Diabetes Talking

Question:

Medscape Chronic Insulin Use Increases Risk of Colorectal Cancer in Type 2 Diabetics

I read this and decided that, although the results were statistically significant, the risks were still low enough not to worry about. Of course, I’m not on insulin… Nicky. — HbA1c 10.5/6.4/<6  Weight 95/81/72 1g Metformin, 75ug Thyroxine T2 DX 05/2004

Response:

Medscape Chronic Insulin Use Increases Risk of Colorectal Cancer in Type 2 Diabetics Oct. 1, 2004 – Chronic insulin therapy significantly increases the risk of colorectal cancer (CRC) in patients with type 2 diabetes mellitus (DM), according to the results of a retrospective cohort study published in the October issue of Gastroenterology. "Insulin is a known in vitro growth factor," writes Yu-Xiao, MD, from the Division of Gastroenterology at the University of Pennsylvania School of Medicine in Philadelphia, Pennsulvania, and colleagues. "Furthermore, in animal models, exogenous insulin injection stimulates the growth of colorectal cancer precursors." According to the authors, clinical studies have shown hyperinsulinemia to be independently associated with increased risk of CRC. Further, studies show that type 2 DM is linked to a 30% to 40% increased risk of developing CRC. To explore the possibility that chronic exogenous insulin therapy may increase the risk of colorectal cancer in type 2 diabetics, they identified 24,918 patients in the U.K.’s General Practice Research Database (GPRD) having at least three years of CRC-free follow-up after a diagnosis of type 2 DM. Patients included in the exposed group (n = 3,160) had a minimum of one year of CRC-free insulin therapy, while those in the control group (n = 21,758) did not require insulin. The investigators confirmed 125 cases of colorectal cancer over the course of the study (exposed group, 9,157 person-years; control group, 85,556 person-years). In a nested case-control analysis, each case was matched with up to 10 control subjects on year of birth, calendar period, and duration of follow-up in the database prior to CRC diagnosis. The incidence of colorectal cancer was significantly higher in the exposed group compared with the control group (197 cases/100,000 person-years vs. 124 cases/100,000 person-years). After adjustments for age and sex, the hazard ratio (HR) for development of CRC associated with a duration of insulin therapy longer than one year was 2.1 (95% confidence interval [CI], 1.2 – 3.4; P = .005). Adjustment for duration of diabetes yielded similar results (HR, 1.9; CI, 1.1 – 3.2, P = .02). Results of the nested case-control analysis showed that continuous insulin use for a period of more than three years was associated with a tripled risk of CRC (adjusted odds ratio [OR], 3.4; 95% CI, 1.5 – 7.7; P = .004) compared with noninsulin users. The risk of CRC was found to increase with duration of exposure to insulin use, the odds ratio increasing by 1.21 for each additional year of insulin use (95% CI, 1.03 – 1.42; P = .02). Those with fewer than three years of insulin therapy had an adjusted OR for CRC of 1.4 (95% CI, 0.6 – 2.9; P = 0.5), while those with three to five years of insulin exposure were at significantly higher risk (OR, 2.9; 95% CI, 1.1 – 7.7; P = .03). Those with more than five years of insulin use were at the greatest risk of developing CRC (OR, 4.7; 95% CI, 1.3 – 16.7; P = .02). "[C]hronic insulin therapy appears to increase significantly the risk of colorectal cancer," the authors write. "[T]hese results highlight the need for adherence to existing colorectal screening guidelines in insulin-treated type 2 diabetes patients." Pointing out that the magnitude of association found in this study is similar to that of a family history of colorectal cancer, the authors suggest that future studies explore the cost-effectiveness of a more stringent CRC screening program for patients with type 2 diabetes requiring insulin. The study was supported by a grant from the National Institutes of Health. Gastroenterology. 2004;127:1044-1050 Reviewed by Gary D. Vogin, MD

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