Impaired Secretion of Glucagon-Like Peptide 1 in Patients with Colorectal Adenoma after an Oral Glucose Load

Abstract

Background/Aims: Obesity and insulin resistance are associated with an increased risk of colorectal adenoma (CRA). Glucagon-like peptide-1 (GLP-1) plays an important role in glucose homeostasis through its amplification of insulin secretion in response to oral nutrients; however, its role in human CRA remains unknown. We investigated oral glucose-mediated GLP-1 secretion in patients with adenoma. Methods: We performed a case-control study of 15 nondiabetic patients with pathologically diagnosed CRA and 10 age-matched healthy controls without adenoma. Plasma concentrations of active GLP-1 were measured during a 75 g oral glucose tolerance test. Results: Mean waist circumference (WC), homeostasis model assessment of insulin resistance (HOMA-IR) values, the total areas under the curve (AUC) of glucose and insulin were significantly higher in patients with CRA than in controls. The total AUC of GLP-1 (p = 0.01) was lower in patients with CRA than in controls. Moreover, the total AUC of GLP-1 showed a negative correlation with WC, total AUC of glucose, and HOMA-IR. Multiple linear regression analyses revealed that the total AUC of GLP-1 was independently correlated with the number and maximum size of CRAs. Conclusion: GLP-1 could actively participate in the development of CRA in humans, particularly in patients with metabolic syndrome.

Association between High Levels of Circulating Chemerin and Colorectal Adenoma in Men

“…However, the results were not statistically significant. These findings were consistent with our previous study showing the association between MS, glucose tolerance, insulin resistance, and the development of CRA [8][9][10][11].…”

“…We have previously reported that visceral fat obesity, MS, hyperinsulinemia, insulin resistance, hypoadiponec-DOI: 10.1159/000501477 tinemia [8][9][10][11], and chronic systemic low-grade inflammation [12,13] are associated with the development of CRA or CRC. Although the association between such factors and CRC has not been fully elucidated, previous studies have indicated that disturbance in the secretion of adipocytokine, insulin resistance, and chronic inflammation are the underlying mechanisms [14,15].…”

Characteristics of the gut microbiome profile in obese patients with colorectal cancer

“…Aging and reduced food intake due to CRC development may have altered the weight of patients with CRC, particularly in the advanced stage. Nevertheless, glucose intolerance and insulin resistance were observed in patients with CRC, which is consistent with previous reports 4–12 that metabolic abnormalities associated with obesity are independent risk factors of CRC development. In addition, TC and LDL levels were lower in patients with CRC than in controls, which may be attributable to the higher proportion of patients with hyperlipidemia in the CRC group.…”

“…Aging and reduced food intake due to CRC development may have altered the weight of patients with CRC, particularly in the advanced stage. Nevertheless, glucose intolerance and insulin resistance were observed in patients with CRC, which is consistent with previous reports [4][5][6][7][8][9][10][11][12] that metabolic abnormalities associated with Figure 5 Comparison of the genera between obese and nonobese patients with colorectal cancer (CRC). In the obese patients with CRC, the genus Enterococcus (P = 0.04) was significantly lower, and the genera Polaribacter (P = 0.03) and Capnocytophaga (P = 0.03) were significantly higher than in the nonobese patients with CRC.…”

“…3 The underlying mechanisms linking obesity to CRC remain a matter of debate; however, metabolic syndrome, insulin resistance, and alterations in adipocytokine concentrations appear to be of great importance. 4 The authors of this study previously demonstrated that visceral fat obesity and metabolic syndrome, insulin resistance following hyperinsulinemia, 5 impaired secretion of adipocytokine [6][7][8] or incretin, 9,10 and systemic low chronic inflammation 11,12 contribute to the development of CRC or colorectal adenoma, which is a well-known precancerous lesion of CRC.…”