Gastroenterology

Gastroenterology

Volume 127, Issue 4, October 2004, Pages 1044-1050
Gastroenterology

Clinical-alimentary tract
Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus patients

https://doi.org/10.1053/j.gastro.2004.07.011Get rights and content

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 ≥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.

Section snippets

Study design

We conducted a retrospective cohort study with a nested case-control analysis in the General Practice Research Database (GPRD). This study was approved by the University of Pennsylvania Institutional Review Board and the GPRD Scientific and Ethical Advising Group.

Source of data

The GPRD was established in 1987. It constitutes the primary outpatient medical record for approximately 700 general practitioner practices in the United Kingdom. Patients in the database are representative of the United Kingdom

Results

The insulin-exposed (i.e., at least 1 year of insulin exposure) group accumulated 9157 person-years of follow-up, and the unexposed group was followed for 85,556 person-years. The median duration of insulin therapy was 3 years (range, 1–13.5 years). The noninsulin users were older than the insulin users (71 years [SD, 12 years] vs. 68 years [SD, 12 years], P < 0.0001). The duration of type 2 diabetes mellitus was significantly longer in insulin users than noninsulin users (13 years [SD, 7

Discussion

This study provides direct epidemiologic support for the hypothesis that long-term insulin therapy is associated with an increased risk of colorectal cancer among type 2 diabetes mellitus patients. Because insulin use is inextricably linked to severity of type 2 diabetes mellitus, it is possible that the observed association is due to the severity of diabetes rather than a true effect of exogenous insulin. However, a causal interpretation is supported by prior experimental and clinical

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    Supported by the National Institutes of Health center grant P30 DK50306.

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