The Relationship Between Inflammatory Factors And Genes In Type 2 Diabetes Mellitus Complicated With Colorectal Cancer

Background:Type 2 diabetes mellitus(type 2 diabetes mellitus,T2DM)is a common chronic disease that seriously damages human health in the world.Due to the influence of sedentary lifestyle,the onset of T2 DM is gradually becoming younger.At present,the pathogenesis of type 2 diabetes is not fully understood,in which carbohydrate,fat metabolism disorders and related chronic inflammatory reaction are considered to be important factors.As a metabolic disorder,diabetes not only affects the systemic and local metabolism,but also affects the metabolic level of cells to a certain extent.When cells in local tissues lose normal regulation of their growth at the genetic level,resulting in clonal abnormal proliferation of cells will form tumors.Colorectal cancer(colorectal cancer,CRC),as a malignant tumor with the highest incidence of digestive system in China,has the characteristics of atypical early symptoms,poor prognosis and high mortality.Colorectal cancer and diabetes are major public health problems in the world.At present,the growth rate of new cases of colorectal cancer and diabetes is alarming.The high morbidity and mortality of these two diseases have a profound impact on the quality of human life and social economy.A large number of epidemiological studies have found that the mortality of colorectal cancer patients with type 2diabetes(T2DM&CRC)is higher than that of people with normal blood glucose,which shows that type 2diabetes is easy to induce colorectal cancer.Metabolic disorders and related chronic inflammatory reactions caused by diabetes are considered to be an important factor in the occurrence and development of tumors.The incidence of type 2 diabetes and colorectal cancer is related to long-term chronic low-grade inflammation of the system.However,the potential biological link between the two diseases is not completely clear.Inflammation and endothelial dysfunction are the precursors of diabetes.The adhesion function of neutrophils and endothelial cells in people with hyperglycemia is impaired,and the injured cells in the state of ischemia and hypoxia gradually migrate to inflammatory sites.this series of oxidative stress is an important part of the pathogenesis of diabetes.A large number of studies have shown that tumors are also closely related to chronic inflammation,such as viral hepatitis and liver cancer,Helicobacter pylori infection and gastric cancer,inflammatory bowel disease and colorectal cancer.It can be seen that type 2diabetes and colorectal cancer are more or less associated with inflammatory related factors.In recent years,some new markers of oxidative stress and inflammation have been found in clinic,such as monocyte count/ high density lipoprotein cholesterol(MHR),platelet count / lymphocyte count(PLR),neutrophil count /lymphocyte count(NLR),etc.Compared with common inflammatory markers,these emerging inflammatory markers can reflect the inflammatory state and degree of the body more objectively and accurately.And it has the advantages of high stability,easy to obtain,affordable and so on.Related studies have proved that NLR,PLR,MHR and other indexes are sensitive to the prediction of some digestive system tumors,and to some extent can be used as independent predictors of disease progression and prognosis of these tumors.The occurrence of type 2 diabetes and colorectal cancer is a slow and complex pathological process,which is affected by many factors.The mechanism of mutual induction and influence between these two common chronic diseases is not clear.After suffering from one of the chronic diseases,the changes of body function metabolism,occurrence,development and prognosis of different individuals may become the inducing factors of another chronic disease.Whether diabetes affects the metabolism of nutrients in tumor cells through long-term chronic low-grade inflammation,which leads to changes in the biological behavior of colorectal cancer,is worthy of our further discussion.Therefore,to explore the correlation between these clinically available new inflammatory factors and type 2 diabetes patients and patients with type 2 diabetes mellitus complicated with colorectal cancer(T2DM&CRC)can not only block the occurrence of tumors in the inflammatory stage.It not only improves the early diagnosis rate of malignant tumor,but also provides a new idea for the clinical diagnosis and treatment of type 2 diabetes patients with colorectal cancer.Objective:To analyze the changes of new clinical inflammatory markers such as neutrophil count /lymphocyte count ratio(NLR),platelet count / lymphocyte count ratio(PLR),monocyte count and high density lipoprotein-cholesterol ratio(MHR)in patients with type 2 diabetes mellitus complicated with colorectal cancer,so as to create conditions for early identification,prevention and treatment of patients with type 2 diabetes mellitus complicated with colorectal cancer.Methods:In this study,137 patients with T2DM&CRC and 124 patients with T2 DM alone were selected as the case group in the Department of Endocrinology,Gastroenterology,Gastrointestinal Surgery and Oncology in Henan people’s Hospital from October 2018 to October 2020,119 healthy subjects from our hospital during the same period were selected as the normal control group.Age and sex were matched with the case group.The distribution frequency of genotypes was tested by Hardy-Weinberg equilibrium test with χ 2test,p > 0.05.The samples were representative of the population,and the SNa Pshot sequencing method was used for genotyping analysis.The method of case-control study was used,and the statistical analysis was carried out by Spss22.0 software.When the test level was P < 0.05,it was statistically significant.Results:1.Comparison of clinical data:(1)there was no significant difference in sex,height,weight and SBP among the three groups(P>0.05).(2)the levels of BMI and DBP in the T2 DM group were significantly higher than those in the control group(P<0.05).(3)the age level of T2DM&CRC group was significantly higher than that of T2 DM group,while the BMI index and DBP level of T2 DM group were significantly lower than those of T2 DM group.2.Comparison of the levels of inflammatory factors:(1)there was no significant difference in the levels of WBC,MON,LYM and PLT among the three groups(P>0.05).(2)the levels of NEU,NLR,LMR,MHR,FPG and Hb A1 c in the T2 DM group were significantly higher than those in the control group,while the levels of PLR and HDL-C in the T2 DM group were significantly lower than those in the control group(P<0.05).(3)the levels of NEU,NLR,PLR and MHR in T2DM&CRC group were significantly higher than those in T2 DM group,while the levels of LMR,HDL-C,FPG and Hb A1 c were significantly lower in 2DM&CRC group.3.Multivariate Logistics regression results showed that age was a risk factor for T2DM&CRC(OR=1.153,P<0.05),PLR was a risk factor for T2DM&CRC and OR=1.012,P < 0.05),MHR was a risk factor for T2DM&CRC(OR=4.188,P<0.05).4.The results of ROC curve analysis showed that: NLR(AUC= 0.733 BI 95% CI: 0.612-0.853,sensitivity 73.3%,specificity 70.0%,Yoden index 0.433,P < 0.01,statistically significant).NLR combined with PLR and MHR predicted that the area under the curve of T2DM&CRC was 0.783(95%CI:0.669-0.898).The best CUT-OFF value of ROC curve was 0.533,with a sensitivity of 63.3% and a specificity of 90%.5.SNPs detection results and comparison: there was no significant difference in FTO rs9939609 locus SNPs among the three groups(P > 0.05).Conclusion:1.The occurrence of T2DM&CRC was correlated with the levels of PLR and MHR,PLR and MHR were risk factors for patients with T2DM&CRC.2.The three inflammatory blood factors NLR,PLR and MHR can predict the incidence of T2DM&CRC,and the combined prediction efficiency of the three inflammatory blood factors is better than that of the three inflammatory blood factors alone.3.There may be no correlation between FTO rs9939609 genotype and T2DM&CRC.