244 Exogenous Insulin Therapy Increases the Risk of Advanced Colorectal Adenoma Among Patients With Type 2 Diabetes Mellitus

Abstract

INTRODUCTION: Endogenous hyperinsulinemia increases the risk of colorectal cancer (CRC) among patients with type 2 diabetes mellitus (T2DM). Exogenous insulin therapy, used by 30% of T2DM patients, further increases systemic levels of insulin and has been shown to increase the risk of CRC in animal models. We sought to evaluate the effect of exogenous insulin therapy on the incidence of advanced adenoma in T2DM patients. METHODS: We conducted a retrospective cohort study among patients with T2DM aged 40–80 at a tertiary healthcare center. Among other inclusion/exclusion criteria (Figure 1), eligible patients must have undergone 2 rounds of colonoscopy examinations – a baseline colonoscopy and a follow-up (index) colonoscopy ≥1 year later. Primary outcome was incident advanced adenomas at index colonoscopy. Primary exposure was long-term (≥1 year) insulin therapy before index colonoscopy. Assuming α = 0.05, background advanced adenoma incidence of 5%, and prevalence of insulin therapy among T2DM of 20%, a cohort size of 865 would be required to have 90% power to detect a 7.5 percentage point increase in advanced adenoma incidence among long-term insulin users. Multivariable logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI). RESULTS: Among patients with ≥1 diagnostic code for DM and ≥2 colonoscopy procedure codes, we randomly selected 1,900 patients for chart review and identified 867 eligible patients (Figure 1). Except for BMI, baseline characteristics between short-term/non-insulin users versus long-term insulin users were not significantly different (Table 1). Characteristics of the baseline and index colonoscopies were similar between the two groups (Table 1). Incidence of advanced adenoma at index colonoscopy was higher among the long-term insulin users versus short-term/non-insulin users (20% versus 4.7%, chi2 P < 0.001). Multivariable adjusted OR for advanced adenoma risk associated with long-term insulin use was 6.2 (95% CI: 3.4–11.3). Long-term insulin use was also associated with increased risk of having ≥3 adenomas (adjusted OR 2.8, 95% CI 1.4–5.4) and having ≥1 right-sided advanced adenoma (adjusted OR 6.9, 95% CI 3.5–13.8) at index colonoscopy. CONCLUSION: Chronic insulin therapy was associated with increased risk of advanced adenoma occurrence in T2DM patients. This novel observation is important for developing a risk-tailored approach to the use of colonoscopy in CRC screening/surveillance in patients with T2DM.