Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus patients.
OBJECTIVE
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.
Yang
Yu-Xiao
YX
Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia 19104-6021, USA. yangy@mail.med.upenn.edu
Hennessy
Sean
S
Lewis
James D
JD
D000368:Aged; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000139:chemically induced*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007328:Insulin / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D012189:Retrospective Studies; D012306:Risk
D007328:Insulin