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Wang K, Chen Y, Zhang M, Wang S, Yao S, Gong Z, Fei B, Huang Z. Metformin suppresses gastric cancer progression by disrupting the STAT1-PRMT1 axis. Biochem Pharmacol 2024; 226:116367. [PMID: 38876258 DOI: 10.1016/j.bcp.2024.116367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 05/24/2024] [Accepted: 06/11/2024] [Indexed: 06/16/2024]
Abstract
Gastric cancer (GC) is a common form of cancer and the leading cause of cancer-related deaths worldwide. Chemotherapy is the primary treatment for patients with unresectable or partially resectable GC. However, its adverse effects and chemoresistance greatly restrict its applicability and efficacy. Although HER2-targeted therapy and immunotherapy have been successfully used for GC treatment, their beneficial population is limited. To expand the range of cancer treatments, drug repurposing has emerged as a promising strategy. In this study, we evaluated the potential of Metformin, an oral anti-hyperglycemic agent, to suppress GC progression both in vivo and in vitro. Functional investigations showed that Metformin significantly inhibits GC proliferation and migration. Furthermore, we discovered that Metformin bound and disrupted STAT1 phosphorylation, inhibiting PRMT1 expression and consequently GC progression. In conclusion, our study not only provides further evidence for the anti-GC role of Metformin but also identifies the direct target mediating the tumor-inhibitory effects of Metformin in GC.
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Affiliation(s)
- Kaiqing Wang
- Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China; Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, China; Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China
| | - Yanyan Chen
- Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China; Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, China
| | - Meimei Zhang
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine, Xi'an 712046, Shaanxi, China
| | - Suzeng Wang
- Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China; Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, China; Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China
| | - Surui Yao
- Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China; Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, China
| | - Zhicheng Gong
- Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China; Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, China.
| | - Bojian Fei
- Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China.
| | - Zhaohui Huang
- Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China; Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, China.
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Ju M, Deng T, Jia X, Gong M, Li Y, Liu F, Yin Y. The causal relationship between anti-diabetic drugs and gastrointestinal disorders: a drug-targeted mendelian randomization study. Diabetol Metab Syndr 2024; 16:141. [PMID: 38918852 PMCID: PMC11201305 DOI: 10.1186/s13098-024-01359-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 05/24/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND The incidence of diabetic gastrointestinal diseases is increasing year by year. This study aimed to investigate the causal relationship between antidiabetic medications and gastrointestinal disorders, with the goal of reducing the incidence of diabetes-related gastrointestinal diseases and exploring the potential repurposing of antidiabetic drugs. METHODS We employed a two-sample Mendelian randomization (TSMR) design to investigate the causal association between antidiabetic medications and gastrointestinal disorders, including gastroesophageal reflux disease (GERD), gastric ulcer (GU), chronic gastritis, acute gastritis, Helicobacter pylori infection, gastric cancer (GC), functional dyspepsia (FD), irritable bowel syndrome (IBS), ulcerative colitis (UC), Crohn's disease (CD), diverticulosis, and colorectal cancer (CRC). To identify potential inhibitors of antidiabetic drug targets, we collected single-nucleotide polymorphisms (SNPs) associated with metformin, GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors, insulin, and its analogs, thiazolidinediones, sulfonylureas, and alpha-glucosidase inhibitors from published genome-wide association study statistics. We then conducted a drug-target Mendelian randomization (MR) analysis using inverse variance weighting (IVW) as the primary analytical method to assess the impact of these inhibitors on gastrointestinal disorders. Additionally, diabetes was selected as a positive control. RESULTS Sulfonylureas were found to significantly reduce the risk of CD (IVW: OR [95% CI] = 0.986 [0.978, 0.995], p = 1.99 × 10- 3), GERD (IVW: OR [95% CI] = 0.649 [0.452, 0.932], p = 1.90 × 10- 2), and chronic gastritis (IVW: OR [95% CI] = 0.991 [0.982, 0.999], p = 4.50 × 10- 2). However, they were associated with an increased risk of GU development (IVW: OR [95%CI] = 2 0.761 [1.259, 6.057], p = 1 0.12 × 10- 2). CONCLUSIONS The results indicated that sulfonylureas had a positive effect on the prevention of CD, GERD, and chronic gastritis but a negative effect on the development of gastric ulcers. However, our research found no causal evidence for the impact of metformin, GLP-1 agonists, SGLT2 inhibitors, DPP 4 inhibitors, insulin and its analogs, thiazolidinediones, or alpha-glucosidase inhibitors on gastrointestinal diseases.
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Affiliation(s)
- Mingyan Ju
- College of Acupuncture and moxibustion, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Tingting Deng
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xuemin Jia
- Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Menglin Gong
- College of Acupuncture and moxibustion, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yuying Li
- College of Acupuncture and moxibustion, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Fanjie Liu
- Bone Biomechanics Engineering Laboratory of Shandong Province, Shandong Medicinal Biotechnology Center (School of Biomedical Sciences), Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
| | - Ying Yin
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
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Xia B, Zeng P, Xue Y, Li Q, Xie J, Xu J, Wu W, Yang X. Identification of potential shared gene signatures between gastric cancer and type 2 diabetes: a data-driven analysis. Front Med (Lausanne) 2024; 11:1382004. [PMID: 38903804 PMCID: PMC11187270 DOI: 10.3389/fmed.2024.1382004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Accepted: 05/22/2024] [Indexed: 06/22/2024] Open
Abstract
Background Gastric cancer (GC) and type 2 diabetes (T2D) contribute to each other, but the interaction mechanisms remain undiscovered. The goal of this research was to explore shared genes as well as crosstalk mechanisms between GC and T2D. Methods The Gene Expression Omnibus (GEO) database served as the source of the GC and T2D datasets. The differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were utilized to identify representative genes. In addition, overlapping genes between the representative genes of the two diseases were used for functional enrichment analysis and protein-protein interaction (PPI) network. Next, hub genes were filtered through two machine learning algorithms. Finally, external validation was undertaken with data from the Cancer Genome Atlas (TCGA) database. Results A total of 292 and 541 DEGs were obtained from the GC (GSE29272) and T2D (GSE164416) datasets, respectively. In addition, 2,704 and 336 module genes were identified in GC and T2D. Following their intersection, 104 crosstalk genes were identified. Enrichment analysis indicated that "ECM-receptor interaction," "AGE-RAGE signaling pathway in diabetic complications," "aging," and "cellular response to copper ion" were mutual pathways. Through the PPI network, 10 genes were identified as candidate hub genes. Machine learning further selected BGN, VCAN, FN1, FBLN1, COL4A5, COL1A1, and COL6A3 as hub genes. Conclusion "ECM-receptor interaction," "AGE-RAGE signaling pathway in diabetic complications," "aging," and "cellular response to copper ion" were revealed as possible crosstalk mechanisms. BGN, VCAN, FN1, FBLN1, COL4A5, COL1A1, and COL6A3 were identified as shared genes and potential therapeutic targets for people suffering from GC and T2D.
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Affiliation(s)
- Bingqing Xia
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Ping Zeng
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yuling Xue
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qian Li
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, China
| | - Jianhui Xie
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, China
| | - Jiamin Xu
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, China
| | - Wenzhen Wu
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, China
| | - Xiaobo Yang
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, China
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Kwon Y, Ha J, Kim D, Hwang J, Park SH, Kwon JW, Park S. The association between weight change after gastric cancer surgery and type 2 diabetes risk: A nationwide cohort study. J Cachexia Sarcopenia Muscle 2023; 14:826-834. [PMID: 36864634 PMCID: PMC10067472 DOI: 10.1002/jcsm.13206] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 11/02/2022] [Accepted: 02/06/2023] [Indexed: 03/04/2023] Open
Abstract
BACKGROUND Although gastric cancer patients generally experience drastic weight decrease post-gastrectomy, the impact of weight decrease on type 2 diabetes risk remains unclear. We investigated the type 2 diabetes risk after gastric cancer surgery according to postoperative weight decrease in gastric cancer survivors in South Korea, the country with the world's highest rate of gastric cancer survival. METHODS This retrospective nationwide cohort study included gastric cancer surgery recipients between 2004 and 2014 who survived for ≥5 years post-surgery. We included patients without a history of diabetes at the time of surgery and those who had not received adjuvant chemotherapy before or after the surgery. Postoperative weight loss was defined as the per cent body weight loss at 3 years post-surgery compared with the baseline. The type 2 diabetes risk was evaluated using Cox regression analyses for five groups of postoperative weight decrease. RESULTS In 5618 included gastric cancer surgery recipients (mean age, 55.7 [standard deviation, SD, 10.9] years; 21.9% female; mean body mass index, 23.7 [SD, 2.9] kg/m2 ), 331 patients (5.9%) developed postoperative type 2 diabetes during follow-up duration of 8.1 years (median; interquartile range, 4.8 years; maximum, 15.2 years). Compared with those who gained weight post-surgery, patients with ≥ -15% to < -10% of postoperative weight decrease (hazard ratio, 0.65; 95% confidence interval, 0.49-0.87; P = 0.004) had the lowest type 2 diabetes risk. A non-linear association occurred between postoperative weight decrease and the type 2 diabetes risk in gastrectomy recipients (Akaike's information criterion [AIC] for non-linear model, 5423.52; AIC for linear model, 5425.61). CONCLUSIONS A U-shaped non-linear association occurred between the type 2 diabetes risk and postoperative weight decrease in gastric cancer survivors who underwent gastrectomy. The lowest type 2 diabetes risk occurred in patients with ≥ -15% to < -10% of postoperative weight decrease at 3 years.
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Affiliation(s)
- Yeongkeun Kwon
- Division of Foregut Surgery, Korea University College of Medicine, Seoul, South Korea.,Center for Obesity and Metabolic Diseases, Korea University Anam Hospital, Seoul, South Korea.,Gut & Metabolism Laboratory, Korea University College of Medicine, Seoul, South Korea
| | - Jane Ha
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, United States
| | - Dohyang Kim
- Department of Statistics, Daegu University, Gyeongsan, South Korea
| | - Jinseub Hwang
- Department of Statistics, Daegu University, Gyeongsan, South Korea
| | - Shin-Hoo Park
- Division of Foregut Surgery, Korea University College of Medicine, Seoul, South Korea.,Center for Obesity and Metabolic Diseases, Korea University Anam Hospital, Seoul, South Korea.,Gut & Metabolism Laboratory, Korea University College of Medicine, Seoul, South Korea
| | - Jin-Won Kwon
- BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, South Korea
| | - Sungsoo Park
- Division of Foregut Surgery, Korea University College of Medicine, Seoul, South Korea.,Center for Obesity and Metabolic Diseases, Korea University Anam Hospital, Seoul, South Korea.,Gut & Metabolism Laboratory, Korea University College of Medicine, Seoul, South Korea
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Remission of type 2 diabetes after gastrectomy for gastric cancer: diabetes prediction score. Gastric Cancer 2022; 25:265-274. [PMID: 34296379 DOI: 10.1007/s10120-021-01216-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 07/08/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Although type 2 diabetes (T2D) remission after gastric cancer surgery has been reported, little is known about the predictors of postoperative T2D remission. METHODS This study used data from a nationwide cohort provided by the National Health Insurance Service in Korea. We developed a diabetes prediction (DP) score, which predicted postoperative T2D remissions using a logistic regression model based on preoperative variables. We applied machine-learning algorithms [random forest, XGboost, and least absolute shrinkage and selection operator (LASSO) regression] and compared their predictive performances with those of the DP score. RESULTS The DP score comprised five parameters: baseline body mass index (< 25 or ≥ 25 kg/m2), surgical procedures (subtotal or total gastrectomy), age (< 65 or ≥ 65 years), fasting plasma glucose levels (≤ 130 or > 130 mg/dL), and antidiabetic medications (combination therapy including sulfonylureas, combination therapy not including sulfonylureas, single sulfonylurea, or single non-sulfonylurea]). The DP score showed a clinically useful predictive performance for T2D remission at 3 years after surgery [training cohort: area under the receiver operating characteristics (AUROC) 0.73, 95% confidence interval (CI), 0.71-0.75; validation cohort: AUROC 0.72, 95% CI 0.69-0.75], which was comparable to that of the machine-learning models (random forest: AUROC 0.71, 95% CI 0.68-0.74; XGboost: AUROC 0.70, 95% CI 0.67-0.73; LASSO regression: AUROC 0.75, 95% CI 0.73-0.78 in the validation cohort). It also predicted the T2D remission at 6 and 9 years after surgery. CONCLUSIONS The DP score is a useful scoring system for predicting T2D remission after gastric cancer surgery.
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Rojas A, Lindner C, Schneider I, Gonzàlez I, Araya H, Morales E, Gómez M, Urdaneta N, Araya P, Morales MA. Diabetes mellitus contribution to the remodeling of the tumor microenvironment in gastric cancer. World J Gastrointest Oncol 2021; 13:1997-2012. [PMID: 35070037 PMCID: PMC8713306 DOI: 10.4251/wjgo.v13.i12.1997] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 06/10/2021] [Accepted: 10/27/2021] [Indexed: 02/06/2023] Open
Abstract
Compelling pieces of evidence derived from both clinical and experimental research has demonstrated the crucial contribution of diabetes mellitus (DM) as a risk factor associated with increased cancer incidence and mortality in many human neoplasms, including gastric cancer (GC). DM is considered a systemic inflammatory disease and therefore, this inflammatory status may have profound effects on the tumor microenvironment (TME), particularly by driving many molecular mechanisms to generate a more aggressive TME. DM is an active driver in the modification of the behavior of many cell components of the TME as well as altering the mechanical properties of the extracellular matrix (ECM), leading to an increased ECM stiffening. Additionally, DM can alter many cellular signaling mechanisms and thus favoring tumor growth, invasion, and metastatic potential, as well as key elements in regulating cellular functions and cross-talks, such as the microRNAs network, the production, and cargo of exosomes, the metabolism of cell stroma and resistance to hypoxia. In the present review, we intend to highlight the mechanistic contributions of DM to the remodeling of TME in GC.
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Affiliation(s)
- Armando Rojas
- Biomedical Research Lab., Medicine Faculty, Catholic University of Maule, Talca 34600000, Chile
| | - Cristian Lindner
- Biomedical Research Lab., Medicine Faculty, Catholic University of Maule, Talca 34600000, Chile
| | - Iván Schneider
- Biomedical Research Lab., Medicine Faculty, Catholic University of Maule, Talca 34600000, Chile
| | - Ileana Gonzàlez
- Biomedical Research Lab., Medicine Faculty, Catholic University of Maule, Talca 34600000, Chile
| | - Hernan Araya
- Department of Clinical Sciences, Medicine Faculty, Catholic University of Maule, Talca 34600000, Chile
- Servicio de Oncología, Hospital Regional de Talca, Talca 34600000, Chile
| | - Erik Morales
- Biomedical Research Lab., Medicine Faculty, Catholic University of Maule, Talca 34600000, Chile
- Servicio de Anatomía Patologica, Hospital Regional de Talca, Talca 34600000, Chile
| | - Milibeth Gómez
- Department of Clinical Sciences, Medicine Faculty, Catholic University of Maule, Talca 34600000, Chile
- Servicio de Oncología, Hospital Regional de Talca, Talca 34600000, Chile
| | - Nelson Urdaneta
- Department of Clinical Sciences, Medicine Faculty, Catholic University of Maule, Talca 34600000, Chile
- Servicio de Oncología, Hospital Regional de Talca, Talca 34600000, Chile
| | - Paulina Araya
- Biomedical Research Lab., Medicine Faculty, Catholic University of Maule, Talca 34600000, Chile
| | - Miguel Angel Morales
- Department of Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, University of Chile, Santiago 8320000, Chile
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Zhang Y, Song M, Yuan C, Chan AT, Schernhammer ES, Wolpin BM, Stampfer MJ, Meyerhardt JA, Fuchs CS, Roberts SB, Rimm EB, Willett WC, Hu FB, Giovannucci EL, Ng K. Unrestrained eating behavior and risk of mortality: A prospective cohort study. Clin Nutr 2021; 40:5419-5429. [PMID: 34653818 PMCID: PMC8571025 DOI: 10.1016/j.clnu.2021.09.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 08/30/2021] [Accepted: 09/10/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND & AIMS Unrestrained eating behavior has been thought to be a proxy for diet frequency, timing, and caloric intake. We investigated the association of unrestrained eating with mortality risk in the Nurses' Health Study prospectively. METHODS During follow-up (1994-2016), 21,953 deaths were documented among 63,999 eligible participants in analyses of eating anything at any time, 22,120 deaths were documented among 65,839 participants in analyses of no concern with figure change. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. RESULTS Eating anything at any time was associated with an increased mortality from cancer (overall HR, 95%CI: 1.07, 1.00-1.13; driven by gastrointestinal tract cancer: 1.30, 1.10-1.54) and respiratory disease (1.16, 1.05-1.29), and decreased cardiovascular disease-specific mortality (0.92, 0.86-0.99), compared to those without this behavior; however, no association was observed between this behavior and all-cause mortality (1.02, 0.99-1.05). Women who reported having no concern with figure change experienced higher risk of mortality from all-cause (1.08, 1.05-1.11), cancer (1.08, 1.02-1.14), and respiratory disease (1.18, 1.08-1.30), compared to those not reporting this behavior. Their combined effect was associated with a higher all-cause (1.09, 1.04-1.14), cancer-specific (overall: 1.18, 1.09-1.28; gastrointestinal tract cancer: 1.36, 1.08-1.71; lung cancer: 1.09; 1.04-1.14), and respiratory disease-specific (1.30, 1.13-1.50) mortality, and was inversely associated with cardiovascular disease-specific mortality (0.88, 0.80-0.98), compared to those exhibiting the opposite. CONCLUSIONS Unrestrained eating was associated with increased risk of all-cause, cancer-specific (particularly for gastrointestinal tract cancer and lung cancer), and respiratory disease-specific mortality, and decreased risk of cardiovascular disease-specific mortality.
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Affiliation(s)
- Yin Zhang
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
| | - Mingyang Song
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
| | - Chen Yuan
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Andrew T Chan
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Eva S Schernhammer
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Center for Public Health, Medical University of Vienna, Vienna, Austria
| | - Brian M Wolpin
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Meir J Stampfer
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
| | - Jeffrey A Meyerhardt
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Charles S Fuchs
- Department of Medical Oncology, Smilow Cancer Hospital and Yale Cancer Center, New Haven, CT, USA; Department of Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Susan B Roberts
- USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA
| | - Eric B Rimm
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
| | - Walter C Willett
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
| | - Frank B Hu
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
| | - Edward L Giovannucci
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
| | - Kimmie Ng
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
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Tu CL, Sue SP, Hsu WH, Huang HY, Wen WL, Lin IT, Chen KH, Sheu NW, Huang SH, Lee MY. Causes of in-hospital death in patients with type 2 diabetes with microvascular and macrovascular complications in Taiwan. Int J Clin Pract 2021; 75:e14491. [PMID: 34115914 DOI: 10.1111/ijcp.14491] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 06/10/2021] [Indexed: 11/29/2022] Open
Abstract
AIMS Diabetes mellitus is a major cause of death worldwide, including Taiwan. The mortality data of the subsets of patients who suffered from microvascular or macrovascular complications is limited. The aim of this study was to investigate the causes of in-hospital death of patients with type 2 diabetes, especially the patients with microvascular, macrovascular and both micro-macrovascular complications. METHODS A total of 12 159 patients with type 2 diabetes were identified from the Taiwan National Health Insurance Research Database (NHIRD) to analyse the causes of death. Type 2 diabetic subjects with microvascular, macrovascular and both micro-macrovascular complications were further classified and compared to patients without microvascular and macrovascular complications in the logistic regression analysis of the risk of death. RESULTS Pneumonia increased risk of in-hospital death in patients with microvascular, macrovascular and both micro-macrovascular complications, with adjusted odds ratios (AORs) of 2.13 (95% confidence interval [CI] 1.09-4.18), 3.26 (1.71-6.24) and 3.96 (2.17-7.22), respectively. Septicaemia increased risk of in-hospital death in patients with macrovascular (AOR 2.57 [1.31-5.04]) and both micro-macrovascular complications (AOR 4.69 [2.58-8.50]). CONCLUSION Pneumonia increased risk of in-hospital death among the type 2 diabetic patients with microvascular, macrovascular and both micro-macrovascular complications. Therefore, efforts aim at preventing pneumonia or decreasing its severity may increase survival.
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Affiliation(s)
- Ching-Ling Tu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Shu-Ping Sue
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Wei-Hao Hsu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsing-Yi Huang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Wei-Lun Wen
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - I-Ting Lin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Kuan-Hsuan Chen
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Nai-Wei Sheu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shu-Heng Huang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Mei-Yueh Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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9
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Aumpan N, Vilaichone RK, Pornthisarn B, Chonprasertsuk S, Siramolpiwat S, Bhanthumkomol P, Nunanan P, Issariyakulkarn N, Ratana-Amornpin S, Miftahussurur M, Mahachai V, Yamaoka Y. Predictors for regression and progression of intestinal metaplasia (IM): A large population-based study from low prevalence area of gastric cancer (IM-predictor trial). PLoS One 2021; 16:e0255601. [PMID: 34379655 PMCID: PMC8357097 DOI: 10.1371/journal.pone.0255601] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 07/19/2021] [Indexed: 12/12/2022] Open
Abstract
Background Gastric intestinal metaplasia (IM) can lead to gastric cancer. Until now, there have been limited studies of predictors for regression and progression of IM. This study aimed to determine risk factors associated with regression or progression of IM for guiding proper management and prevention of gastric cancer. Methods 2,025 patients undergoing gastroscopy in Thammasat University Hospital, Thailand were enrolled during September 2017-August 2019. Patients’ data including baseline characteristics, laboratory results, and histopathology of gastric biopsies from University medical database were extensively reviewed. Results 2,025 patients had mean age of 61.3 years and 44.2% were males. Overall H. pylori prevalence was 47.5%. There were 1,551(76.6%) patients with chronic gastritis and 361(17.8%) with IM. Of 400 patients with chronic gastritis having follow-up endoscopy and repeated gastric biopsies, 104(26%) had persistent H. pylori infection and 27(26%) developed IM during mean follow-up time of 24 months. Persistent H. pylori infection was significantly associated with development of IM (OR 3.16, 95%CI 1.56–6.39, p = 0.001). Regression, persistence, and progression of IM were demonstrated in 57.3%, 39.2%, and 3.5% of patients, respectively. Age >65 years, persistent H. pylori infection, and diabetes mellitus were significantly associated with persistent IM or progression to dysplasia with OR 2.47(95%CI 1.33–4.61, p = 0.004), OR 2.64(95%CI 1.13–6.18, p = 0.025), and OR 2.54(95%CI 1.16–5.54, p = 0.019), respectively. Patients without H. pylori infection had more IM regression than patients with persistent infection (60.4%vs.39.4%, p = 0.035). Patients with persistent H. pylori infection significantly had higher IM progression to dysplasia (15.2%vs.2.1%; OR 11.15, 95%CI 1.18–105.24, p = 0.035) than noninfected. During 24 months of study, 30 patients (1.5%) were diagnosed with gastric cancer. Conclusion Regression of IM could be achieved by successful H. pylori eradication. Persistent H. pylori infection was significantly associated with development and progression of IM to dysplasia. Age >65 years and diabetes mellitus were also significant predictors for IM progression.
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Affiliation(s)
- Natsuda Aumpan
- Center of Excellence in Digestive Diseases and Gastroenterology, Faculty of Medicine, Thammasat University, Pathumthani, Thailand
| | - Ratha-korn Vilaichone
- Center of Excellence in Digestive Diseases and Gastroenterology, Faculty of Medicine, Thammasat University, Pathumthani, Thailand
- Chulabhorn International College of Medicine (CICM), Thammasat University, Pathumthani, Thailand
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- * E-mail:
| | - Bubpha Pornthisarn
- Center of Excellence in Digestive Diseases and Gastroenterology, Faculty of Medicine, Thammasat University, Pathumthani, Thailand
| | - Soonthorn Chonprasertsuk
- Center of Excellence in Digestive Diseases and Gastroenterology, Faculty of Medicine, Thammasat University, Pathumthani, Thailand
| | - Sith Siramolpiwat
- Center of Excellence in Digestive Diseases and Gastroenterology, Faculty of Medicine, Thammasat University, Pathumthani, Thailand
- Chulabhorn International College of Medicine (CICM), Thammasat University, Pathumthani, Thailand
| | - Patommatat Bhanthumkomol
- Center of Excellence in Digestive Diseases and Gastroenterology, Faculty of Medicine, Thammasat University, Pathumthani, Thailand
| | - Pongjarat Nunanan
- Center of Excellence in Digestive Diseases and Gastroenterology, Faculty of Medicine, Thammasat University, Pathumthani, Thailand
| | - Navapan Issariyakulkarn
- Center of Excellence in Digestive Diseases and Gastroenterology, Faculty of Medicine, Thammasat University, Pathumthani, Thailand
| | - Sarita Ratana-Amornpin
- Center of Excellence in Digestive Diseases and Gastroenterology, Faculty of Medicine, Thammasat University, Pathumthani, Thailand
| | - Muhammad Miftahussurur
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Varocha Mahachai
- Chulabhorn International College of Medicine (CICM), Thammasat University, Pathumthani, Thailand
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Japan
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10
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Tseng CH. The Relationship between Diabetes Mellitus and Gastric Cancer and the Potential Benefits of Metformin: An Extensive Review of the Literature. Biomolecules 2021; 11:1022. [PMID: 34356646 PMCID: PMC8301937 DOI: 10.3390/biom11071022] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 07/02/2021] [Accepted: 07/08/2021] [Indexed: 12/14/2022] Open
Abstract
The objective of this review is to summarize the findings of published research that investigated the relationship between diabetes mellitus and gastric cancer (GCa) and the potential benefits of metformin on GCa. Related literature has been extensively reviewed, and findings from studies investigating the relationship between diabetes mellitus and GCa suggest that hyperglycemia, hyperinsulinemia and insulin resistance are closely related to the development of GCa. Although not supported by all, most observational studies suggest an increased risk of GCa in patients with type 2 diabetes mellitus, especially in women and in Asian populations. Incidence of second primary malignancy diagnosed after GCa is significantly higher in diabetes patients. Diabetes patients with GCa may have more complications after gastrectomy or chemotherapy and they may have a poorer prognosis than patients with GCa but without diabetes mellitus. However, glycemic control may improve in the diabetes patients with GCa after receiving gastrectomy, especially after procedures that bypass the duodenum and proximal jejunum, such as Roux-en-Y gastric bypass or Billroth II reconstruction. The potential links between diabetes mellitus and GCa may involve the interactions with shared risk factors (e.g., obesity, hyperglycemia, hyperinsulinemia, insulin resistance, high salt intake, smoking, etc.), Helicobacter pylori (HP) infection, medications (e.g., insulin, metformin, statins, aspirin, proton pump inhibitors, antibiotics, etc.) and comorbidities (e.g., hypertension, dyslipidemia, vascular complications, heart failure, renal failure, etc.). With regards to the potential benefits of metformin on GCa, results of most observational studies suggest a reduced risk of GCa associated with metformin use in patients with T2DM, which can be supported by evidence derived from many in vitro and animal studies. Metformin use may also reduce the risk of HP infection, an important risk factor of GCa. In patients with GCa, metformin users may have improved survival and reduced recurrence. More studies are required to clarify the pathological subtypes/anatomical sites of GCa associated with type 2 diabetes mellitus or prevented by metformin, to confirm whether GCa risk can also be increased in patients with type 1 diabetes mellitus and to explore the possible role of gastric microbiota in the development of GCa.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 10051, Taiwan; ; Tel.: +886-2-2388-3578
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10051, Taiwan
- Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan 350, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei 100, Taiwan
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11
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Kwon Y, Kwon JW, Kim D, Ha J, Park SH, Hwang J, Heo Y, Park S. Predictors of Remission and Relapse of Diabetes after Conventional Gastrectomy for Gastric Cancer: Nationwide Population-Based Cohort Study. J Am Coll Surg 2021; 232:973-981.e2. [PMID: 33831541 DOI: 10.1016/j.jamcollsurg.2021.03.019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 03/06/2021] [Accepted: 03/10/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND We investigated whether preoperative clinical parameters predict diabetes remission and relapse after conventional gastrectomy for cancer and whether postoperative weight changes influence diabetes remission and relapse. STUDY DESIGN This study included 5,150 patients with diabetes who underwent gastrectomy for cancer from 2004 to 2014. Diabetes remission was defined in 3 ways, according to postoperative antidiabetic medication and fasting plasma glucose (FPG) levels. Diabetes relapse was defined as reinitiating antidiabetic medication among patients in diabetes remission. RESULTS Six predictors (higher body mass index [BMI], total gastrectomy, younger age, FPG levels, number of oral hypoglycemic agents [OHAs], and no insulin use) of diabetes remission increased the likelihood of remission by >13-fold (odds ratio [OR], 13.67; 95% confidence interval [CI], 8.65‒19.11). Three factors (younger age, lower FPG levels, and use of only 1 OHA) predicted a 58% decreased likelihood of diabetes relapse (hazard ratio, 0.42; 95% CI 0.35‒0.48). The lowest interval of postoperative BMI decrease (<-20%) showed a >3-fold increased likelihood of diabetes remission than the highest interval (≥-5%; OR 3.14; 95% CI 2.08‒4.75), independent of baseline BMI. CONCLUSIONS Six variables (BMI, type of gastrectomy, age, FPG levels, number of OHAs used, and insulin use/non-use), and 3 variables (age, FPG levels, number of OHAs used) significantly predict diabetes remission and relapse after gastrectomy for cancer, respectively. Greater postoperative weight decrease may increase the likelihood of diabetes remission, independent of baseline weight. Our results may serve as a basis for the establishment of diabetes and weight management strategies after conventional gastrectomy for cancer.
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Affiliation(s)
- Yeongkeun Kwon
- Division of Foregut Surgery, Korea University College of Medicine, Seoul, Korea; Center for Obesity and Metabolic Diseases, Korea University Anam Hospital, Seoul, Korea
| | - Jin-Won Kwon
- BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea
| | - Dohyang Kim
- Department of Statistics, Daegu University, Gyeongbuk, Korea
| | - Jane Ha
- Division of Foregut Surgery, Korea University College of Medicine, Seoul, Korea; Center for Obesity and Metabolic Diseases, Korea University Anam Hospital, Seoul, Korea
| | - Shin-Hoo Park
- Division of Foregut Surgery, Korea University College of Medicine, Seoul, Korea; Center for Obesity and Metabolic Diseases, Korea University Anam Hospital, Seoul, Korea
| | - Jinseub Hwang
- Department of Statistics, Daegu University, Gyeongbuk, Korea
| | - Yoonseok Heo
- Department of Surgery, Inha University School of Medicine, Incheon, Korea
| | - Sungsoo Park
- Division of Foregut Surgery, Korea University College of Medicine, Seoul, Korea; Center for Obesity and Metabolic Diseases, Korea University Anam Hospital, Seoul, Korea.
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12
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Al-Mofarji ST, Hussien H, Mohamed N, Hantoosh S, Abass M, Ali A. The association between gastric bacterial infection and low level of vitamin D among patients with type 2 diabetes mellitus. BAGHDAD JOURNAL OF BIOCHEMISTRY AND APPLIED BIOLOGICAL SCIENCES 2021. [DOI: 10.47419/bjbabs.v2i01.32] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Objectives: The present research aimed to find an association between infection by Helicobacter pylori and vitamin D deficiency in type 2 diabetic Iraqis attending Al-Yarmouk Teaching Hospital.
Methods: According to fasting blood glucose, the samples were divided into a non-diabetic group with ten diabetic individuals and a diabetic group with thirty individuals.
Results: The anti-H. pylori (IgG) levels were 86.77±58.62 NTU/μL in diabetic patients compared with 10.12_7.40 NTU/μL in non-diabetic group. Vitamin D levels were decreased significantly in infected patients compared to non-infected subjects.
Conclusion: The H. pylori-infected patients have recorded the lowest level of vitamin D than non-infected individuals.
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13
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Sheng L, Peng H, Pan Y, Wang C, Zhu Y. Evaluating the effect of diabetes on the prognosis of gastric cancer using a propensity score matching method. J Gastrointest Oncol 2020; 11:999-1008. [PMID: 33209493 DOI: 10.21037/jgo-20-375] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Background Gastric cancer (GC) is one of the malignant tumors with high incidence in China. At present, the relationship between type 2 diabetes (T2DM) and the therapeutic effect of various malignant tumors has attracted more and more attention. This study aimed to investigate whether T2DM is a prognostic factor for patients with GC. Methods Patients who had GC and who were admitted to our hospital from November 2008 to December 2015 were included in the study. Among these patients, 84 patients GC complicated with T2DM (GC + T2DM) were enrolled in the observation group, and 215 patients with normal blood glucose were enrolled in the control group. Patients' general information was collected by referring to their electronic and paper medical records, and their living status was followed up by conducting a telephone survey, referring to their hospitalization record, and performing an outpatient review. A propensity score matching method was used to select a 1:1 matched control for each patient with GC and diabetes. An overall survival curve was established using the Kaplan-Meier method. The survival rate was compared via a log-rank test. A Cox proportional hazards regression model was used to the analyse single and multiple factors affecting patient outcomes. Results Before matching was conducted, the differences in gender, stage, treatment, and comorbidity were found to be statistically significant (P>0.05). After matching was completed, the clinical data and pathological differences between the two groups were not statistically significant (P<0.05). A histogram matching the pre- and post-propensity scores showed that the matching was successful. The results of the Cox regression model revealed that grouping, pathological type, and treatment were the independent risk factors of the survival of patients with GC. Survival analysis found that the 3-year, 5-year, and overall survival rates of the observation group were significantly lower than those of the control group (P<0.05). Conclusions T2DM plays an important role in the development of GC, and is a prognostic factor among patients with GC.
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Affiliation(s)
- Lili Sheng
- Department of Oncology, the First Affiliated Hospital of Wannan Medical College, Wuhu, China
| | - Hui Peng
- Department of Oncology, the First Affiliated Hospital of Wannan Medical College, Wuhu, China
| | - Yang Pan
- Wannan Medical College, Wuhu, China
| | | | - Yiping Zhu
- Department of Oncology, the First Affiliated Hospital of Wannan Medical College, Wuhu, China
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14
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Chung WS, Le PH, Kuo CJ, Chen TH, Kuo CF, Chiou MJ, Chou WC, Yeh TS, Hsu JT. Impact of Metformin Use on Survival in Patients with Gastric Cancer and Diabetes Mellitus Following Gastrectomy. Cancers (Basel) 2020; 12:2013. [PMID: 32717852 PMCID: PMC7465508 DOI: 10.3390/cancers12082013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 07/15/2020] [Accepted: 07/21/2020] [Indexed: 12/19/2022] Open
Abstract
Studies have shown the anticancer effects of metformin in vitro. However, whether metformin can prevent cancer recurrence or prolong survival in patients with gastric cancer (GC) and diabetes mellitus (DM) post-gastrectomy remains unknown. We evaluated the beneficial effects of metformin in patients with GC and DM post-gastrectomy. We recruited 2400 patients with GC (1749 without DM, 651 with DM) who underwent surgery between 1997 and 2010. Patients with DM were stratified into metformin (group 1) and non-metformin (group 2) users. Their clinicopathological data were recorded prospectively, and demographics, recurrence-free survival (RFS), and cancer-specific survival (CSS) were compared. Tumour recurrence risk and cause of death were analysed between groups 1 and 2 among patients with DM stratified by tumour stage. We also compared RFS and overall survival among patients with and without DM. Tumour recurrence occurred in 201 patients with GC: 57 (25%) in group 1 and 144 (37%) in group 2. After adjusting for confounders, metformin significantly prolonged CSS (hazard ratio (HR) = 0.54, 95% confidence interval (CI) = 0.38-0.77) in patients with stage I-III GC and DM. In subgroup analysis, metformin users with stage III GC and DM had significantly prolonged CSS compared to non-metformin users (HR = 0.45, 95% CI = 0.30-0.68), with an insignificant difference in patients with stage I-II GC. Adjusted HRs for RFS and CSS were significantly lower in patients with stage I-III GC and DM than those in patients without DM (0.67 (95% CI = 0.54-0.92) and 0.62 (95% CI = 0.50-0.77), respectively), with an insignificant difference in patients with stage I GC. Metformin significantly reduces tumour recurrence risk and improves CSS in patients with stage III GC and DM post-gastrectomy. Further prospective studies may confirm the efficacy of metformin as an adjunctive treatment for advanced GC postoperatively.
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Affiliation(s)
- Wai-Shan Chung
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan; (W.-S.C.); (T.-S.Y.)
| | - Po-Hsien Le
- Department of Gastroenterology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan; (P.-H.L.); (C.-J.K.); (T.-H.C.)
| | - Chiang-Jung Kuo
- Department of Gastroenterology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan; (P.-H.L.); (C.-J.K.); (T.-H.C.)
| | - Tsung-Hsing Chen
- Department of Gastroenterology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan; (P.-H.L.); (C.-J.K.); (T.-H.C.)
| | - Chang-Fu Kuo
- Department of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan;
| | - Meng-Jiun Chiou
- Center for Artificial Intelligence in Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan 33305, Taiwan;
| | - Wen-Chi Chou
- Department of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan;
| | - Ta-Sen Yeh
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan; (W.-S.C.); (T.-S.Y.)
| | - Jun-Te Hsu
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan; (W.-S.C.); (T.-S.Y.)
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15
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Herold Z, Herold M, Nagy P, Patocs A, Doleschall M, Somogyi A. Serum chromogranin A level continuously rises with the progression of type 1 diabetes, and indicates the presence of both enterochromaffin-like cell hyperplasia and autoimmune gastritis. J Diabetes Investig 2020; 11:865-873. [PMID: 31883432 PMCID: PMC7378417 DOI: 10.1111/jdi.13203] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 12/05/2019] [Accepted: 12/22/2019] [Indexed: 02/05/2023] Open
Abstract
AIMS/INTRODUCTION The relationship of chromogranin A (CgA) levels above the normal range with various outcomes, such as glycated hemoglobin levels, enterochromaffin-like cell hyperplasia and autoimmune gastritis, was investigated in type 1 diabetes patients with special regard to the progression of comorbidities. MATERIALS AND METHODS A cohort study on 153 type 1 diabetes patients was carried out with a prospective branch on clinical and laboratory data, and a retrospective branch on histological data obtained by gastroscopy. RESULTS Patients with CgA levels above the upper limit of the normal range (n = 28) had significantly higher glycated hemoglobin levels (P = 0.0160) than those with CgA in the normal range (n = 125). The correlation between CgA and glycated hemoglobin was significant (P < 0.0001), but weak (R = +0.32). A slight, but steady elevation (P = 0.0410) in CgA level was observed to co-vary with the duration of type 1 diabetes. Enterochromaffin-like cell hyperplasia and autoimmune gastritis was significantly more frequent (P = 0.0087 for both) in the high CgA group. Detailed analyses on gastric tissue samples confirmed a progression of enterochromaffin-like cell hyperplasia (P = 0.0192) accompanied by CgA elevation (P = 0.0316). CONCLUSIONS The early detection and follow up of the later progression of enterochromaffin-like cell hyperplasia and autoimmune gastritis into gastric neuroendocrine tumors, which have ~100-fold greater incidence in type 1 diabetes patients, can be achieved by assessment of CgA levels. Therefore, the use of CgA could be considered as a novel auxiliary biomarker in the care of these type 1 diabetes complications.
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Affiliation(s)
- Zoltan Herold
- 2nd Department of Internal MedicineSemmelweis UniversityBudapestHungary
| | - Magdolna Herold
- 2nd Department of Internal MedicineSemmelweis UniversityBudapestHungary
| | - Peter Nagy
- 1st Department of Pathology and Experimental Cancer ResearchSemmelweis UniversityBudapestHungary
| | - Attila Patocs
- Department of Laboratory MedicineSemmelweis UniversityBudapestHungary
- Hereditary Tumors Research GroupEotvos Lorand Research Network and Semmelweis UniversityBudapestHungary
| | - Marton Doleschall
- Molecular Medicine Research GroupEotvos Lorand Research Network and Semmelweis UniversityBudapestHungary
| | - Aniko Somogyi
- 2nd Department of Internal MedicineSemmelweis UniversityBudapestHungary
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16
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Dulskas A, Patasius A, Linkeviciute-Ulinskiene D, Zabuliene L, Smailyte G. A cohort study of antihyperglycemic medication exposure and survival in patients with gastric cancer. Aging (Albany NY) 2019; 11:7197-7205. [PMID: 31518336 PMCID: PMC6756873 DOI: 10.18632/aging.102245] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 08/22/2019] [Indexed: 12/14/2022]
Abstract
Objective: We aimed to estimate survival in gastric cancer patients with type 2 diabetes mellitus (T2DM) using different antihyperglycemic medication. Methods: Patients with gastric cancer and diabetes between 2003-2013 were identified form The Lithuanian Cancer Registry and The National Health Insurance Fund database. Cohort members were classified into five groups: four groups of T2DM patients according to treatment: metformin users; metformin and other medication users; sulphonylurea users; insulin and other medication users; and non-diabetic group. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate gastric cancer-specific survival and overall survival. Results: 8423 patients met eligibility criteria. Survival analysis showed no differences in gastric cancer-specific survival between non-diabetic and diabetic patient groups. Better survival was observed in the groups of patients using antihyperglycemic medication combinations with metformin, metformin alone or insulin. Lowest survival was observed in diabetic patients who were sulphonylurea users. Survival analysis comparing overall survival between non-diabetic and diabetic patients (p = 0.89) showed no evidence of survival difference between groups and survival differences between antihyperglycemic medication user groups were of borderline significance (p = 0.052). Conclusions: Antihyperglycemic medication use was not associated with a significant effect on survival in patients with gastric cancer and T2DM.
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Affiliation(s)
- Audrius Dulskas
- Department of Abdominal and General Surgery and Oncology, National Cancer Institute, Vilnius LT-08406, Lithuania.,University of Applied Sciences, Faculty of Health Care, Vilnius ELT-08303, Lithuania.,Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius LT-03101, Lithuania
| | - Ausvydas Patasius
- Laboratory of Cancer Epidemiology, National Cancer Institute, Vilnius LT-08406, Lithuania.,Institute of Health Sciences, Faculty of Medicine, Vilnius University, Vilnius LT-03101, Lithuania
| | | | - Lina Zabuliene
- Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius LT-03101, Lithuania
| | - Giedre Smailyte
- Laboratory of Cancer Epidemiology, National Cancer Institute, Vilnius LT-08406, Lithuania.,Institute of Health Sciences, Faculty of Medicine, Vilnius University, Vilnius LT-03101, Lithuania
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17
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Karlin NJ, Buras MR, Kosiorek HE, Verona PM, Cook CB. Glycemic control and survival of patients with coexisting diabetes mellitus and gastric or esophageal cancer. Future Sci OA 2019; 5:FSO397. [PMID: 31285842 PMCID: PMC6609893 DOI: 10.2144/fsoa-2019-0038] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
AIM To examine effects of diabetes mellitus (DM) on survival in gastric or esophageal (GE) cancer and the cancers' effects on glycemic control. MATERIALS & METHODS Patients with GE cancer with and without DM were matched 1 to 1 (2006-2016). Characteristics were compared and survival assessed with Kaplan-Meier method and Cox regression. Mixed models compared hemoglobin A1c and glucose over time. RESULTS Among DM cases, mean hemoglobin A1c was 6.8% in the year after cancer diagnosis. Three-year overall survival was 46% with DM versus 52% without DM (hazard ratio [95% CI]: 1.95 [1.14-3.34]; p = 0.02). CONCLUSION GE cancer and its treatment did not affect glycemic control. Risks of death and progression were greater for patients with DM than patients without DM.
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Affiliation(s)
- Nina J Karlin
- Division of Hematology & Medical Oncology, Department of Internal Medicine, Mayo Clinic Hospital, Phoenix, AZ 85054, USA
- Author for correspondence:
| | - Matthew R Buras
- Division of Endocrinology, Department of Biostatistics, Mayo Clinic, Scottsdale, AZ 85259, USA
| | - Heidi E Kosiorek
- Division of Endocrinology, Department of Biostatistics, Mayo Clinic, Scottsdale, AZ 85259, USA
| | - Patricia M Verona
- Department of Information Technology, Department of Biostatistics, Mayo Clinic Hospital, Phoenix, AZ 85054, USA
| | - Curtiss B Cook
- Department of Internal Medicine, Division of Endocrinology, Mayo Clinic, Scottsdale, AZ 85259, USA
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18
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Affiliation(s)
- Yoon Jin Choi
- Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
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19
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Li P, Tong L, Song Y, Sun J, Shi J, Wu Z, Diao Y, Li Y, Wang Z. Long noncoding RNA H19 participates in metformin-mediated inhibition of gastric cancer cell invasion. J Cell Physiol 2018; 234:4515-4527. [PMID: 30192003 DOI: 10.1002/jcp.27269] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2017] [Accepted: 07/20/2018] [Indexed: 12/30/2022]
Abstract
Recent research suggests that the first-line oral antidiabetes drug metformin may prevent gastric cancer progression and improve prognosis. Many studies have also shown that long noncoding RNAs (lncRNAs) play important roles in many biological processes. Therefore, we aimed to explore whether lncRNAs participate in the mechanisms by which metformin affects gastric cancer cells. In the current study, we found that metformin significantly inhibited the cellular functions of gastric cancer cells through Cell Counting Kit-8 and invasion assays. We found that lncRNA H19 was greatly downregulated in gastric cancer cells treated with metformin using lncRNA microassays. Based on bioinformatics analyses of the Oncomine and The Cancer Genome Atlas databases, H19 is shown to be overexpressed in gastric cancer tissues, with increased expression of H19 relating to advanced pathological tumor stage and pathological tumor node metastasis stage, indicating that H19 may be associated with the invasive ability of gastric cancer. We knocked down H19 in AGS and SGC7901 cell lines and found that knocked-down H19 could decrease gastric cancer cell invasion and that metformin could not further decrease invasion after the knock down. Moreover, H19 depletion increased AMPK activation and decreased MMP9 expression, and metformin could not further activate AMPK or decrease MMP9 in H19 knocked-down gastric cancer cells. In summary, metformin has a profound antitumor effect on gastric cancer cells, and H19 is a key component in the process of metformin suppressing gastric cancer cell invasion.
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Affiliation(s)
- Peiwen Li
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang, China.,Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Linhao Tong
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Yongxi Song
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Jingxu Sun
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Jinxin Shi
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Zhonghua Wu
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Yao Diao
- Department of Nuclear Medicine, The First Hospital of China Medical University, Shenyang, China
| | - Yaming Li
- Department of Nuclear Medicine, The First Hospital of China Medical University, Shenyang, China
| | - Zhenning Wang
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang, China
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Li F, Du H, Li S, Liu J. The Association Between Metabolic Syndrome and Gastric Cancer in Chinese. Front Oncol 2018; 8:326. [PMID: 30191141 PMCID: PMC6116659 DOI: 10.3389/fonc.2018.00326] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 07/31/2018] [Indexed: 01/16/2023] Open
Abstract
Background: Metabolic syndrome (MetS) play a carcinogenic role in variety of cancers and influence the prognosis of cancer patients both systemically and hormonally. Methods: The data of clinicopathologic features and MetS of 808 gastric cancer patients and 1,146 randomly healthy controls were analyzed retrospectively. Results: Higher TG level, lower HDL-C level and higher hypertension frequency were observed in all gastric cancer patients when compared with healthy controls. While, gastric cancer patients had greater waist circumference only in females. Among three definitions of MetS, the MetS identified by the Chinese Diabetes Society (CDS) was associated with the most significant increasing risk of gastric cancer. Comparing all gastric cancer patients with healthy controls, OR of gastric cancer was enhanced by various individual components of the MetS, including higher TG level, lower HDL-C level, hypertension and diabetes; In male subgroup, OR of gastric cancer was enhanced by higher BMI, hypertension and diabetes; In females, OR of gastric cancer was enhanced by lower HDL-C, hypertension and diabetes. MetS was associated with poor differentiated carcinoma, more advanced pathological T, N stage and TNM stage of gastric cancer. Conclusion: The presence of MetS and its components were increased in gastric cancer, especially in gastric cancer patients with poor differentiation and advanced stage, which implies that metabolic disorder may play an important role in the development of gastric cancer.
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Affiliation(s)
- Fangxuan Li
- Department of Cancer Prevention, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Hui Du
- Department of Obstetrics and Gynecology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Shixia Li
- Department of Cancer Prevention, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Juntian Liu
- Department of Cancer Prevention, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
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21
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Tseng CH. Metformin and Helicobacter pylori Infection in Patients With Type 2 Diabetes. Diabetes Care 2018; 41:e42-e43. [PMID: 29437699 DOI: 10.2337/dc17-2551] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Accepted: 01/02/2018] [Indexed: 02/03/2023]
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, Zhunan, Taiwan
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Diabetes mellitus and the risk of gastric cancer: a meta-analysis of cohort studies. Oncotarget 2018; 8:44881-44892. [PMID: 28415651 PMCID: PMC5546528 DOI: 10.18632/oncotarget.16487] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2016] [Accepted: 03/14/2017] [Indexed: 02/06/2023] Open
Abstract
Studies examining the relationship between diabetes mellitus (DM) and the risk of gastric cancer incidence or gastric cancer mortality have produced inconsistent results. The purpose of this study was to evaluate the evidence regarding the relationship between DM and subsequent gastric cancer incidence or gastric cancer mortality risk on the basis of cohort studies. A systematic search of articles in PubMed, EmBase, the Cochrane Library, and reference lists was conducted to identify relevant literature. Twenty-two cohort studies reporting data on 8,559,861 participants were included in the study. Overall, participants with DM had little or no change in the risk of gastric cancer, or gastric cancer mortality. There was no evidence of difference in the RR for gastric cancer between men and women. Participants with DM had a non-significant trend towards an increased risk of gastric cancer mortality in men. There was no significant difference between men and women for this relationship. Finally, although subgroup analysis suggested DM was associated with a significant impact on gastric cancer incidence and gastric cancer mortality risk in several specific populations, a significance based on gender difference was not observed. In conclusion, DM might increase the risk of gastric cancer in men when the study used standard incidence/mortality ratio as effect estimate. Further, DM were associated with higher risk of gastric cancer mortality in men if the mean age at baseline less than 55.0 years, used RR or HR as effect estimate, the study adjusted smoking or not, and the study not adjusted alcohol drinking.
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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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Chen Q, Zhu L, Tang Y, Zhao Z, Yi T, Chen H. Preparation-related structural diversity and medical potential in the treatment of diabetes mellitus with ginseng pectins. Ann N Y Acad Sci 2017; 1401:75-89. [DOI: 10.1111/nyas.13424] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Revised: 05/30/2017] [Accepted: 06/05/2017] [Indexed: 01/12/2023]
Affiliation(s)
- Qilei Chen
- School of Chinese Medicine, Hong Kong Baptist University; Hong Kong Special Administrative Region; Hong Kong P.R. China
| | - Lin Zhu
- Shenzhen Research Institute; The Chinese University of Hong Kong; Shenzhen P.R. China
| | - Yina Tang
- Sichuan Academy of Chinese Medical Sciences; Sichuan P.R. China
| | - Zhongzhen Zhao
- School of Chinese Medicine, Hong Kong Baptist University; Hong Kong Special Administrative Region; Hong Kong P.R. China
| | - Tao Yi
- School of Chinese Medicine, Hong Kong Baptist University; Hong Kong Special Administrative Region; Hong Kong P.R. China
| | - Hubiao Chen
- School of Chinese Medicine, Hong Kong Baptist University; Hong Kong Special Administrative Region; Hong Kong P.R. China
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25
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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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Zhou JC, Guo JF, Teng RY, Wang QC, Wang J, Wei Q, Li ZD, Shen JG, Wang LB. New utility of an old marker: serum low-density lipoprotein predicts histopathological response of neoadjuvant chemotherapy in locally advanced gastric cancer. Onco Targets Ther 2016; 9:5041-7. [PMID: 27574445 PMCID: PMC4990386 DOI: 10.2147/ott.s97061] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Background Although the correlation between metabolic abnormality and gastric cancer has been extensively investigated, the question of whether metabolic parameters might influence the efficacy of chemotherapy in locally advanced gastric cancer is still unanswered. In our present study, we investigated the relationship between serum fasting glucose, lipid levels, and histopathological response of neoadjuvant chemotherapy (NAC) in locally advanced gastric cancers. Patients and methods A total of 128 patients were identified from a prospectively maintained database of patients with locally advanced gastric cancer who received NAC between July 2004 and December 2012. Histopathological response after NAC was analyzed according to Becker’s tumor-regression grade. Univariate analyses and multivariable regression analyses were performed to determine the correlation between tumor size, differentiation, fasting glucose, lipid levels, and tumor histopathological response after NAC. Results Univariate analysis revealed that low-density lipoprotein level and total cholesterol, as well as tumor size and differentiation, correlated significantly with histopathological response. Low-density lipoprotein levels and tumor size were found to be independent predictors for histopathological response, according to multivariable regression analyses. Conclusion In this observational, hypothesis-generating study, serum low-density lipoprotein measurement was found to be useful in predicting chemosensitivity to locally advanced gastric cancer patients undergoing NAC. Incorporation of serum low-density lipoprotein levels into individualized treatment protocols could be considered in clinical practice.
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Affiliation(s)
- Ji-Chun Zhou
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
| | - Ju-Feng Guo
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Department of Surgical Oncology, Hangzhou First People's Hospital, Hangzhou, People's Republic of China
| | - Rong-Yue Teng
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
| | - Qin-Chuan Wang
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
| | - Ji Wang
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
| | - Qun Wei
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Department of International Medicine and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Zi-Duo Li
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Dendritic Cell Biology and Therapeutic Group, ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia
| | - Jian-Guo Shen
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
| | - Lin-Bo Wang
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, People's Republic of China
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Tseng CH. Metformin reduces gastric cancer risk in patients with type 2 diabetes mellitus. Aging (Albany NY) 2016; 8:1636-1649. [PMID: 27587088 PMCID: PMC5032687 DOI: 10.18632/aging.101019] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2016] [Accepted: 08/19/2016] [Indexed: 04/15/2023]
Abstract
This retrospective cohort study investigated whether metformin may reduce gastric cancer risk by using the reimbursement databases of the Taiwan's National Health Insurance. Patients with type 2 diabetes diagnosed during 1999-2005 and newly treated with metformin (n=287971, "ever users of metformin") or other antidiabetic drugs (n=16217, "never users of metformin") were followed until December 31, 2011. The effect of metformin (for ever versus never users, and for tertiles of cumulative duration of therapy) was estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. Results showed that the respective numbers of incident gastric cancer in ever and never users were 759 (0.26%) and 89 (0.55%), with respective incidences of 55.26 and 122.53 per 100,000 person-years. The overall hazard ratio (95% confidence intervals) of 0.448 (0.359-0.558) suggested a significantly lower risk among ever users. In tertile analyses, hazard ratios (95% confidence intervals) for the first (＜21.47 months), second (21.47-45.97 months) and third (＞45.97 months) tertile of cumulative duration was 0.973 (0.773-1.224), 0.422 (0.331-0.537) and 0.120 (0.090-0.161), respectively, while compared to never users. In conclusion, metformin significantly reduces gastric cancer risk, especially when the cumulative duration is more than approximately 2 years.
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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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Sogabe M, Okahisa T, Kimura T, Okamoto K, Miyamoto H, Muguruma N, Takayama T. Influence of metabolic syndrome on upper gastrointestinal disease. Clin J Gastroenterol 2016; 9:191-202. [PMID: 27372302 DOI: 10.1007/s12328-016-0668-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2016] [Accepted: 06/19/2016] [Indexed: 12/22/2022]
Abstract
A recent increase in the rate of obesity as a result of insufficient physical exercise and excess food consumption has been seen in both developed and developing countries throughout the world. Additionally, the recent increased number of obese individuals with lifestyle-related diseases associated with abnormalities in glucose metabolism, dyslipidemia, and hypertension, defined as metabolic syndrome (MS), has been problematic. Although MS has been highlighted as a risk factor for ischemic heart disease and arteriosclerotic diseases, it was also recently shown to be associated with digestive system disorders, including upper gastrointestinal diseases. Unlike high body weight and high body mass index, abdominal obesity with visceral fat accumulation is implicated in the onset of various digestive system diseases because excessive visceral fat accumulation may cause an increase in intra-abdominal pressure, inducing the release of various bioactive substances, known as adipocytokines, including tumor necrosis factor-α, interleukin-6, resistin, leptin, and adiponectin. This review article focuses on upper gastrointestinal disorders and their association with MS, including obesity, visceral fat accumulation, and the major upper gastrointestinal diseases.
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Affiliation(s)
- Masahiro Sogabe
- Department of General Medicine and Community Health Science, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, Tokushima, 770-8503, Japan.
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
| | - Toshiya Okahisa
- Department of General Medicine and Community Health Science, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, Tokushima, 770-8503, Japan
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Tetsuo Kimura
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Koichi Okamoto
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Hiroshi Miyamoto
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Naoki Muguruma
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Tetsuji Takayama
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
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Zhang YC, Wei FX, Han W, Wei ZG, Wang HL, Wang MC, Zhang HH, Zhang YW, Xu XD. Impact of sub-gastrectomy on glucose regulation in gastric cancer patients with T2DM: a follow-up study. Int J Diabetes Dev Ctries 2015. [DOI: 10.1007/s13410-015-0437-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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Tsai MS, Wang YC, Kao YH, Jeng LB, Kao CH. Preexisting Diabetes and Risks of Morbidity and Mortality After Gastrectomy for Gastric Cancer: A Nationwide Database Study. Medicine (Baltimore) 2015; 94:e1467. [PMID: 26376386 PMCID: PMC4635800 DOI: 10.1097/md.0000000000001467] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The purpose of this study was to determine the risk of surgical mortality and morbidity in patients with diabetes mellitus (DM) undergoing a gastrectomy for gastric cancer (GC). Using the Taiwan National Health Insurance Research Database, we identified 6284 patients who underwent gastrectomy for GC from 1999 to 2010. In addition, we created a non-DM control cohort consisting of 6268 patients who received gastrectomy during the same period. Compared with the non-DM cohort, the DM cohort exhibited a higher prevalence of preoperative coexisting medical conditions, namely hypertension, hyperlipidemia, coronary artery disease, chronic kidney disease, chronic pulmonary disease, stroke, and cirrhosis. The odds ratio (OR) of 30-day postoperative mortality after gastrectomy in the DM cohort was 1.04 (95% confidence interval 0.78-1.40) after we adjusted for covariates. The DM cohort did not exhibit a significantly higher risk of 30-day postoperative morbidities. Further analysis revealed that only patients with a history of a DM-related coma exhibited a higher risk of 30-day postoperative mortality (adjusted OR 2.46, 95% confidence interval 1.10 - 5.54). Moreover, the risk of 90-day postoperative mortality was significantly higher in patients with DM-related eye involvement, coma, peripheral circulatory disease, and renal manifestations, in comparison with the non-DM cohort. The risk of 90-day mortality after gastrectomy for GC is higher in patients with DM-related manifestations than those without DM.
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Affiliation(s)
- Ming-Shian Tsai
- From the Department of Surgery (M-ST), E-Da Hospital and I-Shou University, Kaohsiung; Management Office for Health Data; College of Medicine (Y-CW), China Medical University, Taichung; Department of Medical Research (Y-HK), E-Da Hospital and I-Shou University, Kaohsiung; Department of Surgery (L-BJ), Organ Transplantation Center, China Medical University Hospital; Graduate Institute of Clinical Medical Science and School of Medicine (L-BJ, C-HK), College of Medicine, China Medical University; and Department of Nuclear Medicine and PET Center (C-HK), China Medical University Hospital, Taichung, Taiwan
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Zhou Y, Wang Y, Wang S, Shen L. Hyperglycemia Promotes Human Gastric Carcinoma Progression via Aquaporin 3. Dig Dis Sci 2015; 60:2338-45. [PMID: 25777259 DOI: 10.1007/s10620-015-3625-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2014] [Accepted: 03/03/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hyperglycemia plays an important role in the development of gastric carcinoma (GC). Aquaporin 3 (AQP3) is overexpressed in GC and involved in carcinogenesis and progression of GC. Hyperglycemia promotes AQP3 expression in human peritoneal mesothelial cells. AIMS To investigate whether hyperglycemia promotes progression of GC via AQP3. METHODS We enrolled 978 patients with GC and evaluated the correlation between preoperative fasting plasma glucose and clinicopathological features. AQP3 was detected by immunohistochemistry in human GC specimens. Western blotting and real-time quantitative polymerase chain reaction evaluated changes in AQP3 expression in human GC MGC803 and SGC7901 cells after co-culture with high glucose. Transwell migration and Cell Counting Kit-8 assays were used to determine migration and proliferation of GC cells. RESULTS Hyperglycemia (fasting plasma glucose ≥6.1 mM) correlated with tumor size, location, and pTNM stage. AQP3 expression in tumor tissue was associated with fasting plasma glucose levels. High glucose concentration upregulated AQP3 expression in a dose- and time-dependent manner. High glucose concentration promoted GC cell migration markedly, and AQP3 knockdown with siRNA could abolish the increase in cell migration. However, high glucose concentration inhibited cell proliferation, and AQP3 knockdown significantly enhanced the inhibitory effect of high glucose. The ERK and PI3K/AKT signaling pathways were involved in high glucose regulation of AQP3 in human GC cells. CONCLUSION Hyperglycemia promotes GC progress via AQP3. This improves our understanding of the mechanism of hyperglycemia-induced carcinogenesis and provides a potential therapeutic strategy for GC.
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Affiliation(s)
- Yangchun Zhou
- Division of Gastrointestinal Surgery, Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China,
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Liu X, Chen Z, Zhao X, Huang M, Wang C, Peng W, Yin J, Li J, He G, Li X, Zhu X. Effects of IGF2BP2, KCNQ1 and GCKR polymorphisms on clinical outcome in metastatic gastric cancer treated with EOF regimen. Pharmacogenomics 2015; 16:959-70. [PMID: 26115082 DOI: 10.2217/pgs.15.49] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
AIM The present study analyzed Type 2 diabetes mellitus (T2D)-related gene polymorphisms and their impacts on chemotherapeutic response and survival in patients with metastatic gastric cancer (MGC). PATIENTS & METHODS This retrospective study enrolled 108 MGC patients treated with first-line EOF chemotherapy (epirubicin, oxaliplatin and 5-fluorouracil combination chemotherapy). Eleven single nucleotide polymorphisms of five T2D-related genes were determined. RESULTS Among the 11 single nucleotide polymorphisms, three (IGF2BP2 rs4402960, IGF2BP2 rs6769511 and KCNQ1 rs163182) were significantly associated with disease control rate and two (GCKR rs780093 and rs780094) were significantly associated with progression-free and overall survival. CONCLUSION Our results suggest IGF2BP2 and KCNQ1 polymorphisms might be independent predictors of chemotherapeutic response, while GCKR polymorphisms might be independent predictors of survival in MGC patients treated with first-line EOF chemotherapy. Original submitted 30 June 2014; revision submitted 15 April 2015.
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Affiliation(s)
- Xin Liu
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Zhiyu Chen
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Xiaoying Zhao
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Mingzhu Huang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Chenchen Wang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Wei Peng
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Jiliang Yin
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Jin Li
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Guang He
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Xin Li
- Bio-X Center, Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China
| | - Xiaodong Zhu
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
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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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Oberaigner W, Ebenbichler C, Oberaigner K, Juchum M, Schönherr HR, Lechleitner M. Increased cancer incidence risk in type 2 diabetes mellitus: results from a cohort study in Tyrol/Austria. BMC Public Health 2014; 14:1058. [PMID: 25300498 PMCID: PMC4200218 DOI: 10.1186/1471-2458-14-1058] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Accepted: 10/01/2014] [Indexed: 12/13/2022] Open
Abstract
Background Recent meta-analyses revealed an association between type 2 diabetes mellitus (T2DM) and cancer. The strongest relationship was demonstrated for liver and pancreatic cancer, followed by endometrial cancer. We aimed at assessing the association between T2DM and cancer specifically for Tyrolean patients. Methods We investigated cancer incidence in Tyrolean subjects with T2DM by linking the data from the Diabetes and the Cancer Registries. 5709 T2DM patients were included and the sex- and age-adjusted standardized incidence ratio (SIR) was calculated, cancer incidence in the Tyrolean population serving as the standard. Endpoints were the time at which cancer was diagnosed, death or end of the observation period (31 December 2010). Results Site-specific analyses revealed statistically significantly elevated SIRs for cancer of the pancreas (1.78, 95% CI 1.02, 2.89) and corpus (1.79, 95% CI 1.15, 2.66) for women, and cancer of the liver (2.71, 95% CI 1.65, 4.18) and pancreas (1.87, 95% 1.11, 2.96) for men. Sub-analyses performed according to the time of diabetes diagnosis revealed that SIR was highest in the first year after diabetes diagnosis, but SIR was demonstrated to be elevated in women for cancer of the liver (SIR 3.37, 95% CI 1.24, 7.34) and corpus (SIR 1.94, 95% CI 1.09, 3.20) and in men for liver (SIR 2.71, 95% CI 1.40, 4.74) in the period more than five years after diabetes diagnosis. In addition, increased risk at borderline statistical significance was observed in females for liver cancer (SIR 2.40, 95% CI 0.96, 4.94) and cervical cancer (SIR 1.81, 95% CI 0.87, 3.32) and in males for kidney cancer (SIR 1.65, 95% CI 0.99, 2.57). Conclusion This study revealed a higher risk for cancer at certain sites in Tyrolean patients with T2DM. However, it is important to interpret the results with great caution due to inherent methodological problems. Optimized care programs for patients with T2DM should be integrated into the recommended procedures for cancer screening.
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Affiliation(s)
- Willi Oberaigner
- Department of Clinical Epidemiology of the Tyrolean State Hospitals Ltd, Cancer Registry of Tyrol, TILAK GmbH, Anichstrasse 35, Innsbruck, Austria.
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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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Wei ZW, Li JL, Wu Y, Xia GK, Schwarz RE, He YL, Zhang CH. Impact of pre-existing type-2 diabetes on patient outcomes after radical resection for gastric cancer: a retrospective cohort study. Dig Dis Sci 2014; 59:1017-24. [PMID: 24318804 DOI: 10.1007/s10620-013-2965-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Accepted: 11/15/2013] [Indexed: 12/29/2022]
Abstract
BACKGROUND The aim of this study was to evaluate the impact of pre-existing type-2 diabetes on postoperative recovery and prognosis in gastric cancer (GC) patients who underwent radical gastrectomy. RESEARCH DESIGN AND METHODS From June 2001 to June 2011, a total of 1,014 eligible patients were enrolled. Among them, 67 patients were diagnosed with type-2 diabetes. The clinicopathologic features and prognostic data were compared between patients with type-2 diabetes (the DM group) and without diabetes (the non-DM group). RESULTS Median survival was 68.3 months. The 5-year overall survival in the DM group was similar to that in the non-DM group (52.1 vs. 53.0 %, p = 0.411). Propensity score matching analysis demonstrated that the hazard ratio of death in the DM group was 1.191 (95 % confidential index 0.693-2.072; p = 0.531) compared to the-non DM group. Incidence of postoperative complications was higher in the DM group than in the non-DM group (17.9 vs. 8.1 %, p = 0.006). The DM remission rate was 46 % among patients who received Roux-en-Y reconstruction, and 13 % among patients who received Billroth II anastomosis (p = 0.009). The 5-year overall survival rate was 62.1 % for patients with cured or improved DM and 23.4 % for patients with worse or same DM status (p = 0.003). CONCLUSION Type-2 diabetes can be cured by radical gastrectomy plus Roux-en-Y reconstruction in some GC patients. Pre-existing diabetes is associated with increased postoperative complications and decreased survival when it becomes worse after curative dissection for GC.
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Affiliation(s)
- Zhe-Wei Wei
- Department of Gastrointestinopancreatic Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China
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Kim YI, Kim SY, Cho SJ, Park JH, Choi IJ, Lee YJ, Lee EK, Kook MC, Kim CG, Ryu KW, Kim YW. Long-term metformin use reduces gastric cancer risk in type 2 diabetics without insulin treatment: a nationwide cohort study. Aliment Pharmacol Ther 2014; 39:854-63. [PMID: 24612291 DOI: 10.1111/apt.12660] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 11/22/2013] [Accepted: 01/24/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND Metformin use has been associated with a decreased incidence and mortality of various cancers. AIM To evaluate the association between metformin use and gastric cancer. METHODS We randomly selected 100 000 type 2 diabetic patients from the 2004 Korean National Health Insurance claim database, and assessed gastric cancer incidence among 39 989 patients (aged 30-97 years) who were regularly treated with anti-diabetic drugs and followed-up from 2004 to 2010. In total, 26 690 patients had used metformin out of 32 978 diabetics who had not regularly used insulin (insulin non-users), and 5855 patients had used metformin out of 7011 regular insulin users. RESULTS Patients who used metformin showed a lower incidence of gastric cancer than those who did not use metformin, in insulin non-users (P = 0.047, log-rank test). However, in patients on regular insulin, there was no difference of gastric cancer incidence according to metformin use. In insulin non-users, the adjusted hazard ratio (AHR) for metformin use was 0.73 (95% confidential interval [CI], 0.53-1.01) with borderline statistical significance (P = 0.059). Duration of metformin use was associated with the reduction in gastric cancer risk (AHR, 0.88; 95% CI 0.81-0.96, P = 0.003), especially in patients who used metformin for more than 3 years (AHR, 0.57; 95% CI, 0.37-0.87; P = 0.009). CONCLUSION Metformin use >3 years in type 2 diabetics who do not use insulin is associated with a significantly reduced gastric cancer risk.
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Affiliation(s)
- Y-I Kim
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
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Wei XL, Qiu MZ, Lin HX, Zhang Y, Liu JX, Yu HM, Liang WP, Jin Y, Ren C, He MM, Chen WW, Luo HY, Wang ZQ, Zhang DS, Wang FH, Li YH, Xu RH. Patients with old age or proximal tumors benefit from metabolic syndrome in early stage gastric cancer. PLoS One 2014; 9:e89965. [PMID: 24599168 PMCID: PMC3943843 DOI: 10.1371/journal.pone.0089965] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Accepted: 01/25/2014] [Indexed: 12/12/2022] Open
Abstract
Background Metabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated. Methods Clinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed. Results Metabolic syndrome was identified to be associated with a higher tumor cell differentiation (P = 0.036). Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P = 0.009 in multivariate analysis) or patients with proximal gastric cancer (P = 0.047 in multivariate analysis). No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P = 0.052 in univariate analysis). Conclusions Metabolic syndrome was associated with a better tumor cell differentiation in patients with early stage gastric cancer. Moreover, metabolic syndrome was a significant and independent predictor for better survival in patients with old age or proximal tumors.
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Affiliation(s)
- Xiao-li Wei
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Miao-zhen Qiu
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Huan-xin Lin
- Department of Preventive Care, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ying Zhang
- Department of Preventive Care, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Jian-xin Liu
- Department of Preventive Care, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Hong-mei Yu
- Department of Preventive Care, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Wei-ping Liang
- Department of Preventive Care, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ying Jin
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Chao Ren
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ming-ming He
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Wei-wei Chen
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Hui-yan Luo
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Zhi-qiang Wang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Dong-sheng Zhang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Feng-hua Wang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yu-hong Li
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Rui-hua Xu
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- * E-mail:
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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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Abstract
AIM: To systematically assess the association between diabetes mellitus and the risk of gastric cancer.
METHODS: We searched Medline (PubMed), EMBASE, the Cochrane Library and CBN databases from January 1990 to July 2013. We also searched the references of qualifying articles. Cohort studies comparing the risk of gastric cancer between diabetic patients and control subjects were included. Fifteen studies met our criteria, and the quality of these studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Meta-analysis was performed using the random-effects model (DerSimonian-Laird method).
RESULTS: The meta-analysis showed an increased gastric cancer risk in diabetic patients [relative risk (RR) = 1.15, 95%CI: 1.11-1.19].
CONCLUSION: Diabetes mellitus may increase the risk of gastric cancer.
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Tseng CH. Higher risk of mortality from lung cancer in Taiwanese people with diabetes. Diabetes Res Clin Pract 2013; 102:193-201. [PMID: 24262943 DOI: 10.1016/j.diabres.2013.10.019] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2013] [Revised: 08/14/2013] [Accepted: 10/28/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND The association between diabetes and lung cancer is rarely studied in the Asian populations. This study investigated lung cancer mortality trends, mortality rate ratios between people with diabetes and the general population, and associated risk factors in people with diabetes in Taiwan. METHODS Age-standardized trends from 1995 to 2006 were evaluated, followed by calculation of age-sex-specific average mortality rates within the 12-year period in the general population. A total of 113,347 men and 131,573 women with diabetes, aged ≥25 years and recruited in 1995-1998 were followed to 2006. Age-sex-specific mortality rate ratios between people with diabetes and the general population were calculated. Cox regression evaluated the risk factors in the people with diabetes. RESULTS A steady age-standardized trend was observed for either sex. A total of 1580 men and 931 women with diabetes died of lung cancer. Mortality rate ratios showed a significantly higher risk in patients with diabetes: 1.16 (1.04-1.30), 1.42 (1.33-1.53), 1.79 (1.61-1.99) and 4.37 (3.75-5.09) for ≥75, 65-74, 55-64 and 25-54 years old, respectively, for men; and 1.35 (1.18-1.54), 1.41 (1.27-1.57), 1.88 (1.66-2.13) and 3.57 (2.95-4.33), respectively, for women. Age and smoking were significantly associated with lung cancer mortality in the people with diabetes, but sex, diabetes type and insulin use were not. Diabetes duration was significant when those who died of lung cancer within 5 years of diabetes diagnosis were excluded from analysis. CONCLUSIONS People with diabetes have a higher risk of lung cancer mortality and this was most remarkable in the youngest age.
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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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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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Hsu LI, Wang YH, Chiou HY, Wu MM, Yang TY, Chen YH, Tseng CH, Chen CJ. The association of diabetes mellitus with subsequent internal cancers in the arsenic-exposed area of Taiwan. JOURNAL OF ASIAN EARTH SCIENCES 2013; 73:452-459. [DOI: 10.1016/j.jseaes.2013.04.048] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/29/2023]
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Nakamura K, Wada K, Tamai Y, Tsuji M, Kawachi T, Hori A, Takeyama N, Tanabashi S, Matsushita S, Tokimitsu N, Nagata C. Diabetes mellitus and risk of cancer in Takayama: a population-based prospective cohort study in Japan. Cancer Sci 2013; 104:1362-7. [PMID: 23859808 DOI: 10.1111/cas.12235] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2013] [Revised: 06/28/2013] [Accepted: 07/02/2013] [Indexed: 12/13/2022] Open
Abstract
Diabetes mellitus (DM) has been reported to be associated with an increased risk of site-specific cancers; however, few studies have assessed associations of DM with both total and site-specific cancers in Japan. We examined the association of a history of DM with cancer incidence in a population-based prospective cohort study in Japan. A total of 14 173 men and 16 547 women over 35 years old, who completed a self-administered baseline questionnaire in 1992, were followed up for cancer incidence from September 1992 to March 2008. At baseline, 6.3% men and 2.9% women had a history of diabetes. A total of 1974 men and 1514 women were identified as newly diagnosed with cancer. Hazard ratios (HR) and 95% confidence intervals (CI) were determined using Cox proportional hazards models. After controlling for potential confounders, men with DM had a modest risk increase of total cancer occurrence compared with those without DM (HR, 1.09; 95% CI, 0.93-1.29). Increased risk of cancer of the liver (HR, 2.18; 95% CI, 1.27-3.74), bile duct (HR, 2.17; 95% CI, 1.01-4.66), and larynx (HR, 3.61; 95% CI, 1.16-11.2) in diabetic men were observed. In women, significant increased risk of total cancer (HR, 1.35; 95% CI, 1.06-1.73) and stomach cancer (HR, 2.15; 95% CI, 1.30-3.54) were observed among diabetic subjects. These data suggest that people with DM may be at increased risk of both total and some site-specific cancers.
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Affiliation(s)
- Kozue Nakamura
- Department of Epidemiology and Preventive Medicine, Gifu University, Graduate School of Medicine, Gifu, Japan
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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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Diabetes and risk of subsequent gastric cancer: a population-based cohort study in Taiwan. Gastric Cancer 2013; 16:389-96. [PMID: 23053824 DOI: 10.1007/s10120-012-0197-7] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2012] [Accepted: 09/05/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND Epidemiological data concerning the association between diabetes and the subsequent development of gastric cancer are controversial. This population-based retrospective cohort study investigated the subsequent risk of gastric cancer for diabetic patients. METHODS From claims data of the universal health insurance of Taiwan, we identified 19,625 persons aged ≥20 years newly diagnosed with diabetes during 2000-2005. A comparison group (n = 78,500), frequency matched by age, sex, and calendar year, was randomly selected from people without diabetes. Incidence and hazard ratios (HR) of gastric cancer were ascertained during the follow-up period until 2008. We also explored associations of antidiabetic medicines with the incidence of gastric cancer. RESULTS During the follow-up period, 47 subjects in the diabetic group and 216 subjects in the comparison group suffered gastric cancer, with the incidence rates of 4.34 and 4.86 per 10,000 person-years, respectively. During the first 4 years after diabetes diagnosis, the incidence of gastric cancer was relatively low in diabetic patients [adjusted HR = 0.63; 95% confidence interval (CI) = 0.42-0.97]. However, after that time, the diabetic group had a 76% (95% CI = 1.06-2.91) higher risk of developing gastric cancer than the comparison group. In diabetic patients, alpha-glucosidase inhibitors were associated with a significantly decreased risk of gastric cancer (adjusted HR = 0.38; 95% CI = 0.15-0.96). CONCLUSIONS Our findings suggested that the association between diabetes and subsequent risk of gastric cancer may vary over time. Increased risk of gastric cancer was observed in patients with longer duration of diabetes.
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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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Yoon JM, Son KY, Eom CS, Durrance D, Park SM. Pre-existing diabetes mellitus increases the risk of gastric cancer: A meta-analysis. World J Gastroenterol 2013; 19:936-45. [PMID: 23429469 PMCID: PMC3574893 DOI: 10.3748/wjg.v19.i6.936] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2012] [Revised: 10/22/2012] [Accepted: 10/30/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To systematically assess the association between diabetes and incidence of gastric cancer.
METHODS: We searched MedLine (PubMed), EMBASE, and the Cochrane Library without any limitations with respect to publication date or language, we also searched the references of qualifying articles. Case-control studies and cohort studies comparing the risk of gastric cancer between diabetic patients and control subjects were included. We excluded studies reporting only standardized incidence ratios without control groups and those that investigated only mortality but not incidence. Seventeen studies met our criteria, and the qualities of these studies were assessed using the Newcastle-Ottawa Quality Assessment Scale. We performed a meta-analysis of pre-existing diabetes and gastric cancer incidence using the DerSimonian-Laird method for random-effects. For subgroup analyses, we separated the studies by study type, region, sex and method to determine confounding factors and reliability. We also conducted subgroup analyses to examine the effects of smoking, Helicobacter pylori (H. pylori) infection, and cancer site. Publication bias was evaluated using Begg’s test.
RESULTS: A random-effects model meta-analysis showed an increased gastric cancer risk in diabetic patients [relative risk (RR) = 1.19; 95%CI: 1.08-1.31]. Subgroup analyses indicated that this result persisted in cohort studies (RR = 1.20; 95%CI: 1.08-1.34), in studies on populations of both Western (RR = 1.18; 95%CI: 1.03-1.36) and Eastern countries (RR = 1.19; 95%CI: 1.02-1.38), in a female subgroup (RR=1.24; 95%CI: 1.01-1.52), and in highly qualified studies (RR = 1.17; 95%CI: 1.05-1.31). Moreover, these results persisted when the analysis was confined to studies adjusted for well-known gastric cancer risk factors such as smoking (RR = 1.17; 95%CI: 1.01-1.34) and H. pylori infection (RR = 2.35; 95%CI: 1.24-4.46).
CONCLUSION: Pre-existing diabetes mellitus may increase the risk of gastric cancer by approximately 19%. This effect seems to be unrelated to geographical region.
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Mannucci E. Insulin therapy and cancer in type 2 diabetes. ISRN ENDOCRINOLOGY 2012; 2012:240634. [PMID: 23209929 PMCID: PMC3504371 DOI: 10.5402/2012/240634] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/13/2012] [Accepted: 10/03/2012] [Indexed: 01/27/2023]
Abstract
Despite the availability of many other agents, insulin is widely used as a treatment for type 2 diabetes. In vitro, insulin stimulates the growth of cancer cells, through the interaction with insulin-like growth factor-1 (IGF-1) receptors and its own receptors. In observational surveys on type 2 diabetes, insulin therapy is associated with an increased incidence of several forms of cancer, although it is difficult to discriminate the effect of confounders from that of insulin itself. Randomized trials do not confirm the increased risk associated with insulin therapy, although they do not allow to rule out some negative effects on specific forms of cancer, at least at higher doses. Among insulin analogues, glargine has a higher affinity for the IGF-1 receptor and a greater mitogenic potency in vitro than human insulin, but it is extensively metabolized in vitro to products with low IGF-1 receptor affinity. Overall, epidemiological studies suggest a possible increase of risk with glargine, with respect to human insulin, only at high doses and for some forms of cancer (i.e., breast). Data from clinical trials do not confirm, but are still insufficient to totally exclude, such increased risk. However, beneficial effects of insulin outweigh potential cancer risks.
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Affiliation(s)
- Edoardo Mannucci
- Agenzia Diabetologia, Ponte Nuovo, Ospedale di Careggi, Via delle Oblate, 4-50141 Firenze, Italy
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