S0301 Impact of Type 2 Diabetes Mellitus on Colorectal Adenoma-Carcinoma Progression: Which Metabolic Factors Play a Role?

Abstract

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of colorectal cancer. Retrospective studies have shown that T2DM is associated with an increased risk of colorectal adenoma (CRA), but there is no clear consensus on the effects of glycemic control and insulin resistance on the risk of CRA development in subjects with T2DM. In this prospective study, we investigated the effects of glycemic control, insulin resistance, and antihyperglycemic medication use on the incidence of CRA and advanced CRA in subjects with T2DM. METHODS: We measured fasting glucose, insulin, hemoglobin A1c, and C-peptide levels in subjects with T2DM undergoing routine screening colonoscopy. Homeostatic model assessment of insulin resistance (HOMA-IR) was subsequently calculated. Subjects were stratified based on glycemic control and insulin resistance, and medications were analyzed. We recorded size, location, and pathology for each adenoma detected. Advanced adenomas were defined as size >1 cm, presence of >3 adenomas, or presence of villous or tubulovillous features. RESULTS: In 61 subjects with T2DM, 27 were found to have at least one adenomatous polyp (7 with advanced adenoma), yielding an adenoma detection rate (ADR) of 44.26%. Subjects taking a DPP4-inhibitor had a significantly lower ADR compared to subjects not taking a DPP4-inhibitor (P = 0.03). There was no significant difference in ADR between subjects with high versus low A1c (P = 0.83), between subjects with high versus low HOMA-IR (P = 0.57), and between subjects taking and not taking metformin (P = 0.46). (table 1, Figure 1). CONCLUSION: To our knowledge, this is the first prospective study to investigate the association between glycemic control, insulin resistance, and antihyperglycemics with CRA in subjects with established T2DM. At our center, we demonstrated that subjects with T2DM have a higher ADR (44.26%) compared to the national benchmark ADR of ∼25%. DDP4-inhibitor use was noted to confer a significant decrease in CRA development, while metformin did not. Interestingly, glycemic control and insulin resistance, as measured by A1c and HOMA-IR respectively, did not have statistically significant associations with ADR. Rather, T2DM by itself appeared to be a predictor for CRA development, suggesting that the threshold for CRA risk may be lower than previously thought. We plan to expand our study population to include subjects with pre-diabetes, who may already be at increased risk and benefit from more stringent screening guidelines.Table 1Figure 1