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      Higher risk of colorectal cancer in patients with newly diagnosed diabetes mellitus before the age of colorectal cancer screening initiation

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          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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          Epidemiology of type 1 diabetes.

          This article describes the epidemiology of type 1 diabetes mellitus (T1D) around the world and across the lifespan. Epidemiologic patterns of T1D by demographic, geographic, biologic, cultural, and other factors in populations are presented to gain insight about the causes, natural history, risks, and complications of T1D. Data from large epidemiologic studies worldwide indicate that the incidence of T1D has been increasing by 2% to 5% worldwide and that the prevalence of T1D is approximately 1 in 300 in the United States by 18 years of age. Research on risk factors for T1D is an active area of research to identify genetic and environmental triggers that could potentially be targeted for intervention. Although significant advances have been made in the clinical care of T1D with resultant improvements in quality of life and clinical outcomes, much more needs to be done to improve care of, and ultimately find a cure for, T1D. Epidemiologic studies have an important ongoing role to investigate the complex causes, clinical care, prevention, and cure of T1D. Copyright 2010 Elsevier Inc. All rights reserved.
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            Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies.

            To summarise the evidence and evaluate the validity of the associations between type 2 diabetes and the risk of developing or dying from cancer.
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              Insulin and colon cancer.

              Some factors related to Westernization or industrialization increase risk of colon cancer. It is believed widely that this increase in risk is related to the direct effects of dietary fat and fiber in the colonic lumen. However, the fat and fiber hypotheses, at least as originally formulated, do not explain adequately many emerging findings from recent epidemiologic studies. An alternative hypothesis, that hyperinsulinemia promotes colon carcinogenesis, is presented here. Insulin is an important growth factor of colonic epithelial cells and is a mitogen of tumor cell growth in vitro. Epidemiologic evidence supporting the insulin/colon-cancer hypothesis is largely indirect and based on the similarity of factors which produce elevated insulin levels with those related to colon cancer risk. Specifically, obesity--particularly central obesity, physical inactivity, and possibly a low dietary polyunsaturated fat to saturated fat ratio--are major determinants of insulin resistance and hyperinsulinemia, and appear related to colon cancer risk. Moreover, a diet high in refined carbohydrates and low in water-soluble fiber, which is associated with an increased risk of colon cancer, causes rapid intestinal absorption of glucose into the blood leading to postprandial hyperinsulinemia. The combination of insulin resistance and high glycemic load produces particularly high insulin levels. Thus, hyperinsulinemia may explain why obesity, physical inactivity, and a diet low in fruits and vegetables and high in red meat and extensively processed foods, all common in the West, increase colon cancer risk.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                24 April 2017
                2017
                : 7
                : 46527
                Affiliations
                [1 ]Dept. of Gastroenterology and Hepatology, Maastricht University Medical Center , Maastricht, The Netherlands
                [2 ]GROW - School for Oncology and Developmental Biology , Maastricht, The Netherlands
                [3 ]NUTRIM - School for Nutrition, Toxicology and Metabolism , Maastricht, The Netherlands
                [4 ]Dept. of Epidemiology, Maastricht University Medical Center, GROW School for Oncology and Developmental Biology , Maastricht, The Netherlands
                [5 ]PHARMO Institute for Drug Outcomes Research , Utrecht, The Netherlands
                [6 ]Dept. of Hospital Pharmacy, VieCuri Medical Centre , Venlo, The Netherlands
                [7 ]Dept. of Internal Medicine, VieCuri Medical Centre , Venlo, The Netherlands
                [8 ]Dept. of Internal Medicine, Maastricht University Medical Centre , Maastricht, The Netherlands
                [9 ]Dept. of Internal Medicine, Máxima Medical Centre , Eindhoven/Veldhoven, The Netherlands
                [10 ]CAPHRI - School for Public Health and Primary Care , Maastricht, The Netherlands
                [11 ]Dept. of Clinical Epidemiology, VieCuri Medical Centre , Venlo, The Netherlands
                Author notes
                Article
                srep46527
                10.1038/srep46527
                5402260
                28436468
                bef9afad-9745-4de6-8b55-09d23d5d67fc
                Copyright © 2017, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 20 July 2016
                : 22 March 2017
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