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Protective Effect of Diabetes Against Metastasis in Patients With Non–Small Cell Lung Cancer

Protective Effect of Diabetes Against Metastasis in Patients With Non–Small Cell Lung Cancer Cancer can spread by both lymphatic and hematogenous routes, and metastases are found most commonly in organs fed by the downstream lymphatic and blood flow.1 The tumor cells secrete proteinases or induce proteinase secretion by stromal cells that lead to degradation of the architecture of vascular basal membranes, creating local access through which to migrate into vasculature. In patients with long-standing diabetes mellitus, diabetic microangiopathy renders the vascular basal membrane less digestible by tumor cells, which may play a role in impeding neoplastic cell spread and metastasis.2,3 There has been debate in the literature concerning the protective effect of diabetes on patients with cancer in terms of improving their mortality. In reference to the 2 letters published in the ARCHIVES,4,5 we undertook a larger database review to investigate the possible hypothesis that diabetes has a protective effect in patients with coexisting cancers. The objective of the study was to determine whether patients with both cancer and diabetes mellitus have less risk of metastasis and subsequently decreased mortality compared with nondiabetic patients with cancer. A total of 566 patients with non–small cell lung cancer diagnosed between 1996 and 2000 were identified using the Henry Ford Hospital tumor registry. Medical records were reviewed to confirm study eligibility and to obtain data on diabetic status and progression to metastatic disease. Our results showed that stage and diabetes are significant predictors of metastasis. As expected, a higher stage is associated with a greater risk of metastatic progression (risk ratio [RR], 1.70; 95% confidence interval [CI], 1.40-2.07; P<.001). However, diabetes is associated with a lower risk (RR, 0.51; 95% CI, 0.31-0.85; P = .01). When a multivariable model is used to estimate adjusted risks, both stage and diabetes have RR estimates that are virtually unchanged (RR, 0.53 [95% CI, 0.32-0.89, and RR, 1.69 [95% CI, 1.38-2.07], respectively) and which remain statistically significant. Stage and age are the only significant predictors for death (RR, 1.56 [95% CI, 1.38-1.76] and RR, 1.03 [95% CI, 1.02-1.04], respectively). Diabetes does not have a significant association with death. Although the RR is less than 1.00, the P value is .41 and the 95% CI goes from 0.68 to 1.17. As with metastasis, the RRs in the multivariable model are very similar to the unadjusted estimates. Stage and age are still strong predictors of death, and diabetes still has little association with mortality in this model. The results of our study add new information concerning the effect of diabetes in cancer, since all other studies did not look specifically at the rate of metastasis. The results from this study are suggestive that diabetes is associated with a lower risk of metastasis in patients with non–small cell cancer of the lung but is not associated with lower mortality rate. These data provide the basis for future research aimed at understanding whether diabetes-related microvessel changes play a protective role against metastasis in patients with cancer. Also, these findings may prompt further investigation on the molecular level for other methods of improving mortality in patients with cancer. Correspondence: Dr Hanbali, Henry Ford Health Systems, Hematology/Oncology Department, 2799 W Grand Blvd, Clara Ford Pavilion, Fifth Floor, Detroit, MI 48202 (ahanbal1@hfhs.org). References 1. Nerlich AGHagedorn HGBoheim MSchleicher ED Patient with diabetes-induced microangiopathy show a reduced frequency of carcinomas. In Vivo 1998;12667- 670PubMedGoogle Scholar 2. Spranger JKroke AMohlig M et al. Inflammatory cytokines and the risk to develop type 2 diabetes. Diabetes 2003;52812- 817PubMedGoogle ScholarCrossref 3. Tomiyama RKinjo FHokama ASaito A Relationship between diabetes mellitus and the site of colorectal cancer. Am J Gastroenterol 2003;98944- 945PubMedGoogle ScholarCrossref 4. De Giorgio RBarbara GCecconi A et al. Diabetes is associated with longer survival rates in patients with malignant tumors [letter]. Arch Intern Med 2000;1602217PubMedGoogle ScholarCrossref 5. Hiroaki SIshikawa IKurishima K et al. Diabetes is not associated with longer survival in patients with lung cancer [letter]. Arch Intern Med 2001;161485Google ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Protective Effect of Diabetes Against Metastasis in Patients With Non–Small Cell Lung Cancer

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References (5)

Publisher
American Medical Association
Copyright
Copyright © 2007 American Medical Association. All Rights Reserved.
ISSN
0003-9926
DOI
10.1001/archinte.167.5.513-a
pmid
17353502
Publisher site
See Article on Publisher Site

Abstract

Cancer can spread by both lymphatic and hematogenous routes, and metastases are found most commonly in organs fed by the downstream lymphatic and blood flow.1 The tumor cells secrete proteinases or induce proteinase secretion by stromal cells that lead to degradation of the architecture of vascular basal membranes, creating local access through which to migrate into vasculature. In patients with long-standing diabetes mellitus, diabetic microangiopathy renders the vascular basal membrane less digestible by tumor cells, which may play a role in impeding neoplastic cell spread and metastasis.2,3 There has been debate in the literature concerning the protective effect of diabetes on patients with cancer in terms of improving their mortality. In reference to the 2 letters published in the ARCHIVES,4,5 we undertook a larger database review to investigate the possible hypothesis that diabetes has a protective effect in patients with coexisting cancers. The objective of the study was to determine whether patients with both cancer and diabetes mellitus have less risk of metastasis and subsequently decreased mortality compared with nondiabetic patients with cancer. A total of 566 patients with non–small cell lung cancer diagnosed between 1996 and 2000 were identified using the Henry Ford Hospital tumor registry. Medical records were reviewed to confirm study eligibility and to obtain data on diabetic status and progression to metastatic disease. Our results showed that stage and diabetes are significant predictors of metastasis. As expected, a higher stage is associated with a greater risk of metastatic progression (risk ratio [RR], 1.70; 95% confidence interval [CI], 1.40-2.07; P<.001). However, diabetes is associated with a lower risk (RR, 0.51; 95% CI, 0.31-0.85; P = .01). When a multivariable model is used to estimate adjusted risks, both stage and diabetes have RR estimates that are virtually unchanged (RR, 0.53 [95% CI, 0.32-0.89, and RR, 1.69 [95% CI, 1.38-2.07], respectively) and which remain statistically significant. Stage and age are the only significant predictors for death (RR, 1.56 [95% CI, 1.38-1.76] and RR, 1.03 [95% CI, 1.02-1.04], respectively). Diabetes does not have a significant association with death. Although the RR is less than 1.00, the P value is .41 and the 95% CI goes from 0.68 to 1.17. As with metastasis, the RRs in the multivariable model are very similar to the unadjusted estimates. Stage and age are still strong predictors of death, and diabetes still has little association with mortality in this model. The results of our study add new information concerning the effect of diabetes in cancer, since all other studies did not look specifically at the rate of metastasis. The results from this study are suggestive that diabetes is associated with a lower risk of metastasis in patients with non–small cell cancer of the lung but is not associated with lower mortality rate. These data provide the basis for future research aimed at understanding whether diabetes-related microvessel changes play a protective role against metastasis in patients with cancer. Also, these findings may prompt further investigation on the molecular level for other methods of improving mortality in patients with cancer. Correspondence: Dr Hanbali, Henry Ford Health Systems, Hematology/Oncology Department, 2799 W Grand Blvd, Clara Ford Pavilion, Fifth Floor, Detroit, MI 48202 (ahanbal1@hfhs.org). References 1. Nerlich AGHagedorn HGBoheim MSchleicher ED Patient with diabetes-induced microangiopathy show a reduced frequency of carcinomas. In Vivo 1998;12667- 670PubMedGoogle Scholar 2. Spranger JKroke AMohlig M et al. Inflammatory cytokines and the risk to develop type 2 diabetes. Diabetes 2003;52812- 817PubMedGoogle ScholarCrossref 3. Tomiyama RKinjo FHokama ASaito A Relationship between diabetes mellitus and the site of colorectal cancer. Am J Gastroenterol 2003;98944- 945PubMedGoogle ScholarCrossref 4. De Giorgio RBarbara GCecconi A et al. Diabetes is associated with longer survival rates in patients with malignant tumors [letter]. Arch Intern Med 2000;1602217PubMedGoogle ScholarCrossref 5. Hiroaki SIshikawa IKurishima K et al. Diabetes is not associated with longer survival in patients with lung cancer [letter]. Arch Intern Med 2001;161485Google ScholarCrossref

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Mar 12, 2007

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