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1
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Noh ES, Hwang IT. Triglyceride-glucose-alanine aminotransferase index: A noninvasive serum predictor for identifying the severity of pediatric nonalcoholic fatty liver disease. Medicine (Baltimore) 2024; 103:e38241. [PMID: 38941428 PMCID: PMC11466171 DOI: 10.1097/md.0000000000038241] [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: 11/23/2023] [Accepted: 04/25/2024] [Indexed: 06/30/2024] Open
Abstract
We hypothesized that the triglyceride-glucose (TyG)-alanine aminotransferase (ALT) index, which combines the TyG index with ALT, may enhance sensitivity and specificity in detecting the severity of nonalcoholic fatty liver disease (NAFLD). A total of 131 NAFLD patients with a mean age of 11.5 ± 2.29 years were enrolled, and severity was assessed by ultrasound fatty liver index (US-FLI) scoring. The TyG-ALT index was defined as ln(fasting triglyceride [mg/dL] × fasting glucose [mg/dL] × ALT [IU/L]/2). Multiple linear regression analysis revealed a significant association between the TyG-ALT index and US-FLI (β = 0.317, P < .001) after controlling for sex, age, and body mass index. The TyG-ALT index showed a more stable and superior ability to detect the severity of NAFLD compared to both ALT and the TyG index. The area under the curve values, listed in the order of ALT, TyG index, and TyG-ALT index, were as follows: 0.737 (P < .001), 0.599 (P = .055), and 0.704 (P < .001) at US-FLI ≥ 4 points; 0.717 (P < .001), 0.720 (P < .001), and 0.775 (P < .001) at US-FLI ≥ 5 points; and 0.689 (P < .05), 0.748 (P < .01), and 0.775 (P < .001) at US-FLI ≥ 6 points. The TyG-ALT index is associated with US-FLI score and superior to both ALT and the TyG index in predicting NAFLD severity. These findings indicate the potential of the TyG-ALT index in the management of pediatric NAFLD progression.
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Affiliation(s)
- Eu-Seon Noh
- Department of Pediatrics, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Il Tae Hwang
- Department of Pediatrics, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
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2
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Jarasvaraparn C, González IA, Tolliver KM, Haddad NG, Molleston JP. Characteristics, clinical laboratory, histopathology, and outcomes of glycogenic hepatopathy in children. JPGN REPORTS 2024; 5:119-125. [PMID: 38756113 PMCID: PMC11093915 DOI: 10.1002/jpr3.12046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 01/16/2024] [Indexed: 05/18/2024]
Abstract
Introduction Glycogenic hepatopathy (GH) is a rare complication of type I diabetes mellitus (DM1), resulting in abnormal deposition of glycogen in the liver due to poor glycemic control. Clinical characteristics and natural history of GH are not completely understood in children. In this study, we investigated clinical, biochemical, histologic parameters and outcomes in children with GH. Method This was a retrospective review of patients less than 18 years old diagnosed with GH and DM. GH was confirmed on liver biopsy. Medical records were reviewed for clinical presentation, laboratory tests, and clinical outcomes. Liver biopsy findings were reviewed by a pediatric pathologist (I. A. G.). Results Nine children were diagnosed with GH and type 1 DM. The median age at diagnosis of GH was 16 (IQR 14.5-17) years. Duration of diagnosis of DM until GH diagnosis was 7 (IQR 5-11) years. The median frequency of diabetic ketoacidosis before GH diagnosis was three times (IQR 2-5.25). Peak Aspartate transaminase (AST) and Alanine transaminase (ALT) ranged from 115 to 797, and 83-389 units/L, respectively. Only two children had mild fibrosis. Seven of nine had steatosis without steatohepatitis. There was no correlation between glycosylated hemoglobin (HbA1c), or other laboratory tests and liver fibrosis on biopsy. HbA1c was 11.2 (IQR 10.2-12.8) at GH diagnosis and 9.8 (IQR 9.5-10.8) with normalization of liver enzymes. Conclusion GH appears to be related to poor glycemic control in teenagers with long-term diabetes. GH presents with high to very high aminotransferase especially AST > ALT and resolves with modestly improved glycemic control. Diffuse hepatocyte swelling, steatosis, minimal fibrosis without hepatocyte ballooning or lobular inflammation are most common histological features.
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Affiliation(s)
- Chaowapong Jarasvaraparn
- Division of Pediatric Gastroenterology, Hepatology and NutritionIndiana University School of Medicine/Riley Hospital for ChildrenIndianapolisIndianaUSA
- Riley Hospital for Children at IU HealthIndiana University School of MedicineIndianapolisIndianaUSA
| | - Iván A. González
- Riley Hospital for Children at IU HealthIndiana University School of MedicineIndianapolisIndianaUSA
- Department of Pathology and Laboratory MedicineIndiana University School of MedicineIndianapolisIndianaUSA
| | - Kyla M. Tolliver
- Division of Pediatric Gastroenterology, Hepatology and NutritionIndiana University School of Medicine/Riley Hospital for ChildrenIndianapolisIndianaUSA
- Riley Hospital for Children at IU HealthIndiana University School of MedicineIndianapolisIndianaUSA
| | - Nadine G. Haddad
- Riley Hospital for Children at IU HealthIndiana University School of MedicineIndianapolisIndianaUSA
- Division of Pediatric Endocrinology and DiabetesIndiana University School of Medicine/Riley Hospital for ChildrenIndianapolisIndianaUSA
| | - Jean P. Molleston
- Division of Pediatric Gastroenterology, Hepatology and NutritionIndiana University School of Medicine/Riley Hospital for ChildrenIndianapolisIndianaUSA
- Riley Hospital for Children at IU HealthIndiana University School of MedicineIndianapolisIndianaUSA
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Lin Y, Huang H, Chen L, Chen R, Liu J, Zheng S, Ling Q. Assessing Donor Liver Quality and Restoring Graft Function in the Era of Extended Criteria Donors. J Clin Transl Hepatol 2023; 11:219-230. [PMID: 36406331 PMCID: PMC9647107 DOI: 10.14218/jcth.2022.00194] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 06/23/2022] [Accepted: 07/20/2022] [Indexed: 12/04/2022] Open
Abstract
Liver transplantation (LT) is the final treatment option for patients with end-stage liver disease. The increasing donor shortage results in the wide usage of grafts from extended criteria donors across the world. Using such grafts is associated with the elevated incidences of post-transplant complications including initial nonfunction and ischemic biliary tract diseases, which significantly reduce recipient survival. Although several clinical factors have been demonstrated to impact donor liver quality, accurate, comprehensive, and effective assessment systems to guide decision-making for organ usage, restoration or discard are lacking. In addition, the development of biochemical technologies and bioinformatic analysis in recent years helps us better understand graft injury during the perioperative period and find potential ways to restore graft function. Moreover, such advances reveal the molecular profiles of grafts or perfusate that are susceptible to poor graft function and provide insight into finding novel biomarkers for graft quality assessment. Focusing on donors and grafts, we updated potential biomarkers in donor blood, liver tissue, or perfusates that predict graft quality following LT, and summarized strategies for restoring graft function in the era of extended criteria donors. In this review, we also discuss the advantages and drawbacks of these potential biomarkers and offer suggestions for future research.
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Affiliation(s)
- Yimou Lin
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Haitao Huang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Lifeng Chen
- Department of Clinical Engineering and Information Technology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Ruihan Chen
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jimin Liu
- Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
| | - Shusen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Key Laboratory of Combined Multiorgan Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China
| | - Qi Ling
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Key Laboratory of Combined Multiorgan Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China
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4
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A Case of Glycogenic Hepatopathy as a Complication of Poorly Controlled Type 1 Diabetes Mellitus. Case Rep Endocrinol 2022; 2022:8939867. [PMID: 36211537 PMCID: PMC9537034 DOI: 10.1155/2022/8939867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 09/17/2022] [Indexed: 11/17/2022] Open
Abstract
A 23-year-old African American male with a medical history significant for poorly controlled type 1 diabetes mellitus (T1DM) presented with abdominal pain and vomiting. His laboratory workup was consistent with diabetic ketoacidosis (DKA). An acute elevation of liver enzymes was noted as the DKA resolved, with the alanine transferase and aspartate transferase levels elevated to more than 50 times the normal limit within the next 24 hours. Because abnormal liver function tests are found frequently in patients with type 1 diabetes mellitus, it is important to have a broad differential diagnosis. Furthermore, a low threshold of suspicion is required to identify a relatively underdiagnosed etiology like glycogenic hepatopathy (GH). This case report describes how patterns and trends of liver function tests provide important clues to the diagnosis of GH; how imaging modalities like ultrasonography, computerized tomography (CT) scan, and magnetic resonance imaging (MRI) scan could be used to differentiate GH from nonalcoholic fatty liver disease (NAFLD); and how the diagnosis of GH can be made without the need for invasive liver biopsy. The knowledge about GH should prevent its delayed diagnosis and improve the outcomes by appropriately managing uncontrolled type 1 DM.
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Sun Y, Qiang W, Wu R, Yin T, Yuan J, Yuan J, Gu Y. A glycogen storage disease type 1a patient with type 2 diabetes. BMC Med Genomics 2022; 15:205. [PMID: 36167523 PMCID: PMC9516787 DOI: 10.1186/s12920-022-01344-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 08/30/2022] [Indexed: 11/20/2022] Open
Abstract
Background Glycogen storage disease type 1a (GSD1a) is an inborn genetic disease caused by glucose-6-phosphatase-α (G6Pase-α) deficiency and is often observed to lead to endogenous glucose production disorders manifesting as hypoglycemia, hyperuricemia, hyperlipidemia, lactic acidemia, hepatomegaly, and nephromegaly. The development of GSD1a with diabetes is relatively rare, and the underlying pathogenesis remains unclear.
Case presentation Here we describe a case of a 25-year-old Chinese female patient with GSD1a, who developed uncontrolled type 2 diabetes mellitus (T2DM) as a young adult. The patient was diagnosed with GSD1a disease at the age of 10 and was subsequently treated with an uncooked cornstarch diet. Recently, the patient was treated in our hospital for vomiting and electrolyte imbalance and was subsequently diagnosed with T2DM. Owing to the impaired secretory function of the patient’s pancreatic islets, liver dysfunction, hypothyroidism, severe hyperlipidemia, and huge hepatic adenoma, we adopted diet control, insulin therapy, and hepatic adenoma resection to alleviate this situation. The WES discovered compound heterozygous mutations at the exon 5 of G6PC gene at 17th chromosome in the patient, c.648G>T (p.L216 L, NM_000151.4, rs80356484) in her father and c.674T>C (p.L225 P, NM_000151.4, rs1555560128) in her mother. c.648G>T is a well-known splice-site mutation, which causes CTG changing to CTT at protein 216 and creates a new splicing site 91 bp downstream of the authentic splice site, though both codons encode leucine. c.674T>C is a known missense mutation that causes TGC to become CGC at protein 225, thereby changing from coding for leucine to coding for proline.
Conclusion We report a rare case of GSD1a with T2DM. On the basis of the pathogenesis of GSD1a, we recommend attentiveness to possible development of fasting hypoglycemia caused by GSD and postprandial hyperglycemia from diabetes. As the disease is better identified and treated, and as patients with GSD live longer, this challenge may appear more frequently. Therefore, it is necessary to have a deeper and more comprehensive understanding of the pathophysiology of the disease and explore suitable treatment options. Supplementary Information The online version contains supplementary material available at 10.1186/s12920-022-01344-3.
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Affiliation(s)
- Yi Sun
- Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Wenhui Qiang
- Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.,Medical College, Nantong University, Nantong, Jiangsu, China
| | - Runze Wu
- Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.,Medical College, Nantong University, Nantong, Jiangsu, China
| | - Tong Yin
- Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Jie Yuan
- Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Jin Yuan
- Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Yunjuan Gu
- Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China. .,Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu, China.
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HCV Genotype Has No Influence on the Incidence of Diabetes-EpiTer Multicentre Study. J Clin Med 2022; 11:jcm11020379. [PMID: 35054072 PMCID: PMC8780546 DOI: 10.3390/jcm11020379] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 12/30/2021] [Accepted: 01/05/2022] [Indexed: 12/17/2022] Open
Abstract
HCV infection is one of the main reasons for liver cirrhosis and hepatocellular carcinoma. In recent years, one finds more and more extrahepatic manifestations of HCV infection, including its possible influence on the development of diabetes. In the presented work, one finds the frequency analysis of the incidence of diabetes among 2898 HCV infected patients treated in Poland, and the assessment of their relevance to the HCV genotype and the progression of fibrosis. The results indicate that the hepatitis C infection seems to be a risk factor for diabetes in persons with more advanced liver fibrosis, for older people, and for the male gender. Thus, one found no differences regarding the frequency of its incidence depending on HCV genotype, including genotype 3.
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7
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Naderi R, Pourheydar B, Ghiasi R, Shafiei F. Modulatory effect of tropisetron in the liver of streptozotocin-induced diabetes in rats: biochemical and histological evidence. Horm Mol Biol Clin Investig 2020; 41:hmbci-2020-0002. [PMID: 32364517 DOI: 10.1515/hmbci-2020-0002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 04/04/2020] [Indexed: 12/19/2022]
Abstract
Objectives There is an association between diabetes and liver disorders. Oxidative stress plays a crucial role in the pathology of hepatic abnormalities in diabetes. In this study, the effect of Tropisetron on the oxidative damage and histological alterations in the liver of type 1 diabetes mellitus (DM) were evaluated. Methods Thiry-five male Wistar rats were randomly divided into five experimental groups (n = 7): control (C), tropisetron (T), diabetes (D), diabetes + tropisetron (D + T) and diabetes + glibenclamide (D + G). A single injection of streptozotocin (STZ, 50 mg/kg; i.p) was used to induce diabetes. Tropisetron (3 mg/kg; i.p), as a 5-HT3 receptor antagonist and glibenclamide (1 mg/kg; i.p), as a positive control were given once daily for 2 weeks. Finally, animals were euthanized and liver samples were obtained for histopathological examination and biochemical measurements including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) levels. Results There is a significant increase in MDA (p < 0.001) level and a significant decrease (p < 0.001) in SOD and GPx contents in diabetic animals. Tropisetron attenuated MDA levels (p < 0.001) and enhanced SOD (p < 0.05) and GPx (p < 0.01) activities accompanied by histopathological improvement in the diabetes liver. Similar results were achieved in the rats treated with the standard drug, namely: glibenclamide. Conclusions Our findings indicate that tropisetron mitigates liver damage in the diabetes rats in part by attenuation of oxidative stress.
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Affiliation(s)
- Roya Naderi
- Nephrology and Kidney Transplant Research Center, Urmia University of Medical Sciences, Urmia, Islamic Republic of Iran.,Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Islamic Republic of Iran
| | - Bagher Pourheydar
- Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Islamic Republic of Iran.,Department of Anatomical Sciences, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Islamic Republic of Iran
| | - Rafigheh Ghiasi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran.,Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran
| | - Fardin Shafiei
- Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Islamic Republic of Iran
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8
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Wang L, Liu Q, Wang M, Du Y, Tan X, Xu B, Cheung U, Li E, Gilbert RG, Tang D. Effects of fasting on liver glycogen structure in rats with type 2 diabetes. Carbohydr Polym 2020; 237:116144. [PMID: 32241436 DOI: 10.1016/j.carbpol.2020.116144] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 02/08/2020] [Accepted: 03/07/2020] [Indexed: 12/25/2022]
Abstract
Liver glycogen, a highly branched glucose polymer, is important for blood sugar homeostasis. It comprises α particles which are made of linked β particles; the molecular structure changes diurnally. In diabetic liver, the α particles are fragile, easily breaking apart into β particles in chaotropic agents such as dimethyl sulfoxide. We here use size-exclusion chromatography to study how fasting changes liver-glycogen structure in vivo for mice in which type-2 diabetes had previously been induced. Diabetic glycogen degraded enzymatically more quickly in the fasted animals than did glycogen without fasting, with fewer α particles, which however were still fragile. The glycogen had fewer long chains and more shorter chains after fasting. This study gives an overview of the in vivo dynamic changes in α-particles under starvation conditions in both normal and diabetic livers.
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Affiliation(s)
- Liang Wang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China; Department of Bioinformatics, School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Qinghua Liu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China; Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Mengmeng Wang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China; Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Yan Du
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China; Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Xinle Tan
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia; Centre for Nutrition and Food Sciences, Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, Brisbane, Queensland 4072, Australia
| | - Bingju Xu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China; Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Ut Cheung
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia
| | - Enpeng Li
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, College of Agriculture, Yangzhou University, Yangzhou 225009, Jiangsu Province, China
| | - Robert G Gilbert
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia; Centre for Nutrition and Food Sciences, Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, Brisbane, Queensland 4072, Australia; Joint International Research Laboratory of Agriculture and Agri-Product Safety, College of Agriculture, Yangzhou University, Yangzhou 225009, Jiangsu Province, China.
| | - Daoquan Tang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China; Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
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Sahinturk V, Kacar S, Sahin E, Aykanat NEB. Investigation of endoplasmic reticulum stress and sonic hedgehog pathway in diabetic liver injury in mice. Life Sci 2020; 246:117416. [PMID: 32035927 DOI: 10.1016/j.lfs.2020.117416] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 12/31/2019] [Accepted: 02/05/2020] [Indexed: 12/16/2022]
Abstract
AIMS Diabetes is a common metabolic disease which damages many organs including the liver and causes endoplasmic reticulum (ER) stress, which originates from non-folded proteins. Sonic hedgehog (Shh) pathway plays a role in liver regeneration and repair. To our knowledge, there is no study showing the relation between ER stress and Shh pathway in the liver in diabetes. Thus, the aim of this study was to investigate the interaction between ER stress and Shh pathway in the liver of diabetic mice. MAIN METHODS Six groups of male mice were formed as control, diabetes (streptozotocine-treated), Shh activator (SAG-treated), Shh inhibitor (SANT1-treated), diabetes + SAG and diabetes + SANT1. At the end of the experiment, mice were weighed, anaesthetized and euthanized. Blood samples were collected, livers were excised and weighed. Thereafter, blood glucose, serum ALT and AST levels, TOS and TAC levels in liver tissue were measured. ER stress marker (GRP78) and Shh pathway molecules (Gli1 and Smo) were evaluated by immunohistochemistry, H-score and western blot analyses. Besides, histopathological examination was performed. KEY FINDINGS Results showed that GRP78, Gli1 and Smo were increased in liver due to Type 1 diabetes. The SAG agent decreased GRP78 and increased Gli1 and Smo, leading to liver repair, while the inhibitor SANT1 increased GRP78 and decreased Gli1and Smo, causing progression of the liver stress induced by diabetes. SIGNIFICANCE In conclusion, the Shh pathway is related to ER stress and may provide a new strategy for its treatment, especially liver stress induced by diabetes.
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Affiliation(s)
- Varol Sahinturk
- Ekisehir Osmangazi University, Faculty of Medicine, Department of Histology and Embryology, Eskisehir, Turkey.
| | - Sedat Kacar
- Ekisehir Osmangazi University, Faculty of Medicine, Department of Histology and Embryology, Eskisehir, Turkey
| | - Erhan Sahin
- Ekisehir Osmangazi University, Faculty of Medicine, Department of Histology and Embryology, Eskisehir, Turkey
| | - Nuriye Ezgi Bektur Aykanat
- Ekisehir Osmangazi University, Faculty of Medicine, Department of Histology and Embryology, Eskisehir, Turkey
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10
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Vendhan R, Amutha A, Anjana RM, Unnikrishnan R, Mohan V. Clinical profile of nonalcoholic Fatty liver disease among young patients with type 1 diabetes mellitus seen at a diabetes speciality center in India. Endocr Pract 2019; 20:1249-57. [PMID: 25100370 DOI: 10.4158/ep14044.or] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To estimate the prevalence and clinical profile of nonalcoholic fatty liver disease (NAFLD) among young type 1 diabetes mellitus (T1DM) patients at a tertiary care diabetes center in India. METHODS Electronic medical records of T1DM patients (age at first diagnosis of T1DM ≤25 years) registered between January 1992 and May 2013 who had undergone ultrasonography and denied history of any alcohol intake (n = 736) were reviewed. NAFLD was diagnosed if there was any degree of fatty liver. Retinopathy was initially assessed by direct and indirect ophthalmoscopy and later by retinal photography. Nephropathy was diagnosed if urine protein excretion was >500 mg/day, and neuropathy was diagnosed if a patient's vibration perception threshold on biothesiometry was ≥20 V. RESULTS A total of 204/736 (27.7%) T1DM patients had NAFLD. Compared to T1DM subjects without NAFLD those with NAFLD had higher body mass index (BMI) (18.9 ± 4.2 vs. 20.2 ± 4.7 kg/m2, P<.001), waist circumference (67.9 ± 13.2 vs. 71.9 ± 13.3 cm, P<.05), systolic blood pressure (110 ± 15 vs. 116 ± 18 mm Hg, P<.001) and diastolic blood pressure (72 ± 9 vs. 74 ± 10 mm Hg, P<.05), while fasting blood glucose (201 ± 101 vs. 183 ± 101 mg/dL, P<.05) and alkaline phosphatase (419 [12.5] vs. 315 [15.8], P<.001) levels were lower in patients with T1DM with NAFLD. Multiple logistic regression analysis showed a significant association between NAFLD and retinopathy (odds ratio [OR]: 2.01, 95% confidence interval [CI]: 1.13-3.43; P = .017, after adjusting for sex, duration of diabetes, overweight/obesity, hypertension, fasting plasma glucose, nephropathy, and nephropathy (OR: 1.89, 95% CI: 1.02-3.50; P = .042), after adjusting for sex and fasting plasma glucose. CONCLUSIONS This study suggests that NAFLD is also seen among T1DM patients and that it has an independent and significant association with retinopathy and nephropathy.
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Affiliation(s)
- Ramanujam Vendhan
- Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai, India
| | - Anandakumar Amutha
- Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai, India
| | - Ranjit Mohan Anjana
- Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai, India
| | - Ranjit Unnikrishnan
- Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai, India
| | - Viswanathan Mohan
- Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai, India
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11
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Molehin OR, Oloyede OI. Attenuation of oxidative stress and hepatic damage by white butterfly (Clerodendrum volubile) leaves in streptozotocin-induced diabetes in rats. J Basic Clin Physiol Pharmacol 2018; 30:81-89. [PMID: 30133418 DOI: 10.1515/jbcpp-2018-0083] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 07/06/2018] [Indexed: 06/08/2023]
Abstract
Background The negative impact of diabetes on the liver is well documented. The white butterfly (Clerodendrum volubile) leaf has been used in traditional practices for the treatment of various diseases, such as hypertension, diabetes, and rheumatism, but without scientific validation. This work was designed to evaluate the hepatoprotective properties of Clerodendrum volubile leaves on oxidative stress in streptozotocin (STZ)-induced diabetes in rats. Methods The rats were divided into ten groups of five rats each. Diabetes was induced by a single injection of STZ (65 mg/kg body weight; i.p), while the C. volubile extract (at the respective doses of 50, 100 and 200 mg/kg body weight) was given to diabetic and non-diabetic rats orally for 14 days. Metformin (100 mg/kg body weight) served as the positive control. Biochemical assays were conducted on the plasma for hematological parameters, along with hepatic marker damages and antioxidant enzyme determination in vivo to assess hepatic injury. Results The diabetic control rats showed significant increase (p<0.05) in marker enzymes: aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and malondiadehyde with reduction in reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase activities and plasma total protein content. Likewise, there were alterations in hematological indices in the diabetic control rats when compared with the normal control. However, treatment with C. volubile caused a reversal of the above parameters towards normal levels, thereby suggesting the modulating effect of the extract on oxidative stress, which may be a result of the high polyphenolic content and antioxidant capacity. Conclusions The protection of the liver tissues and the modulation of oxidative stress in STZ diabetic rats compare favorably to metformin, a standard antidiabetic drug.
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Affiliation(s)
- Olorunfemi R Molehin
- Department of Biochemistry, Faculty of Science, Ekiti State University, Ado-Ekiti P.M.B.5363 Ado-Ekiti, Nigeria, Phone: +234-803-462-1267, E-mail:
| | - Omotade I Oloyede
- Department of Biochemistry, Faculty of Science, Ekiti State University, Ado-Ekiti, Nigeria
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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: 54] [Impact Index Per Article: 7.7] [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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Ezekian B, Mulvihill MS, Freischlag K, Yerokun BA, Davis RP, Hartwig MG, Knechtle SJ, Barbas AS. Elevated HbA1c in donor organs from patients without a diagnosis of diabetes portends worse liver allograft survival. Clin Transplant 2017; 31. [PMID: 28667782 DOI: 10.1111/ctr.13047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/28/2017] [Indexed: 11/26/2022]
Abstract
Recipients of liver allografts from diabetic donors have decreased graft survival. However, limited data exist on the effects of donor HbA1c. We hypothesized that allografts from nondiabetic donors with elevated HbA1c would be associated with decreased survival. Liver transplant recipients from the UNOS database from nondiabetic donors were stratified into two groups: euglycemic (HbA1c<6.5) and hyperglycemic (HbA1c≥6.5). Propensity score matching (10:1) was used to adjust for donor and recipient characteristics. Kaplan-Meier analysis was used to assess survival. Donors of hyperglycemic allografts were older (49 vs 36, P<.001), were more likely to be non-white, had a higher BMI (29.8 vs 26.2, P<.001), were more likely to engage in heavy cigarette use (1.5% vs 1.3%, P=.004), had higher serum creatinine levels (1.3 vs 1.0, P=.002), and were more likely to be an expanded-criteria donor (35.8% vs 14.4%, P<.001). After propensity matching to account for these differences, allograft survival was significantly decreased in the recipients of hyperglycemic allografts (P=.049), and patient survival showed a trend toward reduction (P=.082). These findings suggest that HbA1c may be a simple and inexpensive test with potential utility for better organ risk stratification.
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Affiliation(s)
- Brian Ezekian
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | | | - Kyle Freischlag
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | | | - Robert P Davis
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Matthew G Hartwig
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Stuart J Knechtle
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Andrew S Barbas
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
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Abd Eldaim MA, Shaban Abd Elrasoul A, Abd Elaziz SA. An aqueous extract from Moringa oleifera leaves ameliorates hepatotoxicity in alloxan-induced diabetic rats. Biochem Cell Biol 2017; 95:524-530. [PMID: 28423281 DOI: 10.1139/bcb-2016-0256] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
This study was carried out to evaluate the possible mechanisms through which an aqueous extract from MO leaves demonstrates hepatoprotective effects in alloxan-induced diabetic rats. Eighty albino rats were assigned to 4 groups. The control group was orally administered sterile saline. The second group was injected with alloxan (150 mg/kg body mass (b.m.)) by intraperitoneal injection (i.p.). The third group was given MO (250 mg/kg b.m.) orally, daily. The fourth group was injected with alloxan, as for the second group, and administrated an aqueous extract of MO leaves, as for the third group. Alloxan induced degenerative changes in hepatic and pancreatic tissues, increased hepatic lipid peroxidation, and increased gene expression of PC and caspase 3. However, it decreased the activities of hepatic SOD and CAT, and gene expression of GS. In contrast, the MO extract prevented changes to the histoarchitecture of hepatic and pancreatic tissues and normalized the reduced hepatic levels of glutathione, as well as the activities of SOD and CAT, and the gene expression of GS, while reducing blood glucose levels, hepatic lipid peroxidation, and the gene expression of PC and caspase 3. This study indicated that an aqueous extract of MO leaves can be a potent antioxidant and used as an hepatoprotective agent.
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Affiliation(s)
- Mabrouk Attia Abd Eldaim
- a Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Menoufia University, Shebeen El-Kom, 32721, Menoufia, Egypt
| | - Ahmed Shaban Abd Elrasoul
- b Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, University of Sadat City, 32897, Egypt
| | - Samy Ahmed Abd Elaziz
- c Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Cairo University, Egypt
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Regulation of hepatic carbohydrate metabolism by Selenium during diabetes. Chem Biol Interact 2015; 232:1-6. [DOI: 10.1016/j.cbi.2015.02.017] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Revised: 02/16/2015] [Accepted: 02/23/2015] [Indexed: 11/20/2022]
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Adeyemi DO, Ukwenya VO, Obuotor EM, Adewole SO. Anti-hepatotoxic activities of Hibiscus sabdariffa L. in animal model of streptozotocin diabetes-induced liver damage. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2014; 14:277. [PMID: 25077880 PMCID: PMC4131030 DOI: 10.1186/1472-6882-14-277] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/02/2014] [Accepted: 07/21/2014] [Indexed: 11/10/2022]
Abstract
BACKGROUND Flavonoid-rich aqueous fraction of methanolic extract of Hibiscus sabdariffa calyx was evaluated for its anti-hepatotoxic activities in streptozotocin-induced diabetic Wistar rats. METHODS Diabetes Mellitus was induced in Wistar rats by a single i.p injection of 80 mg/kg b.w. streptozotocin (STZ) dissolved in 0.1 M citrate buffer (pH 6.3). RESULTS The ameliorative effects of the extract on STZ-diabetes induced liver damage was evident from the histopathological analysis and the biochemical parameters evaluated in the serum and liver homogenates. Reduced levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) (3.76 ± 0.38 μM, 0.42 ± 0.04 U/L, 41.08 ± 3.04 U/ml, 0.82 ± 0.04 U/L respectively) in the liver of diabetic rats were restored to a near normal level in the Hibiscus sabdariffa-treated rats (6.87 ± 0.51 μM, 0.72 ± 0.06 U/L, 87.92 ± 5.26 U/ml, 1.37 ± 0.06 U/L respectively). Elevated levels of aspartate amino transferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) in the serum of diabetic rats were also restored in Hibiscus sabdariffa -treated rats. Examination of stained liver sections revealed hepatic fibrosis and excessive glycogen deposition in the diabetic rats. These pathological changes were ameliorated in the extract-treated rats. CONCLUSION The anti-hepatotoxic activity of Hibiscus sabdariffa extract in STZ diabetic rats could be partly related to its antioxidant activity and the presence of flavonnoids.
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Affiliation(s)
- David O Adeyemi
- />Department of Anatomy and Cell Biology, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Victor O Ukwenya
- />Department of Anatomy, Ekiti State University, Ado Ekiti, Ekiti State Nigeria
| | - Efere M Obuotor
- />Department of Biochemistry, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Stephen O Adewole
- />Department of Anatomy and Cell Biology, Obafemi Awolowo University, Ile-Ife, Nigeria
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Beyond breast cancer: mammographic features and mortality risk in a population of healthy women. PLoS One 2013; 8:e78722. [PMID: 24205300 PMCID: PMC3808289 DOI: 10.1371/journal.pone.0078722] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2013] [Accepted: 09/17/2013] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Breast fibroglandular (dense) tissue is a risk factor for breast cancer. Beyond breast cancer, little is known regarding the prognostic significance of mammographic features. METHODS We evaluated relationships between nondense (fatty) breast area and dense area with all-cause mortality in 4,245 initially healthy women from the Breast Cancer Detection Demonstration Project; 1,361 died during a mean follow-up of 28.2 years. Dense area and total breast area were assessed using planimeter measurements from screening mammograms. Percent density reflects dense area relative to breast area and nondense area was calculated as the difference between total breast area and dense area. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression. RESULTS In age-adjusted models, greater nondense and total breast area were associated with increased risk of death (HR 1.17, 95% CI 1.10-1.24 and HR 1.13, 95% CI 1.06-1.19, per SD difference) while greater dense area and percent density were associated with lower risk of death (HR 0.91, 95% CI 0.86-0.95 and HR 0.87, 95% CI 0.83-0.92, per SD difference). Associations were not attenuated with adjustment for race, education, mammogram type (x-ray or xerogram), smoking status, diabetes and heart disease. With additional adjustment for body mass index, associations were diminished for all features but remained statistically significant for dense area (HR 0.94, 95% CI 0.89-0.99, per SD difference) and percent density (HR 0.93, 95% CI 0.87-0.98, per SD difference). CONCLUSIONS These data indicate that dense area and percent density may relate to survival in healthy women and suggest the potential utility of mammograms beyond prediction of breast cancer risk.
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Detection of potential chronic kidney disease markers in breath using gas chromatography with mass-spectral detection coupled with thermal desorption method. J Chromatogr A 2013; 1301:179-89. [DOI: 10.1016/j.chroma.2013.05.012] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2012] [Revised: 02/22/2013] [Accepted: 05/05/2013] [Indexed: 01/17/2023]
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Murphy RA, Register TC, Shively CA, Carr JJ, Ge Y, Heilbrun ME, Cummings SR, Koster A, Nevitt MC, Satterfield S, Tylvasky FA, Strotmeyer ES, Newman AB, Simonsick EM, Scherzinger A, Goodpaster BH, Launer LJ, Eiriksdottir G, Sigurdsson S, Sigurdsson G, Gudnason V, Lang TF, Kritchevsky SB, Harris TB. Adipose tissue density, a novel biomarker predicting mortality risk in older adults. J Gerontol A Biol Sci Med Sci 2013; 69:109-17. [PMID: 23707956 DOI: 10.1093/gerona/glt070] [Citation(s) in RCA: 96] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Knowledge of adipose composition in relation to mortality may help delineate inconsistent relationships between obesity and mortality in old age. We evaluated relationships between abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density, mortality, biomarkers, and characteristics. METHODS VAT and SAT density were determined from computed tomography scans in persons aged 65 and older, Health ABC (n = 2,735) and AGES-Reykjavik (n = 5,131), and 24 nonhuman primates (NHPs). Associations between adipose density and mortality (4-13 years follow-up) were assessed with Cox proportional hazards models. In NHPs, adipose density was related to serum markers and tissue characteristics. RESULTS Higher density adipose tissue was associated with mortality in both studies with adjustment for risk factors including adipose area, total fat, and body mass index. In women, hazard ratio and 95% CI for the densest quintile (Q5) versus least dense (Q1) for VAT density were 1.95 (1.36-2.80; Health ABC) and 1.88 (1.31-2.69; AGES-Reykjavik) and for SAT density, 1.76 (1.35-2.28; Health ABC) and 1.56 (1.15-2.11; AGES-Reykjavik). In men, VAT density was associated with mortality in Health ABC, 1.52 (1.12-2.08), whereas SAT density was associated with mortality in both Health ABC, 1.58 (1.21-2.07), and AGES-Reykjavik, 1.43 (1.07-1.91). Higher density adipose tissue was associated with smaller adipocytes in NHPs. There were no consistent associations with inflammation in any group. Higher density adipose tissue was associated with lower serum leptin in Health ABC and NHPs, lower leptin mRNA expression in NHPs, and higher serum adiponectin in Health ABC and NHPs. CONCLUSION VAT and SAT density provide a unique marker of mortality risk that does not appear to be inflammation related.
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Affiliation(s)
- Rachel A Murphy
- Laboratory of Population Science, National Institute on Aging, 7201 Wisconsin Ave, 3C-309 Bethesda, MD 20814.
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Diabetes mellitus and risk of hepatocellular carcinoma: findings from the Singapore Chinese Health Study. Br J Cancer 2013; 108:1182-8. [PMID: 23370206 PMCID: PMC3619062 DOI: 10.1038/bjc.2013.25] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background: The increasing prevalence of diabetes may contribute to the rising incidence of hepatocellular carcinoma (HCC) in the US and other developed countries where HCC incidence is relatively low. Data from prospective studies on diabetes and risk of HCC in at-risk populations due to high prevalence of viral hepatitis in southeast Asia are sparse. Methods: The Singapore Chinese Health Study is a prospective cohort of 63 257 middle-aged and older Chinese men and women enrolled in 1993–1998. Besides an in-person interview administered to all participants at baseline, testing of serologic markers of hepatitis B or C infections were performed on a subset of cohort subjects. After a mean follow-up of 14 years, 499 cohort participants developed HCC. Results: A history of diabetes at baseline was associated with a hazard ratio of 2.14 (95% confidence interval, 1.69–2.71). This statistically significant association was comparable in magnitude between men and women, and remained equally strong across strata of subjects defined by the number of years between their first clinical diagnosis of diabetes and time of enrolment in this cohort. Within a nested case-control set of cohort subjects tested for serological markers of hepatitis B or C infections, the diabetes–HCC association was found to be present mainly among those devoid of any markers. Conclusion: A history of diabetes at baseline is highly associated with non-viral HCC. Future studies are warranted to elucidate the biological mechanism underpinning the role of diabetes in nonviral-related hepatocarcinogenesis.
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Uncovering the beginning of diabetes: the cellular redox status and oxidative stress as starting players in hyperglycemic damage. Mol Cell Biochem 2013; 376:103-10. [PMID: 23292031 DOI: 10.1007/s11010-012-1555-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2012] [Accepted: 12/19/2012] [Indexed: 01/18/2023]
Abstract
Early hyperglycemic insult can lead to permanent, cumulative damage that might be one of the earliest causes for a pre-diabetic situation. Despite this, the early phases of hyperglycemic exposure have been poorly studied. We have previously demonstrated that mitochondrial injury takes place early on upon hyperglycemic exposure. In this work, we demonstrate that just 1 h of hyperglycemic exposure is sufficient to induce increased mitochondrial membrane potential and generation. This is accompanied (and probably caused) by a decrease in the cells' NAD(+)/NADH ratio. Furthermore, we show that the modulation of the activity of parallel pathways to glycolysis can alter the effects of hyperglycemic exposure. Activation of the pentose phosphate pathway leads to diminished effects of glucose on the above parameters, either by removing glucose from glycolysis or by NADPH generation. We also demonstrate that the hexosamine pathway inhibition also leads to a decreased effect of excess glucose. So, this work demonstrates the need for increased focus of study on the reductive status of the cell as one of the most important hallmarks of initial hyperglycemic damage.
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Al-Hussaini AA, Sulaiman NM, Alzahrani MD, Alenizi AS, Khan M. Prevalence of hepatopathy in type 1 diabetic children. BMC Pediatr 2012; 12:160. [PMID: 23039762 PMCID: PMC3506494 DOI: 10.1186/1471-2431-12-160] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2012] [Accepted: 10/01/2012] [Indexed: 12/16/2022] Open
Abstract
Background The Prevalence of liver disease among diabetics has been estimated to be between 17% and 100%. Most of these data were obtained from adult studies. The aim of our study was to screen for liver disease among type 1 diabetic children. Methods Children with type 1 diabetes following in clinic have been examined for existence of liver disease, from November 2008 to November 2009. All were subjected to the following: History, physical examination, liver function tests, fasting lipid profile, HbA1C, and ultrasound of the liver. A hyperechogenic liver and/or hepatomegaly on ultrasound were attributed most likely to excess glycogen or fat in the liver, after negative extensive work-up to rule out other underlying liver disease. Results 106 children with type 1 diabetes were studied: age ranged between 8 months to 15.5 years, sixty two patients were females. Twenty two patients (21%) were identified to have abnormal findings on ultrasound of the liver: 10 patients had hepatomegaly and 12 had hyperechogenic liver. The group with hyperechogenic liver had poorer glycemic control than patients with normal liver (Mean HbA1c 12.14% Vs 10.7%; P value = 0.09). Hyperechogenic liver resolved in 60% at 6 months follow-up upon achieving better glycemic control. Conclusions Hyperechogenic liver and/or hepatomegaly are not uncommon in children with type 1 diabetes and tend to be more prevalent among children with poor glycemic control. Type 1 diabetes related hepatopathy is reversible by optimizing glycemic control. Because of its safety, and reliability, ultrasound can be used to screen for hepatopathy in type 1 diabetic child.
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Affiliation(s)
- Abdulrahman A Al-Hussaini
- Division of Pediatric Gastroenterology, Hepatology & Nutrition, University of King Saud bin Abdulaziz for Health sciences Children's Hospital, PO box 59046, King Fahad Medical City, Riyadh, 11525, Kingdom of Saudi Arabia.
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Wu HT, Chen W, Cheng KC, Ku PM, Yeh CH, Cheng JT. Oleic acid activates peroxisome proliferator-activated receptor δ to compensate insulin resistance in steatotic cells. J Nutr Biochem 2012; 23:1264-70. [PMID: 22209682 DOI: 10.1016/j.jnutbio.2011.07.006] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2011] [Revised: 07/09/2011] [Accepted: 07/14/2011] [Indexed: 01/22/2023]
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Citrus unshiu peel extract ameliorates hyperglycemia and hepatic steatosis by altering inflammation and hepatic glucose- and lipid-regulating enzymes in db/db mice. J Nutr Biochem 2012; 24:419-27. [PMID: 22694954 DOI: 10.1016/j.jnutbio.2011.12.009] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2011] [Revised: 12/15/2011] [Accepted: 12/22/2011] [Indexed: 12/15/2022]
Abstract
Insulin resistance in Type 2 diabetes leads to hepatic steatosis that can accompanied by progressive inflammation of the liver. Citrus unshiu peel is a rich source of citrus flavonoids that possess anti-inflammatory, anti-diabetic and lipid-lowering effects. However, the ability of citrus unshiu peel ethanol extract (CPE) to improve hyperglycemia, adiposity and hepatic steatosis in Type 2 diabetes is unknown. Thus, we evaluated the effects of CPE on markers for glucose, lipid metabolism and inflammation in Type 2 diabetic mice. Male C57BL/KsJ-db/db mice were fed a normal diet with CPE (2 g/100 g diet) or rosiglitazone (0.001 g/100 g diet) for 6 weeks. Mice supplemented with the CPE showed a significant decrease in body weight gain, body fat mass and blood glucose level. The antihyperglycemic effect of CPE appeared to be partially mediated through the inhibition of hepatic gluconeogenic phosphoenolpyruvate carboxykinase mRNA expression and its activity and through the induction of insulin/glucagon secretion. CPE also ameliorated hepatic steatosis and hypertriglyceridemia via the inhibition of gene expression and activities of the lipogenic enzymes and the activation of fatty acid oxidation in the liver. These beneficial effects of CPE may be related to increased levels of anti-inflammatory adiponectin and interleukin (IL)-10, and decreased levels of pro-inflammatory markers (IL-6, monocyte chemotactic protein-1, interferon-γ and tumor necrosis factor-α) in the plasma or liver. Taken together, we suggest that CPE has the potential to improve both hyperglycemia and hepatic steatosis in Type 2 diabetes.
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Ren HB, Yu T, Liu C, Li YQ. Diabetes mellitus and increased risk of biliary tract cancer: systematic review and meta-analysis. Cancer Causes Control 2011; 22:837-47. [PMID: 21424210 DOI: 10.1007/s10552-011-9754-3] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2010] [Accepted: 03/02/2011] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Epidemiological evidences indicate that diabetic individuals may have an increased risk of several cancers; however, the relationships between diabetes and risk of cancers of biliary tract or its subsites remain unclear. METHODS To provide a quantitative assessment of this relationship, we identified studies by a literature search of Medline (from 1 January 1966) and EMBASE (from 1 January 1974), through 31 July 2010, and by searching the reference lists of pertinent articles. Summary relative risks with corresponding 95% confidence intervals were calculated with a random-effect model. RESULTS Analysis of 21 studies (8 case-control and 13 cohort studies) found that diabetes was associated with an increased risk of biliary tract cancer, compared with no diabetes (summary RRs = 1.43, 95% CI = 1.18-1.72), with significant heterogeneity among studies (p = 0.001). The positive association was also found between diabetes and risk of gallbladder cancer or extrahepatic cholangiocarcinoma, but not cancer of ampulla of Vater. No significant publication bias was found. CONCLUSION These findings strongly support the link between diabetes and increased risk of cancer of biliary tract and its subsites: gallbladder cancer or extrahepatic cholangiocarcinoma, but not cancer of ampulla of Vater.
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Affiliation(s)
- Hong-Bo Ren
- Department of Gastroenterology, Shandong University Qilu Hospital, Jinan, China
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Karthik D, Ravikumar S. Proteome and phytochemical analysis of Cynodon dactylon leaves extract and its biological activity in diabetic rats. ACTA ACUST UNITED AC 2011. [DOI: 10.1016/j.bionut.2010.09.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
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Karthik D, Ravikumar S. WITHDRAWN: Proteome and phytochemical analysis of Cynodon dactylon leaves extract and its biological activity in diabetic rats. Biomed Pharmacother 2010:S0753-3322(10)00169-1. [PMID: 21237613 DOI: 10.1016/j.biopha.2010.09.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2010] [Accepted: 09/16/2010] [Indexed: 10/19/2022] Open
Abstract
The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.bionut.2010.09.001. The duplicate article has therefore been withdrawn.
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Affiliation(s)
- D Karthik
- Department of Biotechnology, PRIST University, Thanjavur,Tamil Nadu 613 403,India
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Shebl FM, Andreotti G, Rashid A, Gao YT, Yu K, Shen MC, Wang BS, Li Q, Han TQ, Zhang BH, Fraumeni JF, Hsing AW. Diabetes in relation to biliary tract cancer and stones: a population-based study in Shanghai, China. Br J Cancer 2010; 103:115-9. [PMID: 20517308 PMCID: PMC2905288 DOI: 10.1038/sj.bjc.6605706] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Revised: 04/20/2010] [Accepted: 04/28/2010] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Biliary tract cancers are rare but fatal malignancies. Diabetes has been related to biliary stones, but its association with biliary tract cancers is less conclusive. METHODS In a population-based case-control study of 627 cancers, 1037 stones, and 959 controls in Shanghai, China, we examined the association between diabetes and the risks of biliary tract cancer and stones, as well as the effect of potential mediating factors, including serum lipids and biliary stones (for cancer), contributing to the causal pathway from diabetes to biliary diseases. RESULTS Independent of body mass index (BMI), diabetes was significantly associated with gallbladder cancer and biliary stones ((odds ratio (OR) (95% confidence interval)=2.6 (1.5-4.7) and 2.0 (1.2-3.3), respectively). Biliary stones and low serum levels of high-density lipoprotein (HDL) were significant mediators of the diabetes effect on gallbladder cancer risk, accounting for 60 and 17% of the diabetes effect, respectively. High-density lipoprotein was also a significant mediator of the diabetes effect on biliary stones, accounting for 18% of the diabetes effect. CONCLUSIONS Independent of BMI, diabetes is a risk factor for gallbladder cancer, but its effect is mediated in part by biliary stones and serum HDL levels, suggesting that gallbladder cancer risk may be reduced by controlling diabetes, stones, and HDL levels.
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Affiliation(s)
- F M Shebl
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
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Xu KZY, Zhu C, Kim MS, Yamahara J, Li Y. Pomegranate flower ameliorates fatty liver in an animal model of type 2 diabetes and obesity. JOURNAL OF ETHNOPHARMACOLOGY 2009; 123:280-287. [PMID: 19429373 DOI: 10.1016/j.jep.2009.03.035] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/28/2008] [Revised: 03/03/2009] [Accepted: 03/07/2009] [Indexed: 05/27/2023]
Abstract
AIMS OF THE STUDY Fatty liver is the most common cause of abnormal liver function tests. We investigated the effect and its underlying mechanism of pomegranate flower (PGF), a traditional antidiabetic medicine, on fatty liver. MATERIALS AND METHODS At the endpoint of treatment of male Zucker diabetic fatty (ZDF) rats with PGF extract (500 mg/kg, p.o. x 6 weeks), liver weight index, hepatic lipid contents (enzymatic colorimetric methods) and droplet accumulation (Oil Red O staining) were determined. Gene profiles (RT-PCR) were analyzed in the liver of ZDF rats and in human liver-derived HepG2 cell line. RESULTS PGF-treated ZDF rats showed reduced ratio of liver weight to tibia length, hepatic triglyceride contents and lipid droplets. These effects were accompanied by enhanced hepatic gene expression of peroxisome proliferator-activated receptor (PPAR)-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase (ACO), and reduced stearoyl-CoA desaturase-1. In contrast, PGF showed minimal effects on expression of genes responsible for synthesis, hydrolysis or uptake of fatty acid and triglycerides. PGF treatment also increased PPAR-alpha and ACO mRNA levels in HepG2 cells. CONCLUSION Our findings suggest that this Unani medicine ameliorates diabetes and obesity-associated fatty liver, at least in part, by activating hepatic expression of genes responsible for fatty acid oxidation.
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Affiliation(s)
- Kevin Zhe-Yang Xu
- Faculty of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia
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Itoi-Babaya M, Ikegami H, Fujisawa T, Ueda H, Nojima K, Babaya N, Kobayashi M, Noso S, Kawaguchi Y, Yamaji K, Shibata M, Ogihara T. Fatty liver and obesity: phenotypically correlated but genetically distinct traits in a mouse model of type 2 diabetes. Diabetologia 2007; 50:1641-8. [PMID: 17549450 DOI: 10.1007/s00125-007-0700-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2007] [Accepted: 03/29/2007] [Indexed: 01/14/2023]
Abstract
AIMS/HYPOTHESIS Obesity and fatty liver are commonly associated with type 2 diabetes, but the genetic and functional bases linking fatty liver with obesity and diabetes are largely unknown. Our aim was to investigate the association of fatty liver with obesity and other diabetes-related phenotypes and to define the genetic control of obesity and fatty liver. MATERIALS AND METHODS We established 306 F2 mice by crossing Nagoya-Shibata-Yasuda (NSY) mice, an animal model of type 2 diabetes, with control C3H mice, and analysed their phenotypes. Whole-genome screening of F2 mice was performed to identify the loci responsible for fatty liver and obesity. RESULTS A strong association of fatty liver with obesity, hyperinsulinaemia and hyperglycaemia was observed in F2 mice. Using whole-genome screening in 306 F2 mice, we mapped a new locus for fatty liver (Fl1n) on chromosome 6 (maximum logarithm of odds score [MLS] 10.0) and one for body weight (Bw1n) on chromosome 7 (MLS 5.1). Fl1n was linked to epididymal fat weight as well as fatty liver, but its effects were opposite in the two tissues in that the NSY allele increased liver fat but decreased epididymal fat, suggesting a role of Fl1n in partitioning of fat mass. The sequence of peroxisome proliferator-activated receptor gamma (Pparg), a candidate for Fl1n, showed allelic variation between NSY and C3H mice. CONCLUSIONS/INTERPRETATION These data suggest that fatty liver and obesity are phenotypically related but genetically independent. Loci homologous to Fl1n and Bw1n are good candidate genes for susceptibility to fatty liver and obesity in humans.
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Affiliation(s)
- M Itoi-Babaya
- Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Japan
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31
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García A, Xu S, Dewhirst FE, Nambiar PR, Fox JG. Enterohepatic Helicobacter species isolated from the ileum, liver and colon of a baboon with pancreatic islet amyloidosis. J Med Microbiol 2006; 55:1591-1595. [PMID: 17030922 DOI: 10.1099/jmm.0.46707-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Microaerobic bacteria were isolated from a baboon with pancreatic islet amyloidosis and hepatitis. Phenotypic and molecular analyses identified two distinct helicobacters. Analyses of 16S rRNA demonstrated "Helicobacter macacae" in the ileum and liver, and Helicobacter cinaedi in the colon. To the best of the authors' knowledge, this is the first report describing the isolation of enterohepatic Helicobacter species from a baboon.
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Affiliation(s)
- Alexis García
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Shilu Xu
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Floyd E Dewhirst
- Department of Molecular Genetics, The Forsyth Institute, Boston, MA 02115, USA
| | - Prashant R Nambiar
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - James G Fox
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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Saravanan R, Pari L. Succinic acid monoethyl ester, a novel insulinotropic agent: effect on lipid composition and lipid peroxidation in streptozotocin-nicotin-amide induced type 2 diabetic rats. Mol Cell Biochem 2006; 296:165-76. [PMID: 17006620 DOI: 10.1007/s11010-006-9312-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2006] [Accepted: 08/25/2006] [Indexed: 02/02/2023]
Abstract
Succinic acid monoethyl ester (EMS) is recently proposed as an insulinotropic agent for the treatment of non-insulin dependent diabetes mellitus. Oxidative stress has been suggested to be a contributory factor in the development and complications of diabetes. In the present study the effect of EMS and Metformin on plasma glucose, insulin, serum and tissue lipid profile, lipoproteins and lipid peroxidation in streptozotocin-nicotinamide induced type 2 diabetic model was investigated. The carboxylic nutrient EMS was administered intraperitonially (8 micromol/g body weight) to streptozotocin diabetic rats for 30 days. The levels of thiobarbituric acid reactive substances (TBARS) and hydroperoxides in liver and kidney and serum and tissue lipids [cholesterol, triglycerides, phospholipids and free fatty acids] and very low density lipoprotein-cholesterol (VLDL-C) and low density lipoprotein-cholesterol (LDL-C), were significantly increased in diabetic rats, whereas the levels of high-density lipoprotein-cholesterol (HDL-C) and antiatherogenic index (AAI) (ratio of HDL to total cholesterol) were significantly decreased. The effect of EMS was compared with metformin, a reference drug. Treatment with EMS and metformin resulted in a significant reduction of plasma glucose with increase plasma insulin in diabetic rats. EMS also resulted in a significant decrease in serum and tissue lipids and lipid peroxidation products. These biochemical observations were supplemented by histopathological examination of liver and kidney section. Our results suggest the possible antihyperlipidemic and antiperoxidative effect of EMS apart from its antidiabetic effect.
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Affiliation(s)
- Ramalingam Saravanan
- Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, Tamil Nadu 608 002, India
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Affiliation(s)
- Robert E Shangraw
- Department of Anesthesiology, School of Medicine, Oregon Health and Science University, Portland, OR 97201, USA
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Su CC, Wang K, Hsia TL, Chen CS, Tung TH. Association of nonalcoholic fatty liver disease with abnormal aminotransferase and postprandial hyperglycemia. J Clin Gastroenterol 2006; 40:551-554. [PMID: 16825939 DOI: 10.1097/00004836-200607000-00015] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
GOALS This study was conducted to explore the association between nonalcoholic fatty liver disease and glucose metabolism as well as insulin resistance using the homeostasis model assessment method (HOMA). STUDY From July 2003 to June 2004, 23 patients with ultrasound-proved fatty liver and either normal (10 patients) or abnormal (13 patients) serum aminotransferase levels were enrolled. Blood tests included a routine biochemistry, a 75-g glucose oral glucose tolerance test (OGTT) with blood sampled at 30-minute intervals during a 120-minute period. Fasting and 120-minute serum leptin, insulin, and C-peptide concentrations were also measured. RESULTS Using the Mann-Whitney U test, significant differences were found in gamma glutamyl transpeptidase (28.6+/-7.9 vs. 65.1+/-65.9 U/L, P=0.008), fasting insulin (FI) (13.11+/-7.53 vs. 31.76+/-42.95 muU/mL, P=0.02), fasting C-peptide (3.82+/-3.00 vs. 2.17+/-0.43 ng/mL, P=0.01), fasting leptin (10.34+/-4.05 vs. 24.27+/-24.97 ng/mL, P=0.01), HOMA-IR (3.34+/-1.06 vs. 8.81+/-13.18, P=0.02), and HOMA beta-cell function (120.32+/-52.50 vs. 242.20+/-247.29, P=0.02) between normal and abnormal ALT/AST function groups. From the 75-g OGTT, no significant difference of plasma glucose was noted at 0, 30, 60, and 90 minutes but significant change was noted in 120-minute plasma glucose (99.3+/-21.5 vs. 131.4+/-27.3 mg/dL, P=0.004) of 2 groups. CONCLUSIONS In conclusion, patients with fatty liver proved by ultrasound sonography might be at high risk of developing type 2 diabetes, especially when they had elevated liver enzymes. OGTT is warranted for the early diagnosis of these high risk patients.
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Affiliation(s)
- Ching-Chieh Su
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Cardinal Tien Hospital, Taipei, Taiwan.
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Abstract
BACKGROUND Many reports in the literature suggest that chronic hepatitis C virus (HCV) infection is associated with diabetes, but the results are conflicting. The aim of our study was to investigate the seroprevalence of hepatitis B virus (HBV) and HCV infections in type 2 diabetes mellitus (DM) patients. METHODS We collected 820 consecutive type 2 diabetic patients attending 2 of 5 outpatient endocrinology clinics in Far Eastern Memorial Hospital from March to July 2003. The control group consisted of 905 subjects who came for medical check-ups at the Family Medicine Department. We determined hepatitis B surface antigen (HBsAg) and anti-HCV in both groups, using third-generation microparticle enzyme immunoassay. RESULTS No significant difference was found between type 2 DM patients and the control group for seropositivity of HBsAg (13.5% versus 12.4%; odds ratio [OR] = 1.09; 95% confidence interval [CI]: 0.77-1.55; p = 0.441), but anti-HCV seropositivity was detected in 6.8% of patients and 2.6% of the control subjects (OR = 2.87; 95% CI: 1.51-5.46; p < 0.001). In anti-HCV-positive DM patients, abnormal alanine aminotransferase was observed in 61.8%, compared with only 34.2% of anti-HCV-negative DM patients (p < 0.001). We did not observe any difference in risk factors for HCV infection between anti-HCV-positive and -negative DM patients. CONCLUSION The rate of seropositive anti-HCV is 2.8 times higher in type 2 DM patients than non-diabetic control subjects.
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Affiliation(s)
- Hua-Fen Chen
- Division of Endocrinology, Department of Internal Medicine, Far-Eastern Memorial Hospital, Panchiao, Taiwan, ROC
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36
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Lee SH, Kwon HS, Shin JA, Kim WC, Kim JH, Choi YH, Yoon KH, Cha BY, Lee KW, Son HY, Kang SK. A Case of Hepatic Glycogenosis in a Patient with Uncontrolled Type 1 Diabetes Mellitus. ACTA ACUST UNITED AC 2006. [DOI: 10.4093/jkda.2006.30.1.82] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Seung-Hwan Lee
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hyuk-Sang Kwon
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jung-Ah Shin
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Won-Chul Kim
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jeong-Hoon Kim
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yoon-Hee Choi
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kun-Ho Yoon
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Bong-Yun Cha
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kwang-Woo Lee
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ho-Young Son
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sung-Koo Kang
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
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Abstract
Insulin resistance (IR) is the pathophysiological hallmark of nonalcoholic fatty liver disease (NAFLD), one of the most common causes of chronic liver disease in Western countries. We review the definition of IR, the methods for the quantitative assessment of insulin action, the pathophysiology of IR, and the role of IR in the pathogenesis of chronic liver disease. Increased free fatty acid flux from adipose tissue to nonadipose organs, a result of abnormal fat metabolism, leads to hepatic triglyceride accumulation and contributes to impaired glucose metabolism and insulin sensitivity in muscle and in the liver. Several factors secreted or expressed in the adipocyte contribute to the onset of a proinflammatory state, which may be limited to the liver or more extensively expressed throughout the body. IR is the common characteristic of the metabolic syndrome and its related features. It is a systemic disease affecting the nervous system, muscles, pancreas, kidney, heart, and immune system, in addition to the liver. A complex interaction between genes and the environment favors or enhances IR and the phenotypic expression of NAFLD in individual patients. Advanced fibrotic liver disease is associated with multiple features of the metabolic syndrome, and the risk of progressive liver disease should not be underestimated in individuals with metabolic disorders. Finally, the ability of insulin-sensitizing, pharmacological agents to treat NAFLD by reducing IR in the liver (metformin) and in the periphery (thiazolidinediones) are discussed.
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Ji J, Zhang L, Wang P, Mu YM, Zhu XY, Wu YY, Yu H, Zhang B, Chen SM, Sun XZ. Saturated free fatty acid, palmitic acid, induces apoptosis in fetal hepatocytes in culture. ACTA ACUST UNITED AC 2005; 56:369-76. [PMID: 15945276 DOI: 10.1016/j.etp.2005.02.003] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
To investigate the effects of saturated free fatty acid, palmitic acid (PA), on hepatocytes, we administered PA to rat hepatocytes. We demonstrated that PA inhibited the cell growth as a dose- and time-dependent manner in rat hepatocytes. PA-induced morphological changes including swelling, membrane dissolution and formation of debris, and apoptosis with appearance of sub-G1 fraction determined by cell cycle analysis after treatment for 4 days. The level of Bcl-2 was slightly decreased, in contrast, the level of Bax elevated markedly, which resulted in a significant decrease of Bcl-2/Bax ratio after PA treatment on HepG2 cells. These findings demonstrated that PA induces cell death on hepatocytes, perhaps via mitochondria-mediated apoptosis. Furthermore, the present study indicates that PA's cell toxicity may play important roles in the transition from steatosis to steatohepatitis in human especially with obesity.
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Affiliation(s)
- Jun Ji
- Department of Central Laboratory, Dalian Municipal Central Hospital, Xuegong Street 42, Shahekou-qu, Dalian 116033, China
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Nishitani S, Takehana K, Fujitani S, Sonaka I. Branched-chain amino acids improve glucose metabolism in rats with liver cirrhosis. Am J Physiol Gastrointest Liver Physiol 2005; 288:G1292-300. [PMID: 15591158 DOI: 10.1152/ajpgi.00510.2003] [Citation(s) in RCA: 124] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
It is well established that impaired glucose metabolism is a frequent complication in patients with hepatic cirrhosis. We previously showed that leucine, one of the branched-chain amino acids (BCAA), promotes glucose uptake under insulin-free conditions in isolated skeletal muscle from normal rats. The aim of the present study was to evaluate the effects of BCAA on glucose metabolism in a rat model of CCl(4)-induced cirrhosis (CCl(4) rats). Oral glucose tolerance tests were performed on BCAA-treated CCl(4) rats. In the CCl(4) rats, treatment with leucine or isoleucine, but not valine, improved glucose tolerance significantly, with the effect of isoleucine being greater than the effect of leucine. Glucose uptake experiments using isolated soleus muscle from the CCl(4) rats revealed that leucine and isoleucine, but not valine, promoted glucose uptake under insulin-free conditions. To clarify the mechanism of the blood glucose-lowering effects of BCAA, we collected soleus muscles from BCAA-treated CCl(4) rats with or without a glucose load. These samples were used to determine the subcellular location of glucose transporter proteins and glycogen synthase (GS) activity. Oral administration of leucine or isoleucine without a glucose load induced GLUT4 and GLUT1 translocation to the plasma membrane. GS activity was augmented only in leucine-treated rats and was completely inhibited by rapamycin, an inhibitor of mammalian target of rapamycin. In summary, we found that leucine and isoleucine improved glucose metabolism in CCl(4) rats by promoting glucose uptake in skeletal muscle. This effect occurred as a result of upregulation of GLUT4 and GLUT1 and also by mammalian target of rapamycin-dependent activation of GS in skeletal muscle. From these results, we consider that BCAA treatment may have beneficial effects on glucose metabolism in cirrhotic patients.
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Affiliation(s)
- Shinobu Nishitani
- Pharmaceutical Research Laboratories, Ajinomoto Co., Inc., Kawasaki-ku, Kawasaki-shi, Japan.
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40
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Liu CM, Tung TH, Liu JH, Chen VTK, Lin CH, Hsu CT, Chou P. A community-based epidemiological study of elevated serum alanine aminotransferase levels in Kinmen, Taiwan. World J Gastroenterol 2005; 11:1616-1622. [PMID: 15786537 PMCID: PMC4305941 DOI: 10.3748/wjg.v11.i11.1616] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2004] [Revised: 09/08/2004] [Accepted: 11/10/2004] [Indexed: 02/06/2023] Open
Abstract
AIM To explore any gender-related differences in prevalence of and condition-associated factors related to an elevated serum alanine aminotransferase (ALT) level amongst residents of Kinmen, Taiwan. METHODS A total of 11,898 of a potential 20,112 regional residents aged 30 years or more completed a related questionnaire that was carried out by the Yang-Ming Crusade between 1991 and 1994 inclusively, with blood samples being collected by public nurses. The overall questionnaire response rate was 59.3% (52.4% for males and 66.0% for females). RESULTS The prevalence of an elevated serum ALT level for this sub-population was found to be 7.2%, the prevalence revealing a statistically significant decrease with increasing population age (P<0.0001). Males exhibited a greater prevalence of elevated serum ALT level than did females (9.4% vs 5.3%, P<0.0001). Using multiple logistic regression analysis, in addition to male gender, a younger age, greater waist circumference, presence of type-2 diabetes and hyperuricemia were the significant factors associated with an elevated serum ALT level for both males and females. Gender-related differences as regards associated factors were also revealed. For males, obesity was significantly related to an elevated serum ALT level (OR = 1.28, 95%CI: 1.00-1.66) but this was not so for females (OR = 1.09, 95%CI: 0.84-1.42). Hypertriglyceridemia (OR = 1.80, 95%CI: 1.36-2.39) and hyperuricemia (OR = 1.61, 95%CI: 1.03-2.52) were significantly related to elevated serum ALT levels only for females. CONCLUSION Several gender-related differences were noted pertaining to the prevalence of and relationship between obesity, hypertriglyceridemia and hyperuricemia and elevated serum ALT level in the present study.
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Affiliation(s)
- Chi-Ming Liu
- Community Medicine Research Center, National Yang-Ming University, Shih-Pai, 112, Taipei, Taiwan, China.
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Mimasaka S, Funayama M, Azumi J, Morita M. Child death related to insulin omission by mother. ACTA ACUST UNITED AC 2004; 5:72-6. [PMID: 15335542 DOI: 10.1016/s1353-1131(98)90057-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
A 4-year-old child was found dead in her house. She had been suffering from insulin-dependent diabetes mellitus (IDDM) for 3 years. She had been admitted to hospital three times, and attended the hospital once a month. Her glycaemic control remained poor. Autopsy findings revealed a remarkably fatty liver and lack of beta cells in the pancreatic islets of Langerhans. The laboratory reported ketoacidosis, ketonuria, glycosuria, and high levels of vitreous glucose and ketones. Her father had been absent for the 3 days before her death, and the mother should have fed her. Her mother was found drunk on the floor. No detailed history was available because of the mother's death, but the probability of the mother's omission of the insulin injection was suggested. Poor control of IDDM might have also been closely connected to general neglect by the mother. This case was considered child abuse.
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Affiliation(s)
- S Mimasaka
- Department of Legal Medicine, Sapporo Medical University, School of Medicine, S. 1, W. 17, Chuo-ku, Sapporo 060-8556, Japan
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Abstract
Pathologists have long been involved in clinical diagnosis and investigative studies of various forms of liver disease, including alcoholic liver disease. The concept that progressive fatty liver disease may result from causes other than alcohol toxicity can be noted in the literature. However, acceptance of this as a bona fide form of liver disease has been credited to an in-depth study published in 1980 of patients gathered from cases in the files of the pathology department of the Mayo Clinic in whom liver biopsies showed histological similarities to alcoholic steatohepatitis, but for whom clinical evidence of alcohol use was absent. Subsequent studies of the natural history and pathogenesis of non-alcoholic steatohepatitis have relied on detailed histopathological correlations. This chapter will elucidate the constellation of microscopic findings, the issues of concern for pathological evaluation and the knowledge to date of their significance in various forms of fatty liver disease.
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Affiliation(s)
- Elizabeth M Brunt
- Department of Pathology, Saint Louis University School of Medicine, 4th Floor, 3635 Vista Avenue, St. Louis, MO 63110, USA
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Abstract
Type 2 diabetes is strongly associated with nonalcoholic fatty liver disease (NAFLD), a spectrum of liver damage that ranges from relatively benign hepatic steatosis to potentially fatal cirrhosis. The severities of insulin resistance and liver damage parallel each other, with the greatest prevalence of cirrhosis occurring in cirrhotics. However, it is unknown whether one of these conditions causes the other, or if both are consequences of another process. Experimental evidence suggests that both insulin resistance and NAFLD result from a chronic inflammatory state. The mechanisms driving this chronic inflammation are unknown but might include the egress of products from intestinal bacteria into the portal blood, liver, and systemic circulation to trigger a sustained inflammatory cytokine response in genetically susceptible individuals. More research is needed to evaluate this hypothesis and to determine the benefits of treatments that interrupt this pathogenic cascade.
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Affiliation(s)
- Jeanne M Clark
- Department of Medicine, Johns Hopkins University School of Medicine, 912 Ross Building, 720 Rutland Street, Baltimore, MD 21205, USA
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44
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Abstract
The constellation of histopathologic lesions that characterize alcoholic and nonalcoholic steatohepatitis has been well described and has served as the basis for clinical diagnosis, natural history studies, and experimental models for analyses of etiopathogenesis. The lesions common to both entities include, to varying degrees, steatosis, liver cell ballooning, lobular inflammation with a notable component of polymorphonuclear leukocytes, and a characteristic form of fibrosis that is initially located in the perisinusoidal regions of acinar zone 3. Cirrhosis with or without steatosis or steatohepatitis may occur in both entities. Mallory's hyaline is common but not necessary; megamitochondria and varying amounts of iron may be observed in either process. Hepatocellular carcinoma is a recognized complication of both processes, albeit with greater frequency in the former. Alcoholic hepatitis may present with more severe clinical and histologic manifestations than the nonalcoholic counterpart, including significant morbidity and mortality. The perivenular lesions collectively referred to as sclerosing hyaline necrosis are markers of severity, and are not common in nonalcoholics. In many instances, however, the microscopic lesions of these two processes are similar, likely as a reflection of common pathogenetic pathways, and the distinction between the two is ultimately clinically derived.
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Affiliation(s)
- Elizabeth M Brunt
- Department of Pathology, Saint Louis University School of Medicine, 4th Floor, SLUH, 3635 Vista Avenue, St. Louis, MO 63110, USA.
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45
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Abstract
Decreased insulin sensitivity plays a major role in various human diseases. particularly type 2 diabetes mellitus, and is associated with a higher risk of atherosclerosis and cardiovascular complications. Thiazolidinediones, more commonly termed glitazones, are the first drugs to specifically target muscular insulin resistance. They have proven efficacy for reducing plasma glucose levels in patients with type 2 diabetes mellitus treated with diet alone, sulphonylureas, metformin or insulin. In addition, they are associated with some improvement of the cardiovascular risk profile. However, troglitazone, the first compound approved by the Food and Drug Administration in the US, proved to be hepatotoxic and was withdrawn from the market after the report of several dozen deaths or cases of severe hepatic failure requiring liver transplantation. It remains unclear whether or not hepatotoxicity is a class effect or is related to unique properties of troglitazone. Rosiglitazone and pioglitazone, two other glitazones, appear to have similar efficacy with regard to blood glucose control in patients with type 2 diabetes mellitus as compared with troglitazone. In controlled clinical trials, the incidence of significant (> or =3 x upper limit of normal) increases in liver enzyme levels (ALT in particular) was similar with rosiglitazone or pioglitazone as compared with placebo, whereas troglitazone was associated with a 3-fold greater incidence. In contrast to the numerous case reports of acute liver failure in patients receiving troglitzone, only a few case reports of hepatotoxicity have been reported in patients treated with rosiglitazone until now, with a causal relationship remaining uncertain. Furthermore, no single case of severe hepatotoxicity has been reported yet with pioglitazone. It should be mentioned that troglitazone, unlike pioglitazone and rosiglitazone, induces the cytochrome P450 isoform 3A4, which is partly responsible for its metabolism, and may be prone to drug interactions. Importantly enough, obesity, insulin resistance and type 2 diabetes mellitus are associated with liver abnormalities, especially non-alcoholic steatohepatitis, independent of any pharmacological treatment. This association obviously complicates the selection of patients who are good candidates for a treatment with glitazones as well as the monitoring of liver tests after initiation of therapy with any thiazolidinedione compound. While regular monitoring of liver enzymes is still recommended and more long term data are desirable, current evidence from clinical trials and postmarketing experience in the US supports the conclusion that rosiglitazone and pioglitazone do not share the hepatotoxic profile of troglitazone.
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Affiliation(s)
- A J Scheen
- Department of Medicine, CHU Sart Tilman, Liège, Belgium.
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Marchesini G, Brizi M, Bianchi G, Tomassetti S, Bugianesi E, Lenzi M, McCullough AJ, Natale S, Forlani G, Melchionda N. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001; 50:1844-50. [PMID: 11473047 DOI: 10.2337/diabetes.50.8.1844] [Citation(s) in RCA: 1738] [Impact Index Per Article: 72.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Insulin sensitivity (euglycemic clamp, insulin infusion rate: 40 mU. m(-2). min(-1)) was studied in 30 subjects with biopsy-proven nonalcoholic fatty liver disease (NAFLD), normal glucose tolerance, and a BMI <30 kg/m(2). Of those 30 subjects, 9 had pure fatty liver and 21 had evidence of steatohepatitis. In addition, 10 patients with type 2 diabetes under good metabolic control and 10 healthy subjects were studied. Most NAFLD patients had central fat accumulation, increased triglycerides and uric acid, and low HDL cholesterol, irrespective of BMI. Glucose disposal during the clamp was reduced by nearly 50% in NAFLD patients, as well as in patients with normal body weight, to an extent similar to that of the type 2 diabetic patients. Basal free fatty acids were increased, whereas insulin-mediated suppression of lipolysis was less effective (-69% in NAFLD vs. -84% in control subjects; P = 0.003). Postabsorptive hepatic glucose production (HGP), measured by [6,6-(2)H(2)]glucose, was normal. In response to insulin infusion, HGP decreased by only 63% of basal in NAFLD vs. 84% in control subjects (P = 0.002). Compared with type 2 diabetic patients, NAFLD patients were characterized by lower basal HGP, but with similarly reduced insulin-mediated suppression of HGP. There was laboratory evidence of iron overload in many NAFLD patients, but clinical, histological, and biochemical data (including insulin sensitivity) were not correlated with iron status. Four subjects were heterozygous for mutation His63Asp of the HFE gene of familiar hemochromatosis. We concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is characterized by clinical and laboratory data similar to those found in diabetes and obesity. NAFLD may be considered an additional feature of the metabolic syndrome, with specific hepatic insulin resistance.
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Affiliation(s)
- G Marchesini
- Unit of Metabolic Diseases, Department of Internal Medicine and Gastroenterology, University of Bologna, Italy.
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Garrido Serrano A, Guerrero Igea FJ, Lepe Jiménez JA, Palomo Gil S, Grilo Reina A. [Hyperinsulinemia in cirrhotic patients infected with hepatitis C virus]. GASTROENTEROLOGIA Y HEPATOLOGIA 2001; 24:127-31. [PMID: 11261223 DOI: 10.1016/s0210-5705(01)70138-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
AIMS a) To prospectively study the frequency of diabetes mellitus in cirrhotic patients with hepatitis C virus (HCV) infection, comparing it with that in cirrhotic patients without HCV infection and b) to investigate basal insulinemia values in both groups, as well as the possible factors causing insulinemia. MATERIAL AND METHODS Fifty patients with cirrhosis due to HCV infection (group I) and 50 patients with cirrhosis due to other etiologic agents (group II) were studied. In both groups the percentage of diabetic patients, basal insulinemia values and the factors associated with insulin resistance were compared: age, anthropometric indexes, stage of cirrhosis according to Child-Pugh score, plasmatic ferritin concentrations and treatment with drugs inducing insulin resistance. RESULTS The percentage of diabetics in group I was 36% (18/50) compared with 18% (9/50) in group II (p < 0.05) and basal insulinemia values were 23.5 +/- 9.7 microU/ml compared with 15.7 +/- 9.9 microU/ml respectively (p < 0.05). No differences between the groups were found in the following variables: age (58.7 +/- 16.2 vs. 60.6 +/- 10.0 years), weight (73.2 +/- 10.7 vs 73.9 +/- 11.2 Kg), height (161.9 +/- 8.8 vs. 161.1 +/- 6.8 cm), body mass index (28.2 +/- 3.1 vs. 28.5 +/- 5.2 Kg/height m2) or Child-Pugh stage (A: 40 vs 34, B: 7 vs. 10, C: 3 vs. 6, NS). In contrast, serum ferritin concentrations were much higher in patients in group I than in those in group II [137.7 (12.4-410.2) vs. 87.6 (2.4-420.0) ng/ml p < 0.05]. At the time of inclusion in this study 10 patients in group I were receiving diuretics or non-selective beta adrenergic blockers compared with 24 patients in group II (p < 0.05). CONCLUSIONS Diabetes mellitus is more prevalent in patients with cirrhosis due to HVC than in those with cirrhosis due to other etiologic agents. Moreover, basal insulinemia values are higher in these patients, which could be explained by an increase in half insulin resistance associated with an increase in iron deposits.
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St Peter JV, Neafus KL, Khan MA, Vessey JT, Lockheart MS. Factors associated with the risk of liver enzyme elevation in patients with type 2 diabetes treated with a thiazolidinedione. Pharmacotherapy 2001; 21:183-8. [PMID: 11213855 DOI: 10.1592/phco.21.2.183.34107] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
STUDY OBJECTIVE To characterize frequency of liver enzyme elevation in patients with type 2 diabetes mellitus receiving troglitazone. DESIGN Retrospective study. SETTING Hospital-affiliated medical center. PATIENTS Two hundred ninety-one patients with type 2 diabetes mellitus. INTERVENTION Data from patients with an average troglitazone exposure of 412.7 +/- 255.6 days were studied. MEASUREMENTS AND MAIN RESULTS Enzyme elevations more than 1.5 times the upper limit of normal (ULN) occurred in 17 patients (5.8%) and more than 3-fold elevations in 6 (2.1%). The relationship among enzyme elevation events, demographic factors, duration of troglitazone exposure, frequency of monitoring, and concurrent drugs (limited to glucose and lipid-lowering agents) was assessed by multiple logistic regression. Age was an independent predictor of risk (p=0.009), and concurrent insulin therapy approached statistical significance (p=0.051) for 1.5-fold ULN elevation in liver enzymes. Age and concurrent therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors were the only significant predictors of 3-fold ULN elevations (p=0.03 and p=0.04, respectively). CONCLUSION Several factors appear to increase the risk of enzyme elevation events in patients treated with troglitazone.
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Affiliation(s)
- J V St Peter
- Department of Medicine, Hennepin County Medical Center, Minneapolis, MN 55415, USA
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Oki Y, Okubo M, Tanaka S, Nakanishi K, Kobayashi T, Murase T. Diabetes mellitus secondary to glycogen storage disease type III. Diabet Med 2000; 17:810-2. [PMID: 11131107 DOI: 10.1046/j.1464-5491.2000.00378.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND Diabetes mellitus is a rare complication of glycogen storage disease type III (GSD III). CASE REPORT We describe a 47-year-old man with GSD III who developed diabetes mellitus. He was diagnosed as having GSD III at the age of 18 years, and his glucose tolerance was normal at that time. Liver dysfunction and muscle atrophy gradually progressed, and the patient developed diabetes mellitus at the age of 45. When the post-prandial hyperglycaemia worsened, we instituted treatment with an alpha-glucosidase inhibitor, voglibose, and this improved glycaemic control without any adverse effects. CONCLUSIONS We recommend serial evaluation for complications of GSD III, and propose that an alpha-glucosidase inhibitor may be a favourable drug in treating diabetes mellitus secondary to GSD III.
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Affiliation(s)
- Y Oki
- Department of Endocrinology and Metabolism, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
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Affiliation(s)
- D G Fong
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
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