chance association of two very common disorders. It can be classified into three categories: Liver disease related to diabetes, hepatogenous diabetes (HD), and liver disease occurring coincidentally with DM. The criteria for the diagnosis of diabetes associating liver disease are the same for primary diabetes. Two hours post glucose load is a better screening test for HD. HbA1c may not be suitable for diagnosis or monitoring of diabetes associating advanced liver disease. Apart from the increased cardiovascular risk in patients with type 2 DM (T2 DM) and NAFLD, the cardiovascular and retinopathy risk is low in HD. Patients with metabolic derangement should be screened for NAFLD which in turn may predict T2 DM development. Similarly, patients with established T2 DM should also be screened for NAFLD which further contributes to diabetes worsening. Diabetes is a significant risk factor for progression of the chronic liver disease. It is associated with poor patient survival. Treatment of diabetes associating liver disease appears beneficial. Metformin, if tolerated and not contraindicated, is recommended as a first-line therapy for patients with diabetes and chronic liver disease (CLD). If the hepatic disease is severe, insulin secretagogues should be avoided because of the increased risk of hypoglycaemia. Pioglitazone may be useful in patients with fatty liver disease. DPP-4 inhibitors showed effectiveness and safety for the treatment of T2 DM in CLD patients up to those with child B stage. GLP-1 receptor agonists and SGLT-2 inhibitors exhibit positive effects on weight and are associated with minimal risk of hypoglycaemia. Insulin must be used with caution, as hypoglycaemia may be a problem. Insulin analogues are preferred in the context of hypoglycaemia Statins can be used to treat dyslipidaemia in NAFLD, also the use of angiotensin II receptor antagonist for hypertension is safe and beneficial Given the clear association between diabetes mellitus and hepatocellular carcinoma, the strict control of glycaemia with insulin sensitizers can be essential in its prevention. The addition of DM to the currently used scores (Child-Pugh and MELD scores) may enhance the sensitivity and the specificity for prediction of morbidity and mortality rates in cirrhotic patients. In the new era of directly acting antiviral agents (DAAs) for HCV treatment, it is recommended to follow up lipid profile and blood sugar levels following SVR in order to adjust doses of medications used in diabetic (SVR is associated with reduction in insulin requirements) and dyslipidaemic patients (rebound increase in the lipid profile after clearing the virus may increase risk of cardiovascular disease (CVD)). The issues of post liver transplant diabetes and relation between DM and chronic HBV are highlighted. This narrative review and Consensus-based practice guidance (under revision and criticism) are based on a formal review and analysis of the recently published world literature on the topic (Medline search up to September 2017); and the experience of the authors and independent reviewers.
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Affiliation(s)
- Abd Elkhalek Hamed
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt.
| | - Medhat Elsahar
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Police Medical Academy, Egypt
| | | | | | | | | | - Ashraf Ahmed Aboubakr
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | | | | | | | - Reda Elwakil
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Ain Shams University, Egypt
| | - Gamal Esmat
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Kasr Al Aini, Egypt
| | - Samira Salh
- Department of Pharmacy, Cairo University, Egypt
| | | | | | - Sameh Emil Sadek
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | - Maha M Saber
- Department of Clinical Nutrition National Research Centre, Egypt
| | - Hanan Ezelarab
- Department of Clinical Nutrition National Research Centre, Egypt
| | - Asem Ashraf Mahmoud
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | | | | | - Ehab Kamal
- Medical Department, National Research Centre, Egypt
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11
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Kuga GK, Gaspar RC, Muñoz VR, Nakandakari SCBR, Breda L, Sandoval BM, Caetano FH, Leme JACDA, Pauli JR, Gomes RJ. Physical training reverses changes in hepatic mitochondrial diameter of Alloxan-induced diabetic rats. EINSTEIN-SAO PAULO 2018; 16:eAO4353. [PMID: 30088548 PMCID: PMC6110382 DOI: 10.1590/s1679-45082018ao4353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Accepted: 02/19/2018] [Indexed: 12/02/2022] Open
Abstract
OBJECTIVE To investigate the effects of physical training on metabolic and morphological parameters of diabetic rats. METHODS Wistar rats were randomized into four groups: sedentary control, trained control, sedentary diabetic and trained diabetic. Diabetes mellitus was induced by Alloxan (35mg/kg) administration for sedentary diabetic and Trained Diabetic Groups. The exercise protocol consisted of swimming with a load of 2.5% of body weight for 60 minutes per day (5 days per week) for the trained control and Trained Diabetic Groups, during 6 weeks. At the end of the experiment, the rats were sacrificed and blood was collected for determinations of serum glucose, insulin, albumin and total protein. Liver samples were extracted for measurements of glycogen, protein, DNA and mitochondrial diameter determination. RESULTS The sedentary diabetic animals presented decreased body weight, blood insulin, and hepatic glycogen, as well as increased glycemia and mitochondrial diameter. The physical training protocol in diabetic animals was efficient to recovery body weight and liver glycogen, and to decrease the hepatic mitochondrial diameter. CONCLUSION Physical training ameliorated hepatic metabolism and promoted important morphologic adaptations as mitochondrial diameter in liver of the diabetic rats.
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Affiliation(s)
- Gabriel Keine Kuga
- Universidade Estadual Paulista “Júlio de Mesquita Filho”, Rio Claro, SP, Brazil
| | - Rafael Calais Gaspar
- Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas, Limeira, SP, Brazil
| | - Vitor Rosetto Muñoz
- Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas, Limeira, SP, Brazil
| | | | | | | | | | | | - José Rodrigo Pauli
- Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas, Limeira, SP, Brazil
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12
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Kocova M, Milenkova L. Old syndrome-new approach: Mauriac syndrome treated with continuous insulin delivery. SAGE Open Med Case Rep 2018; 6:2050313X18785510. [PMID: 30013788 PMCID: PMC6041848 DOI: 10.1177/2050313x18785510] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2018] [Accepted: 06/06/2018] [Indexed: 11/15/2022] Open
Abstract
Mauriac syndrome has rarely been reported in children and adolescents with a poorly controlled diabetes mellitus type 1. However, it still occurs despite the worldwide improvements of metabolic control. The risks have not been elucidated. We present a 13.5-year-old boy with a typical clinical presentation of Mauriac syndrome consisting of growth delay, cushingoid appearance, hepatomegaly, and delayed puberty. A stepwise correction of glycemic control was introduced using continuous insulin delivery. All symptoms improved during the 2.5-year follow-up. No retinopathy occurred. This patient with Mauriac syndrome followed with continuous glucose monitoring and treated with continuous insulin delivery, resulting in no retinopathy after 2.5 years of follow-up. We suggest that this approach should be recommended in patients with Mauriac syndrome.
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Affiliation(s)
- Mirjana Kocova
- University Pediatric Clinic, Skopje, Republic of Macedonia
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13
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Khoury J, Zohar Y, Shehadeh N, Saadi T. Glycogenic hepatopathy. Hepatobiliary Pancreat Dis Int 2018; 17:113-118. [PMID: 29709217 DOI: 10.1016/j.hbpd.2018.02.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2017] [Accepted: 11/24/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Glycogenic hepatopathy (GH) is a disorder associated with uncontrolled diabetes mellitus, most commonly type 1, expressed as right upper quadrant abdominal pain, hepatomegaly and increased liver enzymes. The diagnosis may be difficult, because laboratory and imaging tests are not pathognomonic. Although GH may be suggested based on clinical presentation and imaging studies, the gold standard for diagnosis is a liver biopsy, showing a significant accumulation of glycogen within the hepatocytes. GH may be diagnosed also after elevated liver enzymes in routine blood tests. GH usually regresses after tight glycemic control. Progression to end-stage liver disease has never been reported. This review aims to increase the awareness to this disease, to suggest a pathway for investigation that may reduce the use of unnecessary tests, especially invasive ones. DATA SOURCES A PubMed database search (up to July 1, 2017) was done with the words "glycogenic hepatopathy", "hepatic glycogenosis", "liver glycogenosis" and "diabetes mellitus-associated glycogen storage hepatopathy". Articles in which diabetes mellitus-associated liver glycogen accumulation was described were included in this review. RESULTS A total of 47 articles were found, describing 126 patients with GH. Hepatocellular disturbance was more profound than cholestatic disturbance. No synthetic failure was reported. CONCLUSIONS GH may be diagnosed conservatively, based on corroborating medical history, physical examination, laboratory tests, imaging studies and response to treatment, even without liver biopsy. In case of doubt about the diagnosis or lack of clinical response to treatment, a liver biopsy may be considered. There is no role for noninvasive tests like fibroscan or fibrotest for the diagnosis of GH or for differentiation of this situation from nonalcoholic fatty liver disease.
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Affiliation(s)
- Johad Khoury
- Internal Medicine B, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Liver Unit, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Yaniv Zohar
- Department of Pathology, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Naim Shehadeh
- Meyer Children's Hospital of Haifa, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Institute of Diabetes, Endocrinology and Metabolism, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Tarek Saadi
- Liver Unit, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Department of Gastroenterology, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
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14
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Sherigar JM, Castro JD, Yin YM, Guss D, Mohanty SR. Glycogenic hepatopathy: A narrative review. World J Hepatol 2018; 10:172-185. [PMID: 29527255 PMCID: PMC5838438 DOI: 10.4254/wjh.v10.i2.172] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2017] [Revised: 12/22/2017] [Accepted: 01/24/2018] [Indexed: 02/06/2023] Open
Abstract
Glycogenic hepatopathy (GH) is a rare complication of the poorly controlled diabetes mellitus characterized by the transient liver dysfunction with elevated liver enzymes and associated hepatomegaly caused by the reversible accumulation of excess glycogen in the hepatocytes. It is predominantly seen in patients with longstanding type 1 diabetes mellitus and rarely reported in association with type 2 diabetes mellitus. Although it was first observed in the pediatric population, since then, it has been reported in adolescents and adults with or without ketoacidosis. The association of GH with hyperglycemia in diabetes has not been well established. One of the essential elements in the pathophysiology of development of GH is the wide fluctuation in both glucose and insulin levels. GH and non-alcoholic fatty liver disease (NAFLD) are clinically indistinguishable, and latter is more prevalent in diabetic patients and can progress to advanced liver disease and cirrhosis. Gradient dual-echo MRI can distinguish GH from NAFLD; however, GH can reliably be diagnosed only by liver biopsy. Adequate glycemic control can result in complete remission of clinical, laboratory and histological abnormalities. There has been a recent report of varying degree of liver fibrosis identified in patients with GH. Future studies are required to understand the biochemical defects underlying GH, noninvasive, rapid diagnostic tests for GH, and to assess the consequence of the fibrosis identified as severe fibrosis may progress to cirrhosis. Awareness of this entity in the medical community including specialists is low. Here we briefly reviewed the English literature on pathogenesis involved, recent progress in the evaluation, differential diagnosis, and management.
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Affiliation(s)
- Jagannath M Sherigar
- Department of Gastroenterology and Hepatology, NYP-Brooklyn Methodist Hospital, Brooklyn, NY 11215, United States
| | - Joline De Castro
- Department of Gastroenterology and Hepatology, NYP-Brooklyn Methodist Hospital, Brooklyn, NY 11215, United States
| | - Yong Mei Yin
- NYP-Brooklyn Methodist Hospital, Brooklyn, NY 11215, United States
| | - Debra Guss
- Department of Gastroenterology and Hepatology, NYP-Brooklyn Methodist Hospital, Brooklyn, NY 11215, United States
| | - Smruti R Mohanty
- Department of Gastroenterology and Hepatology, NYP-Brooklyn Methodist Hospital, Brooklyn, NY 11215, United States
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15
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Silva M, Marques M, Cardoso H, Rodrigues S, Andrade P, Peixoto A, Pardal J, Lopes J, Carneiro F, Macedo G. Glycogenic hepatopathy in young adults: a case series. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2017; 108:673-676. [PMID: 26900767 DOI: 10.17235/reed.2016.3934/2015] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Glycogenic hepatopathy is a rare and under-recognized 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 (AP). 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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Affiliation(s)
- Marco Silva
- Gastroenterology, Centro Hospitalar São João, Portugal
| | | | | | | | - Patrícia Andrade
- Gastroenterology department, Centro Hospitalar São João, Portugal
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16
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Focal Hepatic Glycogenosis in a Patient With Uncontrolled Diabetes Mellitus Type 1. J Comput Assist Tomogr 2017; 42:230-235. [PMID: 28937487 DOI: 10.1097/rct.0000000000000673] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Hepatomegaly and elevated liver enzymes in patients with diabetes are commonly associated with fatty liver disease. However, physicians often forget about another intrinsic substance that can cause a similar clinical picture-glycogen. Liver stores approximately one third of the total body glycogen and is responsible for blood glucose homeostasis. Excessive hepatocellular glycogen accumulation occurs not only in congenital glycogen storage diseases, but also in acquired conditions associated with hyperglycemic-hyperinsulinemic states such as uncontrolled diabetes mellitus, high-dose corticosteroid use, and dumping syndrome. All reported cases of acquired abnormal glycogen deposition described a diffuse form of hepatic glycogenosis with the entire liver involved in the accumulating process. To our knowledge, this is the first reported case of abnormal focal glycogen deposition in a patient with diabetes mellitus type 1 with imaging and pathologic correlation. Awareness of the imaging appearance of focal glycogen deposition can help to distinguish it from other pathologic conditions.
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17
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Glycogenic Hepatopathy: Resolution with Minimal Glucose Control. Case Reports Hepatol 2017; 2017:7651387. [PMID: 28529811 PMCID: PMC5424186 DOI: 10.1155/2017/7651387] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2017] [Accepted: 04/09/2017] [Indexed: 02/06/2023] Open
Abstract
We describe a presentation of glycogenic hepatopathy in a poorly controlled type I diabetic patient. As patients with glycogenic hepatopathy often have nonspecific complaints, diagnosis tends to be delayed and laboratory and imaging data are often indistinguishable from nonalcoholic fatty liver disease. Our patient's diagnosis of glycogenic hepatopathy required a liver biopsy, which demonstrated the characteristic pathology. Her symptoms resolved with minimal alteration to her insulin regimen and only slightly improved glucose control.
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18
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Satyarengga M, Zubatov Y, Frances S, Narayanswami G, Galindo RJ. GLYCOGENIC HEPATOPATHY: A COMPLICATION OF UNCONTROLLED DIABETES. AACE Clin Case Rep 2017; 3:e255-e259. [PMID: 28868358 DOI: 10.4158/ep161483.cr] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVE To describe a case of hepatomegaly and elevated transaminases in a patient with glycogenic hepatopathy (GH) as a complication of uncontrolled diabetes. METHODS Clinical, laboratory, and pathological information are described. RESULTS An 18-year-old male with uncontrolled type 1 diabetes and recurrent diabetic ketoacidosis (DKA) presented with abdominal distention and severe hyperglycemia. Physical examination revealed massive hepatomegaly. Laboratory evaluation showed anion-gap metabolic acidosis, ketonuria, and markedly elevated aspartate and alanine amino transaminases (AST = 1,162 IU/L and ALT = 598 IU/L, respectively). Despite resolution of DKA with insulin infusion, transaminases continued to increase (peak AST = 3,725 U/L, ALT = 1,049 U/L) with no signs of liver failure (normal coagulation profile and albumin level). Abdominal ultrasonography revealed an enlarged liver with moderate echogenicity, consistent with steatosis. Extensive evaluation for causes of hepatitis including toxic, autoimmune, genetic, and infectious diseases was unrevealing. Liver biopsy showed no signs of nonalcoholic fatty liver disease (NAFLD), such as fibrosis, steatosis, or portal inflammation. However, swollen hepatocytes with glycogen accumulation consistent with GH were seen. CONCLUSION GH can present as hepatomegaly and elevated liver transaminases in patients with uncontrolled diabetes. Clinicians should consider GH in patients with uncontrolled diabetes after ruling out other common causes. Liver ultrasound cannot differentiate this condition from the more commonly seen NAFLD. Although liver biopsy remains a gold standard, evaluation with magnetic resonance imaging may be considered as a less invasive alternative in the appropriate clinical setting.
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Affiliation(s)
- Medha Satyarengga
- Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai St Luke's Hospital, New York, New York
| | - Yelena Zubatov
- Division of Endocrinology, Diabetes, and Bone Diseases, Icahn School of Medicine at Mount Sinai, Mount Sinai St Luke's Hospital, New York, New York
| | - Sylvaine Frances
- Division of Endocrinology, Diabetes, and Bone Diseases, Icahn School of Medicine at Mount Sinai, Mount Sinai St Luke's Hospital, New York, New York
| | - Gopal Narayanswami
- Division of Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai St Luke's Hospital, New York, New York
| | - Rodolfo J Galindo
- Division of Endocrinology, Diabetes, and Bone Diseases, Icahn School of Medicine at Mount Sinai, Mount Sinai St Luke's Hospital, New York, New York
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19
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Umpaichitra V. Unusual glycogenic hepatopathy causing abnormal liver enzymes in a morbidly obese adolescent with well-controlled type 2 diabetes: resolved after A1c was normalized by metformin. Clin Obes 2016; 6:281-4. [PMID: 27400632 DOI: 10.1111/cob.12154] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Revised: 05/17/2016] [Accepted: 05/24/2016] [Indexed: 02/06/2023]
Abstract
We report, for the first time, a case of an accumulation of glycogen in the liver causing elevation of liver enzymes in a 15-year-old morbidly obese adolescent male with well-controlled type 2 diabetes. Notably, the patient did not have poorly controlled type 1 diabetes and did not require insulin. After normalization of the A1c with metformin, elevated liver enzymes returned to normal.
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Affiliation(s)
- Vatcharapan Umpaichitra
- Department of Pediatrics, State University of New York (SUNY) Downstate Medical Center and Kings County Hospital Center, Brooklyn, NY, USA
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20
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Irani NR, Venugopal K, Kontorinis N, Lee M, Sinniah R, Bates TR. Glycogenic hepatopathy is an under-recognised cause of hepatomegaly and elevated liver transaminases in type 1 diabetes mellitus. Intern Med J 2016; 45:777-9. [PMID: 26134697 DOI: 10.1111/imj.12807] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2014] [Accepted: 04/29/2015] [Indexed: 12/16/2022]
Abstract
Glycogenic hepatopathy (GH) is an under-recognised complication of type 1 diabetes mellitus (T1DM) not controlled to target resulting in hepatomegaly and elevated liver transaminases. We report the case of a 19-year-old man with T1DM not controlled to target who presented with abdominal pain, hepatomegaly and deranged liver transaminases. He was subsequently diagnosed with GH on liver biopsy, with the mainstay of treatment being reduction in caloric intake and insulin.
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Affiliation(s)
- N R Irani
- Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Western Australia, Australia
| | - K Venugopal
- Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Western Australia, Australia
| | - N Kontorinis
- Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Western Australia, Australia
| | - M Lee
- Department of General Medicine, Swan District Hospital, Perth, Western Australia, Australia
| | - R Sinniah
- Department of Pathology, Royal Perth Hospital, Perth, Western Australia, Australia
| | - T R Bates
- Department of General Medicine, Swan District Hospital, Perth, Western Australia, Australia.,School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia
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21
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Abstract
Liver involvement in diabetes is well recognized in the form of steatohepatitis and glycogenic hepatopathy. More recently, sinusoidal fibrosis, even in the absence of steatosis, has also been suggested to be associated with diabetes (diabetic hepatosclerosis); however, case-control studies are lacking. In addition, microangiopathy (hyaline arteriolosclerosis), a well-known complication of diabetes, has not been well studied in liver. Therefore, we undertook a cross-sectional blinded study with the specific aim of evaluating the association between hepatic sinusoidal fibrosis and hepatic arteriolosclerosis (HA) with diabetes. Liver biopsy findings from 89 diabetic patients obtained between January 2006 and December 2009 were compared with those of 89 nondiabetic patients matched by age and hepatitis C virus infection status. Patients with cirrhosis, liver mass, right heart failure, significant alcohol use, or insufficient available clinical information were excluded. Medical records were reviewed for the presence of diabetes, body mass index, diabetes treatment, and comorbidities at the time of biopsy (eg, underlying liver disease, hypertension, dyslipidemia). Liver biopsies were evaluated blinded to all clinical data (including presence or absence of diabetes) for a variety of histologic features, especially patterns of fibrosis and HA. Diabetic patients had a higher average body mass index (33 vs. 30 m/kg, P=0.0039), prevalence of hypertension (78% vs. 33%, P<0.0001), and dyslipidemia (52% vs. 20%, P<0.0001). Among diabetic patients, 87% had type 2 diabetes, and 57% used insulin. Whereas sinusoidal fibrosis, with or without steatosis, was not significantly associated with the presence of diabetes, HA was significantly more prevalent among diabetic patients compared with controls: 45% versus 29% (P=0.0298). The presence of both diabetes and hypertension had a significant odds for HA: with an adjusted odds ratio of 2.632 (95% confidence interval, 1.178-5.878; P=0.0183). Biliary changes were associated with HA in some cases (10.6%).In this study, we describe the histopathologic entity of HA for the first time. It is a small-vessel complication (microangiopathy) of the liver observed mainly in patients with diabetes who also have arterial hypertension. The clinical and prognostic implications of this finding, particularly regarding liver injury, remain to be further investigated.
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22
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Glycogenic Hepatopathy in Type 1 Diabetes Mellitus. Case Reports Hepatol 2015; 2015:236143. [PMID: 26347835 PMCID: PMC4546963 DOI: 10.1155/2015/236143] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Accepted: 07/28/2015] [Indexed: 12/16/2022] Open
Abstract
Glycogenic hepatopathy is a rare cause of high transaminase levels in type 1 diabetes mellitus. This condition, characterized by elevated liver enzymes and hepatomegaly, is caused by irreversible and excessive accumulation of glycogen in hepatocytes. This is a case report on a 19-year-old male case, diagnosed with glycogenic hepatopathy. After the diagnosis was documented by liver biopsy, the case was put on glycemic control which led to significant decline in hepatomegaly and liver enzymes. It was emphasized that, in type 1 diabetes mellitus cases, hepatopathy should also be considered in the differential diagnoses of elevated liver enzyme and hepatomegaly.
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23
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Julián MT, Alonso N, Ojanguren I, Pizarro E, Ballestar E, Puig-Domingo M. Hepatic glycogenosis: An underdiagnosed complication of diabetes mellitus? World J Diabetes 2015; 6:321-325. [PMID: 25789113 PMCID: PMC4360425 DOI: 10.4239/wjd.v6.i2.321] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2014] [Revised: 10/15/2014] [Accepted: 12/19/2014] [Indexed: 02/05/2023] Open
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.
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24
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Giordano S, Martocchia A, Toussan L, Stefanelli M, Pastore F, Devito A, Risicato MG, Ruco L, Falaschi P. Diagnosis of hepatic glycogenosis in poorly controlled type 1 diabetes mellitus. World J Diabetes 2014; 5:882-888. [PMID: 25512791 PMCID: PMC4265875 DOI: 10.4239/wjd.v5.i6.882] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2014] [Revised: 10/02/2014] [Accepted: 10/27/2014] [Indexed: 02/05/2023] Open
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.
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