Elevated Serum Concentrations of Insulin and Glucose Increase Risk of Recurrent Colorectal Adenomas

Background & Aims: Indicators of insulin resistance have been hypothesized to promote colorectal cancer. Methods: We assayed fasting serum from 375 subjects with and 375 subjects without a recurrent adenoma during the course of the Polyp Prevention Trial to determine baseline concentrations of insulin and glucose, as well as changes in these measurements over the course of 4 years of follow-up evaluation. To estimate the relative risk of adenoma recurrence for each of these serum measures, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression models adjusting for age, sex, body mass index, intervention group, and an interaction term for sex and intervention group. Results: For both insulin and glucose, we found higher risk for subjects in the high quartile compared with the low quartile (OR, 1.56; 95% CI, 1.00–2.43 for insulin; OR, 1.49; 95% CI, 0.95–2.31 for glucose). The association for glucose was most apparent for advanced adenomas (OR, 2.43; 95% CI, 1.23–4.79) but for insulin, we did not observe this pattern. When we restricted the analysis to those without a family history of colorectal cancer, we observed an even stronger association between increased glucose at study entry and adenoma recurrence (OR, 1.78; 95% CI, 1.06–3.01 for all adenomas; OR, 3.52; 95% CI, 1.47–8.42 for advanced adenoma). Conclusions: Our findings suggest that patients with increased insulin and glucose are at higher risk of adenoma recurrence, and for those with increased glucose, the increase in risk for recurrence of advanced adenomas is even greater.

Abbreviations used in this paper: CI, confidence interval, IGF, insulin-like growth factor, IGFBP, insulin-like growth factor binding protein, OR, odds ratio