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Ghazanfar H, Javed N, Qasim A, Zacharia GS, Ghazanfar A, Jyala A, Shehi E, Patel H. Metabolic Dysfunction-Associated Steatohepatitis and Progression to Hepatocellular Carcinoma: A Literature Review. Cancers (Basel) 2024; 16:1214. [PMID: 38539547 PMCID: PMC10969013 DOI: 10.3390/cancers16061214] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Revised: 03/12/2024] [Accepted: 03/19/2024] [Indexed: 11/26/2024] Open
Abstract
The prevalence of metabolic-associated fatty liver disease (MAFLD) is increasing globally due to factors such as urbanization, obesity, poor nutrition, sedentary lifestyles, healthcare accessibility, diagnostic advancements, and genetic influences. Research on MAFLD and HCC risk factors, pathogenesis, and biomarkers has been conducted through a narrative review of relevant studies, with a focus on PubMed and Web of Science databases and exclusion criteria based on article availability and language. Steatosis marks the early stage of MASH advancement, commonly associated with factors of metabolic syndrome such as obesity and type 2 diabetes. Various mechanisms, including heightened lipolysis, hepatic lipogenesis, and consumption of high-calorie diets, contribute to the accumulation of lipids in the liver. Insulin resistance is pivotal in the development of steatosis, as it leads to the release of free fatty acids from adipose tissue. Natural compounds hold promise in regulating lipid metabolism and inflammation to combat these conditions. Liver fibrosis serves as a significant predictor of MASH progression and HCC development, underscoring the need to target fibrosis in treatment approaches. Risk factors for MASH-associated HCC encompass advanced liver fibrosis, older age, male gender, metabolic syndrome, genetic predispositions, and dietary habits, emphasizing the requirement for efficient surveillance and diagnostic measures. Considering these factors, it is important for further studies to determine the biochemical impact of these risk factors in order to establish targeted therapies that can prevent the development of HCC or reduce progression of MASH, indirectly decreasing the risk of HCC.
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Affiliation(s)
- Haider Ghazanfar
- Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Bronx, NY 10457, USA (A.J.); (E.S.)
| | - Nismat Javed
- Department of Internal Medicine, BronxCare Health System, Bronx, NY 10457, USA (G.S.Z.)
| | - Abeer Qasim
- Department of Internal Medicine, BronxCare Health System, Bronx, NY 10457, USA (G.S.Z.)
| | - George Sarin Zacharia
- Department of Internal Medicine, BronxCare Health System, Bronx, NY 10457, USA (G.S.Z.)
| | - Ali Ghazanfar
- Department of Internal Medicine, Fauji Foundation Hospital, Rawalpindi 45000, Pakistan
| | - Abhilasha Jyala
- Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Bronx, NY 10457, USA (A.J.); (E.S.)
| | - Elona Shehi
- Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Bronx, NY 10457, USA (A.J.); (E.S.)
| | - Harish Patel
- Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Bronx, NY 10457, USA (A.J.); (E.S.)
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Bellamy CO, Burt AD. Liver in Systemic Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:1039-1095. [DOI: 10.1016/b978-0-7020-8228-3.00015-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Qin SS, Pan GQ, Meng QB, Liu JB, Tian ZY, Luan SJ. The causal relationship between metabolic factors, drinking, smoking and intrahepatic cholangiocarcinoma: a Mendelian randomization study. Front Oncol 2023; 13:1203685. [PMID: 37427123 PMCID: PMC10325926 DOI: 10.3389/fonc.2023.1203685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 06/05/2023] [Indexed: 07/11/2023] Open
Abstract
Background Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer. While multiple risk factors for iCCA have been established, metabolic diseases (obesity, diabetes, NAFLD, dyslipidemia, and hypertension) and other risk factors, including smoking and drinking, are still controversial due to their potential confounders. Here, Mendelian randomization (MR) analysis was performed to identify the causal relationship between them. Method In this study, we obtained GWAS data related to exposures from corresponding large genome-wide association studies. Summary-level statistical data for iCCA were obtained from the UK Biobank (UKB). We performed a univariable MR analysis to identify whether genetic evidence of exposure was significantly associated with iCCA risk. A multivariable MR analysis was conducted to estimate the independent effects of exposures on iCCA. Results Univariable and multivariable MR analysis based on the large GWAS data indicated that there is little evidence to support the genetic role of metabolic factors, smoking, drinking, and NAFLD in iCCA development (P >0.05). In contrast to most current studies, their impact on iCCA development, if any, might be smaller than we thought. The previous positive results might be due to the comorbidities between diseases and potentially unavoidable confounding factors. Conclusion In this MR study, we found no strong evidence to support causal associations between metabolic factors, NAFLD, smoking, drinking, and iCCA risk.
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Affiliation(s)
- Shan-shan Qin
- Department of Radiology, Qilu Hospital, Shandong University, Jinan, China
| | - Guo-qiang Pan
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
| | - Qun-bo Meng
- Department of Orthopaedical Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Jin-bo Liu
- Department of Orthopaedical Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Zi-yu Tian
- Department of Radiology, Qilu Hospital, Shandong University, Jinan, China
| | - Shou-jing Luan
- Department of Endocrinology, Weifang People’s Hospital, Weifang, China
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Saewai C, Fumaneeshoat O, Thongsuksai P, Ingviya T. Diabetes Mellitus as Cancer Risk: A 14-year, Cross-Sectional Analysis. Nutr Cancer 2023:1-10. [PMID: 37099762 DOI: 10.1080/01635581.2023.2205054] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/28/2023]
Abstract
Diabetes mellitus is widely thought to be a risk factors of cancers, but evidence of the association remains inconclusive, especially in Asian countries where few relevant studies have been conducted. Our study aimed to estimate overall and specific types of cancer risks among diabetes patients in Southern Thailand. Patients diagnosed with diabetes who visited the outpatient clinic of Songklanagarind Hospital during 2004 to 2018 were included. Newly diagnosed cancer patients were identified using the hospital-based cancer registry. Age-standardized incidence ratios (ASRs) and standardized incidence ratios (SIRs) were used to estimate and compare the cancer risks among diabetes patients and the general population in Southern Thailand. Of 29,314 diabetes patients identified during the study period, 1,113 patients had developed cancer. An increased risk for overall cancer was observed in both genders, with SIRs [95% CI] of 2.99 [2.65, 3.39] in men and 3.51 [3.12, 3.96] in women. Increases in the risk of several site-specific cancers including liver cancer, non-melanoma skin cancer, colon cancer and lung cancer in both sexes; prostate cancer, lymphoid leukemia, and multiple myeloma in men; and endometrial, breast, and thyroid cancer in women were observed. Our study found that diabetes generally increased the risk of both overall and site-specific cancers.
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Affiliation(s)
- Chutchawan Saewai
- Department of Family and Preventive Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Orapan Fumaneeshoat
- Department of Family and Preventive Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Paramee Thongsuksai
- Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Thammasin Ingviya
- Department of Family and Preventive Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
- Research Center for Cancer Control in Thailand, Prince of Songkla University, Songkhla, Thailand
- Division of Digital Innovation and Data Analytics, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
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Any Role for Microbiota in Cholangiocarcinoma? A Comprehensive Review. Cells 2023; 12:cells12030370. [PMID: 36766711 PMCID: PMC9913249 DOI: 10.3390/cells12030370] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/09/2023] [Accepted: 01/10/2023] [Indexed: 01/20/2023] Open
Abstract
Alterations in the human microbiota have been linked to carcinogenesis in several cancers. To date, few studies have addressed the role of the microbiota in cholangiocarcinoma (CCA). Our work aims to update the knowledge about the role of the microbiota in the CCA microenvironment, and to highlight possible novel insights for the development of new diagnostic, prognostic, or even therapeutic strategies. We thus conducted a review of the literature. In recent years, great progress has been made in understanding the pathogenesis, the clinical and histological behavior, and the molecular profile of CCA. Much evidence suggests that the bile microbiota plays an essential role in biliary diseases, including CCA. Some studies have demonstrated that alterations in the qualitative and quantitative composition of the intestinal commensal bacteria lead to overall cancer susceptibility through various pathways. Other studies suggest that the gut microbiota plays a role in the pathogenesis and/or progression of CCA. The clinical implications are far-reaching, and the role of the microbiota in the CCA microenvironment may lead to considering the exciting implications of implementing therapeutic strategies that target the microbiota-immune system axis.
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Wang WM, Ou HT, Wen MJ, Su PF, Yang CY, Kuo TH, Wang MC, Lin WH. Association of retinopathy severity with cardiovascular and renal outcomes in patients with type 1 diabetes: a multi-state modeling analysis. Sci Rep 2022; 12:4177. [PMID: 35264740 PMCID: PMC8907198 DOI: 10.1038/s41598-022-08166-4] [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: 08/04/2021] [Accepted: 02/16/2022] [Indexed: 11/21/2022] Open
Abstract
This study aimed to assess the impact of diabetic retinopathy (DR) severity on the incidence of major adverse cardiac events (MACE) and end-stage renal disease (ESRD) in T1D patients. Patients diagnosed with T1D between 1999 and 2013 were identified from patient-level data of Taiwan’s National Health Insurance Research database. A total of 1135 patients were included and classified into mild DR (n = 454), severe DR (n = 227), or non-DR (n = 454) by using propensity score matching. Multi-state model analyses, an extension of competing risk models with adjustment for transition-specific covariates for prediction of subsequent MACE and ESRD, were performed. MACE and ESRD risks were significantly higher in the severe DR patients; a 2.97-fold (1.73, 5.07) and 12.29-fold (6.50, 23.23) increase in the MACE risk among the severe DR patients compared to the mild DR and DR-free patients, respectively; and, a 5.91-fold (3.50, 9.99) and 82.31-fold (29.07, 233.04) greater ESRD risk of severe DR patients than that of the mild DR and DR-free groups, respectively (p < 0.001). Severity of DR was significantly associated with the late diabetes-related vascular events (i.e., MACE, ESRD) among T1D patients.
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Affiliation(s)
- Wei-Ming Wang
- Department of Statistics and Institute of Data Science, College of Management, National Cheng Kung University, Tainan, Taiwan
| | - Huang-Tz Ou
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Department of Pharmacy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Department of Pharmacy, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Miin-Jye Wen
- Department of Statistics and Institute of Data Science, College of Management, National Cheng Kung University, Tainan, Taiwan.,Institute of International Management, College of Management, National Cheng Kung University, Tainan, Taiwan
| | - Pei-Fang Su
- Department of Statistics and Institute of Data Science, College of Management, National Cheng Kung University, Tainan, Taiwan
| | - Chen-Yi Yang
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Te-Hui Kuo
- Department and Institute of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, 138 Sheng-Li Road, Tainan, 70428, Taiwan
| | - Ming-Cheng Wang
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, 138 Sheng-Li Road, Tainan, 70428, Taiwan
| | - Wei-Hung Lin
- Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, 138 Sheng-Li Road, Tainan, 70428, Taiwan. .,Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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Abstract
INTRODUCTION Cholangiocarcinoma is a rare malignancy accounting for 3% of gastrointestinal cancers in the USA. While multiple risk factors for cholangiocarcinoma are established, other potential risk factors are still controversial. Herein, we used a large national database to investigate possible risk factors and associations. METHOD We used the National Inpatient Sample database to review all admissions between 2011 and 2015. We grouped patients based on the presence and absence of cholangiocarcinoma. Using multivariate logistic regression analysis, we assessed the association between obesity, alcohol abuse, smoking, diabetes mellitus and cholangiocarcinoma. RESULTS Out of 30 9552 95 admissions, 20 030 had cholangiocarcinoma. Cholangiocarcinoma patients were older (67 ± 12.8 vs. 57 ± 20.6; P < 0.001) and had fewer female patients (48 vs. 59%; P < 0.001). Multivariate logistic regression analysis showed that diabetes mellitus was associated with cholangiocarcinoma (OR, 1.04; 95% CI, 1.01-1.08; P < 0.001). On the other hand, alcohol, smoking and obesity were all inversely associated with cholangiocarcinoma (OR, 0.75; 95% CI, 0.69-0.81; P < 0.001), (OR, 0.75; 95% CI, 0.71-0.79; P < 0.001) and (OR, 0.71; 95% CI, 0.67-0.75; P < 0.001), respectively. In addition, compared to Whites, Hispanic and Asian/Pacific Islander races were more associated with cholangiocarcinoma (OR, 1.27; 95% CI, 1.21-1.34) and (OR, 1.79; 95% CI, 1.67-1.92) (P < 0.001 for all), respectively, whereas African American race was inversely associated with cholangiocarcinoma (OR, 0.85; 95% CI, 0.81-0.89; P < 0.001). CONCLUSION Patients with a diagnosis of diabetes mellitus or from certain ethnic groups (Hispanic and Asian/Pacific Islander) are associated with increased risk for cholangiocarcinoma.
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Park JH, Hong JY, Park YS, Kang G, Han K, Park JO. Association of prediabetes, diabetes, and diabetes duration with biliary tract cancer risk: A nationwide cohort study. Metabolism 2021; 123:154848. [PMID: 34371066 DOI: 10.1016/j.metabol.2021.154848] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 07/18/2021] [Accepted: 08/03/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS Population-based evidence of the association between diabetes and biliary tract cancer (BTC) risk is lacking. We aimed to evaluate the association of prediabetes, diabetes, and diabetes duration with subsequent risk of BTC, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC), in the Korean general population. METHODS This nationwide cohort study included 9,697,773 adults aged ≥20 years without cancer who underwent national health screening between January and December 2009. Subjects' glycemic status was categorized as normoglycemic, impaired fasting glucose (IFG), newly-diagnosed diabetes, diabetes duration <5 years, and diabetes duration ≥5 years. Incident BTC was identified using claims data. Follow-up continued until December 2017. Cox proportional hazard models were used to estimate multivariable-adjusted hazard ratios and 95% CIs of BTC. RESULTS During a median follow-up of 7.2 years, 13,022 patients were newly diagnosed with BTC. Compared with the normoglycemic group, the IFG, newly-diagnosed diabetes, diabetes duration <5 years, and diabetes duration ≥5 years groups showed the following adjusted hazard ratios (95% CIs) for BTC: 1.08 (1.04-1.12), 1.31 (1.22-1.41), 1.35 (1.27-1.43), and 1.47 (1.39-1.55), respectively. BTC risk significantly increased with deteriorating glycemic status (P for trend <0.001). These results were consistent with those of CCA and GBC analyses. CONCLUSIONS Both IFG and diabetes were independently associated with an increased risk of BTC, including CCA and GBC. A longer diabetes duration was associated with a further increase in BTC risk. Diabetes and even IFG may be modifiable risk factors for BTC.
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Affiliation(s)
- Joo-Hyun Park
- Department of Family Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Republic of Korea
| | - Jung Yong Hong
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
| | - Young Suk Park
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Gunseog Kang
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Joon Oh Park
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
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Prevalence and Initial Diagnosis of Cerebral Palsy in Preterm and Term-Born Children in Taiwan: A Nationwide, Population-Based Cohort Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18178984. [PMID: 34501573 PMCID: PMC8431738 DOI: 10.3390/ijerph18178984] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 08/13/2021] [Accepted: 08/24/2021] [Indexed: 11/23/2022]
Abstract
The aim of this long-term longitudinal study in Taiwan was to estimate and compare the prevalence of cerebral palsy (CP) and to identify the age of CP diagnosis of term-born and preterm children with different birthweights. Records of 1494 extremely low birth weight (ELBW, <1000 g), 3961 very low birth weight (VLBW, 1000–1499 g), 19,612 low birth weight (LBW, 1500–2499 g) preterm, and 100,268 matched term-born children were retrieved from Taiwan′s National Health Insurance Research Database. According to a 12-year retrospective data review, the results showed the highest prevalence of CP in preterm ELBW children (147.3 cases per 1000 neonatal survivors), followed by preterm VLBW (97.2 cases), preterm LBW (27.7 cases), with the lowest prevalence in term-born children (2.5 cases). Regardless of the birthweight group, 90% of preterm children with CP were diagnosed by 4 years of age, but it was 7 years before 90% of term-born children with CP were diagnosed. After removing the children whose CP was caused by brain infections, injuries, or cerebrovascular accidents after 4 months of age, there were similar mean ages at the initial CP diagnosis (1.58–1.64 years of age) across birthweight groups born prematurely, but initial diagnosis occurred at an older age (2.41 years of age) in term-born children. The results indicate that birthweight is reversely correlated with the prevalence of CP in preterm children. Although the three preterm birthweight groups received different types of developmental follow-up programs after birth, it did not influence their age at the initial diagnosis of CP. Furthermore, we suggest that follow-up for at least 4 years after birth for preterm children, and 7 years for term-born children, is optimal for estimating CP prevalence. In order to identify and provide early intervention for term-born children with CP earlier, it is suggested that parents routinely fill out a self-reported motor developmental screening questionnaire and pediatricians conduct a motor developmental examination on term-born children at each time of scheduled vaccination injections.
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Choi J, Lim YS. Secondary prevention of hepatitis B virus-related hepatocellular carcinoma with current antiviral therapies. Kaohsiung J Med Sci 2021; 37:262-267. [PMID: 33502828 DOI: 10.1002/kjm2.12364] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Accepted: 01/05/2021] [Indexed: 12/25/2022] Open
Abstract
Over the past decades, marked advancement has been made in the prevention and treatment of hepatitis B virus (HBV) infection. Due to highly effective antiviral therapies for chronic hepatitis B (CHB), long-term clinical outcomes in patients with CHB has also been dramatically improved. However, current antiviral therapies for CHB cannot completely abolish the risk of hepatocellular carcinoma (HCC). In addition, current treatment guidelines for CHB should be interpreted with caution given that HBV-associated hepatocarcinogenesis could be underway in patients who are not eligible for antiviral therapies by current guidelines. Therefore, efforts to reconcile treatment guidelines with recent clinical evidence should be made for reducing further development of HCC. In this article, we review the secondary prevention of HBV-related HCC with current antiviral therapies.
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Affiliation(s)
- Jonggi Choi
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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Simon TG, Chan AT. Lifestyle and Environmental Approaches for the Primary Prevention of Hepatocellular Carcinoma. Clin Liver Dis 2020; 24:549-576. [PMID: 33012445 PMCID: PMC7536356 DOI: 10.1016/j.cld.2020.06.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Patients with chronic liver disease are at increased risk of developing hepatocellular carcinoma (HCC). Most patients diagnosed with HCC have limited treatment options and a poor overall prognosis, with a 5-year survival less than 15%. Preventing the development of HCC represents the most important strategy. However, current guidelines lack specific recommendations for primary prevention. Lifestyle factors may be central in the pathogenesis of HCC, and primary prevention strategies focused on lifestyle modification could represent an important approach to the prevention of HCC. Both experimental and epidemiologic studies have identified promising chemopreventive agents for the primary prevention of HCC.
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Affiliation(s)
- Tracey G. Simon
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA,Harvard Medical School, Boston, MA,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA
| | - Andrew T. Chan
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA,Harvard Medical School, Boston, MA,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA,Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston MA,Broad Institute, Boston MA,Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston MA
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12
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Chen CL, Kuo MJ, Yen AMF, Yang WS, Kao JH, Chen PJ, Chen HH. Gender Difference in the Association Between Metabolic Factors and Hepatocellular Carcinoma. JNCI Cancer Spectr 2020; 4:pkaa036. [PMID: 33134821 PMCID: PMC7583157 DOI: 10.1093/jncics/pkaa036] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 03/25/2020] [Accepted: 04/30/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND A gender difference in hepatocellular carcinoma (HCC) that men have higher incidence than women has long been noted and can be explained by the cross-talk between sex hormones and hepatitis B virus/hepatitis C virus (HBV/HCV). Whether metabolic factors yield similar sexual difference in non-HBV/HCV-HCC remains elusive. METHODS There were 74 782 hepatitis B surface antigen (HBsAg)/antibody to hepatitis C virus (anti-HCV) negative residents who participated in the Keelung Community-Based Integrated Screening program and were followed in 2000-2007. Incident HCC was identified by linkage to the Taiwan Cancer Registry. Cox proportional hazards regression models were used to estimate the association between metabolic factors and HCC stratified by sex. All statistical tests were 2-sided. RESULTS With 320 829 follow-up person-years, 99 residents developed HCC. The adjusted hazard ratios (aHR) were 2.10 (95% confidence interval [CI] = 1.07 to 4.13) and 3.71 (95% CI = 2.01 to 6.86) for prediabetes and diabetes, respectively, in men. The corresponding adjusted hazard ratios were 1.16 (95% CI = 0.48 to 2.83) and 1.47 (95% CI = 0.65 to 3.34) in women. Compared with normal weight (body mass index [BMI] = 23-25), underweight (BMI < 21, HR = 3.56, 95% CI = 1.18 to 10.8) and overweight (BMI = 25 to <27.3, HR = 3.81, 95% CI = 1.43 to 10.2) were associated with an elevated risk in men. The statistically significant gradient relationship per advanced BMI category was noted in women (aHR = 1.41, 95% CI = 1.07 to 1.87). The HCC-fasting glucose (P = .046) and HCC-BMI (P = .03) associations were statistically significantly modified by sex. Elevated aspartate aminotransferase, aspartate aminotransferase-to-platelet index and fibrosis index, and habitual alcohol consumption were related to HCC only in men, whereas increased alanine aminotransferase and lower platelet levels predicted HCC risk in women. CONCLUSIONS We found that BMI-HCC associations were U-shape for men and linear for women, and the elevated HCC risk began from glucose impairment in men only. Whether good glycemic and weight control can reduce HCC risk warrants further investigation.
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Affiliation(s)
- Chi-Ling Chen
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming-Jeng Kuo
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- Department of Hepatogastroenterology, Tainan Municipal Hospital, Tainan, Taiwan
| | - Amy Ming-Fang Yen
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - Wei-Shiung Yang
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hsiu-Hsi Chen
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
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Benhammou JN, Lin J, Hussain SK, El-Kabany M. Emerging risk factors for nonalcoholic fatty liver disease associated hepatocellular carcinoma. HEPATOMA RESEARCH 2020; 6:35. [PMID: 32685690 PMCID: PMC7367098 DOI: 10.20517/2394-5079.2020.16] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Worldwide, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions and in parallel, hepatocellular carcinoma (HCC) has become one of the fastest growing cancers. Epidemiological studies have not only shed light on the prevalence and incidence of the disease but have also unmasked important environmental risk factors, including the role of diabetes and dyslipidemia in disease pathogenesis. Genetic association studies have identified single nucleotide polymorphisms implicated in NAFLD-HCC, many of which are part of lipid metabolism pathways. Through these clinical studies and subsequently, translational and basic research, the role of statins as a chemoprotective agent has also emerged with ongoing clinical trials assessing their utility in HCC prevention and treatment. In this review, we summarize the recent epidemiological studies describing the burden of NAFLD-HCC in different patient populations and countries. We discuss the genetic and environmental risk factors for NAFLD-HCC and highlight the chemoprotective role of statins and aspirin. We also summarize what is known about NAFLD-HCC in the cirrhosis and non-cirrhosis populations and briefly address the role of surveillance in NAFLD-HCC patients.
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Affiliation(s)
- Jihane N. Benhammou
- Pfleger Liver Institute, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Jonathan Lin
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
| | - Shehnaz K. Hussain
- Department of Epidemiology, Fielding School of Public Health, University of California, CA 90095, USA
- Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Mohamed El-Kabany
- Pfleger Liver Institute, University of California Los Angeles, Los Angeles, CA 90095, USA
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14
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Björkström K, Franzén S, Eliasson B, Miftaraj M, Gudbjörnsdottir S, Trolle-Lagerros Y, Svensson AM, Hagström H. Risk Factors for Severe Liver Disease in Patients With Type 2 Diabetes. Clin Gastroenterol Hepatol 2019; 17:2769-2775.e4. [PMID: 31009793 DOI: 10.1016/j.cgh.2019.04.038] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Revised: 03/21/2019] [Accepted: 04/13/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Type 2 diabetes is a risk factor for development of cirrhosis and hepatocellular carcinoma. However, risk factors that identify persons with the highest risk for these outcomes are missing from unselected, population-based cohorts. METHODS The National Diabetes Register contains data on about 90% of persons in Sweden with type 2 diabetes. In this cohort study, persons with type 2 diabetes listed in the National Diabetes Register were compared with 5 individuals from the general population (controls), matched for age, sex, and county. In total, 406 770 persons with type 2 diabetes and 2 033 850 controls were included and followed for 21 596 934 person-years. We used population-based registers to determine the incidence of severe liver disease, defined as a diagnosis of hepatocellular carcinoma, cirrhosis, decompensation, liver failure and/or death due to liver disease during follow up. Cox regression was performed to estimate the risk of severe liver disease and to examine risk factors in persons with type 2 diabetes. RESULTS Risk for severe liver disease was increased in patients with type 2 diabetes compared to controls (hazard ratio, 2.28; 95% CI, 2.21-2.36). Risk factors associated with severe liver disease in persons with type 2 diabetes were higher age, male sex, hypertension, higher body mass index, lower glomerular filtration rate, microalbuminuria, and smoking. Statins were associated with a decreased risk of severe liver disease. CONCLUSIONS Persons with type 2 diabetes have an increased risk for severe liver disease. Knowledge of risk factors can be helpful in identifying persons with type 2 diabetes who have a high risk for severe liver disease.
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Affiliation(s)
- Karl Björkström
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Stefan Franzén
- Swedish National Diabetes Register, Centre of Registers in Region, Sweden
| | - Björn Eliasson
- Swedish National Diabetes Register, Centre of Registers in Region, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Mervete Miftaraj
- Swedish National Diabetes Register, Centre of Registers in Region, Sweden
| | - Soffia Gudbjörnsdottir
- Swedish National Diabetes Register, Centre of Registers in Region, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Ylva Trolle-Lagerros
- Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Ann-Marie Svensson
- Swedish National Diabetes Register, Centre of Registers in Region, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Hannes Hagström
- Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska University Hospital, Stockholm, Sweden; Unit of Hepatology, Department of Upper Gastrointestinal Diseases, Karolinska University Hospital, Stockholm, Sweden.
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15
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Pocha C, Xie C. Hepatocellular carcinoma in alcoholic and non-alcoholic fatty liver disease-one of a kind or two different enemies? Transl Gastroenterol Hepatol 2019; 4:72. [PMID: 31728429 DOI: 10.21037/tgh.2019.09.01] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 08/22/2019] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular cancer (HCC) is a cancer with an overall poor prognosis and an alarming globally rising incidence. While viral etiology of chronic liver disease and HCC is down-trending, alcohol and excess calorie intake have emerged as major culprits. Alcohol related liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) share similar pathogenetic mechanism of hepatic injury and in promoting development of HCC; yet some genetic and epigenetic features are distinct and may promise clinical utility. Population based intervention are urgently needed to reduce alcohol use and improve metabolic factors such as obesity and diabetes. The goal is to identify at-risk patients, to link these patients to care and to provide effective management of chronic liver disease and HCC. This review focuses on the epidemiology, pathophysiology including genetic and epigenetic altercation as well as clinical aspects of ALD and NAFLD associated HCC.
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Affiliation(s)
- Christine Pocha
- Avera McKennnan Hospital and University Medical Center, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA.,Department of Gastroenterology and Hepatology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Chencheng Xie
- Avera McKennnan Hospital and University Medical Center, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA.,Department of Gastroenterology and Hepatology, Thomas Jefferson University, Philadelphia, PA, USA
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16
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Saffioti F, Roccarina D, Vesterhus M, Hov JR, Rosenberg W, Pinzani M, Pereira SP, Boberg KM, Thorburn D. Cholangiocarcinoma is associated with a raised enhanced liver fibrosis score independent of primary sclerosing cholangitis. Eur J Clin Invest 2019; 49:e13088. [PMID: 30762236 DOI: 10.1111/eci.13088] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 02/11/2019] [Accepted: 02/12/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Cholangiocarcinoma (CCA) complicates primary sclerosing cholangitis (PSC) in 10%-20% of cases, but current tools for prediction of a CCA diagnosis are inadequate. Recently, we demonstrated the utility of the enhanced liver fibrosis (ELF) test to stratify prognosis in PSC. We observed that patients with PSC + CCA had significantly higher ELF score than those with PSC alone. In this study, we aimed to investigate further this association in a larger cohort of PSC patients with CCA compared with patients with PSC or CCA alone. MATERIALS AND METHODS Stored sera from patients with PSC (n = 119), CCA without known chronic liver disease (n = 36) and PSC + CCA (n = 32) were tested for ELF. ELF score, gender, age, age at disease diagnosis, inflammatory bowel disease, PSC duration and severity, and CCA features were compared amongst the three cohorts. Factors related to an elevated ELF score were investigated. RESULTS Enhanced liver fibrosis score was significantly higher in patients with CCA without underlying chronic liver disease and in patients with PSC + CCA compared to those with PSC alone (P < 0.001). In multivariate analysis, elevated ELF score was associated with the diagnosis of CCA independently of age and PSC status (P < 0.001). CONCLUSIONS Enhanced liver fibrosis score was elevated in patients with CCA irrespective of the presence of PSC, and independently of liver disease stage. Our results indicate that the association between high ELF score and CCA may be related to the tumour's desmoplastic nature, independent of background liver fibrosis, suggesting that ELF score could be used to risk stratify for CCA in PSC.
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Affiliation(s)
- Francesca Saffioti
- Sheila Sherlock Liver Centre and UCL Institute for Liver and Digestive Health, University College London & Royal Free London NHS Foundation Trust, London, UK.,Department of Clinical and Experimental Medicine, Division of Clinical and Molecular Hepatology, University of Messina, Messina, Italy
| | - Davide Roccarina
- Sheila Sherlock Liver Centre and UCL Institute for Liver and Digestive Health, University College London & Royal Free London NHS Foundation Trust, London, UK
| | - Mette Vesterhus
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway.,Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Johannes R Hov
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway.,Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - William Rosenberg
- Sheila Sherlock Liver Centre and UCL Institute for Liver and Digestive Health, University College London & Royal Free London NHS Foundation Trust, London, UK
| | - Massimo Pinzani
- Sheila Sherlock Liver Centre and UCL Institute for Liver and Digestive Health, University College London & Royal Free London NHS Foundation Trust, London, UK
| | - Stephen P Pereira
- Sheila Sherlock Liver Centre and UCL Institute for Liver and Digestive Health, University College London & Royal Free London NHS Foundation Trust, London, UK
| | - Kirsten M Boberg
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway.,Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Douglas Thorburn
- Sheila Sherlock Liver Centre and UCL Institute for Liver and Digestive Health, University College London & Royal Free London NHS Foundation Trust, London, UK
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17
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Ko MC, Lin WH, Martini S, Chang YH, Chiu CT, Li CY. A cohort study of age and sex specific risk of pyogenic liver abscess incidence in patients with type 2 diabetes mellitus. Medicine (Baltimore) 2019; 98:e15366. [PMID: 31027123 PMCID: PMC6831277 DOI: 10.1097/md.0000000000015366] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
To investigate the age-sex-specific incidence and relative risk of pyogenic liver abscess (PLA) in patients with type 2 diabetes mellitus (T2DM), and to assess the joint effects of T2DM and other clinical risk factors for PLA on PLA incidence. We used a population-based cohort design with Taiwan's National Health Insurance claim data. Study subjects included 613,921 T2DM patients and 614,613 controls identified in 2000 and were followed to the end of 2010. Cox regression model was employed to calculate the hazard ratio (HR) and 95% confidence interval (CI) of PLA in relation to T2DM. Over an 11-year follow-up, 5336 T2DM and 1850 controls were admitted for PLA, representing a cumulative incidence of 0.87% and 0.30%, respectively. T2DM was significantly associated with increased hazard of PLA (HR, 2.88; 95% CI, 2.73-3.04). We also found that age and gender may significantly modify the relationship between T2DM and PLA, with a higher HR noted in males patients and those aged <45 years. Biliary tract diseases (HR, 8.60; 95% CI, 7.87-9.40) and liver cirrhosis (HR, 7.52; 95% CI, 6.58-8.59) may add substantially additional risk to the incidence of PLA in T2DM patients. The increased risk of PLA in T2DM was greater in male and younger patients. Careful management of biliary tract diseases and liver cirrhosis may also help reduce the incidence of PLA in T2DM patients.
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Affiliation(s)
- Ming-Chung Ko
- Department of Urology, Taipei City Hospital
- Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei
| | - Wei-Hung Lin
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Santi Martini
- Department of Epidemiology, Faculty of Public Health, Universitas Airlangga, Surabaya, Indonesia
| | - Ya-Hui Chang
- Department of Public Health, College of Medicine, National Cheng Kung University
| | - Chang-Ta Chiu
- Department of Dentistry, An Nan Hospital, China Medical University, Tainan
| | - Chung-Yi Li
- Department of Epidemiology, Faculty of Public Health, Universitas Airlangga, Surabaya, Indonesia
- Department of Public Health, College of Medicine, National Cheng Kung University
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
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18
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Menon S, Mathew R. Association between metabolic syndrome and hepatobiliary cancers: A case-control study. Indian J Gastroenterol 2019; 38:61-68. [PMID: 30628006 DOI: 10.1007/s12664-018-0925-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2018] [Accepted: 12/03/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND The incidence of hepatobiliary cancer is steadily increasing. It is unclear if this rise is related to increasing trends in obesity, metabolic syndrome, and lifestyle changes. METHODS A case-control study was performed using the Health Improvement Network (THIN) database. Cases with a diagnosis of liver, bile duct, and gallbladder cancers were matched in a 1:2 fashion with controls and analyzed for potential associations between hepatobiliary cancer and obesity/metabolic syndrome. RESULTS Four thousand two hundred and eighty-seven patients (62% male, 38% female) with hepatobiliary cancers were matched with 8574 controls. On univariate analysis, body mass index (BMI), smoking, diabetes, alcohol consumption, ischemic heart disease, and hypertension were associated with hepatobiliary cancer. Statin use and non-smoking status had an inverse association. On multivariate analysis, BMI, diabetes, hypertension, ischemic heart disease, and insulin use were associated with the risk of hepatobiliary cancer. Statin use and non-smoking status were protective. On modeling BMI, each of diabetes and hypertension as a single covariate, there was a significant association with hepatobiliary cancer (1.59 [1.49-1.69], p < 0.001) which persisted despite adjusting for increasing age (1.006 [1005-1.006], p < 0.001) and background liver cirrhosis (1.037 [1.03-1.044], p < 0.001). CONCLUSIONS Obesity and metabolic syndrome are associated with the risk of hepatobiliary cancer. Statin use seems to be protective.
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Affiliation(s)
- Shyam Menon
- The Royal Wolverhampton NHS Trust, Wolverhampton, UK.
| | - Ray Mathew
- The Royal Wolverhampton NHS Trust, Wolverhampton, UK
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19
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Dietary cholesterol promotes steatohepatitis related hepatocellular carcinoma through dysregulated metabolism and calcium signaling. Nat Commun 2018; 9:4490. [PMID: 30367044 PMCID: PMC6203711 DOI: 10.1038/s41467-018-06931-6] [Citation(s) in RCA: 144] [Impact Index Per Article: 20.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Accepted: 10/01/2018] [Indexed: 01/03/2023] Open
Abstract
The underlining mechanisms of dietary cholesterol and nonalcoholic steatohepatitis (NASH) in contributing to hepatocellular carcinoma (HCC) remain undefined. Here we demonstrated that high-fat-non-cholesterol-fed mice developed simple steatosis, whilst high-fat-high-cholesterol-fed mice developed NASH. Moreover, dietary cholesterol induced larger and more numerous NASH-HCCs than non-cholesterol-induced steatosis-HCCs in diethylnitrosamine-treated mice. NASH-HCCs displayed significantly more aberrant gene expression-enriched signaling pathways and more non-synonymous somatic mutations than steatosis-HCCs (335 ± 84/sample vs 43 ± 13/sample). Integrated genetic and expressional alterations in NASH-HCCs affected distinct genes pertinent to five pathways: calcium, insulin, cell adhesion, axon guidance and metabolism. Some of the novel aberrant gene expression, mutations and core oncogenic pathways identified in cholesterol-associated NASH-HCCs in mice were confirmed in human NASH-HCCs, which included metabolism-related genes (ALDH18A1, CAD, CHKA, POLD4, PSPH and SQLE) and recurrently mutated genes (RYR1, MTOR, SDK1, CACNA1H and RYR2). These findings add insights into the link of cholesterol to NASH and NASH-HCC and provide potential therapeutic targets.
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20
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Ohkuma T, Peters SAE, Woodward M. Sex differences in the association between diabetes and cancer: a systematic review and meta-analysis of 121 cohorts including 20 million individuals and one million events. Diabetologia 2018; 61:2140-2154. [PMID: 30027404 PMCID: PMC6133170 DOI: 10.1007/s00125-018-4664-5] [Citation(s) in RCA: 119] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Accepted: 05/02/2018] [Indexed: 12/14/2022]
Abstract
AIMS/HYPOTHESIS Diabetes has been shown to be a risk factor for some cancers. Whether diabetes confers the same excess risk of cancer, overall and by site, in women and men is unknown. METHODS A systematic search was performed in PubMed for cohort studies published up to December 2016. Selected studies reported sex-specific relative risk (RR) estimates for the association between diabetes and cancer adjusted at least for age in both sexes. Random-effects meta-analyses with inverse-variance weighting were used to obtain pooled sex-specific RRs and women-to-men ratios of RRs (RRRs) for all-site and site-specific cancers. RESULTS Data on all-site cancer events (incident or fatal only) were available from 121 cohorts (19,239,302 individuals; 1,082,592 events). The pooled adjusted RR for all-site cancer associated with diabetes was 1.27 (95% CI 1.21, 1.32) in women and 1.19 (1.13, 1.25) in men. Women with diabetes had ~6% greater risk compared with men with diabetes (the pooled RRR was 1.06, 95% CI 1.03, 1.09). Corresponding pooled RRRs were 1.10 (1.07, 1.13) for all-site cancer incidence and 1.03 (0.99, 1.06) for all-site cancer mortality. Diabetes also conferred a significantly greater RR in women than men for oral, stomach and kidney cancer, and for leukaemia, but a lower RR for liver cancer. CONCLUSIONS/INTERPRETATION Diabetes is a risk factor for all-site cancer for both women and men, but the excess risk of cancer associated with diabetes is slightly greater for women than men. The direction and magnitude of sex differences varies by location of the cancer.
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Affiliation(s)
- Toshiaki Ohkuma
- The George Institute for Global Health, University of New South Wales, Level 10, King George V Building, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, 2050, Australia.
| | - Sanne A E Peters
- The George Institute for Global Health, University of Oxford, Le Gros Clark Building, South Parks Road, Oxford, OX1 3QX, UK
| | - Mark Woodward
- The George Institute for Global Health, University of New South Wales, Level 10, King George V Building, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, 2050, Australia.
- The George Institute for Global Health, University of Oxford, Le Gros Clark Building, South Parks Road, Oxford, OX1 3QX, UK.
- Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA.
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21
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Lu CL, Chang YH, Sun Y, Li CY. A population-based study of epilepsy incidence in association with type 2 diabetes and severe hypoglycaemia. Diabetes Res Clin Pract 2018; 140:97-106. [PMID: 29608979 DOI: 10.1016/j.diabres.2018.03.020] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Revised: 02/27/2018] [Accepted: 03/15/2018] [Indexed: 11/21/2022]
Abstract
AIMS This study was conducted to investigate potential link between type 2 diabetes mellitus (T2DM) and epilepsy, and the role of severe hypoglycaemia (SH) might play in the relationship. METHODS This was a cohort study based on Taiwan's National Health insurance claims. Totally 751,792 people with T2DM and 824,253 matched controls were identified in 2002-2003 and followed to incidence of epilepsy or end of 2011. We used Cox proportional hazard model to relate epilepsy incidence to separate and joint effects of T2DM and SH. A possible mediation effect of SH on the association between T2DM and epilepsy was analyzed. RESULTS Over a 10-year follow-up, patients with T2DM had a higher incidence rate of epilepsy than controls (35.0 vs 21.9 per 10,000 person-years). After controlling for potential confounders including SH, T2DM increased the hazard of epilepsy by some 50%. The stratified analysis further indicated that T2DM (hazard ratio (HR)=1.44, 95% confidence interval (CI) = 1.40-1.47), and SH (HR = 2.22, 95% CI = 1.76-2.81) were both independent risk factors for epilepsy. SH did not modify but mediated 12% of the association between T2DM and epilepsy. CONCLUSION Our findings supported that SH may increase the risk of epilepsy, and that T2DM may increase risk of epilepsy independent of SH.
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Affiliation(s)
- Chin-Li Lu
- Graduate Institute of Food Safety, College of Agriculture and Natural Resources, National Chung Hsing University, Taichung, Taiwan
| | - Ya-Hui Chang
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yu Sun
- Department of Neurology, En Chu Kong Hospital, Sanxia District, New Taipei City, Taiwan
| | - Chung-Yi Li
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan.
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22
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Simon TG, King LY, Chong DQ, Nguyen L, Ma Y, VoPham T, Giovannucci EL, Fuchs CS, Meyerhardt JA, Corey KE, Khalili H, Chung RT, Zhang X, Chan AT. Diabetes, metabolic comorbidities, and risk of hepatocellular carcinoma: Results from two prospective cohort studies. Hepatology 2018; 67:1797-1806. [PMID: 29152763 PMCID: PMC5906170 DOI: 10.1002/hep.29660] [Citation(s) in RCA: 85] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Revised: 11/04/2017] [Accepted: 11/13/2017] [Indexed: 12/31/2022]
Abstract
UNLABELLED Type 2 diabetes (T2D) is a risk factor for hepatocellular carcinoma (HCC). However, it is unknown whether T2D duration or additional metabolic comorbidities further contribute to HCC risk. From the Nurses' Health Study (NHS), 120,826 women were enrolled in 1980, and from the Health Professionals Follow-up Study (HPFS), 50,284 men were enrolled in 1986 and followed through 2012. Physician-diagnosed T2D was ascertained at baseline and updated biennially. Cox proportional hazards regression models were used to calculate age- and multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident HCC. Over 32 years of follow-up (4,488,410 person-years), we documented 112 cases of HCC (69 women, 43 men). T2D was associated with an increased HCC risk (multivariable HR, 4.59; 95% CI, 2.98-7.07), as was an increasing T2D duration (Ptrend < 0.001). Compared to nondiabetics, the multivariable HRs for HCC were 2.96 (95% CI, 1.57-5.60) for 0-<2 years; 6.08 (95% CI, 2.96-12.50) for 2-<10 years; and 7.52 (95% CI, 3.88-14.58) for ≥10 years. Increasing number of metabolic comorbidities (T2D, obesity, hypertension, and dyslipidemia) was associated with increased HCC risk (Ptrend < 0.001); compared to individuals without metabolic comorbidity, those with four metabolic comorbidities had an 8.1-fold increased HCC risk (95% CI, 2.48-26.7). In T2D, neither insulin use nor oral hypoglycemic use was significantly associated with HCC risk (HR, 2.04 [95% CI, 0.69-6.09] and HR, 1.45 [95% CI, 0.69-3.07], respectively). CONCLUSION T2D is independently associated with increased risk for HCC in two prospective cohorts of U.S. men and women. This risk is enhanced with prolonged diabetes duration and with comorbid metabolic conditions, suggesting the importance of insulin resistance in the pathogenesis of HCC. (Hepatology 2018;67:1797-1806).
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Affiliation(s)
- Tracey G. Simon
- Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital,Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital,Harvard Medical School, Boston, MA,Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital
| | - Lindsay Y. King
- Division of Gastroenterology and Hepatology, Duke University, Durham NC
| | | | - Long Nguyen
- Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital,Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital,Harvard Medical School, Boston, MA,Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital
| | - Yanan Ma
- Harvard Medical School, Boston, MA,Department of Biostatistics and Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, PR China,Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston MA
| | - Trang VoPham
- Harvard Medical School, Boston, MA,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA,Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston MA
| | - Edward L. Giovannucci
- Harvard Medical School, Boston, MA,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston MA,Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston MA
| | | | | | - Kathleen E. Corey
- Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital,Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital,Harvard Medical School, Boston, MA,Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital
| | - Hamed Khalili
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital,Harvard Medical School, Boston, MA,Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital
| | - Raymond T. Chung
- Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital,Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital,Harvard Medical School, Boston, MA
| | - Xuehong Zhang
- Harvard Medical School, Boston, MA,Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston MA
| | - Andrew T. Chan
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital,Harvard Medical School, Boston, MA,Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital,Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston MA
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23
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Hsu IL, Lu CL, Li CC, Tsai SH, Chen CZ, Hu SC, Li CY. Population-based cohort study suggesting a significantly increased risk of developing chronic obstructive pulmonary disease in people with type 2 diabetes mellitus. Diabetes Res Clin Pract 2018; 138:66-74. [PMID: 29408706 DOI: 10.1016/j.diabres.2018.01.037] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Revised: 01/05/2018] [Accepted: 01/30/2018] [Indexed: 01/04/2023]
Abstract
AIMS To investigate whether type 2 diabetes mellitus (T2DM) increases the risk of developing chronic obstructive pulmonary disease (COPD). METHODS This population-based cohort study used Taiwan's National Health insurance claim data to investigate the association of T2DM with the risk of COPD. A total of 716,623 pairs of people (patients with T2DM and their age-, sex-, and calendar year-matched controls) were identified in 2002-2003 and were followed until the occurrence of newly-diagnosed COPD or the end of 2011. Cox proportional hazard models were used to relate COPD incidence to T2DM. RESULTS People with T2DM experienced a higher incidence rate of COPD than controls (159.6 vs 122.7 per 104 person-years). After controlling for confounders, T2DM significantly increased the hazard of COPD (hazard ratio [HR] = 1.15, 95% confidence interval = 1.14-1.16). Stratified analysis indicated that the association between T2DM and COPD was slightly greater in women than in men (HR, 1.15 vs. 1.11) and in people aged <65 years than in people aged ≥65 years (HR, 1.17 vs. 1.05 in men; 1.16 vs. 1.13 in women). CONCLUSIONS Our findings demonstrated a modest association of T2DM with the risk of developing COPD, possibly shedding light into the adverse effects of hyperglycemia on pulmonary function.
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Affiliation(s)
- I-Lin Hsu
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Emergency Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chin-Li Lu
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chia-Chun Li
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Sheng-Han Tsai
- Division of Chest Medicine, Department of Internal Medicine, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Chiung-Zuei Chen
- Division of Chest Medicine, Department of Internal Medicine, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Susan C Hu
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chung-Yi Li
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan.
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Chen Y, Wu F, Saito E, Lin Y, Song M, Luu HN, Gupta PC, Sawada N, Tamakoshi A, Shu XO, Koh WP, Xiang YB, Tomata Y, Sugiyama K, Park SK, Matsuo K, Nagata C, Sugawara Y, Qiao YL, You SL, Wang R, Shin MH, Pan WH, Pednekar MS, Tsugane S, Cai H, Yuan JM, Gao YT, Tsuji I, Kanemura S, Ito H, Wada K, Ahn YO, Yoo KY, Ahsan H, Chia KS, Boffetta P, Zheng W, Inoue M, Kang D, Potter JD. Association between type 2 diabetes and risk of cancer mortality: a pooled analysis of over 771,000 individuals in the Asia Cohort Consortium. Diabetologia 2017; 60:1022-1032. [PMID: 28265721 PMCID: PMC5632944 DOI: 10.1007/s00125-017-4229-z] [Citation(s) in RCA: 128] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Accepted: 02/01/2017] [Indexed: 12/12/2022]
Abstract
AIMS/HYPOTHESIS The aims of the study were to evaluate the association between type 2 diabetes and the risk of death from any cancer and specific cancers in East and South Asians. METHODS Pooled analyses were conducted of 19 prospective population-based cohorts included in the Asia Cohort Consortium, comprising data from 658,611 East Asians and 112,686 South Asians. HRs were used to compare individuals with diabetes at baseline with those without diabetes for the risk of death from any cancer and from site-specific cancers, including cancers of the oesophagus, stomach, colorectum, colon, rectum, liver, bile duct, pancreas, lung, breast, endometrium, cervix, ovary, prostate, bladder, kidney and thyroid, as well as lymphoma and leukaemia. RESULTS During a mean follow-up of 12.7 years, 37,343 cancer deaths (36,667 in East Asians and 676 in South Asians) were identified. Baseline diabetes status was statistically significantly associated with an increased risk of death from any cancer (HR 1.26; 95% CI 1.21, 1.31). Significant positive associations with diabetes were observed for cancers of the colorectum (HR 1.41; 95% CI 1.26, 1.57), liver (HR 2.05; 95% CI 1.77, 2.38), bile duct (HR 1.41; 95% CI 1.04, 1.92), gallbladder (HR 1.33; 95% CI 1.10, 1.61), pancreas (HR 1.53; 95% CI 1.32, 1.77), breast (HR 1.72; 95% CI 1.34, 2.19), endometrium (HR 2.73; 95% CI 1.53, 4.85), ovary (HR 1.60; 95% CI 1.06, 2.42), prostate (HR 1.41; 95% CI 1.09, 1.82), kidney (HR 1.84; 95% CI 1.28, 2.64) and thyroid (HR 1.99; 95% CI 1.03, 3.86), as well as lymphoma (HR 1.39; 95% CI 1.04, 1.86). Diabetes was not statistically significantly associated with the risk of death from leukaemia and cancers of the bladder, cervix, oesophagus, stomach and lung. CONCLUSIONS/INTERPRETATION Diabetes was associated with a 26% increased risk of death from any cancer in Asians. The pattern of associations with specific cancers suggests the need for better control (prevention, detection, management) of the growing epidemic of diabetes (as well as obesity), in order to reduce cancer mortality.
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Affiliation(s)
- Yu Chen
- Department of Population Health, New York University School of Medicine, 650 First Avenue, Room 510, New York, NY, 10016, USA.
- Department of Environmental Medicine, New York University School of Medicine, Tuxedo Park, NY, 10987, USA.
| | - Fen Wu
- Department of Population Health, New York University School of Medicine, 650 First Avenue, Room 510, New York, NY, 10016, USA
- Department of Environmental Medicine, New York University School of Medicine, Tuxedo Park, NY, 10987, USA
| | - Eiko Saito
- AXA Department of Health and Human Security, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Yingsong Lin
- Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Minkyo Song
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Hung N Luu
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
- Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, FL, USA
| | - Prakash C Gupta
- Healis Sekhsaria Institute for Public Health, Navi Mumbai, India
| | - Norie Sawada
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Akiko Tamakoshi
- Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Xiao-Ou Shu
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Woon-Puay Koh
- Duke-NUS Medical School Singapore, Singapore, Republic of Singapore
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Republic of Singapore
| | - Yong-Bing Xiang
- Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai, People's Republic of China
| | - Yasutake Tomata
- Tohoku University Graduate School of Medicine, Miyagi Prefecture, Japan
| | - Kemmyo Sugiyama
- Tohoku University Graduate School of Medicine, Miyagi Prefecture, Japan
| | - Sue K Park
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Keitaro Matsuo
- Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan
- Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Chisato Nagata
- Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Yumi Sugawara
- Tohoku University Graduate School of Medicine, Miyagi Prefecture, Japan
| | - You-Lin Qiao
- Cancer Foundation of China, Beijing, People's Republic of China
| | - San-Lin You
- School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan
- Big Data Research Centre, Fu-Jen Catholic University, Taipei, Taiwan
| | - Renwei Wang
- University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
| | - Myung-Hee Shin
- Department of Social and Preventive Medicine, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Wen-Harn Pan
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | | | - Shoichiro Tsugane
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Hui Cai
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Jian-Min Yuan
- Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA
- Division of Cancer Control and Population Science, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
| | - Yu-Tang Gao
- Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai, People's Republic of China
| | - Ichiro Tsuji
- Tohoku University Graduate School of Medicine, Miyagi Prefecture, Japan
| | - Seiki Kanemura
- Tohoku University Graduate School of Medicine, Miyagi Prefecture, Japan
| | - Hidemi Ito
- Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
| | - Keiko Wada
- Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Yoon-Ok Ahn
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Keun-Young Yoo
- Armed Forces Capital Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Habibul Ahsan
- Department of Public Health Sciences, University of Chicago, Chicago, IL, USA
| | - Kee Seng Chia
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Republic of Singapore
| | - Paolo Boffetta
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Wei Zheng
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Manami Inoue
- AXA Department of Health and Human Security, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Daehee Kang
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, South Korea
- Cancer Research Institute, Seoul National University, Seoul, South Korea
| | - John D Potter
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Centre for Public Health Research, Massey University, Wellington, New Zealand
- Department of Epidemiology, University of Washington, Seattle, WA, USA
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Ou HT, Chang KC, Liu YM, Wu JS. Recent trends in the use of antidiabetic medications from 2008 to 2013: A nation-wide population-based study from Taiwan. J Diabetes 2017; 9:256-266. [PMID: 27062145 DOI: 10.1111/1753-0407.12408] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Revised: 03/19/2016] [Accepted: 03/31/2016] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND Studies from other countries indicate that utilization patterns of antidiabetic drugs change significantly after the introduction of newer classes of antidiabetic drugs (e.g. dipeptidyl peptidase-4 inhibitors [DPP-4i]). Evidence on recent trends regarding antidiabetic drug use in Taiwan is lacking, especially for times after the introduction of newer classes of drugs (e.g. DPP-4i). Therefore, the aim of the present study was to assess: (i) recent trends in the use and spending on antidiabetic drugs; (ii) changes in utilization patterns after introduction of newer classes of antidiabetic drugs; and (iii) factors associated with the choice of newer versus older classes of antidiabetic drugs. METHODS Cases of type 2 diabetes were derived from Taiwan's National Health Insurance Research Database. Antidiabetic drug use was measured in terms of total quantity of drug exposure and healthcare spending in each calendar year from 2008 to 2103. Multiple logistic regression analysis was used to assess factors associated with drug choice. RESULTS The use of and healthcare spending on DPP-4i increased significantly from 2008 to 2013, whereas healthcare spending on sulfonylureas decreased. For monotherapy, sulfonylureas were the most common alternatives to metformin, whereas in dual and triple antidiabetic therapies, a DPP-4i was the most common alternative to initial regimens. The use of a DPP-4i was positively associated with the use of beta-blockers, angiotensin II-converting enzyme inhibitors and/or angiotensin receptor blockers, and lipid-lowering agents, but negatively correlated with age, hypertension, severity of diabetes complications, and the use of diuretics and calcium channel blockers. CONCLUSIONS With growing spending on newer antidiabetic drugs, future research on the comparative cost-effectiveness and safety of antidiabetic drugs is anticipated.
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Affiliation(s)
- Huang-Tz Ou
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Kai-Cheng Chang
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Ya-Ming Liu
- Department of Family Medicine, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Jin-Shang Wu
- Department of Economics, School of Social Sciences, National Cheng Kung University, Tainan, Taiwan
- Department of Family Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
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Chiou WY, Chen CA, Lee MS, Lin HY, Li CY, Su YC, Tsai SJ, Hung SK. Pelvic inflammatory disease increases the risk of a second primary malignancy in patients with cervical cancer treated by surgery alone. Medicine (Baltimore) 2016; 95:e5409. [PMID: 27893679 PMCID: PMC5134872 DOI: 10.1097/md.0000000000005409] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
As the number of long-term cervical cancer survivors continues to increase because of improvements in treatment, concerns about second primary malignancy have grown. The high-risk area of second primary cancers in cervical cancer survivors is the pelvis. Pelvic inflammatory disease (PID) could be a useful marker for gynecological cancers. Thus, we designed a large-scale, nationwide, controlled cohort study to investigate whether PID or other risk factors increased the risk of second primary cancers in patients with cervical cancer treated by surgery alone.Between 2000 and 2010, a total of 24,444 cervical cancer patients were identified using the Registry Data for Catastrophic Illness and the National Health Insurance Research Database (NHIRD) of Taiwan. Patients who received definite surgery were selected. To exclude the effect on second primary malignancy by treatment modalities, all cervical patients who ever having received adjuvant or definite radiotherapy or chemotherapy for primary cervical cancer were excluded. Finally, 3860 cervical cancer patients treated by surgery alone without adjuvant treatments were analyzed.Cox proportional hazards model was used for multivariate analysis and the Kaplan-Meier method was used to assess the cumulative risks. Regarding the incidence of second primary cancers, the standardized incidence ratio (SIR) was used.The median follow-up time was 56.6 months. The 6-year cumulative risk of second primary cancers is 0.16% and 0.12% for PID and without PID, respectively. After adjustment for confounders, age of less than 50 years, the presence of diabetes mellitus, and PID were significantly positivity associated with the risk of second primary cancers. The hazard ratios (HRs) of age less than 50 years, diabetes mellitus, and PID were 1.38 (95% CI = 1.11-2.04), 1.40 (95% CI = 1.06-1.85), and 1.35 (95% CI = 1.00-1.81), respectively. A higher incidence of second primary cancers was observed in the genitals, bladder, and colon.In conclusion, the incidence of second primary cancers was higher in the genitals, bladder, and colon in patients with cervical cancer treated with surgery alone. The patients with PID had a higher risk of second primary cancers.
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Affiliation(s)
- Wen-Yen Chiou
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi
- School of Medicine, Tzu Chi University, Hualian
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan
| | - Chien-An Chen
- Department of Radiation Oncology, Zhongxing Branch, Taipei City Hospital, Taipei
| | - Moon-Sing Lee
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi
- School of Medicine, Tzu Chi University, Hualian
| | - Hon-Yi Lin
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi
- School of Medicine, Tzu Chi University, Hualian
| | - Chung-Yi Li
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan
- Department of Public Health, China Medical University, Taichung
| | - Yu-Chieh Su
- Division of Hematology and Oncology, E-Da Hospital, Kaohsiung
- School of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Shiang-Jiun Tsai
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi
| | - Shih-Kai Hung
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi
- School of Medicine, Tzu Chi University, Hualian
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Hou WH, Li CY, Chen LH, Wang LY, Kuo LC, Kuo KN, Shen HN, Chiu CT. Medical claims-based case-control study of temporal relationship between clinical visits for hand syndromes and subsequent diabetes diagnosis: implications for identifying patients with undiagnosed type 2 diabetes mellitus. BMJ Open 2016; 6:e012071. [PMID: 27798003 PMCID: PMC5073620 DOI: 10.1136/bmjopen-2016-012071] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES To investigate whether a temporal relationship is present between clinical visits for diabetes-related hand syndromes (DHSs) and subsequent type 2 diabetes mellitus (T2DM) diagnosis and, accordingly, whether DHSs can be used for identifying patients with undiagnosed T2DM. DESIGN This study had a case-control design nested within a cohort of 1 million people from the general population, which was followed from 2005 to 2010. The odds of prior clinical visits for DHSs, namely carpal tunnel syndrome (CTS), flexor tenosynovitis, limited joint mobility and Dupuytren's disease, were estimated for cases and controls. We used a conditional logistic regression model to estimate the OR and 95% CI of T2DM in association with a history of DHSs. The validity and predictive value of using the history of DHSs in predicting T2DM diagnosis were calculated. SETTING Taiwan National Health Insurance medical claims. PARTICIPANTS We identified 33 571 patients receiving a new diagnosis of T2DM (cases) between 2005 and 2010. Each T2DM case was matched with 5 controls who had the same sex and birth year and were alive on the date of T2DM diagnosis. PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcome measure was T2DM diagnosis. RESULTS The OR of T2DM in association with prior clinical visits was significantly increased for overall DHS and CTS, being 1.15 (95% CI 1.10 to 1.20) and 1.22 (95% CI 1.16 to 1.29), respectively. Moreover, 11% of patients with T2DM made clinical visits for CTS within 3 months prior to T2DM diagnosis. The history of DHSs had low sensitivity (<0.1% to 5.2%) and a positive predictive value (9.9% to 11.7%) in predicting T2DM. CONCLUSIONS Despite the unsatisfactory validity and performance of DHSs as a clinical tool for detecting patients with undiagnosed T2DM, this study provided evidence that clinical visits for DHSs, particularly for CTS, can be a sign of undiagnosed T2DM.
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Affiliation(s)
- Wen-Hsuan Hou
- Cochrane Taiwan, Taipei Medical University, Taipei, Taiwan
- Master Program in Long-Term Care, College of Nursing, Taipei Medical University, Taipei, Taiwan
- School of Gerontology Health Management, College of Nursing, Taipei Medical University, Taipei, Taiwan
- Department of Physical Medicine and Rehabilitation, Taipei Medical University Hospital, Taipei, Taiwan
| | - Chung-Yi Li
- Department and Graduate Institute of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
| | - Lu-Hsuan Chen
- Department and Graduate Institute of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
| | - Liang-Yi Wang
- Department and Graduate Institute of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Li-Chieh Kuo
- Department of Occupational Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ken N Kuo
- Cochrane Taiwan, Taipei Medical University, Taipei, Taiwan
| | - Hsiu-Nien Shen
- Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Chang-Ta Chiu
- Department of Dentistry, Tainan Municipal An-Nan Hospital, China Medical University, Tainan, Taiwan
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Lu CL, Chang HH, Chen HF, Ku LJE, Chang YH, Shen HN, Li CY. Inverse relationship between ambient temperature and admissions for diabetic ketoacidosis and hyperglycemic hyperosmolar state: A 14-year time-series analysis. ENVIRONMENT INTERNATIONAL 2016; 94:642-648. [PMID: 27395337 DOI: 10.1016/j.envint.2016.06.032] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Revised: 06/14/2016] [Accepted: 06/30/2016] [Indexed: 06/06/2023]
Abstract
This study aimed to investigate the association of admissions for diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) with ambient temperature and season, respectively in patients with diabetes mellitus (DM), after excluding known co-morbidities that predispose onset of acute hyperglycemia events. This was a time series correlation analysis based on medical claims of 40,084 and 33,947 episodes of admission for DKA and HHS, respectively over a 14-year period in Taiwan. These episodes were not accompanied by co-morbidities known to trigger incidence of DKA and HHS. Monthly temperature averaged from 19 meteorological stations across Taiwan was correlated with monthly rate of admission for DKA or HHS, respectively, using the 'seasonal Autoregressive Integrated Moving Average' (seasonal ARIMA) regression method. There was an inverse relationship between ambient temperature and rates of admission for DKA (β=-0.035, p<0.001) and HHS (β=-0.016, p<0.001), despite a clear decline in rates of DKA/HHS admission in the second half of the study period. We also noted that winter was significantly associated with increased rates of both DKA (β=0.364, p<0.001) and HHS (β=0.129, p<0.05) admissions, as compared with summer. On the other hand, fall was associated with a significantly lower rate of HHS admission (β=-0.016, p<0.05). Further stratified analyses according to sex and age yield essentially similar results. It is suggested that meteorological data can be used to raise the awareness of acute hyperglycemic complication risk for both patients with diabetes and clinicians to further avoid the occurrence of DKA and HHS.
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Affiliation(s)
- Chin-Li Lu
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hsin-Hui Chang
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hua-Fen Chen
- Department of Endocrinology, Far Eastern Memorial Hospital, New Taipei City, Taiwan; School of Medicine, Fujen Catholic University, New Taipei City, Taiwan
| | - Li-Jung Elizabeth Ku
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ya-Hui Chang
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hsiu-Nien Shen
- Department of Intensive Care Medicine, Chi Mei Medical Center, Yong-Kang District, Tainan, Taiwan.
| | - Chung-Yi Li
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
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Chang YT, Hwang JS, Hung SY, Tsai MS, Wu JL, Sung JM, Wang JD. Cost-effectiveness of hemodialysis and peritoneal dialysis: A national cohort study with 14 years follow-up and matched for comorbidities and propensity score. Sci Rep 2016; 6:30266. [PMID: 27461186 PMCID: PMC4962092 DOI: 10.1038/srep30266] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Accepted: 07/04/2016] [Indexed: 12/15/2022] Open
Abstract
Although treatment for the dialysis population is resource intensive, a cost-effectiveness analysis comparing hemodialysis (HD) and peritoneal dialysis (PD) by matched pairs is still lacking. After matching for clinical characteristics and propensity scores, we identified 4,285 pairs of incident HD and PD patients from a Taiwanese national cohort during 1998-2010. Survival and healthcare expenditure were calculated by data of 14-year follow-up and subsequently extrapolated to lifetime estimates under the assumption of constant excess hazard. We performed a cross-sectional EQ-5D survey on 179 matched pairs of prevalent HD and PD patients of varying dialysis vintages from 12 dialysis units. The product of survival probability and the mean utility value at each time point (dialysis vintage) were summed up throughout lifetime to obtain the quality-adjusted life expectancy (QALE). The results revealed the estimated life expectancy between HD and PD were nearly equal (19.11 versus 19.08 years). The QALE's were also similar, whereas average lifetime healthcare costs were higher in HD than PD (237,795 versus 204,442 USD) and the cost-effectiveness ratios for PD and HD were 13,681 and 16,643 USD per quality-adjusted life year, respectively. In conclusion, PD is more cost-effective than HD, of which the major determinants were the costs for the dialysis modality and its associated complications.
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Affiliation(s)
- Yu-Tzu Chang
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | | | - Shih-Yuan Hung
- Division of Nephrology, Department of Internal Medicine, E-DA Hospital, and School of Medicine for International Students, I-Shou University, Kaohsiung
| | - Min-Sung Tsai
- Division of Nephrology, Department of Internal Medicine, Kuo General Hospital, Tainan, Taiwan
| | - Jia-Ling Wu
- Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Junne-Ming Sung
- Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Jung-Der Wang
- Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Department of Environmental and Occupational Health, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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31
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Si WK, Chung JW, Cho J, Baeg JY, Jang ES, Yoon H, Kim J, Shin CM, Park YS, Hwang JH, Jeong SH, Kim N, Lee DH, Lim S, Kim JW. Predictors of Increased Risk of Hepatocellular Carcinoma in Patients with Type 2 Diabetes. PLoS One 2016; 11:e0158066. [PMID: 27359325 PMCID: PMC4928920 DOI: 10.1371/journal.pone.0158066] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2016] [Accepted: 06/09/2016] [Indexed: 12/20/2022] Open
Abstract
Epidemiological data indicate that type 2 diabetes is associated with increased risk of hepatocellular carcinoma (HCC). However, risk stratification for HCC has not been fully elucidated in diabetic population. The aim of this study was to identify potential predictors of HCC in diabetic patients without chronic viral hepatitis. A cohort of 3,544 diabetic patients without chronic viral hepatitis or alcoholic cirrhosis was established and subjects were randomly allocated into a derivation and a validation set. A scoring system was developed by using potential predictors of increased risk of HCC from the Cox proportional hazards model. The performance of the scoring system was tested for validation by using receiver operating characteristics analysis. During median follow-up of 55 months, 36 cases of HCC developed (190 per 100,000 person-years). The 5- and 10-year cumulative incidences of HCC were 1.0%, and 2.2%, respectively. Multivariate Cox regression analysis showed that age > 65 years, low triglyceride levels and high gamma-glutamyl transferase levels were independently associated with an increased risk of HCC. DM-HCC risk score, a weighted sum of scores from these 3 parameters, predicted 10-year development of HCC with area under the receiver operating characteristics curve of 0.86, and discriminated different risk categories for HCC in the derivation and validation cohort. In conclusion, old age, low triglyceride level and high gamma-glutamyl transferase level may help to identify individuals at high risk of developing HCC in diabetic patients without chronic viral hepatitis or alcoholic cirrhosis.
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Affiliation(s)
- Won Keun Si
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Jung Wha Chung
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Junhyeon Cho
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Joo Yeong Baeg
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Eun Sun Jang
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hyuk Yoon
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jaihwan Kim
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Cheol Min Shin
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Young Soo Park
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jin-Hyeok Hwang
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sook-Hyang Jeong
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Nayoung Kim
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Dong Ho Lee
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Soo Lim
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jin-Wook Kim
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- * E-mail:
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Shen J, Tsoi H, Liang Q, Chu ESH, Liu D, Yu ACS, Chan TF, Li X, Sung JJY, Wong VWS, Yu J. Oncogenic mutations and dysregulated pathways in obesity-associated hepatocellular carcinoma. Oncogene 2016; 35:6271-6280. [PMID: 27132506 PMCID: PMC5153568 DOI: 10.1038/onc.2016.162] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Revised: 04/01/2016] [Accepted: 04/03/2016] [Indexed: 02/07/2023]
Abstract
Epidemiological studies showed that obesity and its related non-alcoholic fatty liver disease (NAFLD) promote hepatocellular carcinoma (HCC) development. We aimed to uncover the genetic alterations of NAFLD-HCC using whole-exome sequencing. We compared HCC development in genetically obese mice and dietary obese mice with wild-type lean mice fed a normal chow after treatment with diethylnitrosamine. HCC tumor and adjacent normal samples from obese and lean mice were then subjected to whole-exome sequencing. Functional and mechanistic importance of the identified mutations in Carboxyl ester lipase (Cel) gene and Harvey rat sarcoma virus oncogene 1 (Hras) was further elucidated. We demonstrated significantly higher incidences of HCC in both genetic and dietary obese mice with NAFLD development as compared with lean mice without NAFLD. The mutational signatures of NAFLD-HCC and lean HCC were distinct, with <3% overlapped. Eight metabolic or oncogenic pathways were found to be significantly enriched by mutated genes in NAFLD-HCC, but only two of these pathways were dysregulated by mutations in lean HCC. In particular, Cel was mutated significantly more frequently in NAFLD-HCC than in lean HCC. The multiple-site mutations in Cel are loss-of-function mutations, with effects similar to Cel knock-down. Mutant Cel caused accumulation of cholesteryl ester in liver cells, which led to induction of endoplasmic reticulum stress and consequently activated the IRE1α/c-Jun N-terminal kinase (JNK)/c-Jun/activating protein-1 (AP-1) signaling cascade to promote liver cell growth. In addition, single-site mutations in Hras at codon 61 were found in NAFLD-HCC but none in lean HCC. The gain-of-function mutations in Hras (Q61R and Q61K) significantly promoted liver cell growth through activating the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/3-phosphoinositide-dependent protein kinase-1 (PDK1)/Akt pathways. In conclusion, we have identified mutation signature and pathways in NAFLD-associated HCC. Mutations in Cel and Hras have important roles in NAFLD-associated hepatocellular carcinogenesis.
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Affiliation(s)
- J Shen
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - H Tsoi
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Q Liang
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - E S H Chu
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - D Liu
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - A C-S Yu
- School of Life Sciences, and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China
| | - T F Chan
- School of Life Sciences, and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China
| | - X Li
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - J J Y Sung
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - V W S Wong
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - J Yu
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
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Wei KC, Lin HY, Hung SK, Huang YT, Lee MS, Wang WH, Wu CS, Su YC, Shen BJ, Tsai SJ, Tsai WT, Chen LC, Li CY, Chiou WY. Leukemia Risk After Cardiac Fluoroscopic Interventions Stratified by Procedure Number, Exposure Latent Time, and Sex: A Nationwide Population-Based Case-Control Study. Medicine (Baltimore) 2016; 95:e2953. [PMID: 26962795 PMCID: PMC4998876 DOI: 10.1097/md.0000000000002953] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
A number of cardiac fluoroscopic interventions have increased rapidly worldwide over the past decade. Percutaneous transluminal coronary angioplasty (PTCA) and stent implantation have become increasingly popular, and these advancements have allowed patients to receive repetitive treatments for restenosis. However, these advancements also significantly increase radiation exposure that may lead to higher cumulative doses of radiation. In the present study, a nationwide population-based case-controlled study was used to explore the risk of leukemia after cardiac angiographic fluoroscopic intervention.A total of 5026 patients with leukemia and 100,520 control patients matched for age and sex (1:20) by a propensity score method without any cancer history were enrolled using the Registry Data for Catastrophic Illness and the National Health Insurance Research Database (NHIRD) of Taiwan between 2008 and 2010. All subjects were retrospectively surveyed (from year 2000) to determine receipt of cardiac fluoroscopic interventions. Data were analyzed using conditional logistic regression models, and estimated crude and adjusted odds ratios (95% confidence interval).After adjusting for age, gender, and comorbidities, PTCA was found to be associated with an increased risk of leukemia with an adjusted OR of 1.566 (95% CI, 1.282-1.912), whereas coronary angiography alone without PTCA and cardiac electrophysiologic study were not. Our results also showed that an increased frequency of PTCA and coronary angiography was associated with a higher risk of leukemia (adjusted OR: 1.326 to 1.530 [all P < 0.05]). Gender subgroup analyses demonstrated that men were associated with a higher risk of leukemia compared with women.These results provide additional data in the quantification of the long-term health effects of radiation exposure derived from the cardiac fluoroscopic diagnostic and therapeutic intervention. PTCA alone or PTCA with coronary angiography was associated with an elevated risk of leukemia. Continued follow-up of existing cohorts will be valuable to help assess lifetime risks of cancer.
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Affiliation(s)
- Kai-Che Wei
- From the Department of Dermatology (K-CW, C-SW), Kaohsiung Veterans General Hospital, Kaohsiung; Institute of Clinical Medicine (K-CW), College of Medicine, National Cheng Kung University, Tainan; Faculty of Yuhing Junior College of Health Care and Management (K-CW), Kaohsiung; Department of Radiation Oncology (H-YL, S-KH, M-SL, BJS, S-JT, W-TT, L-CC, W-YC), Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi; School of Medicine (H-YL, S-KH, M-SL, B-JS, Y-CS, W-YC), Tzu Chi University, Hualien; Master Degree Program in Aging and Long-Term Care (Y-TH), College of Nursing, Kaohsiung Medical University; Department of Cardiology (W-HW), Kaohsiung Veterans General Hospital, Kaohsiung; Division of Hematology Oncology (Y-CS), Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi; Department of Biomedical Imaging and Radiological Sciences (W-TT), National Yang-Ming University, Taipei; Department of Public Health (C-YL, W-YC), College of Medicine, National Cheng Kung University, Tainan; and Department of Public Health (C-YL), China Medical University, Taichung, Taiwan
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Chen LH, Li CY, Kuo LC, Wang LY, Kuo KN, Jou IM, Hou WH. Risk of Hand Syndromes in Patients With Diabetes Mellitus: A Population-Based Cohort Study in Taiwan. Medicine (Baltimore) 2015; 94:e1575. [PMID: 26469895 PMCID: PMC4616773 DOI: 10.1097/md.0000000000001575] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The aim of this study was to assess the overall and cause-specific incidences of diabetic hand syndromes (DHS) in patients with diabetes mellitus (DM) by using age and sex stratifications.The DM and control cohorts comprised 606,152 patients with DM and 609,970 age- and sex-matched subjects, respectively, who were followed up from 2000 to 2008. We estimated the incidence densities (IDs) of overall and cause-specific DHS, namely carpal tunnel syndrome (CTS), stenosing flexor tenosynovitis (SFT), limited joint mobility (LJM), and Dupuytren disease (DD), and calculated the hazard ratios (HRs) of DHS in relation to DM by using a Cox proportional hazards model with adjustment for potential confounders.Over a 9-year period, 51,207 patients with DM (8.45%) and 39,153 matched controls (6.42%) sought ambulatory care visits for various DHS, with an ID of 117.7 and 80.7 per 10,000 person-years, respectively. The highest cause-specific ID was observed for CTS, followed by SFT, LJM, and DD, regardless of the diabetic status. After adjustment for potential confounders, patients with DM had a significantly high HR of overall DHS (1.51, 95% confidence interval [CI] = 1.48-1.53). Men and women aged <35 years had the highest HR (2.64, 95% CI = 2.15-3.24 and 2.99, 95% CI = 2.55-3.50, respectively). Cause-specific analyses revealed that DM was more strongly associated with SFT (HR = 1.90, 95% CI = 1.86-1.95) and DD (HR = 1.83, 95% CI = 1.39-2.39) than with CTS (HR = 1.31, 95% CI = 1.28-1.34) and LJM (HR = 1.24, 95% CI = 1.13-1.35).Men and younger patients with DM have the highest risk of DHS. Certain hand syndromes, such as SFT and DD, were more strongly associated with DM than with other syndromes and require the attention of clinicians.
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Affiliation(s)
- Lu-Hsuan Chen
- From the Department and Graduate Institute of Public Health (L-HC, C-YL, L-YW), College of Medicine, National Cheng Kung University, Tainan; Department of Public Health (C-YL), College of Public Health, China Medical University, Taichung; Department of Occupational Therapy (L-CK), College of Medicine, National Cheng Kung University, Tainan; Center of Evidence-Based Medicine (KNK, W-HH), Taipei Medical University, Taipei; Department of Orthopedics (I-MJ), National Cheng Kung University Hospital, Tainan; Master Program in Long-Term Care (W-HH), College of Nursing, Taipei Medical University, Taipei; School of Gerontology Health Management (W-HH), College of Nursing, Taipei Medical University, Taipei; and Department of Physical Medicine and Rehabilitation (W-HH), Taipei Medical University Hospital, Taipei, Taiwan
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Lu CL, Hsu PC, Shen HN, Chang YH, Chen HF, Li CY. Association Between History of Severe Hypoglycemia and Risk of Falls in Younger and Older Patients With Diabetes. Medicine (Baltimore) 2015; 94:e1339. [PMID: 26287419 PMCID: PMC4616447 DOI: 10.1097/md.0000000000001339] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Accepted: 07/16/2015] [Indexed: 12/30/2022] Open
Abstract
To compare the incidence and relative risk of falls between adults with and without diabetes, and to prospectively assess the role of history of severe hypoglycemia in the putative relationship between diabetes and falls in younger and older people, respectively.The National Health Insurance Research Database in Taiwan was used in this cohort study. Diabetic cases (with and without history of severe hypoglycemia) and nondiabetic people were followed from 2000 to 2009. There were 31,049 people enrolled in each of the 3 groups. Subdistribution hazard ratio (sHR) of falls was estimated with considering death as a competing risk by using Fine and Gray method. Demographic characteristics, diabetes-related complications, and comorbidities associated with falls were adjusted in multivariable Cox regression model.As compared to nondiabetic people, adjusted sHR was 1.13 for diabetes without history of severe hypoglycemia (DwoH) and 1.63 for diabetes with history of severe hypoglycemia (DwH), respectively. DwH group was associated with a higher risk than DwoH (adjusted sHR = 1.57). All of the excessive risks were more pronounced in people younger than 65 years old than in older people.Patients with diabetes had increased risk of falls. Severe hypoglycemia was further associated with a higher risk in diabetes, the increased hazards were particularly pronounced in people younger than 65 years old. Because falls in younger people may result in a greater economic and social loss, our study call for proper attentions to prevention of falls in younger patients (<65 years old) with diabetes.
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Affiliation(s)
- Chin-Li Lu
- From Department of Public Health, Medical College, National Cheng-Kung University, Tainan, Taiwan (C-LL, P-CH, H-NS, Y-HC, C-YL); Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan, Taiwan (P-CH); Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan (H-NS); Department of Endocrinology, Far Eastern Memorial Hospital, Panchiao, New Taipei City, Taiwan (H-FC); and Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan (C-YL)
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Chen YC, Hwang SJ, Li CY, Wu CP, Lin LC. A Taiwanese Nationwide Cohort Study Shows Interferon-Based Therapy for Chronic Hepatitis C Reduces the Risk of Chronic Kidney Disease. Medicine (Baltimore) 2015; 94:e1334. [PMID: 26266379 PMCID: PMC4616715 DOI: 10.1097/md.0000000000001334] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Hepatitis C virus (HCV) infection is a risk factor for chronic kidney disease (CKD). However, it remains unclear whether interferon-based therapy (IBT) for HCV was associated with reduced risk of CKD.From the Taiwan National Health Insurance Research Database, we identified 919 patients who received 3 months or more of IBT as our treated cohort. This cohort was propensity score-matched 1:4 with 3676 controls who had never received IBT for HCV infection (untreated cohort). Cumulative incidences of and hazard ratios (HRs) for CKD were calculated after adjusting for competing mortality.In the matched HCV cohort, the risk of CKD was significantly lower in the treated cohort (7-year cumulative incidence, 2.6%; 95% confidence interval [CI], 0.7%-6.9%) than in the untreated cohort (4%; 95% CI, 3.5%-5.2%) (P < 0.001), with an adjusted HR of 0.42 (95% CI, 0.20-0.92; P = 0.03). The results also held in the overall HCV cohort. The number needed to treat for 1 fewer CKD at 7 years was 58. The reduced risk of CKD was greatest (0.35; 0.14-0.87; P = 0.024) in HCV-infected patients who received 6 months or more of IBT. Multivariable stratified analysis verified that greater risk reduction of CKD was present in HCV-infected patients with hyperlipidemia, diabetes, hypertension, and those without coronary heart disease.In conclusion, IBT, especially for 6 or more months, is associated with reduced risk of CKD in HCV-infected patients. Hyperlipidemia, diabetes, hypertension, and coronary heart disease can modify this association.
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Affiliation(s)
- Yi-Chun Chen
- From the Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi (Y-CC, L-CL); School of Medicine, Tzu Chi University, Hualien (Y-CC); Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung (S-JH); Department and Graduate Institute of Public Health, College of Medicine, National Cheng Hung University, Tainan (C-YL); Department of Public Health, College of Public Health, China Medical University, Taichung (C-YL); and Public Health Department, New Taipei City Government, Taipei, Taiwan (C-PW)
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Hsu PC, Lin WH, Kuo TH, Lee HM, Kuo C, Li CY. A Population-Based Cohort Study of All-Cause and Site-Specific Cancer Incidence Among Patients With Type 1 Diabetes Mellitus in Taiwan. J Epidemiol 2015. [PMID: 26212724 PMCID: PMC4549608 DOI: 10.2188/jea.je20140197] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The relationship between type 1 diabetes mellitus (T1DM) and cancer incidence remains unclear. We sought to assess the all-cause and site-specific cancer incidence in patients with T1DM. METHODS A retrospective cohort study design was employed, in which 14 619 patients with T1DM were retrieved from Taiwan's National Health Insurance medical claims between 2000 and 2007. The study subjects were followed to the end of 2008, and cancer incidence was assessed. We calculated age-, sex-, and calendar year-standardized incidence ratios (SIRs) of all-cause cancer incidence and site-specific neoplasm incidence, with reference to the general population. RESULTS Seven hundred and sixty patients were identified for all-cause cancer over 86,610 person-years, representing an incidence rate of 87.75 cases per 10,000 person-years. The incidence rate was higher in males than in female patients (109.86 vs 69.75 cases per 10,000 person-years). T1DM was associated with a significantly increased SIR of all-cause cancer (1.13; 95% confidence interval [CI], 1.05-1.22). The sex-specific SIR was significantly elevated in female patients (1.19; 95% CI, 1.07-1.33), but the SIR for male patients was insignificantly elevated (1.09; 95% CI, 0.99-1.20). Pancreatic cancer showed the greatest increase in SIR among both male and female patients with T1DM. Male patients experienced significantly increased SIRs for kidney, rectum, liver, and colon neoplasm, and significantly increased SIRs were noted for ovarian, bladder, and colon cancer in female patients. CONCLUSIONS T1DM was associated with a 13% increase in risk of all-cause cancer incidence. Patients with T1DM should be advised to undergo cancer screening for certain types of cancer.
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Affiliation(s)
- Pei-Chun Hsu
- Department and Graduate Institute of Public Health, College of Medicine, National Cheng Kung University
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Chen YC, Su YC, Li CY, Hung SK. 13-year nationwide cohort study of chronic kidney disease risk among treatment-naïve patients with chronic hepatitis B in Taiwan. BMC Nephrol 2015. [PMID: 26199000 PMCID: PMC4508999 DOI: 10.1186/s12882-015-0106-5] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Background Chronic hepatitis B virus (HBV) infection and chronic kidney disease (CKD) have high prevalences in Taiwan and worldwide. However, the association of untreated chronic hepatitis B virus (HBV) infection with chronic kidney disease (CKD) remains unclear. Methods This cohort study used claims data in the Taiwan National Health Insurance Research Database in 1996–2010, in which all diseases were classified by ICD-9-CM codes. We identified 17796 adults who had chronic HBV infection and did not take nucleos(t)ide analogues from 1998 to 2010 and also randomly selected 71184 matched controls without HBV in the same dataset. Cumulative incidences and adjusted hazard ratio (aHR) of incident CKD were evaluated through the end of 2010 after adjusting for competing mortality. Results The risk of CKD was significantly higher in the HBV cohort (13-year cumulative incidence, 6.2 %; 95 % confidence interval [CI], 5.4–7.1 %) than in the non-HBV cohort (2.7 %; 95 % CI, 2.5–3.0 %) (p < 0.001), and the aHR was 2.58 (95 % CI, 1.95-3.42; p < 0.001). Multivariable stratified analysis further verified significant associations of CKD with HBV in men of any age (aHR, 2.98; 95 % CI, 2.32–3.83, p < 0.001 for men aged <50 years; aHR, 1.58; 95 % CI, 1.31–1.91, p < 0.001 for men aged ≧50 years) and women under the age of 50 (aHR, 2.99; 95 % CI, 2.04–4.42, p < 0.001), but no significant association in women aged 50 or over. Conclusion Untreated chronic HBV infection is associated with increased risk of CKD. Hence, high-risk HBV-infected subjects should have targeted monitoring for the development of CKD. Electronic supplementary material The online version of this article (doi:10.1186/s12882-015-0106-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yi-Chun Chen
- Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, No. 2, Minsheng Rd., Dalin Township, Chiayi, County 622, Taiwan. .,School of Medicine, Tzu Chi University, Hualien, Taiwan.
| | - Yu-Chieh Su
- School of Medicine, Tzu Chi University, Hualien, Taiwan. .,Division of Hematology-Oncology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.
| | - Chung-Yi Li
- Department and Graduate Institute of Public Health, College of Medicine, National Cheng Hung University, Tainan, Taiwan. .,Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan.
| | - Shih-Kai Hung
- School of Medicine, Tzu Chi University, Hualien, Taiwan. .,Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.
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Lai YW, Hsueh TY, Hu HY, Chiu YC, Chen SSS, Chiu AW. Varicocele is associated with varicose veins: A population-based case-control study. Int J Urol 2015; 22:972-5. [DOI: 10.1111/iju.12843] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Accepted: 05/24/2015] [Indexed: 11/29/2022]
Affiliation(s)
- Yu-Wei Lai
- Division of Urology; Taipei City Hospital Renai Branch; Taipei Taiwan
- Department of Urology; National Yang-Ming University School of Medicine; Taipei Taiwan
| | - Thomas Y Hsueh
- Division of Urology; Taipei City Hospital Renai Branch; Taipei Taiwan
- Department of Urology; National Yang-Ming University School of Medicine; Taipei Taiwan
| | - Hsiao-Yun Hu
- Department of Education and Research; Taipei City Hospital; Taipei Taiwan
- Departmentof Public Health; Institute of Public Health; National Yang-Ming University; Taipei Taiwan
| | - Yi-Chun Chiu
- Division of Urology; Taipei City Hospital Renai Branch; Taipei Taiwan
- Department of Urology; National Yang-Ming University School of Medicine; Taipei Taiwan
| | - Saint Shiou-Sheng Chen
- Division of Urology; Taipei City Hospital Renai Branch; Taipei Taiwan
- Department of Urology; National Yang-Ming University School of Medicine; Taipei Taiwan
| | - Allen W Chiu
- Division of Urology; Taipei City Hospital Renai Branch; Taipei Taiwan
- Department of Urology; National Yang-Ming University School of Medicine; Taipei Taiwan
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Mittal S, White DL, Kanwal F, Sussman N, El-Serag HB. Nonalcoholic Fatty Liver Disease (NAFLD) and Hepatocellular Carcinoma: How Common? CURRENT HEPATOLOGY REPORTS 2015; 14:87-98. [DOI: 10.1007/s11901-015-0259-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Oda K, Uto H, Mawatari S, Ido A. Clinical features of hepatocellular carcinoma associated with nonalcoholic fatty liver disease: a review of human studies. Clin J Gastroenterol 2015; 8:1-9. [PMID: 25575848 DOI: 10.1007/s12328-014-0548-5] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2014] [Accepted: 12/17/2014] [Indexed: 02/06/2023]
Abstract
Most cases of hepatocellular carcinoma (HCC) in Japan develop in the background of chronic liver disease caused by hepatitis C virus (HCV). Recently, however, HCV-associated HCC has been shown to be decreasing, while non-B and non-C HCC (NBNC-HCC), which is negative for HCV and hepatitis B virus infection, has increased. The main cause of NBNC-HCC is alcoholic liver disease, but the recent increase of NBNC-HCC is thought to be due to an increase in patients with nonalcoholic fatty liver disease (NAFLD). Approximately 10% of NAFLD cases involve nonalcoholic steatohepatitis (NASH), and NASH can progress to liver cirrhosis and its associated complications such as HCC. There are no accurate data on the percentage of NASH-related HCC among all-cause HCC in Japan, because no large-scale investigation has been performed. However, the rate is thought to be about 3% of overall HCC, which is lower than that in the United States. The incidence of HCC in patients with NASH-related cirrhosis is thought to be 2% per year, which is lower than that in HCV-related cirrhosis. Risks for NASH-related HCC include advanced hepatic fibrosis, older age, and being male. NAFLD that includes NASH is associated with metabolic syndrome, which includes obesity and diabetes, and metabolic syndrome is a risk factor for HCC. Genetic factors and dietary patterns may also be related to NASH-related HCC. Thus, regular HCC surveillance, as performed for patients with viral chronic liver disease, is required for patients with NAFLD, and diagnostic markers are required for simple, rapid and specific detection of NASH-related HCC.
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Affiliation(s)
- Kohei Oda
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima, 890-8544, Japan
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Lin WH, Hsu CH, Chen HF, Liu CC, Li CY. Mortality of patients with type 2 diabetes in Taiwan: a 10-year nationwide follow-up study. Diabetes Res Clin Pract 2015; 107:178-86. [PMID: 25451891 DOI: 10.1016/j.diabres.2014.09.021] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2014] [Revised: 06/06/2014] [Accepted: 09/14/2014] [Indexed: 12/31/2022]
Abstract
AIMS This study aims to investigate the distribution of underlying-causes-of-death (UCOD) among deceased patients with type 2 diabetes mellitus (DM) in Taiwan and assess the influence of socio-demographic characteristics on mortality in type 2 DM patients. METHODS A cohort study on patients who sought medical care for type 2 DM from 2000 to 2008 was conducted on 65,599 type 2 DM patients retrieved from the 1-million beneficiaries randomly selected from Taiwan's National Health Insurance Database. The study cohort was then linked to Taiwan's Mortality Registry to ascertain the patients who died between 2000 and 2009. We examined the distribution of UCOD in the deceased subjects. The hazard ratios of mortality in relation to socio-demographic characteristics were estimated from Cox proportional hazard model. RESULTS The leading causes of death in type 2 DM included neoplasm (22.68%), cardiovascular diseases (21.46%), and endocrine diseases (20.78%). Male gender and older ages were associated with significantly increased risk of mortality. In addition, lower urbanization and greater co-morbidity score were also significantly associated with an increased risk of mortality with a dose-gradient pattern. CONCLUSIONS Neoplasm accounts for the largest portion (22.68%) of deaths in type 2 DM patients closely followed by with cardiovascular diseases (21.46%). An increased risk of mortality in type 2 DM patients in lower urbanized areas may reflect poor diabetes care in these areas.
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Affiliation(s)
- Wei-Hung Lin
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chih-Hui Hsu
- Department and Graduate Institute of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hua-Fen Chen
- Department of Endocrinology, Far Eastern Memorial Hospital, Panchiao, New Taipei City, Taiwan
| | - Chi-Chu Liu
- Department of Anesthesia, Sin-Lau Hospital, Tainan City, Taiwan.
| | - Chung-Yi Li
- Department and Graduate Institute of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
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Chang YT, Liu CC, Tsai LM, Li CY, Sung JM. Separate and joint effects of diabetes mellitus and chronic kidney disease on the risk of acute coronary syndrome: a population-based cohort study. Medicine (Baltimore) 2014; 93:e261. [PMID: 25526451 PMCID: PMC4603129 DOI: 10.1097/md.0000000000000261] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Patient with diabetes (DM) and chronic kidney disease (CKD) are at a higher risk of developing acute coronary syndrome (ACS). However, only a few studies have investigated the separate and joint effects of DM and CKD on the risk of ACS, especially population-based studies under age-, sex- and various cardiovascular risk factor-stratifications. By using a national diabetes cohort derived from the Taiwan National Health Insurance Research Database, we identified a total of 416,143 DM and 541,724 non-DM patients, including 51,208 DM/CKD and 8,894 non-DM/CKD patients, in 2000 who did not have a history of ACS (ICD-9: 410.X, 413.9, 411.1) before 2000. We then prospectively investigated the incidence of ACS by linking to inpatient claims data from 2000 to 2007. A Cox proportional hazard model was used to estimate the relative risk of ACS in individuals with DM and/or CKD under various stratifications. Age- and sex-specific incidence rates were similar between the non-DM/CKD and DM/non-CKD groups, except for female patients under 45 years, in whom DM was associated with a higher risk of ACS than CKD (8.21 vs. 3.82 per 1000 person-years). In the group aged <45 years, the DM/non-CKD patients were associated with a higher relative hazard of ACS than those in the non-DM/CKD group when compared with the non-DM/non-CKD group (men: adjusted hazard ratios [AHR]:1.77; 95% confidence interval [CI]:1.61-1.93 vs. 1.42 [95% CI: 0.73-2.73]; women 1.97 [95% CI: 1.76-2.20] vs. 1.13 [95% CI: 0.36-3.52]). This discrepancy in AHR was reduced with increasing age. The co-existence of DM and CKD further enhanced the AHR in a multiplicative independent manner. A significant age-modification effect was noted in the DM individuals regardless of their CKD status, but not in the non-DM/CKD group. In stratification by various cardiovascular risk factors, diabetes had a higher risk of ACS than CKD in patients with ≤2 selected risk factors, with the exception of the hyperlipidemia and hypertension subgroup. When all three selected risk factors were included, CKD was associated with a higher risk of ACS than DM (AHR: 1.43 [1.27-1.60] vs. 1.25 [1.22-1.29]). In conclusion, DM and CKD were associated with different levels of risk for ACS according to age, sex and certain cardiovascular risk factors. Strategies aimed at preventing ACS should therefore be individualized according to the presence of DM, CKD and various cardiovascular risk factors.
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Affiliation(s)
- Yu-Tzu Chang
- From the Department of Internal Medicine, National Cheng Kung University Hospital, Tainan (Y-TC, L-MT, J-MS); Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Y-TC); Health Promotion Administration, Ministry of Health and Welfare, Taipei, Taiwan (C-CL); Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan (C-CL, C-YL, J-MS); and Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan (C-YL)
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A nationwide cohort study suggests chronic hepatitis B virus infection increases the risk of end-stage renal disease among patients in Taiwan. Kidney Int 2014; 87:1030-8. [PMID: 25426815 DOI: 10.1038/ki.2014.363] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2014] [Revised: 08/25/2014] [Accepted: 09/11/2014] [Indexed: 02/06/2023]
Abstract
The association of chronic hepatitis B virus (HBV) infection with end-stage renal disease (ESRD) is unclear. To help clarify this we conducted a nationwide cohort study to measure the association by analyzing the claims data from the Taiwan National Health Insurance Research Database with ICD-9 codes used to identify diseases. We identified 17,758 adults who had chronic HBV infection and had not taken nucleos(t)ide analogs from 1999 to 2010 and randomly selected 71,032 matched controls without HBV in the same data set. The risk of ESRD was compared between these two cohorts. Cumulative incidences and hazard ratios were calculated after adjusting for competing mortality. The risk of ESRD was significantly higher in the HBV cohort (12-year cumulative incidence, 1.9%) than in the non-HBV cohort (0.49%) with a significant adjusted hazard ratio of 3.85. Multivariable stratified analysis further verified significant associations of ESRD with HBV in men of any age and women under the age of 60 years, but no significant association in women aged ⩾60 years. Thus, a large national cohort study indicates that untreated chronic HBV infection is associated with increased risk of ESRD. Hence, high-risk HBV-infected patients should have targeted monitoring for the development of ESRD.
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Chiou WY, Chang CM, Tseng KC, Hung SK, Lin HY, Chen YC, Su YC, Tseng CW, Tsai SJ, Lee MS, Li CY. Effect of liver cirrhosis on metastasis in colorectal cancer patients: a nationwide population-based cohort study. Jpn J Clin Oncol 2014; 45:160-8. [PMID: 25378650 DOI: 10.1093/jjco/hyu178] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE The aim of this study is to evaluate the liver metastasis risk among colorectal cancer patients with liver cirrhosis. METHODS This was a nationwide population-based cohort study of 2973 newly diagnosed colorectal cancer patients with liver cirrhosis and 11 892 age-sex matched controls enrolled in Taiwan between 2000 and 2010. The cumulative risk by Kaplan-Meier method, hazard ratio by the multivariate Cox proportional model and the incidence density were evaluated. RESULTS The median time interval from the colorectal cancer diagnosis to the liver metastasis event was 7.42 months for liver cirrhosis group and 7.67 months for non-liver cirrhosis group. The incidence density of liver metastasis was higher in the liver cirrhosis group (61.92/1000 person-years) than in the non-liver cirrhosis group (47.48/1000 person-years), with a significantly adjusted hazard ratio of 1.15 (95% CI = 1.04-1.28, P = 0.007). The 10-year cumulative risk of liver metastasis for the liver cirrhosis and the non-liver cirrhosis group was 27.1 and 23.6%, respectively (P = 0.006). For early cancer stage with locoregional disease patients receiving surgery alone without adjuvant anti-cancer treatments, patients with liver cirrhosis (10-year cumulative risk 23.9 vs. 15.7%, P < 0.001) or cirrhotic symptoms (10-year cumulative risk 25.6 vs. 16.6%, P = 0.009) both still had higher liver metastasis risk compared with their counterparts. For etiologies of liver cirrhosis, the 10-year cumulative risk for hepatitis B virus and hepatitis C virus, hepatitis B virus, hepatitis C virus, other causes and non-liver cirrhosis were 29.5, 28.9, 27.5, 26.7 and 23.4%, respectively, (P = 0.03). CONCLUSIONS Our study found that liver metastasis risk was underestimated and even higher in colorectal cancer patients with liver cirrhosis.
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Affiliation(s)
- Wen-Yen Chiou
- Department of Radiation Oncology, Buddhist Dalin Tzu Chi Hospital, Chiayi School of Medicine, Tzu Chi University, Hualien Department of Public Health, College of Medicine, National Cheng Kung University, Tainan
| | - Chun-Ming Chang
- School of Medicine, Tzu Chi University, Hualien Department of Surgery, Buddhist Dalin Tzu Chi Hospital, Chiayi
| | - Kuo-Chih Tseng
- School of Medicine, Tzu Chi University, Hualien Division of Gastroenterology, Department of Internal Medicine, Buddhist Dalin Tzu Chi Hospital, Chiayi
| | - Shih-Kai Hung
- Department of Radiation Oncology, Buddhist Dalin Tzu Chi Hospital, Chiayi School of Medicine, Tzu Chi University, Hualien
| | - Hon-Yi Lin
- Department of Radiation Oncology, Buddhist Dalin Tzu Chi Hospital, Chiayi School of Medicine, Tzu Chi University, Hualien
| | - Yi-Chun Chen
- School of Medicine, Tzu Chi University, Hualien Division of Nephrology, Department of Internal Medicine, Buddhist Dalin Tzu Chi Hospital, Chiayi
| | - Yu-Chieh Su
- School of Medicine, Tzu Chi University, Hualien Division of Hematology-Oncology, Department of Internal Medicine, Buddhist Dalin Tzu Chi Hospital, Chiayi, Taiwan
| | - Chih-Wei Tseng
- School of Medicine, Tzu Chi University, Hualien Division of Gastroenterology, Department of Internal Medicine, Buddhist Dalin Tzu Chi Hospital, Chiayi
| | - Shiang-Jiun Tsai
- Department of Radiation Oncology, Buddhist Dalin Tzu Chi Hospital, Chiayi
| | - Moon-Sing Lee
- Department of Radiation Oncology, Buddhist Dalin Tzu Chi Hospital, Chiayi School of Medicine, Tzu Chi University, Hualien
| | - Chung-Yi Li
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan
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A large scale population-based cohort study on the risk of ovarian neoplasm in patients with type 2 diabetes mellitus. Gynecol Oncol 2014; 134:576-80. [DOI: 10.1016/j.ygyno.2014.07.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2014] [Revised: 06/28/2014] [Accepted: 07/01/2014] [Indexed: 02/01/2023]
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Starup-Linde J, Karlstad O, Eriksen SA, Vestergaard P, Bronsveld HK, de Vries F, Andersen M, Auvinen A, Haukka J, Hjellvik V, Bazelier MT, Boer AD, Furu K, De Bruin ML. CARING (CAncer Risk and INsulin analoGues): the association of diabetes mellitus and cancer risk with focus on possible determinants - a systematic review and a meta-analysis. Curr Drug Saf 2014; 8:296-332. [PMID: 24215312 PMCID: PMC5421136 DOI: 10.2174/15748863113086660071] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2013] [Revised: 10/27/2013] [Accepted: 10/30/2013] [Indexed: 12/11/2022]
Abstract
Background: Patients suffering from diabetes mellitus (DM) may experience an increased risk of cancer; however, it is not certain whether this effect is due to diabetes per se. Objective: To examine the association between DM and cancers by a systematic review and meta-analysis according to the PRISMA guidelines. Data Sources: The systematic literature search includes Medline at PubMed, Embase, Cinahl, Bibliotek.dk, Cochrane library, Web of Science and SveMed+ with the search terms: “Diabetes mellitus”, “Neoplasms”, and “Risk of cancer”. Study Eligibility Criteria: The included studies compared the risk of cancer in diabetic patients versus non-diabetic patients. All types of observational study designs were included. Results: Diabetes patients were at a substantially increased risk of liver (RR=2.1), and pancreas (RR=2.2) cancer. Modestly elevated significant risks were also found for ovary (RR=1.2), breast (RR=1.1), cervix (RR=1.3), endometrial (RR=1.4), several digestive tract (RR=1.1-1.5), kidney (RR=1.4), and bladder cancer (RR=1.1). The findings were similar for men and women, and unrelated to study design. Meta-regression analyses showed limited effect modification of body mass index, and possible effect modification of age, gender, with some influence of study characteristics (population source, cancer- and diabetes ascertainment). Limitations: Publication bias seemed to be present. Only published data were used in the analyses. Conclusions: The systematic review and meta-analysis confirm the previous results of increased cancer risk in diabetes and extend this to additional cancer sites. Physicians in contact with patients with diabetes should be aware that diabetes patients are at an increased risk of cancer.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | - Marie L De Bruin
- Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, Tage Hansens Gade 2, 8000 Aarhus C, Denmark.
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Tsai WH, Hwang YS, Hung TY, Weng SF, Lin SJ, Chang WT. Association between mechanical ventilation and neurodevelopmental disorders in a nationwide cohort of extremely low birth weight infants. RESEARCH IN DEVELOPMENTAL DISABILITIES 2014; 35:1544-1550. [PMID: 24769371 DOI: 10.1016/j.ridd.2014.03.048] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/18/2014] [Accepted: 03/25/2014] [Indexed: 06/03/2023]
Abstract
Mechanical ventilation for preterm infants independently contributes to poor neurodevelopmental performance. However, few studies have investigated the association between the duration of mechanical ventilation and the risk for various developmental disorders in extremely low birth weight (ELBW) (<1000g) infants. Using a large nationwide database, we did a 10-year retrospective follow-up study to explore the effect of mechanical ventilation on the incidence of cerebral palsy (CP), autism spectrum disorder (ASD), intellectual disability (ID), and attention-deficit/hyperactivity disorder (ADHD) in ELBW infants born between 1998 and 2001. Seven hundred twenty-eight ELBW infants without diagnoses of brain insults or focal brain lesions in the initial hospital stay were identified and divided into three groups (days on ventilator: ≦2, 3-14, ≧15 days). After adjusting for demographic and medical factors, the infants in the ≧15 days group had higher risks for CP (adjusted hazard ratio: 2.66; 95% confidence interval: 1.50-4.59; p<0.001) and ADHD (adjusted hazard ratio: 1.95; 95% confidence interval: 1.02-3.76; p<0.05), than did infants in the ≦2 days group. The risk for ASD or ID was not significantly different between the three groups. We conclude that mechanical ventilation for ≧15 days increased the risk for CP and ADHD in ELBW infants even without significant neonatal brain damage. Developing a brain-protective respiratory support strategy in response to real-time cerebral hemodynamic and oxygenation changes has the potential to improve neurodevelopmental outcomes in ELBW infants.
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Affiliation(s)
- Wen-Hui Tsai
- Institute of Clinical Medicine, National Cheng Kung University College of Medicine, Tainan 701, Taiwan; Division of Neonatology, Chi Mei Medical Center, Tainan 710, Taiwan
| | - Yea-Shwu Hwang
- Department of Occupational Therapy, National Cheng Kung University College of Medicine, Tainan 701, Taiwan
| | - Te-Yu Hung
- Department of Pediatrics, Chi Mei Medical Center, Tainan 710, Taiwan
| | - Shih-Feng Weng
- Department of Medical Research, Chi Mei Medical Center, Tainan 710, Taiwan
| | - Shio-Jean Lin
- Department of Pediatrics, Chi Mei Medical Center, Tainan 710, Taiwan
| | - Wen-Tsan Chang
- Department of Biochemistry and Molecular Biology, National Cheng Kung University College of Medicine, Tainan 701, Taiwan; Institute of Basic Medical Sciences, National Cheng Kung University College of Medicine, Tainan 701, Taiwan.
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Harman DJ, Kaye PV, Harris R, Suzuki A, Gazis A, Aithal GP. Prevalence and natural history of histologically proven chronic liver disease in a longitudinal cohort of patients with type 1 diabetes. Hepatology 2014; 60:158-68. [PMID: 24585431 DOI: 10.1002/hep.27098] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2013] [Accepted: 02/25/2014] [Indexed: 12/15/2022]
Abstract
UNLABELLED Although a higher prevalence of raised liver enzymes and altered echotexture on ultrasound have been reported in patients with type 1 diabetes mellitus (T1DM), the histological spectrum and natural history of chronic liver disease (CLD) in T1DM is unknown. We investigated the prevalence and outcome of histologically proven CLD in a longitudinal cohort of patients with T1DM. We identified patients who have had liver biopsy from a computerized database (DIAMOND; Hicom Technology, Brookwood, UK) containing longitudinal data for over 95% of type 1 diabetes patients from an overall catchment population of 700,000 people. Gender-matched patients with oral hypoglycemic-treated (T2OH) and insulin-treated type 2 diabetes (T2IN) who had liver biopsy formed two comparative cohorts. We collated clinical and histological data, as well as long-term outcomes of all three groups, and compared T1DM cirrhosis incidence to UK general population data. Of 4,644 patients with T1DM, 57 (1.2%) underwent liver biopsy. Of these, 53.1% of patients had steatosis, 20.4% had nonalcoholic steatohepatitis, and 73.5% had fibrosis on index liver biopsy. Cirrhosis was diagnosed in 14 patients (24.6%) during follow-up. T1DM with age under 55 years had an odds ratio of 1.875 (95% confidence interval: 0.936-3.757) for cirrhosis incidence, compared to the general population. Longitudinal liver-related outcomes were similar comparing the T1DM cohort and respective type 2 diabetes cohorts--when adjusted for important confounders, diabetic cohort type did not predict altered risk of incident cirrhosis or portal hypertension. CONCLUSION Type 1 diabetes is associated with a previously unrecognized burden of CLD and its complications.
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Affiliation(s)
- David J Harman
- National Institute for Health Research Nottingham Digestive Diseases Biomedical Research Unit (NDDBRU), Nottingham University Hospitals NHS Trust and University of Nottingham, United Kingdom
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Lin CC, Chiang JH, Li CI, Liu CS, Lin WY, Hsieh TF, Li TC. Cancer risks among patients with type 2 diabetes: a 10-year follow-up study of a nationwide population-based cohort in Taiwan. BMC Cancer 2014; 14:381. [PMID: 24884617 PMCID: PMC4057814 DOI: 10.1186/1471-2407-14-381] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2013] [Accepted: 05/20/2014] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND This study aims to determine cancer risks among patients with type 2 diabetes through a follow-up study on a nationwide population-based cohort that included Taiwanese diabetic patients and general population in Taiwan as well as to estimate the population attributable fraction (PAF) of site-specific cancer risks that can be attributed to type 2 diabetes in Taiwanese population by using standardized incidence ratios (SIRs, 95% CI). METHODS Subjects with type 2 diabetes consisted of 472,979 patients aged ≥ 20 years, whereas general population consisted of 9,411,249 individuals of the same age limit but are not diabetic. Subjects were identified from 1997 to 1998 and followed up until December 31, 2007 or until the first manifestation of any cancer. RESULTS Cancer sites with increased risks in men, which were consistent with the main and sensitivity analyses, included pancreas (SIR=1.62; 95% CI=1.53 to 1.72), liver (1.61; 1.57 to 1.64), kidney (1.32; 1.25 to 1.40), oral (1.16, 1.12 to 1.21), and colorectal (1.19, 1.15 to 1.22). Cancer sites with increased risks in women included liver (1.55; 1.51 to 1.60), pancreas (1.44; 1.34 to 1.55), kidney (1.38; 1.30 to 1.46), endometrium (1.36; 1.26 to 1.47), bladder (1.19; 1.11 to 1.27), colorectal (1.16; 1.13 to 1.20), and breast (1.14; 1.09 to 1.18). Overall, PAFs were highest for liver cancer in men (4.0%) and women (3.7%), followed by pancreas (3.4%) and kidney (1.6%) cancers in men, and then for endometrium (1.8%) and kidney (1.8%) cancers in women. CONCLUSION Our data suggested that increased cancer risks are associated with type 2 diabetes.
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Affiliation(s)
| | | | | | | | | | | | - Tsai-Chung Li
- Graduate Institute of Biostatistics, College of Management, China Medical University, 91 Hsueh-Shih Road, Taichung 40421, Taiwan.
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