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Wu XQ, Deng LH, Xue Q, Li X, Li MH, Wang JT. Metformin administration in prevention of colorectal polyps in type 2 diabetes mellitus patients. World J Clin Cases 2024; 12:4206-4216. [PMID: 39015918 PMCID: PMC11235560 DOI: 10.12998/wjcc.v12.i20.4206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 05/07/2024] [Accepted: 05/29/2024] [Indexed: 06/30/2024] Open
Abstract
BACKGROUND Colorectal polyps are frequently observed in patients with type 2 diabetes mellitus (DM), posing a significant risk for colorectal cancer. Metformin, a widely prescribed biguanidine drug for type 2 DM, has been suggested to have potential chemoprophylactic effects against various cancers. AIM To explore the correlation between colorectal polyps and metformin use in type 2 DM patients. METHODS Type 2 DM patients were categorized into polyp and non-polyp groups. Following this, all patients were categorized into the type 2 DM-metformin, type 2 DM-non-metformin, and non-type 2 DM groups. Based on the baseline colonoscopy results, we performed pairwise comparisons of the incidence of colorectal polyps among the three groups. Additionally, we analyzed the relationship between colorectal polyps and the duration of metformin use and between the size and number of polyps and metformin use. Simultaneously, we focused on the specific pathological types of polyps and analyzed their relationship with metformin use. Finally, we compared the incidence of polyps between metformin and non-metformin groups according to the interval colonoscopy results. RESULTS The rate of metformin use in patients with colorectal polyps was 0.502 times that of patients without colorectal polyps [odds ratio (OR) = 0.502, 95% confidence interval (CI): 0.365-0.689; P < 0.001]. The incidence of colorectal polyps did not differ significantly between the type 2 DM-metformin and non-type 2 DM groups (P > 0.05). Furthermore, the correlations between the duration of metformin use and the incidence of colorectal polyps and between the size and number of polyps and metformin use were not statistically significant (P > 0.05). Metformin use did not affect the incidence of colorectal polyps during interval colonoscopy (P > 0.05). CONCLUSION Metformin use and colorectal polyp incidence in type 2 DM patients showed a negative correlation, independent of the hypoglycemic effect of metformin.
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Affiliation(s)
- Xiao-Qing Wu
- Department of Geriatrics, Peking University People's Hospital, Beijing 100044, China
| | - Li-Hua Deng
- Department of Geriatrics, Peking University People's Hospital, Beijing 100044, China
| | - Qian Xue
- Department of Geriatrics, Peking University People's Hospital, Beijing 100044, China
| | - Xia Li
- Department of Geriatrics, Peking University People's Hospital, Beijing 100044, China
| | - Meng-Han Li
- Department of Geriatrics, Peking University People's Hospital, Beijing 100044, China
| | - Jing-Tong Wang
- Department of Geriatrics, Peking University People's Hospital, Beijing 100044, China
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2
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Rogers M, Gill D, Ahlqvist E, Robinson T, Mariosa D, Johansson M, Cortez Cardoso Penha R, Dossus L, Gunter MJ, Moreno V, Davey Smith G, Martin RM, Yarmolinsky J. Genetically proxied impaired GIPR signaling and risk of 6 cancers. iScience 2023; 26:106848. [PMID: 37250804 PMCID: PMC10209536 DOI: 10.1016/j.isci.2023.106848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 03/15/2023] [Accepted: 05/04/2023] [Indexed: 05/31/2023] Open
Abstract
Preclinical and genetic studies suggest that impaired glucose-dependent insulinotropic polypeptide receptor (GIPR) signaling worsens glycemic control. The relationship between GIPR signaling and the risk of cancers influenced by impaired glucose homeostasis is unclear. We examined the association of a variant in GIPR, rs1800437 (E354Q), shown to impair long-term GIPR signaling and lower circulating glucose-dependent insulinotropic peptide concentrations, with risk of 6 cancers influenced by impaired glucose homeostasis (breast, colorectal, endometrial, lung, pancreatic, and renal) in up to 235,698 cases and 333,932 controls. Each copy of E354Q was associated with a higher risk of overall and luminal A-like breast cancer and this association was consistent in replication and colocalization analyses. E354Q was also associated with higher postprandial glucose concentrations but diminished insulin secretion and lower testosterone concentrations. Our human genetics analysis suggests an adverse effect of the GIPR E354Q variant on breast cancer risk, supporting further evaluation of GIPR signaling in breast cancer prevention.
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Affiliation(s)
- Miranda Rogers
- MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, BS8 2PS Bristol, UK
| | - Dipender Gill
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, W2 1PG London, UK
- Chief Scientific Office, Research and Early Development, Novo Nordisk, 2300 Copenhagen, Denmark
| | - Emma Ahlqvist
- Department of Clinical Sciences, Lund University, Lund, 22362 Malmö, Sweden
| | - Tim Robinson
- MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, BS8 2PS Bristol, UK
| | - Daniela Mariosa
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), 69007 Lyon, France
| | - Mattias Johansson
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), 69007 Lyon, France
| | | | - Laure Dossus
- Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC/WHO), 69007 Lyon, France
| | - Marc J. Gunter
- Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC/WHO), 69007 Lyon, France
| | - Victor Moreno
- Biomarkers and Susceptibility Unit, Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), 08908 L'Hospitalet de Llobregat, Barcelona, Spain
- Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute(IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
- Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, 08036 Barcelona, Spain
| | - George Davey Smith
- MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, BS8 2PS Bristol, UK
| | - Richard M. Martin
- MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, BS8 2PS Bristol, UK
- University Hospitals Bristol and Weston NHS Foundation Trust, National Institute for Health Research Bristol Biomedical Research Centre, University of Bristol, BS8 2BN Bristol, UK
| | - James Yarmolinsky
- MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, BS8 2PS Bristol, UK
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SGLT-2 Inhibitors in Cancer Treatment-Mechanisms of Action and Emerging New Perspectives. Cancers (Basel) 2022; 14:cancers14235811. [PMID: 36497303 PMCID: PMC9738342 DOI: 10.3390/cancers14235811] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 11/11/2022] [Accepted: 11/22/2022] [Indexed: 11/29/2022] Open
Abstract
A new group of antidiabetic drugs, sodium-glucose cotransporter 2 inhibitors (SGLT-2 inhibitors), have recently been shown to have anticancer effects and their expression has been confirmed in many cancer cell lines. Given the metabolic reprogramming of these cells in a glucose-based model, the ability of SGLT-2 inhibitors to block the glucose uptake by cancer cells appears to be an attractive therapeutic approach. In addition to tumour cells, SGLT-2s are only found in the proximal tubules in the kidneys. Furthermore, as numerous clinical trials have shown, the use of SGLT-2 inhibitors is well-tolerated and safe in patients with diabetes and/or heart failure. In vitro cell culture studies and preclinical in vivo studies have confirmed that SGLT-2 inhibitors exhibit antiproliferative effects on certain types of cancer. However, the mechanisms of this action remain unclear. Even in those tumour cell types in which SGLT-2 is present, there is sometimes an SGLT-2-independent mechanism of anticancer action of this group of drugs. This article presents the current state of knowledge of the potential mechanisms of the anticancer action of SGLT-2 inhibitors and their possible future application in clinical oncology.
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Obesity: The Fat Tissue Disease Version of Cancer. Cells 2022; 11:cells11121872. [PMID: 35741001 PMCID: PMC9221301 DOI: 10.3390/cells11121872] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 06/02/2022] [Accepted: 06/06/2022] [Indexed: 02/06/2023] Open
Abstract
Obesity is a disease with high potential for fatality. It perfectly fits the disease definition, as cancer does. This is because it damages body structure and functions, both mechanically and biologically, and alters physical, mental, and social health. In addition, it shares many common morbid characteristics with the most feared disease, cancer. For example, it is influenced by a sophisticated interaction between a person’s genetics, the environment, and an increasing number of other backgrounds. Furthermore, it displays abnormal cell growth and proliferation events, only limited to white fat, resulting in adipose tissue taking up an increasing amount of space within the body. This occurs through fat “metastases” and via altered signaling that further aggravates the pathology of obesity by inducing ubiquitous dishomeostasis. These metastases can be made graver by angiogenesis, which might boost diseased tissue growth. More common features with cancer include its progressive escalation through different levels of severity and its possibility of re-onset after recovery. Despite all these similarities with cancer, obesity is substantially less agitating for most people. Thus, the ideas proposed herein could have utility to sensitize the public opinion about the hard reality of obesity. This is increasingly needed, as the obesity pandemic has waged a fierce war against our bodies and society in general, while there is still doubt about whether it is a real disease or not. Hence, raising public consciousness to properly face health issues is crucial to improving our health instead of gaining weight unhealthily. It is obviously illogical to fight cancer extremely seriously on the one hand and to consider dying with obesity as self-inflicted on the other. In fact, obesity merits a top position among the most lethal diseases besides cancer.
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Shi J, Li S, Qi Y, Li P, Sun W, He P, Ji H, Hou Z. Effects of Insulin Pathway on Glucose and Lipid Metabolism Disorder in Different Pathological Types of Colorectal Adenomas. EXPLORATORY RESEARCH AND HYPOTHESIS IN MEDICINE 2021; 000:000-000. [DOI: 10.14218/erhm.2021.00018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Shi N, Shi Y, Xu J, Si Y, Yang T, Zhang M, Ng DM, Li X, Xie F. SGLT-2i and Risk of Malignancy in Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials. Front Public Health 2021; 9:668368. [PMID: 34164370 PMCID: PMC8215266 DOI: 10.3389/fpubh.2021.668368] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 05/03/2021] [Indexed: 12/25/2022] Open
Abstract
Background: Currently, the association between sodium-glucose cotransporter 2 inhibitor (SGLT-2i) and malignancy risk has yet to be fully elucidated. This meta-analysis aimed to determine the relationship between SGLT-2i and malignancy risk in type 2 diabetes (T2D) patients. Methods: We searched PubMed, ScienceDirect, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science to identify randomized controlled trials (RCTs) published up to August 2020 related to T2D patients treated with SGLT-2i vs. placebo or other hypoglycemic agents. The meta-analysis's primary outcome was malignancies' incidence, and the results were evaluated using risk ratio (RR) and 95% confidence interval (CI). Results: We reviewed 76 articles (77 RCTs), comprising 45,162 and 43,811 patients in SGLT-2i and control groups, respectively. Compared with the control group, SGLT-2i had no significant association with augmented overall malignancy risk in T2D patients (RR = 1.05, 95% CI = 0.97–1.14, P = 0.20), but ertugliflozin may upsurge the risk (RR = 1.80, 95% CI = 1.02–3.17, P = 0.04). Compared with active hypoglycemic agents, dapagliflozin may increase (RR = 2.71, 95% CI = 1.46–6.43, P = 0.02) and empagliflozin may decrease (RR = 0.67, 95% CI = 0.45–0.98, P = 0.04) the malignancy risk. Compared with placebo, empagliflozin may exhibit risk increase (RR = 1.25, 95% CI = 1.05–1.49, P = 0.01), primarily in digestive system (RR = 1.48, 95% CI = 0.99–2.21, P = 0.05). Conclusions: Our results proposed that in diverse comparisons, ertugliflozin and dapagliflozin seemed to increase the malignancy risk in T2D patients. Empagliflozin may cause malignancy risk reduction compared with active hypoglycemic agents but increase overall risk primarily in the digestive system compared with placebo. In short, the relationship between SGLT-2i and malignancy in T2D patients remains unclear.
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Affiliation(s)
- Nanjing Shi
- Department of Endocrinology, Affiliated Hangzhou First People' Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yetan Shi
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jingsi Xu
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yuexiu Si
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Tong Yang
- Department of Tumor High Intensity Focused Ultrasound Therapy, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Mengting Zhang
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | | | - Xiangyuan Li
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Fei Xie
- Department of Endocrinology, Ningbo Yinzhou No. 2 Hospital, Ningbo, China
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Kim DB, Lee KM, Lee JM, Ko SH, Han KD, Park YG. Waist circumference, body mass index, and colorectal cancer risk according to diabetes status: A Korean nationwide population-based cohort study. J Gastroenterol Hepatol 2021; 36:397-405. [PMID: 32542773 DOI: 10.1111/jgh.15152] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 05/24/2020] [Accepted: 06/05/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIM We investigated the relationship of BMI and waist circumference with the risk of colorectal cancer (CRC) using a population-based cohort database and to explore the relationship of CRC with diabetes status. METHODS Retrospective data (age >20 years) on anthropometric variables, blood parameters of fasting sugar, lipid levels, and blood pressure were collected from the National Health Insurance Corporation database between 2009 and 2012. Cox regression models were used to estimate hazard ratio (HR) and corresponding 95% confidence intervals (95% CI). RESULTS Of the 23 121 360 people studied, 120 579 were diagnosed with CRC after a median follow-up period of 5.4 years. Both waist circumference and body mass index were positively associated with increased risk of CRC, regardless of age or sex. After mutual adjustment, only waist circumference was significantly associated with increased risk of CRC (HR = 1.275, 95% CI: 1.205-1.349). When the risk of CRC was compared according to diabetes status among people with the same waist circumference range, risk of CRC was higher for those with worse diabetes status. CONCLUSION When waist circumference and body mass index were mutually adjusted, only waist circumference was associated with CRC risk. In addition, the risk of CRC is gradually higher in those with worsening diabetes, even if their waist circumferences are within the same range.
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Affiliation(s)
- Dae Bum Kim
- Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Kang-Moon Lee
- Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Ji Min Lee
- Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Seung-Hyun Ko
- Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Kyung-Do Han
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Yong Gyu Park
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, South Korea
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Toorang F, Sasanfar B, Hekmatdoost A, Narmcheshm S, Hadji M, Ebrahimpour-Koujan S, Amini N, Zendehdel K. Macronutrients Intake and Stomach Cancer Risk in Iran: A Hospital-based Case-Control Study. J Res Health Sci 2021; 21:e00507. [PMID: 34024765 PMCID: PMC8957691 DOI: 10.34172/jrhs.2021.38] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 11/22/2020] [Accepted: 12/15/2020] [Indexed: 12/24/2022] Open
Abstract
Background: Stomach cancer (SC) is one of the most common cancers in the world. Dietary risk factors of SC are not fully understood. This study aimed to investigate the association between macronutrient intakes and the risk of SC.
Study design: A hospital-based case-control study.
Methods: The data were obtained from a hospital-based case-control study conducted at the Cancer Institute of Iran from 2010 to 2012. Patients were 40 years or older and were diagnosed with SC in less than one year with no history of any cancers. On the other hand, the controls were healthy subjects who were caregivers or visitors of the patients. Demographic characteristics were collected using a structured questionnaire through face to face interviews by trained interviewers. Dietary data were obtained using a validated Diet History Questionnaire. The age and gender-adjusted odds ratios (ORs), as well as the adjusted ORs of age, gender, energy, education, smoking, and body mass index, were reported for continuous and tertiles of intakes.
Results: Totally, 207 SC patients and 217 controls participated in this study. In the full adjusted model, after comparing the highest tertiles to the lowest ones, the intake of sucrose (OR: 2.94; 95% CI: 1.66-5.19; P-trend<0.001), protein (OR: 2.04; 95% CI: 1.17-3.55; P-trend=0.011), cholesterol (OR: 2.22; 95% CI: 1.28-3.85; P-trend=0.005), and percent of calories from protein (OR: 3.09; 95% CI: 1.69-5.61; P-trend<1.001) showed a positive significant association with SC. Moreover, a significantly negative association was found between the percent of calories obtained from carbohydrates and SC (OR: 0. 57; 95% CI: 0.33-0.98; P-trend=0.015).
Conclusion: The findings in this study showed that macronutrient intakes might be associated with the etiology of SC in Iran.
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Affiliation(s)
- Fatemeh Toorang
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.,Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Science, Tehran, Iran
| | - Bahareh Sasanfar
- Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Science, Tehran, Iran.,Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Azita Hekmatdoost
- Department of Clinical Nutrition, Faculty of Nutrition and Food Technology, National Research Institute of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences and Health Services, Tehran, Iran
| | - Saba Narmcheshm
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.,Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Science, Tehran, Iran
| | - Maryam Hadji
- Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Science, Tehran, Iran.,Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Soraiya Ebrahimpour-Koujan
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Neda Amini
- Department of Surgery, Sinai Hospital of Baltimore, Baltimore, USA.,Department of Surgery, Johns Hopkins Hospital, Baltimore, USA
| | - Kazem Zendehdel
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.,Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Science, Tehran, Iran
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Lin C, Cai X, Yang W, Lv F, Nie L, Ji L. Glycemic control and the incidence of neoplasm in patients with type 2 diabetes: a meta-analysis of randomized controlled trials. Endocrine 2020; 70:232-242. [PMID: 32533507 DOI: 10.1007/s12020-020-02376-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 05/29/2020] [Indexed: 12/28/2022]
Abstract
PURPOSE Previous epidemiologic studies indicate an increased risk of cancer and cancer mortality in patients with type 2 diabetes (T2D). Whether the resolution of hyperglycemia will lead to reduced risk of neoplasm in T2D remains uncertain. Therefore, we performed a meta-analysis to assess the association between glycemic control and incidence of neoplasm in T2D patients. METHODS Randomized controlled trials (RCTs) in T2D with significant HbA1c reduction difference between intensive/active and standard/control groups plus follow-up ≥48 weeks were included and analyzed by fixed-effect models, random-effect model, and meta-regression analysis accordingly. RESULTS Overall, 52 studies were included. Compared with standard/control treatment, intensive/active treatment led to significantly greater HbA1c reduction from baseline (WMD = -0.51%, 95% CI, -0.55 to -0.46%, P < 0.001), but was not associated with a decreased incidence of neoplasm (OR = 0.99, 95% CI, 0.94-1.03, I2 = 2%) in T2D. Meta-regression analysis indicated that HbA1c reduction difference between intensive/active treatment and standard/control treatment was not associated with the incidence of neoplasm in T2D patients (β = -0.0011, 95% CI, -0.0058 to 0.0035, P = 0.625). In neoplasm-site subgroup analysis, a decreased incidence of breast neoplasm was observed in T2D patients using dipeptidyl-peptidase-4 inhibitor (OR = 0.56, 95% CI, 0.35-0.89, I2 = 0%) and incidence of prostate neoplasm was reduced in T2D patients with glucagon-like peptide-1 receptor agonist treatment (OR = 0.66, 95% CI, 0.47-0.91, I2 = 0%). CONCLUSION Improved glycemic control in short and medium periods achieved by existing glucose-lowering drugs or strategies may not confer reduced risk of neoplasm in patients with T2D. Studies with longer follow-up duration are needed to better elucidate the long-period effects.
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Affiliation(s)
- Chu Lin
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Xiaoling Cai
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China.
| | - Wenjia Yang
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Fang Lv
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Lin Nie
- Department of Endocrinology and Metabolism, Beijing Airport Hospital, Beijing, China
| | - Linong Ji
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China.
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Ma JW, Lai TJ, Hu SY, Lin TC, Ho WC, Tsan YT. Effect of ambient air pollution on the incidence of colorectal cancer among a diabetic population: a nationwide nested case-control study in Taiwan. BMJ Open 2020; 10:e036955. [PMID: 33115890 PMCID: PMC7594369 DOI: 10.1136/bmjopen-2020-036955] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
OBJECTIVES An increasing number of studies had shown that air pollution exposure may aggravate blood glucose control in patients with diabetes, an independent risk factor for colorectal cancer (CRC) proposed by some researchers. This study aimed to investigate the impact of exposure to ambient particulate matter with aerodynamic diameters ≤2.5 μm (PM2.5) on the incidence of CRC among a diabetic population. DESIGN A nested case-control study. SETTING A subset data retrieved from the Taiwan's National Health Insurance Research Database. PARTICIPANTS We identified patients with newly diagnosed diabetes (n=1 164 962) during 1999-2013. Participants who had subsequently developed an incident of CRC were placed into the case group, while controls were matched to the cases at a 4:1 ratio by age, gender, date of diabetes diagnosis and the index date of CRC diagnosis. METHODS AND OUTCOME MEASURES All variables associated with the risk of CRC entered into a multinomial logistic regression model. The dose-response relationship between various average concentrations of PM2.5 exposure and the incidence of CRC was estimated by logistic regression. RESULTS The study included a total of 7719 incident CRC cases matched with 30 876 controls of random sampling. The mean annual concentration of PM2.5 was 35.3 µg/m3. After adjusting for potential confounders, a dose-response relationship was observed between the CRC risks and each interquartile increase of PM2.5 concentration (Q1-Q2: 1.03 (0.95-1.11), Q2-Q3: 1.06 (0.98-1.15), ≥Q3: 1.19 (1.10-1.28) in model 2. The adjusted ORs (95% CI) of CRC incidence for each 10 µg/m3 increment of PM2.5 was 1.08 (1.04-1.11). Moreover, a faster growing adapted Diabetes Complications Severity Index (aDCSI) score was noticed in CRC group compared with the controls, which also showed a significant association in our multivariate analysis (adjusted OR=1.28, 95% CI 1.18 to 1.38). CONCLUSIONS Long-term exposure to high concentrations of PM2.5 may contribute to an increased incidence of CRC among diabetic populations.
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Affiliation(s)
- Jen-Wen Ma
- Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Ting-Ju Lai
- Department of Public Health, China Medical University, Taichung, Taiwan
| | - Sung-Yuan Hu
- Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Tzu-Chieh Lin
- Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Wen-Chao Ho
- Department of Public Health, China Medical University, Taichung, Taiwan
| | - Yu-Tse Tsan
- Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Division of Occupational Medicine, Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
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11
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Sumida Y, Shima T, Mitsumoto Y, Katayama T, Umemura A, Yamaguchi K, Itoh Y, Yoneda M, Okanoue T. Epidemiology: Pathogenesis, and Diagnostic Strategy of Diabetic Liver Disease in Japan. Int J Mol Sci 2020; 21:E4337. [PMID: 32570776 PMCID: PMC7352222 DOI: 10.3390/ijms21124337] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 06/08/2020] [Accepted: 06/16/2020] [Indexed: 12/14/2022] Open
Abstract
Type 2 diabetes (T2D) is closely associated with nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to cirrhosis, hepatocellular carcinoma (HCC), and hepatic decompensation. Patients with T2D have twice the risk of HCC incidence compared with those without T2D. Because the hepatic fibrosis grade is the main determinant of mortality in patients with NAFLD, identifying patients with advanced fibrosis using non-invasive tests (NITs) or imaging modalities is crucial. Globally, the fibrosis-4 index (FIB-4 index), NAFLD fibrosis score, and enhanced liver fibrosis test have been established to evaluate hepatic fibrosis. Two-step algorithms using FIB-4 index as first triaging tool are globally accepted. It remains unknown which kinds of NITs or elastography are best as the second step tool. In Japan, type IV collagen 7s or the CA-fibrosis index (comprising type IV collagen 7s and aspartate aminotransferase (AST)) is believed to precisely predict advanced fibrosis in NAFLD. Patients with NAFLD who have high non-invasive test results should be screened for HCC or esophageal varices. Risk factors of rapid fibrosis progression in NAFLD includes age, severe obesity, presence of T2D, menopause in women, and a patatin-like phospholipase domain containing the 3 GG genotype. Patients with NAFLD who have these risk factors should be intensively treated with lifestyle modification or pharmacotherapies for preventing liver-related mortality.
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Affiliation(s)
- Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan;
| | - Toshihide Shima
- Center of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka 564-0013, Japan; (T.S.); (Y.M.); (T.K.); (T.O.)
| | - Yasuhide Mitsumoto
- Center of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka 564-0013, Japan; (T.S.); (Y.M.); (T.K.); (T.O.)
| | - Takafumi Katayama
- Center of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka 564-0013, Japan; (T.S.); (Y.M.); (T.K.); (T.O.)
| | - Atsushi Umemura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (A.U.); (K.Y.); (Y.I.)
| | - Kanji Yamaguchi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (A.U.); (K.Y.); (Y.I.)
| | - Yoshito Itoh
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (A.U.); (K.Y.); (Y.I.)
| | - Masashi Yoneda
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan;
| | - Takeshi Okanoue
- Center of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka 564-0013, Japan; (T.S.); (Y.M.); (T.K.); (T.O.)
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Survival Benefit for Metformin Through Better Tumor Response by Neoadjuvant Concurrent Chemoradiotherapy in Rectal Cancer. Dis Colon Rectum 2020; 63:758-768. [PMID: 32384406 DOI: 10.1097/dcr.0000000000001624] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Metformin may reduce cancer risk and mortality and improve radiotherapy responses in several malignancies. OBJECTIVE This study aimed to compare tumor responses and prognoses of metformin and nonmetformin groups of diabetic patients receiving neoadjuvant concurrent chemoradiotherapy for rectal cancer. DESIGN This is a retrospective study. SETTING This study was conducted at a single institution in the Republic of Korea. PATIENTS Between January 2000 and November 2017, 104 patients with rectal cancer who were taking diabetes medication and treated with neoadjuvant concurrent chemoradiotherapy followed by radical surgery were reviewed. Patients were divided into those taking (n = 62) and not taking metformin (n = 42). Tumor responses, survival, and other outcomes were analyzed. MAIN OUTCOME MEASURES Tumor response, rectal cancer-specific survival, and disease-free survival rates were measured. RESULTS Tumor regression grade (p = 0.002), pathological complete response (p = 0.037), and N downstaging (p < 0.001) after neoadjuvant concurrent chemoradiotherapy were significantly higher in the metformin group than in the nonmetformin group. In analysis of cancer-specific mortality, metformin use, differentiation (well, moderate vs poor), pathological Union for International Cancer Control stage (3 vs 1-2), ypN stage (1-2 vs 0), and N downstaging (HR, 0.256 (95% CI, 0.082-0.794), p = 0.018; HR, 0.147 (95% CI, 0.031-0.697), p = 0.016; HR, 3.693 (95% CI, 1.283-10.635), p = 0.015; HR, 3.181 (95% CI, 1.155-8.759), p = 0.025, and HR, 0.175 (95% CI, 0.040-0.769), p = 0.021) were significant factors related to mortality in diabetic patients with rectal cancer. In addition, in the multivariate analysis of cancer recurrence, the interaction between metformin use and lymph node downstaging was a significant predictive factor (HR, 0.222 (95% CI, 0.077-0.639); p = 0.005). LIMITATIONS This was a small retrospective study conducted at a single institution. CONCLUSIONS Metformin use was associated with better tumor responses and cancer-specific survival, as well as a lower risk of cancer recurrence, in patients with diabetes mellitus who had lymph node downstaging after neoadjuvant concurrent chemoradiotherapy in rectal cancer. See Video Abstract at http://links.lww.com/DCR/B185. BENEFICIO EN SUPERVIVENCIA CON METFORMINA A TRAVÉS DE UNA MEJOR RESPUESTA TUMORAL CON QUIMIORRADIOTERAPIA CONCURRENTE NEOADYUVANTE EN CÁNCER RECTAL: La metformina puede reducir el riesgo de cáncer y la mortalidad y mejorar las respuestas a la radioterapia en varios tumores malignos.Comparar las respuestas tumorales y los pronósticos de los grupos con metformina y sin metformina de pacientes diabéticos que reciben quimiorradioterapia concurrente neoadyuvante para cáncer de recto.Estudio retrospectivo.Institución única en la República de Corea.Se revisaron 104 pacientes entre enero de 2000 y noviembre de 2017, con cáncer rectal que tomaban medicamentos para diabetes y que fueron tratados con quimiorradioterapia concurrente neoadyuvante seguida de cirugía radical. Los pacientes se dividieron en aquellos que tomaban (n = 62) y los que no tomaban metformina (n = 42). Se analizaron las respuestas tumorales, la supervivencia y otros resultados.Se midieron las tasas de la respuesta tumoral, la supervivencia específica de cáncer rectal y de la supervivencia libre de enfermedad.El grado de regresión tumoral (p = 0.002), la remisión patológica completa (p = 0.037) y la reducción de la etapa N (p < 0.001) después de la quimiorradioterapia concurrente neoadyuvante fueron significativamente mayores en el grupo de metformina que en el grupo sin metformina. En el análisis de la mortalidad específica por cáncer, el uso de metformina, la diferenciación (bien, moderada vs pobre), el estadio patológico UICC (3 vs 1-2), el estadio ypN (1-2 vs 0) y la disminución de la etapa N (hazard ratios [intervalos de confianza 95%]: 0.256 [0.082-0.794], p = 0.018; 0.147 [0.031-0.697], p = 0.016; 3.693 [1.283-10.635], p = 0.015; 3.181 [1.155-8.759], p = 0.025 y 0.175 [0.040-0.769], p = 0.021, respectivamente) fueron factores significativos relacionados con la mortalidad en pacientes diabéticos con cáncer rectal. Adicionalmente, en el análisis multivariado de la recurrencia del cáncer, la interacción entre el uso de metformina y la disminución de la etapa ganglionar (N) fue un factor predictivo significativo (hazard ratios [intervalos de confianza del 95%]: 0.222 [0.077-0.639]; p = 0.005).Este fue un estudio retrospectivo pequeño realizado en un solo instituto.El uso de metformina se asoció con mejores respuestas tumorales y supervivencia específica de cáncer, así como un menor riesgo de recurrencia del cáncer, en pacientes con disminución de la etapa ganglionar (N) después de quimiorradioterapia concurrente neoadyuvante en pacientes con cáncer rectal y diabetes. Consulte Video Resumen en http://links.lww.com/DCR/B185. (Traducción-Dr. Jorge Silva Velazco).
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Wong CKH, Man KKC, Chan EWY, Wu T, Tse ETY, Wong ICK, Lam CLK. DPP4i, thiazolidinediones, or insulin and risks of cancer in patients with type 2 diabetes mellitus on metformin-sulfonylurea dual therapy with inadequate control. BMJ Open Diabetes Res Care 2020; 8:8/1/e001346. [PMID: 32532851 PMCID: PMC7295418 DOI: 10.1136/bmjdrc-2020-001346] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 04/15/2020] [Accepted: 05/04/2020] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION This study aims to compare the risks of cancer among patients with type 2 diabetes mellitus (T2DM) on metformin-sulfonylurea dual therapy intensified with dipeptidyl peptidase 4 inhibitors (DPP4i), thiazolidinediones, or insulin. RESEARCH DESIGN AND METHODS We assembled a retrospective cohort data of 20 577 patients who were free of cancer and on metformin-sulfonylurea dual therapy, and whose drug treatments were intensified with DPP4i (n=9957), insulin (n=7760), or thiazolidinediones (n=2860) from January 2006 to December 2017. Propensity-score weighting was used to balance out baseline covariates across the three groups. HRs for any types of cancer, cancer mortality, and all-cause mortality were assessed using Cox proportional-hazards models. RESULTS Over a mean follow-up period of 34 months with 58 539 person-years, cumulative incidences of cancer, cancer mortality, and all-cause mortality were 0.028, 0.009, and 0.072, respectively. Patients intensified with insulin had the highest incidence of all-cause mortality (incidence rate=3.22/100 person-years) and the insulin itself posed the greatest risk (HR 2.46, 95% CI 2.25 to 2.70, p<0.001; 2.44, 95% CI 2.23 to 2.67) compared with thiazolidinediones and DPP4i, respectively. Comparing between thiazolidinediones and DPP4i, thiazolidinediones was associated with higher risk of cancer (HR 1.43, 95% CI 1.25 to 1.63) but not cancer mortality (HR 1.21, 95% CI 0.92 to 1.58) and all-cause mortality (HR 0.99, 95% CI 0.88 to 1.11). Insulin was associated with the greatest risk of cancer mortality (HR 1.36, 95% CI 1.09 to 1.71; 1.65, 95% CI 1.31 to 2.07) compared with thiazolidinediones and DPP4i, respectively. CONCLUSIONS For patients with T2DM on metformin-sulfonylurea dual therapy, the addition of DPP4i was the third-line medication least likely to be associated with cancer mortality and cancer effect among three options, and posed no increased risk for all-cause mortality when compared with thiazolidinediones.
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Affiliation(s)
- Carlos K H Wong
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Kenneth K C Man
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China
- Research Department of Policy and Practice, University College London School of Pharmacy, London, UK
| | - Esther W Y Chan
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China
| | - Tingting Wu
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Emily T Y Tse
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Ian C K Wong
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China
- Research Department of Policy and Practice, University College London School of Pharmacy, London, UK
| | - Cindy L K Lam
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
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Xu X, Zhu Y, Li J, Wang S. Dietary fiber, glycemic index, glycemic load and renal cell carcinoma risk. Carcinogenesis 2020; 40:441-447. [PMID: 30859214 DOI: 10.1093/carcin/bgz049] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Revised: 01/22/2019] [Accepted: 03/08/2019] [Indexed: 01/11/2023] Open
Abstract
Several epidemiological studies have investigated the potential association between dietary fiber, glycemic index (GI) or glycemic load (GL), and renal cell carcinoma (RCC) risk with inconsistent results. The aim of this study was to systematically evaluate this issue with a meta-analysis approach. A comprehensive literature search up to March 2018 was performed in PubMed and Web of Science databases. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated with a random-effects model. Twelve studies were finally included in this study (eight for fiber analysis, five for GI and five for GL). A significant positive association was observed between GI and the risk of RCC (summary RR 1.16, 95% CI 1.02-1.32), and no significant heterogeneity was detected among studies (I2 = 22.8%, P = 0.262). A significant inverse association was found between fiber intake and the risk of RCC (summary RR 0.82, 95% CI 0.72-0.92), and no significant heterogeneity was observed across studies (I2 = 27.6%, P = 0.218). GL was not significantly associated with RCC risk (summary RR 1.14, 95% CI 0.81-1.60), and significant heterogeneity was found across studies (I2 = 78.6%, P < 0.001). In conclusion, this systematic review and meta-analysis suggests that dietary GI and fiber may be associated with the risk of RCC. Further large prospective cohort studies are still warranted to confirm our preliminary findings.
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Affiliation(s)
| | - Yi Zhu
- Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Jiangfeng Li
- Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Song Wang
- Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
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Renzi C, Kaushal A, Emery J, Hamilton W, Neal RD, Rachet B, Rubin G, Singh H, Walter FM, de Wit NJ, Lyratzopoulos G. Comorbid chronic diseases and cancer diagnosis: disease-specific effects and underlying mechanisms. Nat Rev Clin Oncol 2019; 16:746-761. [PMID: 31350467 DOI: 10.1038/s41571-019-0249-6] [Citation(s) in RCA: 90] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/25/2019] [Indexed: 02/06/2023]
Abstract
An earlier diagnosis is a key strategy for improving the outcomes of patients with cancer. However, achieving this goal can be challenging, particularly for the growing number of people with one or more chronic conditions (comorbidity/multimorbidity) at the time of diagnosis. Pre-existing chronic diseases might affect patient participation in cancer screening, help-seeking for new and/or changing symptoms and clinicians' decision-making on the use of diagnostic investigations. Evidence suggests, for example, that pre-existing pulmonary, cardiovascular, neurological and psychiatric conditions are all associated with a more advanced stage of cancer at diagnosis. By contrast, hypertension and certain gastrointestinal and musculoskeletal conditions might be associated with a more timely diagnosis. In this Review, we propose a comprehensive framework that encompasses the effects of disease-specific, patient-related and health-care-related factors on the diagnosis of cancer in individuals with pre-existing chronic illnesses. Several previously postulated aetiological mechanisms (including alternative explanations, competing demands and surveillance effects) are integrated with newly identified mechanisms, such as false reassurances, or patient concerns about appearing to be a hypochondriac. By considering specific effects of chronic diseases on diagnostic processes and outcomes, tailored early diagnosis initiatives can be developed to improve the outcomes of the large proportion of patients with cancer who have pre-existing chronic conditions.
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Affiliation(s)
- Cristina Renzi
- ECHO (Epidemiology of Cancer Healthcare and Outcomes) Research Group, Department of Behavioural Science and Health, Institute of Epidemiology & Health Care, University College London, London, UK.
- Cancer Survival Group, Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
| | - Aradhna Kaushal
- ECHO (Epidemiology of Cancer Healthcare and Outcomes) Research Group, Department of Behavioural Science and Health, Institute of Epidemiology & Health Care, University College London, London, UK
| | - Jon Emery
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia
| | - Willie Hamilton
- St Luke's Campus, University of Exeter Medical School, Exeter, UK
| | - Richard D Neal
- Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
| | - Bernard Rachet
- Cancer Survival Group, Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
| | - Greg Rubin
- Institute of Health and Society, Sir James Spence Institute, Newcastle University, Royal Victoria Infirmary, Newcastle upon Tyne, UK
| | - Hardeep Singh
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, TX, USA
| | - Fiona M Walter
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Niek J de Wit
- Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht University, Utrecht, Netherlands
| | - Georgios Lyratzopoulos
- ECHO (Epidemiology of Cancer Healthcare and Outcomes) Research Group, Department of Behavioural Science and Health, Institute of Epidemiology & Health Care, University College London, London, UK
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
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Shima T, Uto H, Ueki K, Kohgo Y, Yasui K, Nakamura N, Nakatou T, Takamura T, Kawata S, Notsumata K, Sakai K, Tateishi R, Okanoue T. Hepatocellular carcinoma as a leading cause of cancer-related deaths in Japanese type 2 diabetes mellitus patients. J Gastroenterol 2019; 54:64-77. [PMID: 30006904 DOI: 10.1007/s00535-018-1494-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2017] [Accepted: 06/30/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND We reported a cross-sectional study on causes of liver injury in Japanese type 2 diabetes mellitus (T2D) patients (JG 2013). We assessed overall and cause-specific mortality risk during follow-up of patients enrolled in JG 2013. METHODS This was a longitudinal, multicenter cohort study. Of the 5642 Japanese T2D patients who visited T2D clinics of nine hospitals in the original study, 3,999 patients were followed up for an average of 4.5 years. Expected deaths in T2D patients were estimated using age-specific mortality rates in the general population (GP) of Japan. Standardized mortality ratios (SMRs) were calculated to compare mortality between T2D patients and GP. RESULTS All-cancer mortality was significantly higher in T2D patients than in the GP [SMR 1.58, 95% confidence interval (CI) 1.33-1.87]. Among malignancies, hepatocellular carcinoma (HCC) conferred the highest mortality risk in T2D patients (SMR 3.57, 95% CI 2.41-5.10). HCC-associated mortality risk in T2D patients remained significantly high (SMR 2.56, 95% CI 1.64-3.97) after adjusting for high positivity rates of hepatitis B surface antigen (1.7%) and anti-hepatitis C virus (5.3%). In T2D patients with platelet counts < 200 × 103/μl, SMR of HCC increased from 3.57 to 6.58 (95% CI 4.34-9.58). T2D patients with platelet count > 200 × 103/μl showed no increase in mortality risk (SMR 0.68) of HCC. CONCLUSIONS HCC-associated mortality risk was the highest among all cancers in Japanese T2D patients. Regular follow-up may be important for T2D patients with platelet counts < 200 × 103/μl for early detection of HCC.
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Affiliation(s)
- Toshihide Shima
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Hirofumi Uto
- Department of Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Kohjiro Ueki
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yutaka Kohgo
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical College, Asahikawa, Japan
| | - Kohichiroh Yasui
- Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Naoto Nakamura
- Department of Endocrinology Diabetes and Metabolism, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tatsuaki Nakatou
- Diabetes Center, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Toshinari Takamura
- Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Sumio Kawata
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Kazuo Notsumata
- Department of Gastroenterology, Fukui-ken Saiseikai Hospital, Fukui, Japan
| | - Kyoko Sakai
- Department of Clinical Laboratory, Saiseikai Suita Hospital, Suita, Japan.,Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Takeshi Okanoue
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan.
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Abstract
Type 2 diabetes mellitus and cancer are correlated with changes in insulin signaling, a pathway that is frequently upregulated in neoplastic tissue but impaired in tissues that are classically targeted by insulin in type 2 diabetes mellitus. Many antidiabetes treatments, particularly metformin, enhance insulin signaling, but this pathway can be inhibited by specific cancer treatments. The modulation of cancer growth by metformin and of insulin sensitivity by anticancer drugs is so common that this phenomenon is being studied in hundreds of clinical trials on cancer. Many meta-analyses have consistently shown a moderate but direct effect of body mass index on the incidence of multiple myeloma and lymphoma and the elevated risk of leukemia in adults. Moreover, new epidemiological and preclinical studies indicate metformin as a therapeutic agent in patients with leukemia, lymphomas, and multiple myeloma. In this article, we review current findings on the anticancer activities of metformin and the underlying mechanisms from preclinical and ongoing studies in hematologic malignancies.
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Lam C, Cronin K, Ballard R, Mariotto A. Differences in cancer survival among white and black cancer patients by presence of diabetes mellitus: Estimations based on SEER-Medicare-linked data resource. Cancer Med 2018; 7:3434-3444. [PMID: 29790667 PMCID: PMC6051153 DOI: 10.1002/cam4.1554] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2017] [Revised: 02/28/2018] [Accepted: 04/23/2018] [Indexed: 02/06/2023] Open
Abstract
Diabetes prevalence and racial health disparities in the diabetic population are increasing in the US. Population‐based cancer‐specific survival estimates for cancer patients with diabetes have not been assessed. The Surveillance, Epidemiology, and End Results (SEER)‐Medicare linkage provided data on cancer‐specific deaths and diabetes prevalence among 14 separate cohorts representing 1 068 098 cancer patients ages 66 + years diagnosed between 2000 and 2011 in 17 SEER areas. Cancer‐specific survival estimates were calculated by diabetes status adjusted by age, stage, comorbidities, and cancer treatment, and stratified by cancer site and sex with whites without diabetes as the reference group. Black patients had the highest diabetes prevalence particularly among women. Risks of cancer deaths were increased across most cancer sites for patients with diabetes regardless of race. Among men the largest effect of having diabetes on cancer‐specific deaths were observed for black men diagnosed with Non‐Hodgkin lymphoma (NHL) (HR = 1.53, 95%CI = 1.33‐1.76) and prostate cancer (HR = 1.37, 95%CI = 1.32‐1.42). Diabetes prevalence was higher for black females compared to white females across all 14 cancer sites and higher for most sites when compared to white and black males. Among women the largest effect of having diabetes on cancer‐specific deaths were observed for black women diagnosed with corpus/uterus cancer (HR = 1.66, 95%CI = 1.54‐1.79), Hodgkin lymphoma (HR = 1.62, 95%CI = 1.02‐2.56) and breast ER+ (HR = 1.39, 95%CI = 1.32‐1.47). The co‐occurrence of diabetes and cancer significantly increases the risk of cancer death. Our study suggests that these risks may vary by cancer site, and indicates the need for future research to address racial and sex disparities and enhance understanding how prevalent diabetes may affect cancer deaths.
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Affiliation(s)
- Clara Lam
- Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA
| | - Kathleen Cronin
- Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA
| | - Rachel Ballard
- Office of Disease Prevention, Office of the Director, National Institutes of Health, Rockville, MD, USA
| | - Angela Mariotto
- Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA
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Storey S, Von Ah D. Impact of Hyperglycemia and Age on Outcomes in Patients With Acute Myeloid Leukemia. Oncol Nurs Forum 2017; 43:595-601. [PMID: 27541552 DOI: 10.1188/16.onf.595-601] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
PURPOSE/OBJECTIVES To examine the prevalence and impact of hyperglycemia on health outcomes (number of neutropenic days, infection, and hospital length of stay) in patients hospitalized for acute myeloid leukemia (AML) receiving initial induction therapy.
. DESIGN Retrospective, descriptive study.
. SETTING A large urban hospital in Indianapolis, Indiana.
. SAMPLE 103 patients with AML and a subset of 41 patients aged 65 years or older.
. METHODS Demographics and medical information were extracted from electronic health records. Serum-fasting blood glucose was used to assess glycemic status. The association of hyperglycemia with the health outcomes was analyzed. A subset of patients aged 65 years or older was also analyzed.
. MAIN RESEARCH VARIABLES Hyperglycemia, age, and health outcomes in patients with AML.
. FINDINGS Forty patients experienced hyperglycemia during initial induction for AML. In the larger sample, no associations were noted between hyperglycemia and health outcomes. A significant relationship (p = 0.022) was noted between hyperglycemia and infection in patients aged 65 years or older. Patients aged 65 years or older had 5.6 times the risk of developing infection as those aged younger than 65 years. Although not statistically significant, patients aged 65 years or older with hyperglycemia had 2.5 more days of neutropenia and 1.5 days longer hospital length of stay.
. CONCLUSIONS This study provides preliminary evidence that hyperglycemia is prevalent during initial induction for AML and may have harmful consequences, particularly for patients aged 65 years or older. More research is needed to determine clinically significant levels of hyperglycemia and their impact on health outcomes.
. IMPLICATIONS FOR NURSING Oncology nurses can assess and proactively collaborate with members of the healthcare team to implement strategies to prevent or mitigate the harmful consequences of hyperglycemia.
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Liraglutide, a glucagon-like peptide-1 analog, induce autophagy and senescence in HepG2 cells. Eur J Pharmacol 2017; 809:32-41. [DOI: 10.1016/j.ejphar.2017.05.015] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2016] [Revised: 05/03/2017] [Accepted: 05/09/2017] [Indexed: 02/06/2023]
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Bronsveld HK, Peeters PJHL, de Groot MCH, de Boer A, Schmidt MK, De Bruin ML. Trends in breast cancer incidence among women with type-2 diabetes in British general practice. Prim Care Diabetes 2017; 11:373-382. [PMID: 28237628 DOI: 10.1016/j.pcd.2017.02.001] [Citation(s) in RCA: 9] [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: 12/03/2016] [Revised: 02/03/2017] [Accepted: 02/04/2017] [Indexed: 12/26/2022]
Abstract
AIMS To quantify breast cancer incidence in women with type-2 diabetes and assess age-standardized trends in invasive breast cancer incidence over time and by age groups. METHODS A population-based cohort study was conducted using the British general practice database (Clinical Practice Research Datalink) using data from 1989 to 2012. All adult women prescribed anti-hyperglycemic medication were selected and matched (1:1) on age and clinical practice to a reference cohort without diabetes. RESULTS During approximately 1.6 million person years (py), 2371 breast cancer cases were diagnosed in the diabetes cohort (n=147,998) and 2252 in the reference cohort (n=147,998). Incidence of breast cancer, overall or by age groups, among women with diabetes remained stable over time. The (overall) age-standardized breast cancer IR per 100,000 py of the diabetes cohort (150, 95%CI:143-157) resembled that observed in the reference cohort (148, 95%CI:141-156); with an incidence rate ratio (IRR) of 1.01 (95%CI:0.94-1.08, p>0.05). CONCLUSIONS Currently, around 2880 women with type-2 diabetes are diagnosed with breast cancer per year in the United Kingdom. However, breast cancer incidence remained stable in the last 10 years and seems to be comparable in women with and without diabetes.
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Affiliation(s)
- Heleen K Bronsveld
- Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; Division Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
| | - Paul J H L Peeters
- Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
| | - Mark C H de Groot
- Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; Department of Clinical Chemistry and Haematology, Division of Laboratory and Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.
| | - Anthonius de Boer
- Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
| | - Marjanka K Schmidt
- Division Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
| | - Marie L De Bruin
- Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; Copenhagen Centre for Regulatory Science, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
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22
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Higher risk of colorectal cancer in patients with newly diagnosed diabetes mellitus before the age of colorectal cancer screening initiation. Sci Rep 2017; 7:46527. [PMID: 28436468 PMCID: PMC5402260 DOI: 10.1038/srep46527] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Accepted: 03/22/2017] [Indexed: 12/27/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM) is associated with greater risk for colorectal cancer (CRC). The age of onset of T2DM is decreasing worldwide. An increased CRC risk in young T2DM patients could be relevant for the age at which to initiate CRC screening. We report on CRC risk in T2DM patients with attention to age of diagnosis. We used pharmacy data (from 1998 to 2010) from the PHARMO Database Network linked to the Eindhoven Cancer Registry. Multivariable time-dependent Cox regression analyses were conducted to calculate hazard ratios (HR) for developing CRC comparing T2DM with non-T2DM. During 2,599,925 years of follow-up, 394 CRC cases among 41,716 diabetes patients (mean age 64.0 yr, 48% men) and 1,939 CRC cases among 325,054 non-diabetic patients (mean age 51.2 yr, 46% men) were identified. Diabetes was associated with an increased CRC risk in both men and women (HR 1.3, 95% CI 1.2-1.5), particularly in the first 6 months after T2DM diagnosis and pronounced in the proximal colon. This risk was even higher in men younger than 55 years (HR 2.0, 95% CI 1.0-3.8). T2DM was associated with a time-varying and subsite-specific increased CRC risk, which was even higher in men aged <55 years.
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Gnana kumar G, Amala G, Gowtham SM. Recent advancements, key challenges and solutions in non-enzymatic electrochemical glucose sensors based on graphene platforms. RSC Adv 2017. [DOI: 10.1039/c7ra02845h] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
This review elucidates the recent advances in graphene platforms in electrochemical non-enzymatic glucose sensors and provides solutions for existing bottlenecks.
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Affiliation(s)
- G. Gnana kumar
- Department of Physical Chemistry
- School of Chemistry
- Madurai Kamaraj University
- Madurai 625 021
- India
| | - G. Amala
- Department of Physical Chemistry
- School of Chemistry
- Madurai Kamaraj University
- Madurai 625 021
- India
| | - S. M. Gowtham
- School of Chemistry
- Madurai Kamaraj University
- Madurai 625 021
- India
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He W, Yu S, Wang L, He M, Cao X, Li Y, Xiao H. Exendin-4 inhibits growth and augments apoptosis of ovarian cancer cells. Mol Cell Endocrinol 2016; 436:240-9. [PMID: 27496641 DOI: 10.1016/j.mce.2016.07.032] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Revised: 07/16/2016] [Accepted: 07/26/2016] [Indexed: 12/23/2022]
Abstract
Glucagon-like peptide (GLP)-1 promotes proliferation and survival in β-cell; however, whether GLP-1 receptor agonists promote growth of human ovarian cancer cells remain unknown. We aimed to explore the effects of GLP-1 agents on ovarian cancer cells. GLP-1 receptor expression in human ovarian cancer tissues was detected by immunohistochemical analysis. The effects of exendin-4, a GLP-1R agonist, were investigated on proliferation, migration and invasion, apoptosis in vitro and tumor formation in nude mice of ovarian cancer cells. Our study demonstrated that GLP-1R expressed in both human ovarian cancer tissues and cell lines. Exendin-4 inhibited growth, migration and invasion and enhanced apoptosis of ovarian cancer cells through inhibition of the PI3K/Akt pathway. And exendin-4 attenuated tumor formation by ovarian cancer cells in vivo. Our study suggests that GLP-1R agonists do not promote the growth of ovarian cancer and may even have anticancer effect on selected diabetic patients with ovarian cancer.
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Affiliation(s)
- Wenjing He
- Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China
| | - Shuang Yu
- Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China
| | - Liantang Wang
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Mian He
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiaopei Cao
- Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China
| | - Yanbing Li
- Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China
| | - Haipeng Xiao
- Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
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Abstract
Answer questions and earn CME/CNE Comorbidity is common among cancer patients and, with an aging population, is becoming more so. Comorbidity potentially affects the development, stage at diagnosis, treatment, and outcomes of people with cancer. Despite the intimate relationship between comorbidity and cancer, there is limited consensus on how to record, interpret, or manage comorbidity in the context of cancer, with the result that patients who have comorbidity are less likely to receive treatment with curative intent. Evidence in this area is lacking because of the frequent exclusion of patients with comorbidity from randomized controlled trials. There is evidence that some patients with comorbidity have potentially curative treatment unnecessarily modified, compromising optimal care. Patients with comorbidity have poorer survival, poorer quality of life, and higher health care costs. Strategies to address these issues include improving the evidence base for patients with comorbidity, further development of clinical tools to assist decision making, improved integration and coordination of care, and skill development for clinicians. CA Cancer J Clin 2016;66:337-350. © 2016 American Cancer Society.
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Affiliation(s)
- Diana Sarfati
- Director, Cancer Control and Screening Research Group, University of Otago, Wellington, New Zealand
| | - Bogda Koczwara
- Senior Staff Specialist, Flinders Center for Innovation in Cancer, Flinders University, Adelaide, South Australia, Australia
| | - Christopher Jackson
- Senior Lecturer in Medicine, Department of Medicine, Dunedin School of Medicine, University of Otago, Wellington, New Zealand
- Consultant Medical Oncologist, Southern District Health Board, Dunedin, New Zealand
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Xu J, Ye Y, Wu H, Duerksen-Hughes P, Zhang H, Li P, Huang J, Yang J, Wu Y, Xia D. Association between markers of glucose metabolism and risk of colorectal cancer. BMJ Open 2016; 6:e011430. [PMID: 27354075 PMCID: PMC4932260 DOI: 10.1136/bmjopen-2016-011430] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES Independent epidemiological studies have evaluated the association between markers of glucose metabolism (including fasting glucose, fasting insulin, homeostasis model of risk assessment-insulin resistance (HOMA-IR), glycated haemoglobin (HbA1c) and C peptide) and the risk of colorectal cancer (CRC). However, such associations have not been systematically analysed and no clear conclusions have been drawn. Therefore, we addressed this issue using a meta-analysis approach. DESIGN Systematic review and meta-analysis. DATA SOURCES PubMed and EMBASE were searched up to May 2015. PRIMARY AND SECONDARY OUTCOME MEASURES Either a fixed-effects or random-effects model was adopted to estimate overall ORs for the association between markers of glucose metabolism and the risk of CRC. In addition, dose-response, meta-regression, subgroup and publication bias analyses were conducted. RESULTS 35 studies involving 25 566 patients and 5 706 361 participants were included. Higher levels of fasting glucose, fasting insulin, HOMA-IR, HbA1c and C peptide were all significantly associated with increased risk of CRC (fasting glucose, pooled OR=1.12, 95% CI 1.06 to 1.18; fasting insulin, pooled OR=1.42, 95% CI 1.19 to 1.69; HOMA-IR, pooled OR=1.47, 95% CI 1.24 to 1.74; HbA1c, pooled OR=1.22, 95% CI 1.02 to 1.47 (with borderline significance); C peptide, pooled OR=1.27, 95% CI 1.08 to 1.49). Subgroup analysis suggested that a higher HOMA-IR value was significantly associated with CRC risk in all subgroups, including gender, study design and geographic region. For the relative long-term markers, the association was significant for HbA1c in case-control studies, while C peptide was significantly associated with CRC risk in both the male group and colon cancer. CONCLUSIONS The real-time composite index HOMA-IR is a better indicator for CRC risk than are fasting glucose and fasting insulin. The relative long-term markers, HbA1c and C peptide, are also valid predictors for CRC risk. Considering the included case-control studies in the current analysis, more cohort studies are warranted to enhance future analysis.
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Affiliation(s)
- Jinming Xu
- Zhejiang University School of Public Health, Hangzhou, China
- Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, China
| | - Yao Ye
- Zhejiang University School of Public Health, Hangzhou, China
- Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, China
| | - Han Wu
- Zhejiang University School of Public Health, Hangzhou, China
- Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China
| | - Penelope Duerksen-Hughes
- Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California, USA
| | - Honghe Zhang
- Zhejiang University School of Public Health, Hangzhou, China
- Department of Pathology, Zhejiang University School of Medicine, Hangzhou, China
| | - Peiwei Li
- Zhejiang University School of Public Health, Hangzhou, China
- Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jian Huang
- Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jun Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yihua Wu
- Zhejiang University School of Public Health, Hangzhou, China
- Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, China
| | - Dajing Xia
- Zhejiang University School of Public Health, Hangzhou, China
- Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, China
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Current Advances in the Biochemical and Physiological Aspects of the Treatment of Type 2 Diabetes Mellitus with Thiazolidinediones. PPAR Res 2016; 2016:7614270. [PMID: 27313601 PMCID: PMC4893583 DOI: 10.1155/2016/7614270] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Accepted: 04/24/2016] [Indexed: 12/19/2022] Open
Abstract
The present review summarizes the current advances in the biochemical and physiological aspects in the treatment of type 2 diabetes mellitus (DM2) with thiazolidinediones (TZDs). DM2 is a metabolic disorder characterized by hyperglycemia, triggering the abnormal activation of physiological pathways such as glucose autooxidation, polyol's pathway, formation of advance glycation end (AGE) products, and glycolysis, leading to the overproduction of reactive oxygen species (ROS) and proinflammatory cytokines, which are responsible for the micro- and macrovascular complications of the disease. The treatment of DM2 has been directed toward the reduction of hyperglycemia using different drugs such as insulin sensitizers, as the case of TZDs, which are able to lower blood glucose levels and circulating triglycerides by binding to the nuclear peroxisome proliferator-activated receptor gamma (PPARγ) as full agonists. When TZDs interact with PPARγ, the receptor regulates the transcription of different genes involved in glucose homeostasis, insulin resistance, and adipogenesis. However, TZDs exhibit some adverse effects such as fluid retention, weight gain, hepatotoxicity, plasma-volume expansion, hemodilution, edema, bone fractures, and congestive heart failure, which limits their use in DM2 patients.
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Shibata Y, Kagechika K, Ota M, Yamaguchi M, Setoguchi M, Kubo H, Chiba K, Takano H, Akiyama C, Ono M, Nishi M, Usui H. Synthesis and Structure-Activity Relationships of 2-Aminoacetamide Derivatives as Peroxisome Proliferator-Activated Receptor α/γ Dual Agonists. Chem Pharm Bull (Tokyo) 2016; 63:591-602. [PMID: 26235167 DOI: 10.1248/cpb.c15-00221] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
We describe the design, syntheses, and structure-activity relationships of novel zwitterionic compounds as nonthiazolidinedion-based peroxisome proliferator-activated receptor (PPAR) α/γ dual agonists. In our previous report, we obtained compound 1 showing potent PPARα/γ dual agonistic activities, together with a sufficient glucose-lowering effect in db/db mice. However, this compound possessed an issue, i.e., the 1,3,4-oxadiazole ring was not stable in acidic conditions. Thus, we carried out further optimization to improve the stability while maintaining the other favorable profile features including potent PPARα/γ dual agonistic activity. We addressed the issue by changing the oxadiazole ring to a bioisostere amide group. These amide derivatives were stable in acidic conditions and decreased plasma glucose and plasma triglyceride levels significantly without marked weight gain.
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29
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Ye Y, Wu Y, Xu J, Ding K, Shan X, Xia D. Association between dietary carbohydrate intake, glycemic index and glycemic load, and risk of gastric cancer. Eur J Nutr 2016; 56:1169-1177. [PMID: 26873099 DOI: 10.1007/s00394-016-1166-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2015] [Accepted: 01/22/2016] [Indexed: 12/22/2022]
Abstract
PURPOSE The association between dietary carbohydrate intake, glycemic index (GI) and glycemic load (GL), and risk of gastric cancer (GC) has been investigated by many studies. However, the results of these studies were controversial. The aim of our study was to systematically assess this issue. METHODS PUBMED and EMBASE were searched up to March 2015, and either a fixed- or a random-effects model was adopted to estimate overall relative risks (RRs). Dose-response, meta-regression, subgroup, and publication bias analyses were applied. RESULTS Twenty-six studies with approximately 540,000 participants were finally included in this meta-analysis. High level of dietary carbohydrate intake (pooled RR 1.17, 95 % CI 0.91-1.50), GI (pooled RR 1.17, 95 % CI 0.80-1.69), and GL (pooled RR 1.06, 95 % CI 0.90-1.26) were all nonsignificantly associated with incidence of GC. In addition, no significant dose-response relationship was observed between carbohydrate intake, GI and GL, and the risk of GC. However, further subgroup analyses based on gender and geographic region suggested a significant association between higher carbohydrate intake (pooled RR 1.52, 95 % CI 1.10-2.08), GL (pooled RR 1.41, 95 % CI 1.04-1.92), and GC risk in males subgroup, and between higher carbohydrate intake (pooled RR 1.69, 95 % CI 1.36-2.09) and GC risk in Asian studies. CONCLUSIONS No significant association was found between dietary carbohydrate intake, GI and GL, and risk of GC. However, significantly positive association was observed in the males subgroup and Asian studies.
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Affiliation(s)
- Yao Ye
- Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, 310058, Zhejiang, China.,Department of Oncology, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, 310009, Zhejiang, China
| | - Yihua Wu
- Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, 310058, Zhejiang, China. .,Department of Epidemiology and Health Statistics, Zhejiang University School of Public Health, Hangzhou, 310058, Zhejiang, China.
| | - Jinming Xu
- Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, 310058, Zhejiang, China.,Department of Oncology, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, 310009, Zhejiang, China
| | - Kefeng Ding
- Department of Oncology, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, 310009, Zhejiang, China
| | - Xiaoyun Shan
- Jinhua Central Hospital, Jinhua Hospital of Zhejiang University, Jinhua, 321000, Zhejiang, China
| | - Dajing Xia
- Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, 310058, Zhejiang, China. .,Zhejiang University School of Public Health, Hangzhou, 310058, China.
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Singh S, Earle CC, Bae SJ, Fischer HD, Yun L, Austin PC, Rochon PA, Anderson GM, Lipscombe L. Incidence of Diabetes in Colorectal Cancer Survivors. J Natl Cancer Inst 2016; 108:djv402. [DOI: 10.1093/jnci/djv402] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Accepted: 12/01/2015] [Indexed: 01/05/2023] Open
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Villadolid J, Ersek JL, Fong MK, Sirianno L, Story ES. Management of hyperglycemia from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) targeting T790M-mediated resistance. Transl Lung Cancer Res 2015; 4:576-83. [PMID: 26629426 DOI: 10.3978/j.issn.2218-6751.2015.10.01] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients are associated with sensitivity to small molecule tyrosine kinase inhibitors (TKIs) such as erlotinib, gefitinib, and afatinib. Although studies show an increased progression free survival (PFS) with use of EGFR TKIs in the first-line setting, most patients will develop resistance to therapy after the first 8-16 months. T790M is an acquired resistance mutation reported in 60-70% of patients who initially responded to a prior EGFR TKI. Recently, EGFR TKIs targeting T790M have been developed to overcome resistance with positive results in PFS and objective response rate in patients who have had disease progression on at least one TKI. Two EGFR TKIs targeting T790M, AZD9291 and rociletinib, are new active treatment options for NSCLC but differ in adverse effect profiles. Dose-limiting hyperglycemia has been reported with rociletinib and has required dose reduction, an oral antihyperglycemic, or both, without discontinuation of therapy. This suggests that patients may be effectively treated chronically for hyperglycemia associated with EGFR TKIs targeting T790M, however, guidelines for treatment of hyperglycemia in this setting have not been published. We discuss mechanisms of hyperglycemia associated with TKIs and initial management of hyperglycemia, including benefits and limitations of oral antihyperglycemic options, adjustment of therapy based on grade of hyperglycemia, and recommendations for follow-up glucose monitoring.
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Affiliation(s)
- Jeryl Villadolid
- 1 Department of Pharmacy, 2 Department of Solid Tumor Oncology and Investigational Therapeutics, 3 Department of Solid Tumor Oncology, 4 Endocrine Center, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC 28204, USA
| | - Jennifer L Ersek
- 1 Department of Pharmacy, 2 Department of Solid Tumor Oncology and Investigational Therapeutics, 3 Department of Solid Tumor Oncology, 4 Endocrine Center, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC 28204, USA
| | - Mei Ka Fong
- 1 Department of Pharmacy, 2 Department of Solid Tumor Oncology and Investigational Therapeutics, 3 Department of Solid Tumor Oncology, 4 Endocrine Center, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC 28204, USA
| | - Lindsey Sirianno
- 1 Department of Pharmacy, 2 Department of Solid Tumor Oncology and Investigational Therapeutics, 3 Department of Solid Tumor Oncology, 4 Endocrine Center, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC 28204, USA
| | - Ellen S Story
- 1 Department of Pharmacy, 2 Department of Solid Tumor Oncology and Investigational Therapeutics, 3 Department of Solid Tumor Oncology, 4 Endocrine Center, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC 28204, USA
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Friis S, Kesminiene A, Espina C, Auvinen A, Straif K, Schüz J. European Code against Cancer 4th Edition: Medical exposures, including hormone therapy, and cancer. Cancer Epidemiol 2015; 39 Suppl 1:S107-19. [PMID: 26390952 DOI: 10.1016/j.canep.2015.08.003] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Revised: 07/27/2015] [Accepted: 08/06/2015] [Indexed: 12/13/2022]
Abstract
The 4th edition of the European Code against Cancer recommends limiting - or avoiding when possible - the use of hormone replacement therapy (HRT) because of the increased risk of cancer, nevertheless acknowledging that prescription of HRT may be indicated under certain medical conditions. Current evidence shows that HRT, generally prescribed as menopausal hormone therapy, is associated with an increased risk of cancers of the breast, endometrium, and ovary, with the risk pattern depending on factors such as the type of therapy (oestrogen-only or combined oestrogen-progestogen), duration of treatment, and initiation according to the time of menopause. Carcinogenicity has also been established for anti-neoplastic agents used in cancer therapy, immunosuppressants, oestrogen-progestogen contraceptives, and tamoxifen. Medical use of ionising radiation, an established carcinogen, can provide major health benefits; however, prudent practices need to be in place, with procedures and techniques providing the needed diagnostic information or therapeutic gain with the lowest possible radiation exposure. For pharmaceutical drugs and medical radiation exposure with convincing evidence on their carcinogenicity, health benefits have to be balanced against the risks; potential increases in long-term cancer risk should be considered in the context of the often substantial and immediate health benefits from diagnosis and/or treatment. Thus, apart from HRT, no general recommendations on reducing cancer risk were given for carcinogenic drugs and medical radiation in the 4th edition of European Code against Cancer. It is crucial that the application of these measures relies on medical expertise and thorough benefit-risk evaluation. This also pertains to cancer-preventive drugs, and self-medication with aspirin or other potential chemopreventive drugs is strongly discouraged because of the possibility of serious, potentially lethal, adverse events.
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Affiliation(s)
- Søren Friis
- Danish Cancer Society Research Center, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark; Department of Public Health, University of Copenhagen, 2100 Copenhagen, and Department of Clinical Epidemiology, Faculty of Health, Aarhus University Hospital, 8200 Aarhus N, Denmark
| | - Ausrele Kesminiene
- International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69372 Lyon, France
| | - Carolina Espina
- International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69372 Lyon, France
| | - Anssi Auvinen
- School of Health Sciences, University of Tampere, FI-33014 Tampere, Finland; STUK-Radiation and Nuclear Safety Authority, Research and Environmental Surveillance, FI-00881 Helsinki, Finland
| | - Kurt Straif
- International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69372 Lyon, France
| | - Joachim Schüz
- International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69372 Lyon, France.
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Valent F. Diabetes mellitus and cancer of the digestive organs: An Italian population-based cohort study. J Diabetes Complications 2015; 29:1056-61. [PMID: 26275864 DOI: 10.1016/j.jdiacomp.2015.07.017] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Revised: 06/22/2015] [Accepted: 07/17/2015] [Indexed: 12/14/2022]
Abstract
AIMS The association between diabetes mellitus and the occurrence of digestive organs cancers was investigated in the Italian region Friuli Venezia Giulia. The risk of cancer associated with oral antidiabetic drugs among subjects with type 2 diabetes was also assessed. METHODS This was a retrospective population-based cohort study based on the 2002-2014 regional administrative health data. Incident digestive cancers were identified through the hospital discharge diagnoses. The incidence rates of cancer at different sites were calculated for type 1 and 2 diabetics and for non-diabetics. Proportional hazard models were built to assess the risk of cancer associated with diabetes and antidiabetic drugs. RESULTS Diabetes was associated with increased risk of digestive cancers. Liver and pancreatic cancers were associated with the highest hazard ratios. Among type 2 diabetics, total number of metformin prescriptions was associated with reduced risk of most types of digestive cancers; sulfonylureas with reduced risk of stomach and pancreatic cancer. CONCLUSIONS In this Italian population the excess risk of digestive cancers for diabetic patients was confirmed. Further research is needed to clarify the role of antidiabetic drugs.
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Affiliation(s)
- Francesca Valent
- Epidemiological Service, Regional Health Directorate, Region Friuli Venezia Giulia, Via Pozzuolo 330, 33100 Udine, Italy.
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Abstract
OBJECTIVE The true rate of new-onset diabetes (NODM) after distal pancreatectomy (DP) is not known. This systematic review was carried out to obtain exact percentages regarding the incidence of NODM after DP for different indications. BACKGROUND Distal pancreatectomy is the standard procedure for removal of benign or (potentially) malignant lesions from the pancreatic body or tail and increasingly used for removal of often benign lesions. It is associated with low mortality rates, though postoperative diabetes remains a serious problem. METHODS Embase, PubMed, Medline, Web of Science, the Cochrane Library, and Google Scholar were searched for articles reporting incidence of NODM after DP. Methodological quality of the included studies was assessed by means of the Newcastle-Ottawa scale for cohort studies and the Moga scale for case series. Mean weighted overall percentages of NODM after DP for different indications were calculated with 95% confidence intervals (CI) and corresponding P values. RESULTS Twenty-six studies were included, comprising 1.731 patients undergoing DP. The average cumulative incidence of NODM after DP performed for chronic pancreatitis was 39% and for benign or (potentially) malignant lesions it was 14%. Comparing the proportions of these 2 groups showed a significant difference (95% CI: 0.351-0.434 and 0.110-0.172, respectively, P < 0.000). The average percentage of insulin-dependent diabetes among patients with NODM after DP was 77%. CONCLUSIONS This review is the largest of its kind to assess the cumulative incidence of NODM after DP and shows that NODM is a frequently occurring complication, with incidence depending on the preexisting disease and follow-up time. Because NODM can affect quality of life, patients undergoing DP should be preoperatively provided with this information as specific as possible.
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Bosetti C, Franchi M, Nicotra F, Asciutto R, Merlino L, La Vecchia C, Corrao G. Insulin and other antidiabetic drugs and hepatocellular carcinoma risk: a nested case-control study based on Italian healthcare utilization databases. Pharmacoepidemiol Drug Saf 2015; 24:771-8. [PMID: 26013675 DOI: 10.1002/pds.3801] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2014] [Revised: 03/31/2015] [Accepted: 04/22/2015] [Indexed: 12/16/2022]
Abstract
PURPOSE Insulin and other antidiabetic drugs may modulate hepatocellular carcinoma (HCC) risk in diabetics. METHODS We have analyzed the role of various antidiabetic drugs on HCC in a nested case-control study using the healthcare utilization databases of the Lombardy Region in Italy. This included 190 diabetic subjects with a hospital discharge reporting a diagnosis of malignant HCC and 3772 diabetic control subjects matched to each case on sex, age, date at cohort entry, and duration of follow-up. RESULTS Increased risks of HCC were found for use of insulin (odds ratio [OR] = 3.73, 95% confidence interval [CI] 2.52-5.51), sulfonylureas (OR = 1.39, 95%CI 0.98-1.99), and repaglinide (OR = 2.12, 95%CI 1.38-3.26), while a reduced risk was found for use of metformin (OR = 0.57, 95%CI 0.41-0.79). The risk of HCC increased with increasing duration of insulin use (OR = 2.52 for <1 year, 5.41 for 1-2 years, and 6.01 for ≥2 years; p for trend < 0.001), while no clear pattern with duration was observed for sulfonylureas, repaglinide, and metformin. CONCLUSION Our study supports the evidence that patients with diabetes using metformin, and possibly other antidiabetic drugs that increase insulin sensibility, have a reduced risk of HCC, while those using insulin or drugs that increase circulating insulin, such as insulin secretagogues, have an increased risk. Whether these associations are causal, or influenced by different severity of diabetes and/or possible residual bias or misclassification, is still open to discussion.
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Affiliation(s)
- Cristina Bosetti
- Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy
| | - Matteo Franchi
- Department of Statistics, Unit di Biostatistics and Epidemiology, Università Milano-Bicocca, Milan, Italy
| | - Federica Nicotra
- Department of Statistics, Unit di Biostatistics and Epidemiology, Università Milano-Bicocca, Milan, Italy
| | - Rosario Asciutto
- Department of Sciences for the Health Promotion and Mother and Child Care "G. D'Alessandro", Hygiene Section, University of Palermo, Palermo, Italy
| | - Luca Merlino
- Unità Organizzativa Governo dei Dati, delle Strategie e Piani del Sistema Sanitario, Regione Lombardia, Milan, Italy
| | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - Giovanni Corrao
- Department of Statistics, Unit di Biostatistics and Epidemiology, Università Milano-Bicocca, Milan, Italy
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Michalopoulos G, Vrakas S, Ntouli V, Lamprinakos S, Makris K, Tzathas C. Sessile serrated adenomas versus conventional adenomas. Different polyps in different populations? Indian J Gastroenterol 2015; 34:245-51. [PMID: 25917523 DOI: 10.1007/s12664-015-0562-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Accepted: 04/02/2015] [Indexed: 02/04/2023]
Abstract
PURPOSE The aim of this study was to determine risk factors for the development of sessile serrated adenomas (SSA/Ps) as well as to study differences between groups with SSA/Ps and conventional adenomas (tubular, tubulovillus and villus) in the general population. METHODS One hundred patients with normal colonoscopies, 27 patients with 53 SSA/Ps and 69 patients with 156 conventional adenomas were studied, epidemiological data were collected and calculations of body mass index and waist-to-hip ratio were performed prior to endoscopy. A univariate and a multivariate logistic regression analysis were performed using Stata 9.0. RESULTS SSA/Ps had a positive association with increasing age (p = 0.01), heavy smoking (≥20 packet years) (p = 0.001) and past history of polyps (p = 0.004) in comparison to normal population. SSA/Ps showed an inverse association with conventional adenomas for diabetes mellitus (p < 0.001) and arterial hypertension (p = 0.001). Meanwhile, female sex was positively associated with SSA/P development in comparison to conventional adenomas (p = 0.031). CONCLUSIONS Heavy smoking as a significant risk factor for developing SSA/Ps was confirmed from this study. It also seemed that patients with diabetes mellitus and/or hypertension developed conventional adenomas more frequently than SSA/Ps; on the contrary, females were at higher risk of developing SSA/Ps than conventional adenomas.
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Affiliation(s)
- Georgios Michalopoulos
- Gastroenterology Department, Tzaneion General Hospital of Piraeus, Zani and Afenbtouli, 1, Piraeus, 18536, Greece,
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Liu X, Hemminki K, Försti A, Sundquist K, Sundquist J, Ji J. Cancer risk in patients with type 2 diabetes mellitus and their relatives. Int J Cancer 2015; 137:903-10. [PMID: 25604005 DOI: 10.1002/ijc.29440] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2014] [Accepted: 01/08/2015] [Indexed: 11/09/2022]
Abstract
Epidemiological studies indicate that risks of certain cancers are increased in individuals hospitalized for type 2 diabetes mellitus (T2DM), which may not be representative of the entire population of T2DM patients as most of them are treated in primary health cares. To examine the subsequent cancer risk in individuals with T2DM from hospitals and primary health cares, and in their siblings and spouses, standardized incidence ratios (SIRs) were used to assess systematically risks of 35 cancer sites/types in individuals with T2DM using a nationwide Swedish database covering the period 1964 through 2010. Increased SIRs were recorded for 24 cancer sites/types in individuals with T2DM. The highest SIRs were for pancreatic cancer and liver cancer (2.98 and 2.43, respectively). A decreased SIR was noted for prostate cancer. Five cancers showed increased SIRs during the whole follow-up period: colon, liver, pancreatic, endometrial and kidney cancers. T2DM patients in inpatient, outpatient and primary health care showed similar risk patterns. The overall SIRs for cancer in the siblings and spouses of individuals with T2DM were 0.97 and 1.01, respectively. The insulin users showed an overall increased risk of cancer. This study showed increased risks of 24 cancers in individuals with T2DM, but not in their siblings or spouses, suggesting that the profound metabolic disturbances of the underlying disease may explain the observed increases. Further studies examining the endogenous and exogenous factors underlying these associations are needed.
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Affiliation(s)
- Xiangdong Liu
- Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden
| | - Kari Hemminki
- Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden.,Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Asta Försti
- Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden.,Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Kristina Sundquist
- Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden.,Stanford Prevention Research Center, Stanford University School of Medicine, CA
| | - Jan Sundquist
- Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden.,Stanford Prevention Research Center, Stanford University School of Medicine, CA
| | - Jianguang Ji
- Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden
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Ata N, Dal K, Kucukazman M, Yeniova AÖ, Karakaya S, Unsal O, Dagdeviren M, Akın KO, Baser S, Beyan E, Ertugrul DT. The effect of glycemic control on CEA, CA 19-9, amylase and lipase levels. Open Med (Wars) 2014; 10:8-13. [PMID: 28352671 PMCID: PMC5152950 DOI: 10.1515/med-2015-0002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2014] [Accepted: 07/29/2014] [Indexed: 12/22/2022] Open
Abstract
Background Diabetes mellitus is closely related to pancreas cancer. In this study we aimed to investigate the effect of hyperglycemia on tumor and inflammation markers, as well as pancreatic exocrine functions. Methods A total of 98 consecutive diabetic patients with poor glycemic control, and 50 healthy controls were included in the study. We measured hsCRP, erythrocyte sedimentation rate (ESR), CA19-9, CEA, amylase and lipase in addition to routine biochemistry tests, before and after euglycemia was achieved. Results Fasting blood glucose, HbA1c, CA19-9, CEA, hsCRP, ESR, triglycerides, AST, ALT, GGT, ALP, total cholesterol and LDL-C levels decreased significantly with the regulation of glycemic control. Amylase and lipase levels increased with the regulation of glycemic control. After glycemic control, CA19-9 and CEA levels were still higher, whereas amylase and lipase levels were still lower in the diabetic group compared with the control group. Basal HbA1c showed significant correlation with CA19-9, CEA, amylase and lipase. Conclusions We propose to repeat observations of tumor markers after hyperglycemia is resolved, in order to avoid unnecessary invasive tests. Our data also suggest that pancreatic exocrine function was improved with lowering blood glucose in a short period of time.
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Affiliation(s)
- Naim Ata
- Kecioren Training and Research Hospital, Department of Internal Medicine. Ardahan street. No:2506380 Keçiören, Ankara, Turkey
| | - Kürşat Dal
- Kecioren Training and Research Hospital, Department of Internal Medicine. Ardahan street. No:2506380 Keçiören, Ankara, Turkey
| | - Metin Kucukazman
- Kecioren Training and Research Hospital, Department of Internal Medicine. Ardahan street. No:2506380 Keçiören, Ankara, Turkey
| | - Abdullah Ö Yeniova
- Kecioren Training and Research Hospital, Department of Internal Medicine. Ardahan street. No:2506380 Keçiören, Ankara, Turkey, Tel: +90 312 3569000
| | - Serdar Karakaya
- Kecioren Training and Research Hospital, Department of Internal Medicine. Ardahan street. No:2506380 Keçiören, Ankara, Turkey
| | - Oktay Unsal
- Kecioren Training and Research Hospital, Department of Internal Medicine. Ardahan street. No:2506380 Keçiören, Ankara, Turkey
| | - Murat Dagdeviren
- Kecioren Training and Research Hospital, Department of Internal Medicine. Ardahan street. No:2506380 Keçiören, Ankara, Turkey
| | - Kadir O Akın
- Kecioren Training and Research Hospital, Department of Clinical Biochemistry. Ardahan street. No:2506380 Keçiören, Ankara, Turkey
| | - Salih Baser
- Kecioren Training and Research Hospital, Department of Internal Medicine. Ardahan street. No:2506380 Keçiören, Ankara, Turkey
| | - Esin Beyan
- Kecioren Training and Research Hospital, Department of Internal Medicine. Ardahan street. No:2506380 Keçiören, Ankara, Turkey
| | - Derun T Ertugrul
- Kecioren Training and Research Hospital, Department of Internal Medicine. Ardahan street. No:2506380 Keçiören, Ankara, Turkey
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Zhao H, Wang L, Wei R, Xiu D, Tao M, Ke J, Liu Y, Yang J, Hong T. Activation of glucagon-like peptide-1 receptor inhibits tumourigenicity and metastasis of human pancreatic cancer cells via PI3K/Akt pathway. Diabetes Obes Metab 2014; 16:850-60. [PMID: 24641303 DOI: 10.1111/dom.12291] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Revised: 01/14/2014] [Accepted: 03/11/2014] [Indexed: 01/18/2023]
Abstract
AIMS It has been reported that glucagon-like peptide-1 (GLP-1) agents are associated with an increased risk of pancreatic cancer in patients with type 2 diabetes. Reports have indicated that GLP-1 promotes pancreatic metaplasia and premalignant lesions. The aims of this study were to determine the effects of GLP-1-based therapy on pancreatic cancer cells. METHODS Immunohistochemistry was used to investigate GLP-1 receptor (GLP-1R) expression in 30 human pancreatic cancer tissues. We also analysed associated clinicopathological data and each patient's prognosis. Two human pancreatic cancer cell lines were used to evaluate the in vitro effects of the GLP-1R agonist liraglutide on cell growth, migration and invasion. Mouse xenograft models of human pancreatic cancer were established to evaluate the effects of liraglutide in vivo. RESULTS Human pancreatic cancer tissues showed lower levels or a lack of GLP-1R expression when compared with levels in the tumour-adjacent pancreatic tissues. Negative GLP-1R expression occurred more frequently in advanced tumours with larger diameters and lymphatic metastasis, and was associated with a poor prognosis. GLP-1R activation with liraglutide inhibited tumourigenicity and metastasis of human pancreatic cancer cells in vitro and in vivo. Akt activation was dose-dependently inhibited by liraglutide, and the PI3K inhibitors, LY294002 and wortmannin, displayed similar suppressive effects to liraglutide in human pancreatic cancer cells. CONCLUSIONS GLP-1R activation has an antitumour effect on human pancreatic cancers via inhibition of the PI3K/Akt pathway. This finding suggests that GLP-1-based therapies may be beneficial, rather than harmful, in treating type 2 diabetic patients with pancreatic cancer.
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Affiliation(s)
- H Zhao
- Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China
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Onitilo AA, Engel JM, Stankowski RV. Cardiovascular toxicity associated with adjuvant trastuzumab therapy: prevalence, patient characteristics, and risk factors. Ther Adv Drug Saf 2014; 5:154-66. [PMID: 25083270 DOI: 10.1177/2042098614529603] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Before the advent of the human epidermal growth factor receptor 2 (HER2)-targeted monoclonal antibody trastuzumab, HER2-positive breast cancers were difficult to treat and had a poor prognosis. Adjuvant trastuzumab is now an important part of the treatment regimen for many women with HER2-positive breast cancer and has undoubtedly resulted in a significant improvement in prognosis, but it is associated with a risk for cardiotoxicity. In this review, we describe the prevalence, patient characteristics, and risk factors for cardiotoxicity associated with use of adjuvant trastuzumab. Understanding risk factors for trastuzumab-induced cardiotoxicity and appropriate patient monitoring during trastuzumab treatment allows for safe and effective use of this important adjuvant therapy.
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Affiliation(s)
- Adedayo A Onitilo
- Department of Hematology/Oncology, Marshfield Clinic Weston Center, 3501 Cranberry Boulevard, Weston, WI 54476, USA
| | - Jessica M Engel
- Marshfield Clinic Cancer Care at St. Michaels, Stevens Point, WI, USA
| | - Rachel V Stankowski
- Office of Scientific Writing, Marshfield Clinic Research Foundation, Marshfield, WI, USA
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Detection bias may be the main cause of increased cancer incidence among diabetics: results from the Rotterdam Study. Eur J Cancer 2014; 50:2449-55. [PMID: 25047425 DOI: 10.1016/j.ejca.2014.06.019] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2014] [Revised: 06/23/2014] [Accepted: 06/24/2014] [Indexed: 12/18/2022]
Abstract
AIM Type 2 diabetes is associated with an increased cancer risk. Most studies on this topic analyse diabetes as a risk factor without adjusting for diabetes duration before cancer occurrence. This study aimed to investigate the association between diabetes duration and cancer risk in more detail. METHODS In this prospective cohort study, diabetes diagnosis was based on clinical information and use of glucose lowering medication. Details on incident cancers were obtained via general practitioners and linkage to pathology registers. Cox proportional hazards models were used with onset and duration of diabetes as time-varying determinants. RESULTS The study comprised 10,181 individuals. Diabetes was associated with an increased overall risk of incident cancers (hazard ratio (HR) 1.2, 95% confidence interval (CI) 1.07-1.39) and pancreatic cancer (HR 2.9, 95% CI 1.75-4.89). A diagnosis of diabetes less than three months before the diagnosis of cancer was associated with strongly increased risks of all- (HR 3.3, 95% CI 2.50-4.32) and pancreatic cancers (HR 28.7, 95% CI 6.32-130.58). CONCLUSION The magnitude of the association between diabetes and an increased risk of cancer seems to be inflated by detection- or protopathic bias. Future studies investigating this association should adjust for diabetes duration and include a plausible aetiological risk window.
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Cufí S, Corominas-Faja B, Lopez-Bonet E, Bonavia R, Pernas S, López IÁ, Dorca J, Martínez S, López NB, Fernández SD, Cuyàs E, Visa J, Rodríguez-Gallego E, Quirantes-Piné R, Segura-Carretero A, Joven J, Martin-Castillo B, Menendez JA. Dietary restriction-resistant human tumors harboring the PIK3CA-activating mutation H1047R are sensitive to metformin. Oncotarget 2014; 4:1484-95. [PMID: 23986086 PMCID: PMC3824528 DOI: 10.18632/oncotarget.1234] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Cancer cells expressing constitutively active phosphatidylinositol-3 kinase (PI3K) are proliferative regardless of the absence of insulin, and they form dietary restriction (DR)-resistant tumors in vivo. Because the binding of insulin to its receptors activates the PI3K/AKT/mammalian target of rapamycin (mTOR) signaling cascade, activating mutations in the PIK3CA oncogene may determine tumor response to DR-like pharmacological strategies targeting the insulin and mTOR pathways. The anti-diabetic drug metformin is a stereotypical DR mimetic that exerts its anti-cancer activity through a dual mechanism involving insulin-related (systemic) and mTOR-related (cell-autonomous) effects. However, it remains unclear whether PIK3CA-activating mutations might preclude the anti-cancer activity of metformin in vivo. To model the oncogenic PIK3CA-driven early stages of cancer, we used the clonal breast cancer cell line MCF10DCIS.com, which harbors the gain-of-function H1047R hot-spot mutation in the catalytic domain of the PI3KCA gene and has been shown to form DR-refractory xenotumors. To model PIK3CA-activating mutations in late stages of cancer, we took advantage of the isogenic conversion of a PIK3CA-wild-type tumor into a PIK3CA H1047R-mutated tumor using the highly metastatic colorectal cancer cell line SW48. MCF10DCIS.com xenotumors, although only modestly affected by treatment with oral metformin (approximately 40% tumor growth inhibition), were highly sensitive to the intraperitoneal (i.p.) administration of metformin, the anti-cancer activity of which increased in a time-dependent manner and reached >80% tumor growth inhibition by the end of the treatment. Metformin treatment via the i.p. route significantly reduced the proliferation factor mitotic activity index (MAI) and decreased tumor cellularity in MCF10DCIS.com cancer tissues. Whereas SW48-wild-type (PIK3CA+/+) cells rapidly formed metformin-refractory xenotumors in mice, ad libitum access to water containing metformin significantly reduced the growth of SW48-mutated (PIK3CAH1047R/+) xenotumors by approximately 50%. Thus, metformin can no longer be considered as a bona fide DR mimetic, at least in terms of anti-cancer activity, because tumors harboring the insulin-unresponsive, DR-resistant, PIK3CA-activating mutation H1047R remain sensitive to the anti-tumoral effects of the drug. Given the high prevalence of PIK3CA mutations in human carcinomas and the emerging role of PIK3CA mutation status in the treatment selection process, these findings might have a significant impact on the design of future trials evaluating the potential of combining metformin with targeted therapy.
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Affiliation(s)
- Sílvia Cufí
- Metabolism and Cancer Group, Translational Research Laboratory, Catalan Institute of Oncology, Girona, Catalonia, Spain
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Wu JW, Boudreau DM, Park Y, Simonds NI, Freedman AN. Commonly used diabetes and cardiovascular medications and cancer recurrence and cancer-specific mortality: a review of the literature. Expert Opin Drug Saf 2014; 13:1071-99. [PMID: 24999107 DOI: 10.1517/14740338.2014.926887] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Cancer most commonly arises in the elderly who are often burdened with comorbidities. Medications used for treating these comorbidities may alter cancer prognosis. Understanding the impact of these medications on cancer is important in order to make effective evidence-based decisions about managing comorbidities while improving cancer outcomes. AREAS COVERED The evidence on diabetes, statins, antihypertensive and anti-inflammatory medications and their association with cancer recurrence and cancer-specific mortality are reviewed. The strengths and limitations of the existing literature, the current state of the field and future directions are discussed. EXPERT OPINION Metformin and aspirin were associated with a reduced risk of cancer recurrence and cancer-specific mortality. The evidence for statins and antihypertensive medications on cancer survival was inconsistent. There were few studies to suggest that any of the medication classes of interest were associated with negative effects on cancer survival. Methodological shortcomings within observational studies, such as confounding, distinguishing between use of medications pre-cancer versus post-cancer diagnosis/treatment, misclassification of exposures/outcomes, informative censoring and competing risks, must be considered. New observational studies addressing these limitations are essential. Some clinical trials are underway to further investigate the beneficial effects of these drugs and completed trials have confirmed results demonstrated in observational studies.
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Affiliation(s)
- Jennifer W Wu
- McGill University, Epidemiology, Biostatistics, and Occupational Health , 1020 Pine Avenue, Montreal, Quebec, H3A 1A2 , Canada
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Rampal S, Yang MH, Sung J, Son HJ, Choi YH, Lee JH, Kim YH, Chang DK, Rhee PL, Rhee JC, Guallar E, Cho J. Association between markers of glucose metabolism and risk of colorectal adenoma. Gastroenterology 2014; 147:78-87.e3. [PMID: 24632359 DOI: 10.1053/j.gastro.2014.03.006] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2013] [Revised: 02/27/2014] [Accepted: 03/05/2014] [Indexed: 01/02/2023]
Abstract
BACKGROUND & AIMS Diabetes is a risk factor for colorectal cancer. We studied the association between markers of glucose metabolism and metabolic syndrome and the presence of colorectal adenomas in a large number of asymptomatic men and women attending a health screening program in South Korea. We also investigated whether these associations depend on adenoma location. METHODS In a cross-sectional study, we measured fasting levels of glucose, insulin, hemoglobin A1c, and C-peptide and calculated homeostatic model assessment (HOMA) values (used to quantify insulin resistance) for 19,361 asymptomatic South Korean subjects who underwent colonoscopy examinations from January 2006 to June 2009. Participants completed a standardized self-administered health questionnaire and a validated semiquantitative food frequency questionnaire. Blood samples were collected on the day of the colonoscopy; fasting blood samples were also collected. Robust Poisson regression was used to model the associations of glucose markers with the prevalence of any adenoma. RESULTS Using detailed multivariable-adjusted dose-response models, the prevalence ratios (aPR, 95% confidence interval [CI]) for any adenoma, comparing the 90th with the 10th percentile, were 1.08 (1.00-1.16; P = .04) for fasting glucose, 1.07 (0.99-1.15; P = .10) for insulin, 1.09 (1.02-1.18, P = .02) for HOMA, 1.09 (1.01-1.17; P = .02) for hemoglobin A1c, and 1.14 (1.05-1.24; P = .002) for C-peptide. The corresponding ratios for nonadvanced adenomas were 1.11 (0.99-1.25; P = .08), 1.10 (0.98-1.24; P = .12), 1.15 (1.02-1.29; P = .02), 1.14 (1.01-1.28; P = .03), and 1.20 (1.05-1.37; P = .007), respectively. The corresponding ratios for advanced adenomas were 1.32 (0.94-1.84; P = .11), 1.23 (0.87-1.75; P = .24), 1.30 (0.92-1.85; P = .14), 1.13 (0.79-1.61; P = .50), and 1.67 (1.15-2.42; P = .007), respectively. Metabolic syndrome was associated with the prevalence of any adenoma (aPR, 1.18; 95% CI, 1.13-1.24; P < .001), nonadvanced adenoma (aPR, 1.30; 95% CI, 1.20-1.40; P < .001), and advanced adenoma (aPR, 1.42; 95% CI, 1.14-1.78; P = .002). Associations were similar for adenomas located in the distal versus proximal colon. CONCLUSIONS Increasing levels of glucose, HOMA values, levels of hemoglobin A1c and C-peptide, and metabolic syndrome are significantly associated with the prevalence of adenomas. Adenomas should be added to the list of consequences of altered glucose metabolism.
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Affiliation(s)
- Sanjay Rampal
- Department of Social and Preventive Medicine, Julius Centre University of Malaya, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
| | - Moon Hee Yang
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jidong Sung
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Hee Jung Son
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
| | - Yoon-Ho Choi
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jun Haeng Lee
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Young-Ho Kim
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Dong Kyung Chang
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Poong-Lyul Rhee
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jong Chul Rhee
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Eliseo Guallar
- Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of Medicine and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Juhee Cho
- Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea; Biostatistics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, South Korea.
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Xu CX, Zhu HH, Zhu YM. Diabetes and cancer: Associations, mechanisms, and implications for medical practice. World J Diabetes 2014; 5:372-380. [PMID: 24936258 PMCID: PMC4058741 DOI: 10.4239/wjd.v5.i3.372] [Citation(s) in RCA: 100] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Revised: 02/07/2014] [Accepted: 04/17/2014] [Indexed: 02/05/2023] Open
Abstract
Both diabetes mellitus and cancer are prevalent diseases worldwide. It is evident that there is a substantial increase in cancer incidence in diabetic patients. Epidemiologic studies have indicated that diabetic patients are at significantly higher risk of common cancers including pancreatic, liver, breast, colorectal, urinary tract, gastric and female reproductive cancers. Mortality due to cancer is moderately increased among patients with diabetes compared with those without. There is increasing evidence that some cancers are associated with diabetes, but the underlying mechanisms of this potential association have not been fully elucidated. Insulin is a potent growth factor that promotes cell proliferation and carcinogenesis directly and/or through insulin-like growth factor 1 (IGF-1). Hyperinsulinemia leads to an increase in the bioactivity of IGF-1 by inhibiting IGF binding protein-1. Hyperglycemia serves as a subordinate plausible explanation of carcinogenesis. High glucose may exert direct and indirect effects upon cancer cells to promote proliferation. Also chronic inflammation is considered as a hallmark of carcinogenesis. The multiple drugs involved in the treatment of diabetes seem to modify the risk of cancer. Screening to detect cancer at an early stage and appropriate treatment of diabetic patients with cancer are important to improve their prognosis. This paper summarizes the associations between diabetes and common cancers, interprets possible mechanisms involved, and addresses implications for medical practice.
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Salinas-Martínez AM, Flores-Cortés LI, Cardona-Chavarría JM, Hernández-Gutiérrez B, Abundis A, Vázquez-Lara J, González-Guajardo EE. Prediabetes, diabetes, and risk of breast cancer: a case-control study. Arch Med Res 2014; 45:432-8. [PMID: 24937172 DOI: 10.1016/j.arcmed.2014.06.004] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2014] [Accepted: 06/05/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Although underlying mechanisms have been described to account for the association between prediabetes and diabetes with breast cancer, reported results have been inconsistent. We undertook this study to determine whether prediabetes and diabetes are risk factors for breast cancer in Mexican women with no family history of breast cancer in the mother, daughters, or sisters. METHODS A case-control study was carried out during 2011-2013. "Case" referred to patients with a histopathological diagnosis of breast cancer (incident and primary cases) (n = 240); "controls" were those with a BI-RADS 1 or 2 mammography result (n = 406). Categorization of prediabetes and diabetes was based on self-reporting or fasting glucose and glycated hemoglobin blood sampling results. Reproductive and sociodemographic data were collected by interview. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated using multivariate unconditional binary logistic regression analysis. RESULTS Prediabetes increased the risk of breast cancer in postmenopausal women (adjusted OR 2.08, 95% CI 1.10-3.96) as did diabetes (adjusted OR 2.85, 95% CI 1.55-5.26). A history of diabetes preceding breast cancer by ≥7 years and <7 years were both associated with an increased risk for breast cancer (adjusted OR 2.80, 95% CI 1.40-5.60 and 3.00, 95% CI 1.50-5.90, respectively). CONCLUSIONS This is the first study in Mexico evaluating prediabetes and diabetes as breast cancer risk factors in women with no first-degree relatives with breast cancer. Our findings suggest that women with prediabetes and diabetes should be considered a more vulnerable population for early breast cancer detection.
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Affiliation(s)
- Ana María Salinas-Martínez
- Unidad de Investigación Epidemiológica y en Servicios de Salud No. 34, Instituto Mexicano del Seguro Social, Centro Médico Nacional del Norte, Monterrey, N.L., México; Universidad Autónoma de Nuevo León, Facultad de Salud Pública y Nutrición, Monterrey, N.L., México.
| | - Lillian Ivette Flores-Cortés
- Unidad de Investigación Epidemiológica y en Servicios de Salud No. 34, Instituto Mexicano del Seguro Social, Centro Médico Nacional del Norte, Monterrey, N.L., México
| | - Juan Manuel Cardona-Chavarría
- Unidad de Investigación Epidemiológica y en Servicios de Salud No. 34, Instituto Mexicano del Seguro Social, Centro Médico Nacional del Norte, Monterrey, N.L., México
| | - Brenda Hernández-Gutiérrez
- Unidad de Investigación Epidemiológica y en Servicios de Salud No. 34, Instituto Mexicano del Seguro Social, Centro Médico Nacional del Norte, Monterrey, N.L., México
| | - Alberto Abundis
- Unidad Médica de Alta Especialidad, Hospital de Ginecología y Obstetricia No. 23, Instituto Mexicano del Seguro Social, Monterrey, N.L., México
| | - Julia Vázquez-Lara
- Unidad Médica de Alta Especialidad, Hospital de Ginecología y Obstetricia No. 23, Instituto Mexicano del Seguro Social, Monterrey, N.L., México
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Onitilo AA, Stankowski RV, Berg RL, Engel JM, Williams GM, Doi SA. A novel method for studying the temporal relationship between type 2 diabetes mellitus and cancer using the electronic medical record. BMC Med Inform Decis Mak 2014; 14:38. [PMID: 24886371 PMCID: PMC4022430 DOI: 10.1186/1472-6947-14-38] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2013] [Accepted: 04/29/2014] [Indexed: 11/15/2022] Open
Abstract
Background We developed an algorithm for the identification of patients with type 2 diabetes and ascertainment of the date of diabetes onset for examination of the temporal relationship between diabetes and cancer using data in the electronic medical record (EMR). Methods The Marshfield Clinic EMR was searched for patients who developed type 2 diabetes between January 1, 1995 and December 31, 2009 using a combination of diagnostic codes and laboratory data. Subjects without diabetes were also identified and matched to subjects with diabetes by age, gender, smoking history, residence, and date of diabetes onset/reference date. Results The final cohort consisted of 11,236 subjects with and 54,365 subjects without diabetes. Stringent requirements for laboratory values resulted in a decrease in the number of potential subjects by nearly 70%. Mean observation time in the EMR was similar for both groups with 13—14 years before and 5–7 years after the reference date. The two cohorts were largely similar except that BMI and frequency of healthcare encounters were greater in subjects with diabetes. Conclusion The cohort described here will be useful for the examination of the temporal relationship between diabetes and cancer and is unique in that it allows for determination of the date of diabetes onset with reasonable accuracy.
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Affiliation(s)
- Adedayo A Onitilo
- Department of Hematology/Oncology, Marshfield Clinic Weston Center, 3501 Cranberry Boulevard, Weston, WI 54476, USA.
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Freire-de-Lima L. Sweet and sour: the impact of differential glycosylation in cancer cells undergoing epithelial-mesenchymal transition. Front Oncol 2014; 4:59. [PMID: 24724053 PMCID: PMC3971198 DOI: 10.3389/fonc.2014.00059] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Accepted: 03/11/2014] [Indexed: 01/11/2023] Open
Abstract
Glycosylation changes are a feature of disease states. One clear example is cancer cells, which commonly express glycans at atypical levels or with different structural attributes than those found in normal cells. Epithelial–mesenchymal transition (EMT) was initially recognized as an important step for morphogenesis during embryonic development, and is now shown to be one of the key steps promoting tumor metastasis. Cancer cells undergoing EMT are characterized by significant changes in glycosylation of the extracellular matrix (ECM) components and cell-surface glycoconjugates. Current scientific methodology enables all hallmarks of EMT to be monitored in vitro and this experimental model has been extensively used in oncology research during the last 10 years. Several studies have shown that cell-surface carbohydrates attached to proteins through the amino acids, serine, or threonine (O-glycans), are involved in tumor progression and metastasis, however, the impact of O-glycans on EMT is poorly understood. Recent studies have demonstrated that transforming growth factor-beta (TGF-β), a known EMT inducer, has the ability to promote the up-regulation of a site-specific O-glycosylation in the IIICS domain of human oncofetal fibronectin, a major ECM component expressed by cancer cells and embryonic tissues. Armed with the knowledge that cell-surface glycoconjugates play a major role in the maintenance of cell homeostasis and that EMT is closely associated with glycosylation changes, we may benefit from understanding how unusual glycans can govern the molecular pathways associated with cancer progression. This review initially focuses on some well-known changes found in O-glycans expressed by cancer cells, and then discusses how these alterations may modulate the EMT process.
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Affiliation(s)
- Leonardo Freire-de-Lima
- Laboratório de Glicobiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro , Rio de Janeiro , RJ, Brazil
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The Relationship of Type 2 Diabetes, Oral Diabetes Medications, and Insulin Therapy to Risk for Breast Cancer. Curr Nutr Rep 2014. [DOI: 10.1007/s13668-013-0066-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Kasuga M, Ueki K, Tajima N, Noda M, Ohashi K, Noto H, Goto A, Ogawa W, Sakai R, Tsugane S, Hamajima N, Nakagama H, Tajima K, Miyazono K, Imai K. Report of the Japan Diabetes Society/Japanese Cancer Association Joint Committee on Diabetes and Cancer. Cancer Sci 2014; 104:965-76. [PMID: 23879470 DOI: 10.1111/cas.12203] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2013] [Accepted: 05/12/2013] [Indexed: 02/06/2023] Open
Abstract
In recent years, diabetes has been shown to be associated with cancer risk, and this has led to a joint committee being formed, enlisting experts from the Japan Diabetes Society and the Japanese Cancer Association to address this issue. Epidemiological data in Japan provides evidence to demonstrate that diabetes is associated with increased risk for cancers, especially colorectal, liver, and pancreatic cancers. The mechanisms through which diabetes is assumed to promote oncogenesis include insulin resistance and associated hyperinsulinemia, hyperglycemia, and inflammation. Common risk factors for type 2 diabetes and cancer include aging, male sex, obesity, physical inactivity, inappropriate diet (excessive red/processed meat intake, inadequate vegetable/fruit/dietary fiber intake), excessive alcohol drinking, and smoking. Given that inappropriate diet/exercise, smoking and excessive alcohol drinking are common risk factors for diabetes and cancer, diet/exercise therapy, smoking cessation and alcohol moderation may be associated with decreased risk for cancer in diabetic patients. There is as yet limited evidence as to whether any particular antidiabetic agents may influence cancer risk.
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Affiliation(s)
- Masato Kasuga
- National Center for Global Health and Medicine, Tokyo, Japan
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