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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThe worldwide epidemic of obesity has triggered a concomitant surge in cases of type 2 diabetes. Both are related to cancer through IGF-1, hyperinsulinemia, and other factors. This article discusses the association between obesity, diabetes, and cancer and their connection to insulin and IGFs.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInsulin\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EObesity\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EThe worldwide epidemic of obesity has triggered a concomitant surge in cases of type 2 diabetes. Both are related to cancer through IGF-1, hyperinsulinemia, and other factors (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). Derek LeRoith, MD, PhD, Mount Sinai Medical Center, New York, USA, recipient of the Gerald D. Aurbach Award, spoke about the association between obesity, diabetes, and cancer and their connection to insulin and IGFs.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/5\/4\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Impact of Diabetes and Obesity on Cancer Development.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1187393752\u0022 data-figure-caption=\u0022Impact of Diabetes and Obesity on Cancer Development.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/5\/4\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/5\/4\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/5\/4\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12293\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-3\u0022 class=\u0022first-child\u0022\u003EImpact of Diabetes and Obesity on Cancer Development.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from D. LeRoith, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-4\u0022\u003EObesity is one of the most serious public health problems of this century [Scott and Batterham. \u003Cem\u003EAm J Physiol Regul Integr Comp Physiol\u003C\/em\u003E 2011]. In the United States alone, it affects about 12 million (16.9%) children aged 2 to 19 years and over 75 million (33.7%) adults [American Heart Association 2011]. Worldwide, an estimated 17.6 million children aged \u0026lt;5 years are overweight, and some 400 million adults are obese.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EStatistics show that 58% of diabetes cases can be attributed to a body mass index \u0026gt;30 kg\/m\u003Csup\u003E2\u003C\/sup\u003E [World Heart Federation 2011] and that at least 20 different cancers are associated with obesity [Hemminki K et al. \u003Cem\u003EEur J Cancer Prev\u003C\/em\u003E 2011] (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). The majority of patients with type 2 diabetes are overweight or obese [Ross SA et al. \u003Cem\u003ECurr Med Res Opin\u003C\/em\u003E 2011].\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/12294\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/12294\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12294\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-6\u0022 class=\u0022first-child\u0022\u003ECancers Associated with Obesity.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-7\u0022\u003ETogether, the widespread epidemics of obesity and type 2 diabetes have underscored the importance of these disorders as risk factors for cancer and renewed interest in the study of the involvement of hyperinsulinemia and IGF-IR signaling in the development and progression of cancer.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EDr. LeRoith discussed the mechanisms that involve the insulin\/IGF-1 system and cancer and type 2 diabetes, with a focus on IGF-IR, hyperinsulinemia, and insulin receptors (IRs) in cancer. IGF-I and IGF-II, along with insulin, play key roles in cell survival, growth, and proliferation, as well as in the metabolic effects of insulin.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003ETwo features demonstrate the relationship between the IGF system and cancer: most epithelial cancers and cancer cell lines demonstrate increased expression of IGF-1R compared with adjacent normal tissue, and epidemiological studies show an increased relative risk of developing prostate, colon, breast, and other cancers when circulating IGF-1 is in the upper quartile of the normal range.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EMutations in tumor suppressor genes that are commonly found in cancers may explain the enhanced expression of the IGF-IRs [Lane DP and Hupp TR. \u003Cem\u003EDrug Discov Today\u003C\/em\u003E 2003]. Tissue and cell culture studies indicate higher expression of IGF-1R in cancer cells. This increase is the result of both enhanced promoter activity and increased translation.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EThe IGF-IR promoter is a downstream target for tumor suppression action. Enhanced promoter activity is seen in many cancer cells that express mutated tumor suppressor gene products, such as p53 and WT1. Enhanced translation is seen with deletion or mutation of PTEN, another common tumor suppressor that is mutated in cancers.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EBlocking the activation of IGF-1R inhibits cancer growth both \u003Cem\u003Ein vitro\u003C\/em\u003E and \u003Cem\u003Ein vivo.\u003C\/em\u003E This has led to the development of numerous humanized IGF-1R-blocking antibodies and a number of tyrosine kinase inhibitors of IGF-IR signaling that have entered various phases of preclinical and clinical testing in various epithelial cancers and sarcomas.\u003C\/p\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EInsulin Promotes Cancer in Obesity and Type 2 Diabetes\u003C\/h2\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EData show that type 2 diabetes increases breast cancer risk and mortality, and hyperinsulinemia has been identified as a major factor that links these two diseases. Conversely, early administration of insulin-sensitizing therapy may reduce breast cancer risk and mortality in patients with type 2 diabetes [Fierz et al. \u003Cem\u003EDiabetes\u003C\/em\u003E 2010].\u003C\/p\u003E\n         \u003Cp id=\u0022p-14\u0022\u003EAccording to Dr. LeRoith, an animal model of insulin resistance has demonstrated the direct causality between endogenous hyperinsulinemia and cancer growth and metastases. Results show that inhibiting tyrosine kinase reduces mammary tumors, despite marked hyperinsulinemia\u003C\/p\u003E\n         \u003Cp id=\u0022p-15\u0022\u003EOverexpression of IRs in cancer cells may explain their increased sensitivity to hyperinsulinemia. In addition, isoform A (IR-A), together with autocrine production of its ligand, IGF-II, is emerging as an important mechanism of normal and cancer stem cell expansion and is a feature of several malignancies [Belfiore A and Malaguarnera R. \u003Cem\u003EEndocrin Relat Cancer\u003C\/em\u003E 2011].\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EThe Role of Obesity and Type 2 Diabetes\u003C\/h2\u003E\n         \u003Cp id=\u0022p-16\u0022\u003EThe association between obesity, type 2 diabetes, and certain types of cancers is well established. For example, half of all patients with pancreatic cancer are diabetic at the time of diagnosis [Magruder JT et al. \u003Cem\u003EPancreas\u003C\/em\u003E 2011], but it remains unclear whether diabetes that is associated with pancreatic cancer is a cause or an effect of the condition. Increased weight is also known to worsen glycemic control and increase the risk of diabetes progression. However, results from large, prospective clinical trials have shown that weight reduction significantly improves glycemic control in type 2 diabetes patients and lowers the risk of progression of diabetes, as well as cancer [Ross SA et al. \u003Cem\u003ECurr Med Res Opin\u003C\/em\u003E 2011].\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ETackling the Problem\u003C\/h2\u003E\n         \u003Cp id=\u0022p-17\u0022\u003EComplex genetic, endocrine, and biological forces tend to limit the efficacy of cancer therapy. For example, \u003Cem\u003Ede novo\u003C\/em\u003E activation of the IR-A\/IGF-II autocrine loop represents a mechanism of resistance to anticancer therapies [Belfiore A and Malaguarnera R. \u003Cem\u003EEndocr Relat Cancer\u003C\/em\u003E 2011]; treatment-related weight gain is a side effect of many oral antidiabetes agents and insulin; and several anticancer treatments may induce or worsen insulin resistance. In addition, diabetes treatments may influence the risk of cancer independently of their effect on glycemia and complicate investigation of the association between diabetes and cancer [Wild SH. \u003Cem\u003EDiabetologia\u003C\/em\u003E 2011].\u003C\/p\u003E\n         \u003Cp id=\u0022p-18\u0022\u003EIncreasing knowledge of the IR role in cancer has important implications for cancer prevention, which should include control of insulin resistance and hyperinsulinemia in the population and meticulous evaluation of new antidiabetic drugs for their metabolic:mitogenic ratio. Future anticancer therapies need to target the IR-A pathway to inhibit the tumor-promoting effect of IR without impairing the metabolic effect of insulin.\u003C\/p\u003E\n         \u003Cp id=\u0022p-19\u0022\u003EThe prevention and treatment of obesity and type 2 diabetes are equally vital. Type 2 diabetes is a global public health crisis that threatens the economies of all nations, particularly developing countries. Epidemiological studies and randomized clinical trials show that type 2 diabetes is largely preventable through diet and lifestyle modifications [Hu FB. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2011].\u003C\/p\u003E\n         \u003Cp id=\u0022p-20\u0022\u003ETranslating these findings into practice, however, requires fundamental changes in public policies, the food and built environments, and health systems [Hu FB. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2011]. To curb the escalating epidemics of obesity, diabetes, and cancer, primary prevention through the promotion of a healthy diet and lifestyle needs to be a global public health priority.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/11\/5\/4.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzn1s3\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzn1s3\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzn1s3\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}