Increased levels of serum glucose-dependent insulinotropic polypeptide as a novel risk factor for human colorectal adenoma

Abstract

Obesity and insulin resistance are thought to be risk factors for colorectal adenoma. Glucose-dependent insulinotropic polypeptide (GIP) stimulates insulin secretion from the pancreas and promotes fat accumulation in adipocytes. The association between serum GIP and the risk of colorectal adenoma has not been examined previously. We investigated this association in 370 subjects who underwent total colonoscopy during thorough physical checkups between January and December 2008. We used a cross-sectional design and classified the subjects into a colorectal adenoma group and a control group without adenoma according to their endoscopic findings. Serum GIP concentrations in samples of venous blood obtained after an overnight fast were measured using a sandwich enzyme-linked immunosorbent assay kit. The mean levels of fasting GIP (34.9 ± 49.5 vs 25.0 ± 20.1 pg/mL, P = .04), triglyceride, glucose, and insulin and the values of the homeostasis model assessment of insulin resistance in the colorectal adenoma group were significantly higher than those in the control group. Multiple logistic regression analysis showed that the highest quartile of fasting GIP levels was associated with a significantly high risk of colorectal adenoma (odds ratio, 2.1; 95% confidence interval, 1.08-3.96; P = .01) in comparison with the lowest quartile. Quartile analysis demonstrated that increased levels of GIP were related to increased levels of fasting insulin and values of homeostasis model assessment β-cell. These results suggest that an increased level of fasting GIP is associated with an increased risk of colorectal adenoma.