Yu-Xiao Yang1, Sean Hennessy, James D Lewis. 1. Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia 19104-6021, USA. yangy@mail.med.upenn.edu
Abstract
BACKGROUND & AIMS: Endogenous hyperinsulinemia in the context of type 2 diabetes mellitus is potentially associated with an increased risk of colorectal cancer. We aimed to determine whether insulin therapy might increase the risk of colorectal cancer among type 2 diabetes mellitus patients. METHODS: We conducted a retrospective cohort study among all patients with a diagnosis of type 2 diabetes mellitus in the General Practice Research Database from the United Kingdom. We excluded patients with <3 years of colorectal cancer-free database follow-up after the diabetes diagnosis as well as those insulin users who developed colorectal cancer after <1 year of insulin therapy. The remaining insulin users and the noninsulin-using type 2 diabetic patients were followed for the occurrence of colorectal cancer. Hazard ratios (HR) were determined in Cox proportional hazard analysis. A nested case-control study was conducted to perform multivariable analysis and to determine a duration-response effect. RESULTS: The incidence of colorectal cancer in insulin users (n = 3160) was 197 per 100,000 person-years, compared with 124 per 100,000 person-years in type 2 diabetes mellitus patients not receiving insulin (n = 21,758). The age- and sex-adjusted HR of colorectal cancer associated with > or =1 year of insulin use was 2.1 (95% CI: 1.2-3.4, P = 0.005). The positive association strengthened after adjusting for potential confounders. The multivariable odds ratio associated with each incremental year of insulin therapy was 1.21 (95% CI: 1.03-1.42, P = 0.02). CONCLUSIONS: Chronic insulin therapy significantly increases the risk of colorectal cancer among type 2 diabetes mellitus patients.
BACKGROUND & AIMS: Endogenous hyperinsulinemia in the context of type 2 diabetes mellitus is potentially associated with an increased risk of colorectal cancer. We aimed to determine whether insulin therapy might increase the risk of colorectal cancer among type 2 diabetes mellituspatients. METHODS: We conducted a retrospective cohort study among all patients with a diagnosis of type 2 diabetes mellitus in the General Practice Research Database from the United Kingdom. We excluded patients with <3 years of colorectal cancer-free database follow-up after the diabetes diagnosis as well as those insulin users who developed colorectal cancer after <1 year of insulin therapy. The remaining insulin users and the noninsulin-using type 2 diabeticpatients were followed for the occurrence of colorectal cancer. Hazard ratios (HR) were determined in Cox proportional hazard analysis. A nested case-control study was conducted to perform multivariable analysis and to determine a duration-response effect. RESULTS: The incidence of colorectal cancer in insulin users (n = 3160) was 197 per 100,000 person-years, compared with 124 per 100,000 person-years in type 2 diabetes mellituspatients not receiving insulin (n = 21,758). The age- and sex-adjusted HR of colorectal cancer associated with > or =1 year of insulin use was 2.1 (95% CI: 1.2-3.4, P = 0.005). The positive association strengthened after adjusting for potential confounders. The multivariable odds ratio associated with each incremental year of insulin therapy was 1.21 (95% CI: 1.03-1.42, P = 0.02). CONCLUSIONS: Chronic insulin therapy significantly increases the risk of colorectal cancer among type 2 diabetes mellituspatients.
Authors: Ying Bao; Katharina Nimptsch; Jeffrey A Meyerhardt; Andrew T Chan; Kimmie Ng; Dominique S Michaud; Jennie C Brand-Miller; Walter C Willett; Edward Giovannucci; Charles S Fuchs Journal: Cancer Epidemiol Biomarkers Prev Date: 2010-10-05 Impact factor: 4.254
Authors: Ming Zhao; Zhu-li Wan; Linda Whittaker; Bin Xu; Nelson B Phillips; Panayotis G Katsoyannis; Faramarz Ismail-Beigi; Jonathan Whittaker; Michael A Weiss Journal: J Biol Chem Date: 2009-09-22 Impact factor: 5.157