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Objective To explore the relationship between insulin resistance, glucose and lipid metabolism related molecules and colorectal polyps. Methods A total of 262 healthy people who underwent colonoscopy in Shandong cancer hospital from June 2019 to September 2020 were selected. The levels of serum vascular cell adhesion molecule-1 (VCAM-1), fibroblast growth factor 19 (FGF19), insulin like growth factor (IGF-1), fasting blood glucose and fasting blood insulin were detected by enzyme-linked immunosorbent assay (ELISA). Insulin resistance index (HOMA-IR) was calculated, and the influencing factors of occurrence, pathological type, size and number of polyps were analyzed. Results Among 262 cases, 116 cases were polyp free, 113 cases were adenomatous polyp and 33 cases were inflammatory polyp. HOMA-IR, VCAM-1 and FGF19 in polyp group were 2.904±1.754, (334.415±139.573) ng/ ml and (135.865± 98.470) pg/ ml, respectively, which were higher than 2. 369 ± 1. 306, (302.480± 99. 946) ng/ ml and (110.694±76.044) ng/ ml in non-polyp group, respectively (P < 0.05). Multivariate Logistic regression analysis showed that the gender (OR =4.269, 95%CI: 1.963-9.405) and FGF19 (77.0-131.4 pg/ ml: OR = 2.385, 95%CI: 1.155-4.926) were independent factors of colorectal polyps. The gender (OR =3.799, 95% CI: 1.650-8.748) and FGF19 (77.0-131.4 pg/ ml: OR = 2.290, 95%CI: 1.072-4.891) were independent factors of colorectal adenomatous polyps. The gender(OR = 6.725, 95% CI: 1.853-24.410) and fasting plasma glucose (=6.5 mmol/ L: OR =0.047, 95%CI: 0.009-0.245) were independent factors of colorectal inflammatory polyps. The gender (OR = 3.539, 95% CI: 1.293-9.689) was an independent factor for the occurrence of single polyp. The gender (OR =5.063, 95% CI: 2.048-12.515), FGF19 (77.0-131.4 pg/ ml: OR =2.502, 95%CI: 1.102-5.681), fasting plasma glucose (=6.5 mmol/ L: OR = 0.282, 95%CI: 0.095- 0.839) were independent factors of multiple polyps. The gender (OR =3.416, 95% CI: 1.134-10.289) and fasting insulin (=9.4 µU/ ml: OR = 9.480, 95% CI: 1.485-60.521) were independent risk factors for colorectal polyps<0.5 cm. The gender (OR=3.151, 95%CI: 1.244-7.984) and fasting plasma glucose (=6.5 mmol/ L: OR =0.310, 95%CI: 0.102-0.941) were independent risk factors for colorectal polyps with the size of 0.5-0.9 cm. The gender (OR =22.649, 95%CI: 4.154-123.485), age (55 to 64 years old: OR = 4.473, 95%CI: 1.070-18.704; =65 years old: OR = 5.815, 95%CI: 1.300-26.009), BMI (=28 kg/ m2: OR = 5.310, 95%CI: 1.224-23.032) and FGF19 (77.0-131.4 pg/ ml: OR =7.474, 95%CI: 1.903-29.351) were independent factors for colorectal polyps with size = 1.0 cm. Gender stratification analysis showed that FGF19 was an independent factor for the occurrence of male polyps (77.0-131.4 pg/ ml: OR =6.109, 95%CI: 1.688-22.104) and adenomas (77.0-131.4 pg/ ml: OR =6.401, 95%CI: 1.717-23.864). The age (55 to 64 years old: OR = 3.783, 95%CI: 1.052-13.611) and VCAM-1 (=352.8 ng/ ml: OR = 4.341, 95%CI: 1.142-16.493) were independent risk factors of female polyps. The age (55 to 64 years old: OR = 5.743, 95%CI: 1.205-27.362, =65 years old: OR =6.885, 95%CI: 1.143-41.467), VCAM-1 (=352.8 ng/ ml: OR =6.313, 95%CI: 1.415-28.159) and IGF-1 (=7.6 ng/ ml: OR = 5.621, 95%CI: 1.069-29.543) were independent factors of female adenoma. Conclusions The occurrences of colorectal polyps and adenomatous polyps are related to insulin resistance and glucose and lipid metabolism. Serum FGF19 is an independent influencing factor for the occurrence of colorectal polyps and adenomatous polyps, and is a potential serological diagnostic marker and therapeutic target for colorectal polyps and adenomatous polyps. [ABSTRACT FROM AUTHOR]