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Zhu Y, Liu J, Wang B. Integrated Approach for Biomarker Discovery and Mechanistic Insights into the Co-Pathogenesis of Type 2 Diabetes Mellitus and Non-Hodgkin Lymphoma. Diabetes Metab Syndr Obes 2025; 18:267-282. [PMID: 39906693 PMCID: PMC11793108 DOI: 10.2147/dmso.s503449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 01/18/2025] [Indexed: 02/06/2025] Open
Abstract
Background Type 2 diabetes mellitus (T2DM) is associated with an increased risk of non-Hodgkin lymphoma (NHL), but the underlying mechanisms remain unclear. This study aimed to identify potential biomarkers and elucidate the molecular mechanisms underlying the co-pathogenesis of T2DM and NHL. Methods Microarray datasets of T2DM and NHL were downloaded from the Gene Expression Omnibus database. Subsequently, a protein-protein interaction network was constructed based on the common differentially expressed genes (DEGs) between T2DM and NHL to explore regulatory interactions. Functional analyses were performed to explore underlying mechanisms. Topological analysis and machine learning algorithms were applied to refine hub gene selection. Finally, quantitative real-time polymerase chain reaction was performed to validate hub genes in clinical samples. Results Intersection analysis of DEGs from the T2DM and NHL datasets identified 81 shared genes. Functional analyses suggested that immune-related pathways played a significant role in the co-pathogenesis of T2DM and NHL. Topological analysis and machine learning identified three hub genes: GZMM, HSPG2, and SERPING1. Correlation analysis revealed significant correlations between these hub genes and immune cells, underscoring the importance of immune dysregulation in shared pathogenesis. The expression of these genes was successfully validated in clinical samples. Conclusion This study suggested the pivotal role of immune dysregulation in the co-pathogenesis of T2DM and NHL and identified and validated three hub genes as key contributors. These findings provide insight into the complex interplay between T2DM and NHL.
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Affiliation(s)
- Yidong Zhu
- Department of Traditional Chinese Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China
| | - Jun Liu
- Department of Traditional Chinese Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China
| | - Bo Wang
- Department of Endocrinology, Yangpu Hospital, Tongji University School of Medicine, Shanghai, 200090, People’s Republic of China
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Huang YA, Wen MC, Tsai SF, Wu MJ, Yu TM, Chuang YW, Huang ST, Chen CH. Outcome of Brain Lymphoma in a High Epstein-Barr Virus-Prevalence Country After Kidney Transplantation. Transplant Proc 2023:S0041-1345(23)00220-8. [PMID: 37105830 DOI: 10.1016/j.transproceed.2023.03.048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 03/27/2023] [Indexed: 04/29/2023]
Abstract
BACKGROUND The incidence of post-transplant lymphoproliferative disorder (PTLD) in adult kidney transplant (KTx) recipients is less common in Taiwan. In our institute, we observed that brain lymphoma was the most notorious type. METHODS The study describes the clinical, histologic, and radiological features of primary central nervous lymphoma (PCNSL) and the outcomes and associations with Epstein-Barr virus (EBV) infection in our center. RESULTS Among 1470 KTx recipients, 5 patients had tissue-proven brain lymphoma (0.34%). The brain pathology disclosed diffuse large B-cell lymphoma in all patients. EBV was detected through in situ hybridization for Epstein-Barr encoding region (EBER) to disclose the EBV inclusion in the nuclei of lymphoma cells. The first treatment step was the reduction of immunosuppressants; 4 patients received whole-brain radiotherapy after complete resection of PCNSL, and 1 received concurrent chemoradiotherapy. Only one patient had poor performance status at the time of diagnosis and had a poor response to treatment with steroids. Four patients survived (mean 36.5 months, range 8.6 to 57.6 months), but one died after rapid neurologic deterioration. CONCLUSION Epstein-Barr virus inclusion was found in PCNSL in our patients; however, the role of EBV in PCNSL remains to be clarified. Post-transplant lymphoproliferative disorder is a rare malignancy after KTx with a predilection of brain involvement in Taiwan. We report a successful care experience in a patient with primary CNS lymphoma with better survival.
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Affiliation(s)
- Yi-An Huang
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan
| | - Mei-Chin Wen
- Department of Pathology, China Medical University Hsinchu Hospital, Hsinchu City, Taiwan
| | - Shang-Feng Tsai
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan; Department of Life Science, Tunghai University, Taichung City, Taiwan; Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung City, Taiwan
| | - Ming-Ju Wu
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan; Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung City, Taiwan
| | - Tong-Min Yu
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan
| | - Ya-Wen Chuang
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan; Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung City, Taiwan
| | - Shih-Ting Huang
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan
| | - Cheng-Hsu Chen
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan; Department of Life Science, Tunghai University, Taichung City, Taiwan; Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung City, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan.
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Wang Z, Phillips LS, Rohan TE, Ho GYF, Shadyab AH, Bidulescu A, Rudick CN, Pan K, Chen Z, Luo J. Diabetes, metformin use and risk of non-Hodgkin's lymphoma in postmenopausal women: A prospective cohort analysis in the Women's Health Initiative. Int J Cancer 2023; 152:1556-1569. [PMID: 36444502 DOI: 10.1002/ijc.34376] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 11/06/2022] [Accepted: 11/09/2022] [Indexed: 11/30/2022]
Abstract
Epidemiologic evidence is limited about associations between T2DM, metformin, and the risk of non-Hodgkin's lymphoma (NHL). We aimed to examine associations between T2DM, metformin, and the risk of NHL in the Women's Health Initiative (WHI) Study. Information on T2DM status (diabetes status/types of antidiabetic drug use/diabetes duration) from study enrollment and during follow-up were assessed. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate associations of T2DM status with risks of overall NHL and its three major subtypes [diffuse large B-cell lymphoma (DLBCL, n = 476), follicular lymphoma (FL, n = 301) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL, n = 136)] based on multivariable-adjusted Cox proportional hazards models. During a median follow-up of 18.86 years (range, 0.01-25.13; SD ± 6.55), a total of 1637 women developed NHL among 147 885 postmenopausal women. Women with T2DM and with self-reported oral medication use had 38% and 55% higher risk of DLBCL, respectively [multivariable-adjusted model HR = 1.38, 95% CI (1.06-1.81) and HR = 1.55, 95% CI (1.16-2.06)] compared to the reference group (nondiabetics/untreated diabetes). Risks of NHL and DLBCL [multivariable-adjusted model: HR = 1.28, 95% CI (1.06-1.54) and HR = 1.56, 95% CI (1.13-2.14), respectively] were significantly higher in associations with relatively short duration (≤7 years) of diabetes, compared to reference group. Additionally, an increased risk of DLBCL [HR = 1.76, 95% CI (1.13-2.75)] was found in metformin users compared to the reference group. Postmenopausal women who had T2DM, who were oral antidiabetic drug users, especially metformin, and who had a shorter diabetes duration may have higher risks of DLBCL. Further well-designed research is needed to confirm our findings.
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Affiliation(s)
- Zikun Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Indiana University Bloomington, Bloomington, Indiana, USA
| | - Lawrence S Phillips
- Atlanta VA Medical Center, Decatur, Georgia, USA.,Division of Endocrinology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Thomas E Rohan
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA
| | - Gloria Y F Ho
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA
| | - Aladdin H Shadyab
- Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, California, USA
| | - Aurelian Bidulescu
- Department of Epidemiology and Biostatistics, School of Public Health, Indiana University Bloomington, Bloomington, Indiana, USA
| | - Charles N Rudick
- Department of Pharmacology and Toxicology, Medical Sciences Program, Indiana University School of Medicine-Bloomington, Bloomington, Indiana, USA
| | - Kathy Pan
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
| | - Zhongxue Chen
- Department of Mathematics and Statistics, College of Arts, Sciences and Education, Florida International University, Miami, Florida, USA
| | - Juhua Luo
- Department of Epidemiology and Biostatistics, School of Public Health, Indiana University Bloomington, Bloomington, Indiana, USA
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Zhao JZ, Lu YC, Wang YM, Xiao BL, Li HY, Lee SC, Wang LJ. Association between diabetes and acute lymphocytic leukemia, acute myeloid leukemia, non-Hopkin lymphoma, and multiple myeloma. Int J Diabetes Dev Ctries 2021. [DOI: 10.1007/s13410-021-01021-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
Abstract
Objective
Diabetes increases the risk for cancers. However, whether it is associated with hematologic malignancies is not clear. The present study investigated the association between diabetes and acute lymphocytic leukemia (ALL), acute myeloid leukemia (ML), non-Hopkin lymphoma (NHL), and multiple myeloma (MM).
Methods
Newly diagnosed adult cancer patients were recruited consecutively from our clinical database. Peoples from a local enterprise were recruited to create a small-scale population-based dataset. We compared the diabetes prevalence between the cancer patients and the local people; an increase in diabetes prevalence in the cancer patients suggests an association between diabetes and the cancer(s).
Results
We found that the prevalence of diabetes was 19.7%, 21.3%, 12.5%, and 12.0% in ALL, AML, NHL, and MM, respectively, which was higher than that (9.1%) in the local people. Despite that there were more male than female cancer patients, there were more female than male diabetic patients. The increase in diabetes prevalence occurred in ALL and NHL patients aged 18 to 39 years old as well as in AML patients over 40. In MM patients, the increase in diabetes prevalence (18.6%) occurred only in females. Approximately 70% of the diabetic patients were undiagnosed before the diagnosis of the blood cancer. Approximately half of the pre-existing diabetic patients had anti-diabetic treatment, with over 70% of them still had poor glycemic control.
Conclusions
Our results suggest that diabetes is associated with ALL, AML, NHL, and MM, at least in adult patients.
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Kang J, Jin SM, Kim SJ, Kim D, Han K, Jeong SM, Chang J, Rhee SY, Choi T, Shin DW. Obesity-Independent Association between Glycemic Status and the Risk of Hematologic Malignancy: A Nationwide Population-Based Longitudinal Cohort Study. Cancers (Basel) 2021; 13:4760. [PMID: 34638244 PMCID: PMC8507554 DOI: 10.3390/cancers13194760] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 09/10/2021] [Accepted: 09/17/2021] [Indexed: 11/17/2022] Open
Abstract
There have been conflicting results regarding the association between diabetes and the risk of hematologic malignancies, and its interaction with obesity is unknown. This study determined the risk of hematologic malignancies according to the glycemic status in a population-based study involving health screening 9,774,625 participants. The baseline glycemic status of the participants was categorized into no diabetes, impaired fasting glucose (IFG), newly detected diabetes, diabetes duration <5 years, and diabetes duration ≥5 year groups. The risks of overall and specific hematologic malignancies were estimated using a Cox regression analysis. During a median follow up of 7.3 years, 14,733 hematologic malignancies developed. The adjusted hazard ratio (aHR) for the risk of all the hematologic malignancies was 0.99 (95% confidence interval (CI) 0.95-1.02) for IFG, 0.99 (95% CI 0.91-1.08) for newly detected diabetes, 1.03 (95% CI 0.96-1.11) for diabetes duration <5 years, and 1.11 (95% CI 1.03, 1.20) for diabetes duration ≥5 year groups. The association was independent from obesity. The risk of non-Hodgkin's lymphoma (NHL) increased according to the progression of dysglycemia towards a longer diabetes duration, while Hodgkin's lymphoma did not. This study in Korea demonstrated diabetes to be associated with an increased risk of hematologic malignancies independent of obesity. The NHL risk increased with the diabetes duration.
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Affiliation(s)
- Jihun Kang
- Department of Family Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan 49267, Korea;
| | - Sang-Man Jin
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
| | - Seok Jin Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea;
| | - Dahye Kim
- Department of Medical Statistics, The Catholic University of Korea, Seoul 03083, Korea;
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul 06978, Korea;
| | - Su-Min Jeong
- Department of Family Medicine, Boramae Medical Center, Seoul Metropolitan Government-Seoul National University, Seoul 07061, Korea;
| | - JiWon Chang
- Supportive Care Center, Samsung Medical Center, Seoul 06351, Korea;
- Department of Family Medicine, Samsung Medical Center, Seoul 06351, Korea
| | - Sang Youl Rhee
- Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul 02453, Korea;
| | - Taewoong Choi
- Division of Hematologic Malignancies and Cellular Therapy, Duke University Medical Center, Durham, NC 27710, USA;
| | - Dong Wook Shin
- Supportive Care Center, Samsung Medical Center, Seoul 06351, Korea;
- Department of Family Medicine, Samsung Medical Center, Seoul 06351, Korea
- Department of Clinical Research Design & Evaluation/Department of Digital Health, Samsung Advanced Institute for Health Science & Technology (SAIHST), Sungkyunkwan University, Seoul 06351, Korea
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Nivolumab-caused hyperprogression of diffuse large B-cell lymphoma of the testis and spontaneous remission of type 2 diabetes mellitus in an elderly patient: a case report. Anticancer Drugs 2021; 32:575-579. [PMID: 33595946 DOI: 10.1097/cad.0000000000001033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Nivolumab has been used in a variety of advanced malignant tumors. Cases of autoimmune diabetes associated with Nivolumab therapy have been reported gradually in recent years. This article reported a case of primary testicular lymphoma in an elderly patient with type 2 diabetes mellitus (T2DM). After treatment with Nivolumab, the primary disease was hyperprogressive disease but the blood glucose was relieved for a long time. Nivolumab may relieve the previous T2DM in diffuse large B-cell lymphoma patients; the potential mechanism needs to be further explored.
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Hu Y, Xu YJ, Li MZ, Lan YX, Mao L, Ning QY, Xu W, Yang HL, Zhang YZ. [The prognostic impact of diabetic mellitus and hyperglycemia during DLBCL treatment on patients with diffuse large B-cell lymphoma]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2021; 42:151-157. [PMID: 33858047 PMCID: PMC8071671 DOI: 10.3760/cma.j.issn.0253-2727.2021.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Indexed: 11/24/2022]
Abstract
Objective: This study aims to investigate the clinical features and prognostic factors of patients with diffuse large B-cell lymphoma (DLBCL) and assess the prognostic value of diabetes mellitus (DM) and hyperglycemia during DLBCL treatment in DLBCL. Methods: The clinical data of 481 newly diagnosed DLBCL patients from January 1, 2009 to December 31, 2019 at Tianjin Medical University Cancer Institute and Hospital and Sun Yat-sen University Cancer Center were retrospectively collected, focusing on their blood glucose levels before and during treatment. Cox regression method was used for univariate analysis to assess prognostic factors, and the Kaplan-Meier method was used to draw survival curves to assess the prognostic value of DM and hyperglycemia during DLBCL treatment in patients with DLBCL. Results: Eighty-two (17.0%) patients had DM before DLBCL diagnosis and treatment, and 88 (18.3%) patients had at least one blood glucose increase during DLBCL treatment. Cox univariate analysis showed that age, Ann Arbor stage, international prognostic index, and DM were associated with overall survival (OS) and progression-free survival (PFS) (all P<0.05) . The pairwise comparison between the two groups showed that the OS (P=0.001) and PFS (P<0.001) of patients with pre-existing DM were significantly worse than those of patients without abnormal blood glucose. Moreover, the OS (P=0.003) and PFS (P<0.001) of patients with hyperglycemia during DLBCL treatment were significantly worse than those of patients without abnormal blood glucose. No significant difference exists between patients with DM and patients with hyperglycemia during DLBCL treatment (OS, P=0.557; PFS, P=0.463) . Additionally, patients with adequate glycemic control during chemotherapy had a better prognosis compared with patients with poor glycemic control (OS, P=0.037; PFS, P=0.007) . Conclusion: DM is an important factor affecting the prognosis of patients with DLBCL. Moreover, hyperglycemia during treatment is related to the poor prognosis of patients with DLBCL.
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Affiliation(s)
- Y Hu
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Y J Xu
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - M Z Li
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Y X Lan
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - L Mao
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Q Y Ning
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - W Xu
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - H L Yang
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Y Z Zhang
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
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Wang Y, Liu X, Yan P, Bi Y, Liu Y, Zhang ZJ. Association between type 1 and type 2 diabetes and risk of non-Hodgkin's lymphoma: A meta-analysis of cohort studies. DIABETES & METABOLISM 2020; 46:8-19. [PMID: 31039401 DOI: 10.1016/j.diabet.2019.04.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Revised: 04/12/2019] [Accepted: 04/14/2019] [Indexed: 12/14/2022]
Abstract
AIM Diabetes mellitus (DM) is thought to be associated with an increased risk of non-Hodgkin's lymphoma (NHL), although the evidence so far remains inconsistent. Thus, our study aimed to further assess this association. METHODS Electronic searches were performed of the PubMed, Web of Science and Embase databases up to 11 March 2019. A random-effects model was used to calculate summary relative risks (RRs) with corresponding 95% confidence intervals (CIs). RESULTS A total of 20 articles including data from 35 cohort studies matched our inclusion criteria, and 31 RRs were calculated for type 2 DM; the summary RR was 1.20 (95% CI: 1.12-1.30, I2 = 84.7%). Also, four RRs were calculated for type 1 DM, and the result was significant (RR: 1.55, 95% CI: 1.15-2.08, I2 = 0.0%). The results of subgroup analyses demonstrated that the association between DM and NHL was much more substantial in an Asian population, while sensitivity analyses suggested the robustness of a positive association between DM and NHL risk. In addition, the RR of NHL correlated negatively with duration of DM, with the highest risk found in patients within 1-2 years of DM diagnosis. CONCLUSION Our study findings suggest a moderate increase in risk of NHL in type 1 and 2 DM patients. Future studies should investigate the effects of duration of DM and antidiabetes interventions on NHL risk.
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Affiliation(s)
- Y Wang
- Department of Preventive Medicine, School of Health Sciences, Wuhan University, No. 185 Donghu road, Wuhan 430071, PR China
| | - X Liu
- Department of Preventive Medicine, School of Health Sciences, Wuhan University, No. 185 Donghu road, Wuhan 430071, PR China
| | - P Yan
- Department of Preventive Medicine, School of Health Sciences, Wuhan University, No. 185 Donghu road, Wuhan 430071, PR China
| | - Y Bi
- Department of Preventive Medicine, School of Health Sciences, Wuhan University, No. 185 Donghu road, Wuhan 430071, PR China
| | - Y Liu
- Department of Statistics and Management, School of Management, Wuhan Institute of Technology, Wuhan, 430205, PR China
| | - Z-J Zhang
- Department of Preventive Medicine, School of Health Sciences, Wuhan University, No. 185 Donghu road, Wuhan 430071, PR China.
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Tseng CH. Metformin is associated with a lower risk of non-Hodgkin lymphoma in patients with type 2 diabetes. DIABETES & METABOLISM 2019; 45:458-464. [PMID: 31129317 DOI: 10.1016/j.diabet.2019.05.002] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/19/2018] [Revised: 05/12/2019] [Accepted: 05/19/2019] [Indexed: 01/07/2023]
Abstract
BACKGROUND Whether metformin use might affect the risk of non-Hodgkin lymphoma (NHL) remained to be answered. METHODS A total of 610,089 newly diagnosed type 2 diabetes patients with 2 or more times of prescription of antidiabetic drugs during 1999-2009 were enrolled from Taiwan's National Health Insurance database. They were followed up for NHL incidence until December 31, 2011. Both intention-to-treat and per-protocol analyses were conducted. Cox regression incorporated with the inverse probability of treatment-weighting using propensity scores was used to estimate hazard ratios. RESULTS There were 414,783 metformin initiators and 195,306 non-metformin initiators within the initial 12-month of prescriptions of antidiabetic drugs. After a median follow-up of 5.07 years in metformin initiators and 6.78 years in non-metformin initiators, 1076 and 755 patients were diagnosed of new-onset NHL, respectively. The respective incidence was 47.74 and 57.68 per 100,000 person-years and the hazard ratio for metformin initiators versus non-metformin initiators was 0.849 (95% confidence interval 0.773-0.932) in the intention-to-treat analysis. In the per-protocol analysis, the hazard ratio was 0.706 (95% confidence interval 0.616-0.808). Sensitivity analyses after excluding patients with irregular follow-up, with an extension of minimal observation periods of 24 or 36 months, with incretin-based therapies, or in patients enrolled during 2 different periods (i.e., 1999-2003 and 2004-2009) consistently showed a lower risk among metformin initiators in both the intention-to-treat and the per-protocol analyses. CONCLUSIONS Metformin use is associated with a lower risk of NHL compared with non-metformin antidiabetics.
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Affiliation(s)
- C-H Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Division of Environmental Health and Occupational Medicine of the National Health Research Institutes, Zhunan, Taiwan.
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Gao R, Liang JH, Man TS, Wang L, Zhu HY, Wu W, Fan L, Li JY, Yang T, Xu W. Diabetes mellitus predicts inferior survival in diffuse large B-cell lymphoma: a propensity score-matched analysis. Cancer Manag Res 2019; 11:2849-2870. [PMID: 31114337 PMCID: PMC6497839 DOI: 10.2147/cmar.s185319] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2018] [Accepted: 02/11/2019] [Indexed: 01/03/2023] Open
Abstract
Purpose: Diabetes mellitus (DM) is associated with elevated cancer risk and poor survival. The objective of this study was to assess the prognostic value of DM in diffuse large B-cell lymphoma (DLBCL). Methods: Five hundred and fifty-three newly diagnosed DLBCL patients whose treatments included rituximab were recruited. Propensity score-matched method was performed to balance baseline characteristics and eliminate possible bias. Multivariate Cox regression analyses screened the prognostic risk factors in relation to progression-free survival (PFS) and cancer-specific survival (CSS). Receiver-operator characteristic curves and the corresponding areas under the curve (AUC) assessed the predictive accuracy of international prognostic index (IPI) together with DM. Results: One hundred and nine patients (19.71%) had pre-existing DM. In the propensity-matched cohort, DM was associated with unfavorable PFS and CSS in rituximab era, and it was an independent risk factor for both inferior PFS and CSS, especially in patients with age ≤60 years, IPI 0-2, B symptoms and lactate dehydrogenase ≤upper limit of normal. Prediabetics also demonstrated inferior prognostic outcomes compared to patients with no diabetic tendency. DM as one additional point to IPI had larger AUC compared with IPI alone in CSS prediction and could improve the prognostic capacity of IPI. Conclusion: The results indicate that preexisting DM is an important risk factor for survival. It could help predict life expectancy and build refined prognostication models for DLBCL.
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Affiliation(s)
- Rui Gao
- Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing210029, People’s Republic of China
| | - Jin-Hua Liang
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing210029, People’s Republic of China
| | - Tian-Shuo Man
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing210029, People’s Republic of China
| | - Li Wang
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing210029, People’s Republic of China
| | - Hua-Yuan Zhu
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing210029, People’s Republic of China
| | - Wei Wu
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing210029, People’s Republic of China
| | - Lei Fan
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing210029, People’s Republic of China
| | - Jian-Yong Li
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing210029, People’s Republic of China
| | - Tao Yang
- Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing210029, People’s Republic of China
| | - Wei Xu
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing210029, People’s Republic of China
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11
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Zhu D, Zhang X, Zhang D, Li T, Yang C. RETRACTED: Extranodal natural killer/T-cell lymphoma masquerading a diabetic foot ulcer. Diabetes Res Clin Pract 2018; 137:208-212. [PMID: 29407271 DOI: 10.1016/j.diabres.2018.01.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Accepted: 01/17/2018] [Indexed: 11/23/2022]
Abstract
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief due to an author reporting that they were listed without their permission.
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Affiliation(s)
- Di Zhu
- Department of Endocrinology, Air Force General Hospital of P.L.A, China
| | - Xiaotian Zhang
- Department of Cardiology, 75600 Military Hospital of P.L.A, China
| | - Da Zhang
- Department of Endocrinology, Air Force General Hospital of P.L.A, China
| | - Teng Li
- Department of Pathology, Air Force General Hospital of P.L.A, China
| | - Caizhe Yang
- Department of Endocrinology, Air Force General Hospital of P.L.A, China.
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12
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Type 2 diabetes mellitus is more prevalent among patients with thyroid carcinoma and influences overall survival: a propensity score matching analysis. Oncotarget 2017; 8:97528-97536. [PMID: 29228629 PMCID: PMC5722581 DOI: 10.18632/oncotarget.22179] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Accepted: 08/26/2017] [Indexed: 12/29/2022] Open
Abstract
The relationship between Type 2 Diabetes Mellitus(T2DM) and cancer risk has been investigated for more than a decade. Many types of cancer were confirmed to be related with T2DM. The aim of this study is to identify the relationship between T2DM and the prevalence and long-term survivals of Thyroid Carcinoma(TC) using propensity score matching. In present study, 1658 thyroid nodule patients who were diagnosis in Beijing Shijitan hospital were divided into two groups: the TC group (N = 455, 27.4%), and the benign thyroid nodule(BTN) group (N = 1203, 73.6%). Propensity scores analyses were used to compare the overall survival (OS) and recurrence-free survival (RFS) between patients with or without T2DM. After propensity scores analyses, the prevalance of T2DM was significantly increased in the TC group compared with BTN group. Of the 455 TC patients, with T2DM in thyroid carcinoma was associated with increasing 1-, 3-, 5-year OS rates from 98.8, 76.5, and 70.9% to 99.7, 92.2, and 82.7%, respectively (P=0.017). While the 1-, 3-, and 5-year RFS rates in the group with T2DM were 92.3, 69.5, and 58.3%, which were significantly lower than those in the group without T2DM (97.6, 82.7, and 72.4%, P=0.009). After propensity scores analyses, with T2DM was significantly associated with increased risks of OS and RFS in the entire TC cohort.
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Zhou XL, Xue WH, Ding XF, Li LF, Dou MM, Zhang WJ, Lv Z, Fan ZR, Zhao J, Wang LX. Association between metformin and the risk of gastric cancer in patients with type 2 diabetes mellitus: a meta-analysis of cohort studies. Oncotarget 2017; 8:55622-55631. [PMID: 28903449 PMCID: PMC5589688 DOI: 10.18632/oncotarget.16973] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Accepted: 03/13/2017] [Indexed: 12/12/2022] Open
Abstract
Objectives The objective of this study was to evaluate the association between metformin therapy and the incidence of gastric cancer (GC) in patients with type 2 diabetes mellitus (T2DM). Methods We systemically searched the following databases for studies published between the databases’ dates of inception and Nov. 2016: PubMed, Embase, the Cochrane Library, the Web of Science, and the China National Knowledge Infrastructure (CNKI). Hazard ratios (HR)and corresponding 95% confidence intervals (CIs) for the association between metformin therapy and the incidence of GC in patients with T2DM were the outcome measures assessed in this study. STATA 12.0 (Stata Corporation, College Station, Texas, USA) was used to conduct the statistical analysis. Results A total of seven cohort studies including 591,077 patients met all the criteria for inclusion in the analysis. Our data showed that metformin therapy was associated with a significantly lower incidence of GC in patients with T2DM than other types of therapy (HR=0.763, 95% CI: 0.642˜0.905). Subgroup analysis showed that patients living in Taiwan benefitted more from metformin therapy than patients living in any other region, as metformin significantly decreased the risk of GC in patients living in Taiwan but did not significantly decrease the risk of GC in patients living in other regions (HR=0.514, 95% CI: 0.384-0.688). The results of the present analysis support the idea that metformin facilitates reductions in the risk of T2DM-related GC. Conclusions The risk of GC among patients with T2DM is lower in patients receiving metformin therapy than in patients not receiving metformin therapy.
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Affiliation(s)
- Xue-Liang Zhou
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Wen-Hua Xue
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Xian-Fei Ding
- Department of General ICU, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Li-Feng Li
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Meng-Meng Dou
- Department of Integrated Traditional and Western Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Wei-Jie Zhang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Zhuan Lv
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Zhi-Rui Fan
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Jie Zhao
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Liu-Xing Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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Tseng CH. Factors Associated with Cancer- and Non-Cancer-Related Deaths among Taiwanese Patients with Diabetes after 17 Years of Follow-Up. PLoS One 2016; 11:e0147916. [PMID: 27906989 PMCID: PMC5132220 DOI: 10.1371/journal.pone.0147916] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2015] [Accepted: 11/04/2016] [Indexed: 01/19/2023] Open
Abstract
OBJECTIVE A previous 12-year follow-up of a large diabetes cohort in Taiwan suggested a survival advantage in the patients with obesity. The present study further investigated additional determinants for cancer and non-cancer death in the cohort after a follow-up of 17 years. METHODS A cohort of 92546 diabetes patients recruited since 1995 was followed for vital status by matching the National Death Certificate Database until 2011. Cox regression estimated the hazard ratios for the following variables: age at baseline, sex, diabetes type, screen-detected diabetes (diabetes diagnosed accidentally through epidemiological screening programs or during visits to medical settings without a history of diabetes), diabetes duration, body mass index, insulin use, hypertension, smoking, and living region. Fasting glucose and history of dyslipidemia were available for additional adjustment in a subcohort of the patients (n = 14559). RESULTS A total of 40229 diabetes patients (43.5% of the cohort) died during follow-up and 10.9% died under the age of 60. Insulin use and smoking significantly predicted cancer and non-cancer death. The adjusted hazard ratio (95% confidence interval) associated with insulin use was 1.161 (1.052-1.281) for cancer death and 1.469 (1.413-1.526) for non-cancer death. Screen-detected diabetes and body mass index were consistently associated with a lower risk, but diabetes duration a higher risk, for non-cancer death, with adjusted hazard ratio of 0.683 (0.666-0.702), 0.955 (0.951-0.958) and 1.018 (1.017-1.020), respectively. Diabetes type had a null association disregarding the causes of death and living in rural areas was significantly associated with a higher mortality from non-cancer death. Hypertension, fasting glucose and dyslipidemia showed differential impacts on cancer and non-cancer death, and were significantly predictive for non-cancer death. CONCLUSIONS Screen-detected diabetes and a higher body mass index provide a survival advantage, especially for non-cancer death. However, insulin use is associated with a significantly higher risk of either cancer or non-cancer death.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Division of Environmental Health and Occupational Medicine of the National Health Research Institutes, Taipei, Taiwan
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15
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Yoo B, Park Y, Park K, Kim H. A 9-year Trend in the Prevalence of Allergic Disease Based on National Health Insurance Data. J Prev Med Public Health 2015; 48:301-9. [PMID: 26639744 PMCID: PMC4676638 DOI: 10.3961/jpmph.15.011] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2015] [Accepted: 10/26/2015] [Indexed: 12/16/2022] Open
Abstract
Objectives: To investigate trends in the prevalence of allergic disease over a 9-year period. Methods: Using National Health Insurance Service (NHIS) data, the annual number of patients with allergic disease was obtained for each regional subdivisions (small cities, counties, and districts) from 2003 to 2011. Annual populations for each sub-region were obtained and used to calculate the standardized prevalence. To compare prevalence within the study period, data was standardized spatially and temporally. For standardization, demographic data was used to obtain the registered population and demographic structure for 2010, which was used to perform direct standardization of previous years. In addition, a geographic information system (GIS) was used to visualize prevalence for individual sub-regions, and allergic diseases were categorized into five groups according to prevalence. Results: The nationwide outpatient prevalence of allergic rhinitis increased approximately 2.3-fold, from 1.27% in 2003 to 2.97% in 2013, while inpatient prevalence also increased approximately 2.4-fold,. The outpatient prevalence of asthma increased 1.2-fold, and inpatient prevalence increased 1.3-fold. The outpatient prevalence of atopic dermatitis decreased approximately 12%, and inpatient prevalence decreased 5%. Conclusions: There was a large difference between prevalence estimated from actual treatment data and prevalence based on patients’ self-reported data, particularly for allergic rhinitis. Prevalence must continually be calculated and trends should be analyzed for the efficient management of allergic diseases. To this end, prevalence studies using NHIS claims data may be useful.
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Affiliation(s)
- Byoungin Yoo
- Department of Preventive Medicine, Soonchunhyang University College of Medicine, Chunan, Korea
| | - Yoonhyung Park
- Department of Preventive Medicine, Soonchunhyang University College of Medicine, Chunan, Korea
| | - Kwanjun Park
- Department of Preventive Medicine, Soonchunhyang University College of Medicine, Chunan, Korea
| | - Hoseob Kim
- Department of Preventive Medicine, Soonchunhyang University College of Medicine, Chunan, Korea
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16
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Tseng CH. Type 2 Diabetes Mellitus and Kidney Cancer Risk: A Retrospective Cohort Analysis of the National Health Insurance. PLoS One 2015; 10:e0142480. [PMID: 26559055 PMCID: PMC4641625 DOI: 10.1371/journal.pone.0142480] [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] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Accepted: 10/22/2015] [Indexed: 12/29/2022] Open
Abstract
PURPOSE To evaluate the association between incidence of any kidney cancer and type 2 diabetes mellitus. METHODS A random sample of 1,000,000 subjects covered by the National Health Insurance was recruited. A total of 998728 people (115655 diabetes and 883073 non-diabetes) without kidney cancer at recruitment were followed from 2003 to 2005. The cumulative incidence of kidney cancer from 2003 to 2005 in diabetic patients and non-diabetic people in all ages and in age <40, 40-64, 65-74 and ≥ 75 years were calculated in the diabetic patients and the non-diabetic people, respectively. Logistic regression was used to estimate the odds ratios comparing diabetic patients to non-diabetic people in the respective age groups. Multivariable-adjusted odds ratios for kidney cancer with regards to diabetes status and diabetes duration (as a continuous variable or categorized into subgroups of non-diabetes, diabetes duration <1 year, 1-2.9 years, 3-4.9 years and ≥ 5 years) were estimated after multivariable adjustment. The multivariable-adjusted odds ratios for all baseline variables were also estimated for diabetic patients and non-diabetic people, respectively. RESULTS The 3-year cumulative incidence of kidney cancer in the diabetic patients and the non-diabetic people was 166.9 and 33.1 per 100,000 person-years, respectively. The incidence increased with regards to increasing age in both the diabetic patients and the non-diabetic people, but a higher risk of kidney cancer for the diabetic patients compared to the non-diabetic people was consistently observed in different age groups. After multivariable adjustment, the odds ratio for diabetic patients versus non-diabetic people was 1.7 (95% confidence interval: 1.3-2.1, P<0.01). While compared to the non-diabetic people, the odds ratio (95% confidence interval) for diabetes duration <1, 1-2.9 years, 3-4.9 years and ≥ 5 years was 1.5 (0.8-2.7), 1.6 (1.0-2.4), 1.6 (1.1-2.4) and 1.7 (1.3-2.3), respectively (P-trend <0.01). Analyses conducted in the diabetic patients and the non-diabetic people, respectively, consistently showed age, nephropathy and end-stage renal disease as significant risk factors of kidney cancer. Additionally, living in metropolitan Taipei region might also be associated with a higher risk of kidney cancer in the non-diabetic people, indicating a potential link between kidney cancer and some factors related to urbanization. CONCLUSIONS Patients with type 2 diabetes mellitus have a significantly higher risk of kidney cancer.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Division of Environmental Health and Occupational Medicine of the National Health Research Institutes, Zhunan, Taiwan
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17
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Bae MJ, Kim SS, Kim WJ, Yi YS, Jeon YK, Kim BH, Lee BJ, Lee JC, Kim IJ, Wang SG, Kim YK. High prevalence of papillary thyroid cancer in Korean women with insulin resistance. Head Neck 2015; 38:66-71. [PMID: 25196854 DOI: 10.1002/hed.23848] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/03/2014] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND The purpose of this study was to determine if hyperinsulinemia and/or insulin resistance are/is associated with the prevalence of papillary thyroid cancer (PTC) in Korean women. METHODS This study included 735 female patients with PTC and 537 female non-PTC control subjects. Multiple logistic regression analysis was performed to evaluate the associations between hyperinsulinemia/insulin resistance and the occurrence of PTC. RESULTS The prevalence of PTC was significantly correlated with increased insulin, glucose levels, and a high homeostasis model of assessment-insulin resistance (HOMA-IR). The multivariate adjusted odds ratios for the prevalence of PTC in the highest quartile groups for insulin, glucose, and HOMA-IR were 2.88, 9.32, and 4.07 (all p < .001), respectively, compared with the lowest quartile groups. Pathological analyses revealed that increased serum glucose, insulin levels, and a higher HOMA-IR were associated with the multifocality of PTC. CONCLUSION Hyperinsulinemia and/or insulin resistance may be associated with the development of PTC, but not disease severity in Korean women.
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Affiliation(s)
- Min Jung Bae
- Kim Yong Ki Internal Medicine Clinic, Busan, Korea
| | - Sang Soo Kim
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea.,Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Won Jin Kim
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea.,Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Yang Seon Yi
- Department of Internal Medicine, Busan Veterans Hospital, Busan, Korea
| | - Yun Kyung Jeon
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea.,Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Bo Hyun Kim
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea.,Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Byung Joo Lee
- Department of Otolaryngology, Pusan National University Hospital, Busan, Korea
| | - Jin Choon Lee
- Department of Otolaryngology, Pusan National University Hospital, Busan, Korea
| | - In Joo Kim
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea.,Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Soo Geun Wang
- Department of Otolaryngology, Pusan National University Hospital, Busan, Korea
| | - Yong Ki Kim
- Kim Yong Ki Internal Medicine Clinic, Busan, Korea
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18
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Tseng CH, Lee KY, Tseng FH. An updated review on cancer risk associated with incretin mimetics and enhancers. JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH. PART C, ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS 2015; 33:67-124. [PMID: 25803196 DOI: 10.1080/10590501.2015.1003496] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
Incretin-based therapies, including the use of incretin mimetics of glucagon-like peptide-1 receptor (GLP-1R) agonists and incretin enhancers of dipeptidyl-peptidase 4 (DPP-4) inhibitors, are widely used by clinicians for glucose lowering in patients with type 2 diabetes mellitus. These agents have benefits of a lower risk of hypoglycemia, being neutral for body weight for DPP-4 inhibitors and having a potential for weight reduction with GLP-1R agonists. They may also have a neutral or beneficial cardiovascular effect. Despite these benefits, an increased risk of cancer (especially pancreatic cancer and thyroid cancer) associated with incretin-based therapies has been reported. In this article, we reviewed related literature of experimental animal and observational human studies, clinical trials, and meta-analyses published until December 15, 2014. Current studies suggested a probable role of GLP-1R activation on the development of pancreatic cancer and thyroid cancer in rodents, but such an effect in humans is not remarkable due to the lower or lack of expression of GLP-1R on human pancreatic ductal cells and thyroid tissues. Findings in human studies are controversial and inconclusive. In the analyses of the US Food and Drug Administration adverse events reporting system, a significantly higher risk of pancreatic cancer was observed for GLP-1R agonists and DPP-4 inhibitors, but a significantly higher risk of thyroid cancer was only observed for GLP-1R agonists. Such a higher risk of pancreatic cancer or thyroid cancer could not be similarly demonstrated in other human observational studies or analyses of data from clinical trials. With regards to cancers other than pancreatic cancer and thyroid cancer, available studies supported a neutral association in humans. Some preliminary studies even suggested a potentially beneficial effect on the development of other cancers with the use of incretins. Based on current evidence, continuous monitoring of the cancer issues related to incretin-based therapies is required, even though the benefits may outweigh the potential cancer risk in the general patients with type 2 diabetes mellitus.
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Affiliation(s)
- Chin-Hsiao Tseng
- a Department of Internal Medicine , National Taiwan University Hospital , Taipei , Taiwan
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Tseng CH. Metformin reduces thyroid cancer risk in Taiwanese patients with type 2 diabetes. PLoS One 2014; 9:e109852. [PMID: 25303400 PMCID: PMC4193839 DOI: 10.1371/journal.pone.0109852] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Accepted: 09/04/2014] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Whether metformin may affect thyroid cancer risk has not been studied. This study investigated the association between metformin use and thyroid cancer risk in Taiwanese patients with type 2 diabetes mellitus. METHODS The reimbursement databases of all diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2006 and 1,414,723 patients with type 2 diabetes were followed for thyroid cancer incidence until the end of 2009. Incidences for ever-users, never-users and subgroups of metformin exposure using tertile cutoffs for cumulative duration of therapy and cumulative dose were calculated and adjusted hazard ratios were estimated by Cox regression. Additional sensitivity analyses were conducted. RESULTS There were 795,321 ever-users and 619,402 never-users, with respective numbers of incident thyroid cancer of 683 (0.09%) and 1,614 (0.26%), and respective incidence of 24.09 and 87.33 per 100,000 person-years. The overall fully adjusted hazard ratio (95% confidence interval) was 0.683 (0.598-0.780), and all categories of the dose-response parameters showed significantly lower risk with P-trends < 0.0001. The protective effect of metformin on thyroid cancer incidence was also supported by sensitivity analyses, disregarding age (< 50 or ≥ 50 years) and sex; and was not affected by excluding users of insulin, sulfonylurea, and insulin and/or sulfonylurea respectively, by previous diagnosis of other cancers or by potential detection examinations that might lead to differential diagnosis of thyroid cancer. CONCLUSIONS This study provides evidence for the first time that metformin use in patients with type 2 diabetes may reduce the risk of thyroid cancer.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Division of Environmental Health and Occupational Medicine of the National Health Research Institutes, Taipei, Taiwan
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20
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Tseng CH. Diabetes and breast cancer in Taiwanese women: a detection bias? Eur J Clin Invest 2014; 44:910-917. [PMID: 25104332 DOI: 10.1111/eci.12323] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2014] [Accepted: 08/04/2014] [Indexed: 12/19/2022]
Abstract
PURPOSE To evaluate whether diabetes is a risk factor for breast cancer considering confounders and potential detection examinations. METHODS National Health Insurance data on 501,747 women without breast cancer were retrieved. Three-year cumulative incidence (2003-2005) and risk ratios (RRs) between diabetic and nondiabetic women were calculated. Potential detection examinations were compared between diabetic and nondiabetic women by chi-square test. Odds ratios (ORs) were estimated by logistic regression for diabetes status/duration with and without adjustment for potential detection examinations and confounders. RESULTS The crude RR (95% confidence interval [CI]) for all ages, and age groups < 50, 50-64 and ≥ 65 years, was 2·62 (2·31-2·91), 2·69 (2·11-3·44), 1·39 (1·15-1·68) and 1·37 (1·03-1·84), respectively. Patients with diabetes more frequently received potential detection examinations than nondiabetes (17·5% vs. 7·4%, P-value < 0·001). The unadjusted OR (95% CI) for breast cancer for diabetes status (yes vs. no) was 2·63 (2·31-2·98) and was significant for any diabetes duration. The OR for diabetes status was 1·81 (95% CI: 1·59-2·06) after adjustment for potential detection examinations. In models adjusted for potential detection examinations, age, living region, occupation, comorbidities and used medications, OR for diabetes status attenuated to 1·13 (95% CI 0·96-1·32, P-value = 0·14) and none was significant for any diabetes duration. Potential detection examinations were associated with a fivefold to sevenfold higher risk in various models, indicating a strong impact of detection bias. CONCLUSIONS An association between diabetes and breast cancer is observed, but this can be due to potential detection bias and confounders.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Taipei, Taiwan
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21
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Karlstad O, Starup-Linde J, Vestergaard P, Hjellvik V, Bazelier MT, Schmidt MK, Andersen M, Auvinen A, Haukka J, Furu K, de Vries F, De Bruin ML. Use of insulin and insulin analogs and risk of cancer - systematic review and meta-analysis of observational studies. Curr Drug Saf 2014; 8:333-48. [PMID: 24215311 PMCID: PMC3899599 DOI: 10.2174/15680266113136660067] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2013] [Revised: 10/29/2013] [Accepted: 10/31/2013] [Indexed: 12/12/2022]
Abstract
Background: An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified. Objective: To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes. Data Sources: Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. Study Eligibility Criteria (PICOS): Population: diabetes patients. Exposure: Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs. Outcome: Any incident cancer. Study Design: Cohort and case-control studies. Results: 42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer. Limitations: Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders. Conclusions: Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Marie L De Bruin
- Norwegian Institute of Public Health, P.O.Box 4404 Nydalen, N-0403 Oslo, Norway.
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22
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Tseng CH. Diabetes but not insulin increases the risk of lung cancer: a Taiwanese population-based study. PLoS One 2014; 9:e101553. [PMID: 24991802 PMCID: PMC4081573 DOI: 10.1371/journal.pone.0101553] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2014] [Accepted: 06/07/2014] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND The trend of lung cancer incidence in Taiwan is unknown, and the association between type 2 diabetes/insulin use and lung cancer is rarely studied. METHODS The trends of lung cancer incidence in 1979-2007 in the Taiwanese general population were calculated. A random sample of 1,000,000 subjects covered by the National Health Insurance in 2005 was recruited. A total of 494,002 men and 502,948 women and without lung cancer were followed for the annual cumulative incidence of lung cancer in 2005, with calculation of the risk ratios between diabetic and non-diabetic subjects. Logistic regression estimated the adjusted odds ratios for risk factors. RESULTS The trends increased significantly in both sexes (P<0.0001). The sex-specific annual cumulative incidence increased with age in either the diabetic or non-diabetic subjects, but the risk ratios attenuated with age. In logistic regressions, diabetes was associated with a significantly higher risk, with odds ratios (95% confidence interval) for diabetes duration <1, 1-3, 3-5 and ≥5 years versus non-diabetes of 2.189 (1.498-3.200), 1.420 (1.014-1.988), 1.545 (1.132-2.109), and 1.329 (1.063-1.660), respectively. Such an association was not related to a higher detection with chest X-ray examination. Insulin use and medications including oral anti-diabetic drugs, statin, fibrate, and anti-hypertensive agents were not significantly associated with lung cancer. Age, male sex, and chronic obstructive pulmonary disease were positively; but dyslipidemia, stroke and higher socioeconomic status were negatively associated with lung cancer. CONCLUSIONS Diabetes is significantly associated with a higher risk of lung cancer, but insulin use does not increase the risk.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Division of Environmental Health and Occupational Medicine of the National Health Research Institutes, Taipei, Taiwan
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Sen S, He Y, Koya D, Kanasaki K. Cancer biology in diabetes. J Diabetes Investig 2014; 5:251-64. [PMID: 24843770 PMCID: PMC4020326 DOI: 10.1111/jdi.12208] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2013] [Revised: 01/09/2014] [Accepted: 01/13/2014] [Indexed: 12/13/2022] Open
Abstract
Diabetes is a serious metabolic disease that causes multiple organ dysfunctions. Recent evidence suggests that diabetes could contribute to the initiation and progression of certain cancers in addition to the classic diabetic complications. Furthermore, some of the drugs used clinically to treat patients with diabetes might affect cancer initiation, progression and mortality. The recent discovery of the possible anticancer effects of metformin, a classic antidiabetic drug, has led physicians and scientists to reconsider the interaction between diabetes and cancer. In the present review, we analyze recent reports in this field, and explore possible mechanistic links between diabetes and cancer biology.
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Affiliation(s)
- Shi Sen
- Division of Diabetes & EndocrinologyKanazawa Medical UniversityIshikawaJapan
- The Department of Vascular and Thyroid SurgeryThe Affiliated Hospital of Luzhou Medical CollegeLuzhouChina
| | - Yanzheng He
- The Department of Vascular and Thyroid SurgeryThe Affiliated Hospital of Luzhou Medical CollegeLuzhouChina
| | - Daisuke Koya
- Division of Diabetes & EndocrinologyKanazawa Medical UniversityIshikawaJapan
| | - Keizo Kanasaki
- Division of Diabetes & EndocrinologyKanazawa Medical UniversityIshikawaJapan
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Tseng CH, Tseng FH. Diabetes and gastric cancer: the potential links. World J Gastroenterol 2014; 20:1701-1711. [PMID: 24587649 PMCID: PMC3930970 DOI: 10.3748/wjg.v20.i7.1701] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2013] [Revised: 11/18/2013] [Accepted: 12/05/2013] [Indexed: 02/06/2023] Open
Abstract
This article reviews the epidemiological evidence linking diabetes and gastric cancer and discusses some of the potential mechanisms, confounders and biases in the evaluation of such an association. Findings from four meta-analyses published from 2011 to 2013 suggest a positive link, which may be more remarkable in females and in the Asian populations. Putative mechanisms may involve shared risk factors, hyperglycemia, Helicobacter pylori (H. pylori) infection, high salt intake, medications and comorbidities. Diabetes may increase the risk of gastric cancer through shared risk factors including obesity, insulin resistance, hyperinsulinemia and smoking. Hyperglycemia, even before the clinical diagnosis of diabetes, may predict gastric cancer in some epidemiological studies, which is supported by in vitro, and in vivo studies. Patients with diabetes may also have a higher risk of gastric cancer through the higher infection rate, lower eradication rate and higher reinfection rate of H. pylori. High salt intake can act synergistically with H. pylori infection in the induction of gastric cancer. Whether a higher risk of gastric cancer in patients with diabetes may be ascribed to a higher intake of salt due to the loss of taste sensation awaits further investigation. The use of medications such as insulin, metformin, sulfonylureas, aspirin, statins and antibiotics may also influence the risk of gastric cancer, but most of them have not been extensively studied. Comorbidities may affect the development of gastric cancer through the use of medications and changes in lifestyle, dietary intake, and the metabolism of drugs. Finally, a potential detection bias related to gastrointestinal symptoms more commonly seen in patients with diabetes and with multiple comorbidities should be pointed out. Taking into account the inconsistent findings and the potential confounders and detection bias in previous epidemiological studies, it is expected that there are still more to be explored for the clarification of the association between diabetes and gastric cancer.
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Tseng CH. A review on thiazolidinediones and bladder cancer in human studies. JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH. PART C, ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS 2014; 32:1-45. [PMID: 24598039 DOI: 10.1080/10590501.2014.877645] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
There is a concern of an increased risk of bladder cancer associated with the use of thiazolidinediones, a class of oral glucose-lowering drugs commonly used in patients with type 2 diabetes with a mechanism of improving insulin resistance. Human studies on related issues are reviewed, followed by a discussion on potential concerns on the causal inference in current studies. Pioglitazone and rosiglitazone are discussed separately, and findings from different geographical regions are presented. Randomized controlled trials designed for primarily answering such a cancer link are lacking, and evidence from clinical trials with available data for evaluating the association may not be informative. Observational studies have been reported with the use of population-based administrative databases, single-hospital records, drug adverse event reporting system, and case series collection. Meta-analysis has also been performed by six different groups of investigators. These studies showed a signal of higher risk of bladder cancer associated with pioglitazone, especially at a higher cumulative dose or after prolonged exposure; however, a weaker signal or null association is observed with rosiglitazone. In addition, there are some concerns on the causal inference, which may be related to the use of secondary databases, biases in sampling, differential detection, and confounding by indications. Lack of full control of smoking and potential biases related to study designs and statistical approaches such as prevalent user bias and immortal time bias may be major limitations in some studies. Overlapping populations and opposing conclusions in studies using the same databases may be of concern and weaken the reported conclusions of the studies. Because randomized controlled trials are expensive and unethical in providing an answer to this cancer issue, observational studies are expected to be the main source in providing an answer in the future. Furthermore, international comparison studies using well-designed and uniform methodology to clarify the risk in specific sexes, ethnicities, and other subgroups and to evaluate the interaction with other environmental risk factors or medications will be helpful to identify patients at risk.
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Affiliation(s)
- Chin-Hsiao Tseng
- a Department of Internal Medicine , National Taiwan University College of Medicine , Taipei , Taiwan
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Tseng CH. Diabetes, insulin use, smoking, and pancreatic cancer mortality in Taiwan. Acta Diabetol 2013; 50:879-886. [PMID: 23508375 DOI: 10.1007/s00592-013-0471-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2013] [Accepted: 03/07/2013] [Indexed: 12/13/2022]
Abstract
The aim of the study was to evaluate the link between diabetes and pancreatic cancer (PC) mortality and the joint effect of smoking and insulin use on PC mortality. A total of 39,988 men and 46,909 women with type 2 diabetes, aged ≥25 years and recruited in 1995-1998, were followed to 2006 for PC mortality. Age-sex-specific mortality rate ratios for diabetic patients versus the general population were calculated. Cox regression was used to evaluate hazard ratios for PC mortality for covariates including age, sex, diabetes duration, body mass index, smoking, insulin use, and area of residence. The interaction and joint effect of smoking and insulin use were also evaluated. A total of 89 men and 63 women died of PC. The mortality rate ratios (95 % CI) showed a significantly higher risk in diabetic patients with a magnitude most remarkable at the youngest age: 1.51 (1.15, 1.98), 2.02 (1.35, 3.03), and 8.36 (5.39, 12.98) for ≥65, 55-64, and 25-54 years old, respectively, for men; and 1.16 (0.84, 1.59), 2.12 (1.39, 3.23) and 3.33 (1.14, 9.68), respectively, for women. In multivariable Cox regression analysis, only age was significantly predictive for PC mortality. Although smoking and insulin use might be associated with a 50 % higher risk when analyzed as individual risk factors, they did not reach statistical significance. The interaction term of smoking and insulin use was also not statistically significant in additional modeling. However, smoking and insulin use jointly increased the risk with an adjusted hazard ratio (95 % CI) of 3.04 (1.37, 6.73) when compared to patients who did not smoke and did not use insulin. Diabetic patients have a significantly higher risk of PC mortality. In patients with type 2 diabetes, smoking and insulin use may jointly increase the risk by threefold.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, No. 7 Chung-Shan South Road, Taipei, 100, Taiwan,
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Tseng CH. Rosiglitazone is not associated with an increased risk of bladder cancer. Cancer Epidemiol 2013; 37:385-389. [DOI: 10.1016/j.canep.2013.03.013] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2013] [Revised: 03/28/2013] [Accepted: 03/31/2013] [Indexed: 02/06/2023]
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Abstract
BACKGROUND The association between diabetes and gastric cancer is rarely studied, and the risk associated with insulin use is not known. MATERIALS AND METHODS Gastric cancer prevalence rates in 2005 were calculated in 329,198 insurants aged 45 years or older and without type 1 diabetes from a random sample of 1,000,000 insurants of the National Health Insurance in Taiwan. Logistic regression evaluated whether diabetes or insulin use could be an independent risk factor after adjustment for age, sex, occupation, and living region. Sensitivity analyses were performed by excluding patients with diabetes duration <5 years and by excluding patients with cancers other than gastric cancer. RESULTS A total of 1464 cases of gastric cancer were identified. The prevalence of gastric cancer in diabetic and nondiabetic subjects were 595.0 and 387.7 per 100,000 population (P<0.0001), respectively. In diabetic patients, the respective prevalence of gastric cancer in insulin users and nonusers were 656.0 and 589.5 (P=0.4743). Adjusted odds ratio for diabetic versus nondiabetic subjects was 1.139 (1.022 to 1.270), and for insulin users versus nonusers in the diabetic patients was 1.002 (0.745 to 1.346). Age and male sex were also associated with significantly higher risk of gastric cancer, but the association with occupation and living region were not consistent. Results from sensitivity analyses were similar. CONCLUSIONS Diabetic patients may have a 14% higher risk of gastric cancer. However, insulin use is not related to the increased risk.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
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Tseng CH. Diabetes and thyroid cancer mortality: a 12-year prospective follow-up of Taiwanese. Eur J Clin Invest 2013; 43:595-601. [PMID: 23550697 DOI: 10.1111/eci.12086] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2013] [Accepted: 03/10/2013] [Indexed: 12/20/2022]
Abstract
BACKGROUND The association between diabetes and thyroid cancer is rarely studied. This study evaluated thyroid cancer mortality trend in Taiwanese population, mortality rate ratios between diabetic patients and general population, and risk factors in diabetic patients. METHODS In general population, age-standardized trends were evaluated from 1995 to 2006. A total of 113,347 diabetic men and 131,573 diabetic women aged ≥ 25 years recruited during 1995-1998 were followed to 2006. Age- and sex-specific mortality rate ratios were calculated and Cox's regression evaluated the risk factors. RESULTS A steady trend of thyroid cancer mortality was observed in the general population. A total of 20 diabetic men and 45 diabetic women died of thyroid cancer, with overall mortality rate 2.32 and 4.26 per 100,000 person-years, respectively. Mortality rate ratios showed positive association with magnitude increased with decreasing age: 1.85 (0.77, 4.43), 1.21 (0.54, 2.73), 2.53 (1.14, 5.59) and 5.80 (2.10, 16.01) for ≥ 75, 65-74, 55-64 and 25-54 years old, respectively, for men; and 0.78 (0.35, 1.74), 2.03 (1.31, 3.13), 2.99 (1.77, 5.04) and 5.34 (2.20, 13.00), respectively, for women. After adjustment, only age was significantly associated with thyroid cancer mortality. Sex, diabetes duration, diabetes type, body mass index, smoking, insulin use and area of residence were not significantly predictive for thyroid cancer mortality. CONCLUSIONS The annual thyroid cancer mortality during 1995-2006 in the Taiwanese general population has been steady. Our data suggest a higher risk in diabetic patients, with especially higher mortality rate ratios in younger age. Obesity, smoking and insulin use are not modifiable risk factor.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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31
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Lu HJ, Huang YC, Liu CY, Hung MH, Hu MH, Wu CY, Hong YC, Hsiao LT, Gau JP, Liu JH, Hsu HC, Chiou TJ, Tzeng CH, Yu YB. Diminishing prognostic role of preexisting diabetes mellitus for patients with diffuse large B-cell lymphoma in the rituximab era. Ann Hematol 2013; 92:1495-501. [DOI: 10.1007/s00277-013-1789-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2013] [Accepted: 04/30/2013] [Indexed: 01/05/2023]
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Shih SR, Chiu WY, Chang TC, Tseng CH. Diabetes and thyroid cancer risk: literature review. EXPERIMENTAL DIABETES RESEARCH 2012; 2012:578285. [PMID: 22778714 PMCID: PMC3384966 DOI: 10.1155/2012/578285] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/30/2012] [Revised: 03/30/2012] [Accepted: 04/20/2012] [Indexed: 12/13/2022]
Abstract
Diabetic patients have a higher risk of various types of cancer. However, whether diabetes may increase the risk of thyroid cancer has not been extensively studied. This paper reviews and summarizes the current literature studying the relationship between diabetes mellitus and thyroid cancer, and the possible mechanisms linking such an association. Epidemiologic studies showed significant or nonsignificant increases in thyroid cancer risk in diabetic women and nonsignificant increase or no change in thyroid cancer risk in diabetic men. A recent pooled analysis, including 5 prospective studies from the USA, showed that the summary hazard ratio (95% confidence interval) for women was 1.19 (0.84-1.69) and was 0.96 (0.65-1.42) for men. Therefore, the results are controversial and the association between diabetes and thyroid cancer is probably weak. Further studies are necessary to confirm their relationship. Proposed mechanisms for such a possible link between diabetes and thyroid cancer include elevated levels of thyroid-stimulating hormone, insulin, glucose and triglycerides, insulin resistance, obesity, vitamin D deficiency, and antidiabetic medications such as insulin or sulfonylureas.
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Affiliation(s)
- Shyang-Rong Shih
- Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung Shan South Road, Taipei 10002, Taiwan
- National Taiwan University College of Medicine, Taipei, Taiwan
| | - Wei-Yih Chiu
- Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung Shan South Road, Taipei 10002, Taiwan
- National Taiwan University College of Medicine, Taipei, Taiwan
| | - Tien-Chun Chang
- Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung Shan South Road, Taipei 10002, Taiwan
- National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung Shan South Road, Taipei 10002, Taiwan
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Chiu WY, Shih SR, Tseng CH. A review on the association between glucagon-like peptide-1 receptor agonists and thyroid cancer. EXPERIMENTAL DIABETES RESEARCH 2012; 2012:924168. [PMID: 22693487 PMCID: PMC3368340 DOI: 10.1155/2012/924168] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/15/2012] [Accepted: 04/01/2012] [Indexed: 01/11/2023]
Abstract
There is a concern on the risk of thyroid cancer associated with glucagon-like peptide-1 (GLP-1) analogs including liraglutide and exenatide. In this article, we review related experimental studies, clinical trials and observational human studies currently available. In rodents, liraglutide activated the GLP-1 receptors on C-cells, causing an increased incidence of C-cell neoplasia. Animal experiments with monkeys demonstrated no increase in calcitonin release and no C-cell proliferation after long-term liraglutide administration. Longitudinal 2-year data from clinical trials do not support any significant risk for the activation or growth of C-cell cancer in humans in response to liraglutide. However, an analysis of the FDA adverse event reporting system database suggested an increased risk for thyroid cancer associated with exenatide after its marketing. Noticeably, a recent study discovered that GLP-1 receptor could also be expressed in human papillary thyroid carcinomas (PTC), but the impact of GLP-1 analogs on PTC is not known. Therefore, GLP-1 analogs might increase the risk of thyroid C-cell pathology in rodents, but its risk in humans awaits confirmation. Since GLP-1 receptor is also expressed in PTC besides C-cells, it is important to investigate the actions of GLP-1 on different subtypes of thyroid cancer in the future.
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Affiliation(s)
- Wei-Yih Chiu
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan
| | - Shyang-Rong Shih
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan
| | - Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan
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Tseng CH. Pioglitazone and bladder cancer in human studies: is it diabetes itself, diabetes drugs, flawed analyses or different ethnicities? J Formos Med Assoc 2012; 111:123-131. [PMID: 22423665 DOI: 10.1016/j.jfma.2011.10.003] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2011] [Revised: 10/05/2011] [Accepted: 10/31/2011] [Indexed: 12/13/2022] Open
Abstract
This article reviews human observations on pioglitazone and bladder cancer risk. The PROspective pioglitAzone Clinical Trial In macroVascular Events trial showed an imbalance in bladder cancer between users of pioglitazone and placebo (14 versus six cases, p = 0.069). However, after excluding bladder cancer probably ascribed to other etiology, a blind assessment concluded that the imbalance might not be related to pioglitazone. Epidemiologic studies conducted in the United States and France using insurance databases independently suggested that pioglitazone use for >2 years might confer a 20%-40% higher risk. Another study evaluating bladder cancer risk in diabetic patients using the National Health Insurance in Taiwan did not find any incident bladder cancer case among 422 pioglitazone users for a follow-up of up to 3 years. Because observational studies may suffer from selection and information bias, and inadequate adjustment for confounders may inflate the estimated risk, causal inference from these studies should be interpreted with caution. While investigating cancer risk associated with a medication, indication bias should also be attended, especially when the medication is used at a late stage of the disease. Because pioglitazone is usually a second or third line antidiabetic agent, the users are always characterized by older age, longer diabetes duration, poorer glycemic control, and higher rates of complications and comorbidities. Biased estimates will also result if these differences are not appropriately addressed in the analyses. Current evidence neither concludes nor excludes a causal role of pioglitazone on bladder cancer. Clinical trials aiming at evaluating the risk of cancer associated with a medication is not ethical and may not be expected to provide an answer on the issue of pioglitazone-related bladder cancer. However, a meta-analysis using all available clinical trials to compare the bladder cancer risk between pioglitazone and comparators will be helpful. Well-conducted epidemiologic observational studies are probably other options. Because bladder cancer incidence and their risk factors may differ significantly among different ethnicities, a clarification of such a link in different ethnicities is needed, better by using long-term databases with large and representative sample size and appropriate adjustment for confounders. Furthermore, the interactions with other comorbidities and concomitant medications should be addressed.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
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Tseng CH. Pioglitazone and bladder cancer: a population-based study of Taiwanese. Diabetes Care 2012; 35:278-280. [PMID: 22210574 PMCID: PMC3263866 DOI: 10.2337/dc11-1449] [Citation(s) in RCA: 108] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2011] [Accepted: 11/11/2011] [Indexed: 02/03/2023]
Abstract
OBJECTIVE The association between pioglitazone and bladder cancer has not been investigated in Asians. We aimed to investigate this association. RESEARCH DESIGN AND METHODS A total of 1,000,000 individuals were randomly sampled from the National Health Insurance database, and incident cases of bladder cancer during the period from 1 January 2006 to 31 December 2009 were analyzed among 54,928 patients with type 2 diabetes and without previous bladder cancer. RESULTS Among 165 incident case subjects, 10 (0.39%) were ever users and 155 (0.30%) were never users of pioglitazone (adjusted hazard ratio in full model 1.305 [95% CI 0.661-2.576]). All bladder cancer in ever users occurred within a duration of therapy <24 months, suggesting an early effect of pioglitazone on bladder cancer or late use of pioglitazone in high-risk patients. CONCLUSIONS The association between pioglitazone and bladder cancer was not significant. However, confirmation of this finding is required because of the possible lack of statistical power owing to the small number of events.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
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Tseng CH, Tseng FH. Peroxisome proliferator-activated receptor agonists and bladder cancer: lessons from animal studies. JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH. PART C, ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS 2012; 30:368-402. [PMID: 23167631 DOI: 10.1080/10590501.2012.735519] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
This article reviews available animal studies on the possible link between the use of peroxisome proliferator-activated receptor (PPAR) agonists and bladder cancer, with further discussion on the possible implications to humans. Carcinogenicity studies suggest that the PPARγ agonist pioglitazone and dual PPARα/γ agonists such as ragaglitazar, muraglitazar, and naveglitazar may increase the risk of bladder cancer in a dose-responsive pattern in rats. It is interesting that bladder cancer related to PPAR agonists shows remarkable species- and sex-specificity and has a predilection to occur in the ventral dome of bladder in rodents. While male rats treated with pioglitazone or muraglitazar have a higher propensity to develop bladder cancer than female rats, mice of both sexes do not develop bladder cancer even when exposed to very high doses. Direct genotoxicity or cytotoxicity of PPAR agonists is unlikely to be the mode of action because most of the parent compounds or their metabolites of the PPAR agonists are neither mutagenic nor genotoxic, and they are rarely excreted in the urine; but a receptor-mediated PPAR effect cannot be excluded. Some suggest a "urolithiasis hypothesis" referring to the formation of urinary solids and calculi, which subsequently causes bladder necrosis, regenerative proliferation, hypertrophy, and cancer. However, whether these animal findings could have human relevance is not yet fully understood. Some argue that the urolithiasis-induced bladder cancer might be rat-specific and would probably not be applicable to humans. An effect of increased urinary growth factors induced by PPAR agonists has also been proposed, but this requires more investigations. Before fully clarified, a balance between the risks and benefits of the use of pioglitazone, an approved oral antidiabetic agent that has recently been linked to an increased but not yet confirmed risk of bladder cancer in humans, should be justified for individual use.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
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