Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus patients

Gastroenterology. 2004 Oct;127(4):1044-50. doi: 10.1053/j.gastro.2004.07.011.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Cohort Studies
  • Colorectal Neoplasms / chemically induced*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Humans
  • Insulin / adverse effects*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Retrospective Studies
  • Risk


  • Insulin