| Objectives: To comprehensively describe the prevalence and incidence of diabetes,to expolore the risk factors of prediabetes and the development of prediabetes into diabetes in Jinchang cohort,to further reveal the dose-response relationships between various risk factors an prediabetes and diabetes,and to expolore the phosphorylation of JAK2 / STAT5 signal pathway proteins in different stages of diabetes in this population,so as to provide scientific basis for the targeted population to prevent diabetes.Methods:.The prevalence and incidence of prediabetes and diabetes in Jinchang cohort were showed in this study;Logistic regression model and Cox regression model were used to analyze the role of various factors in each stage of diabetes development;Additive model was used to estimate the interaction between heavy metals exposure and other related factors in prediabetes abd diabetes;Restricted cubic splines function was used to analyze the dose-response relationship between physiological and biochemical indicators and prediabetes,diabetes and blood glucose;Elisa was used to detect the concentration of JAK2 / STAT5 signal pathway proteins,and t-test was used to compare the difference of proteins concentration in different group.Results: 1.In Jinchang cohort,the prevalence of prediabetes was 18.25%(20.09% for men and 15.41% for women),and the incidence was 19.55%(21.24% for men and 17.20% for women).The prevalence of diabetes was 8.17%(9.44% for men and 6.19% for women).Among the patients with prediabetes in Jinchang cohort,the incidence of diabetes was 15.65%(15.78% for men and 15.37% for women)2.Multivariate logistic regression showed that heavy metals exposure,blood pressure,total cholesterol,triglyceride,overweight and obesity were the risk factors of prediabetes.The risk of prediabetes in middle metals exposure group an high metals exposure group increased by 1.20 times and 1.25 times respectively compared to low exposure group.Compared with normal blood pressure,prehypertension,mild hypertension and moderate hypertension were the risk factors of prediabetes.The ORs of prediabetes was 1.13(95% CI: 1.02-1.25)in marginal increase in total cholesterol,and 1.16(95% CI: 1.04-1.29)in increase of triglyceride;In overweight group and obesity group,the ORs of prediabetes were 1.34(95% CI: 1.22-1.47)and 1.89(95% CI: 1.61-2.23),respectively.3.Multivariate Cox regression showed that heavy metals exposure,blood pressure,total cholesterol,triglyceride,education level,overweight and obesity were the risk factors of prediabetes,and the HRs of prediabetes was 1.61(95% CI: 1.49-1.74)in high metals exposure;with the increase of blood pressure,the risk of prediabetes increased;the marginal increase and increase in total cholesterol and triglyceride increased the risk of prediabetes.There were dose-response relationships between BMI,systolic blood pressure,diastolic blood pressure,total cholesterol,high-density lipoprotein cholesterol and the risk of prediabetes(P < 0.05).4.Multivariate logistic regression showed that heavy metals exposure,tea index,blood pressure,triglyceride,overweight and obesity were the risk factors for the development of prediabetes to diabetes;the risk of diabetes in prediabetes patients with high metals exposure increased by 1.32 times;the ORs of diabetes in prediabetes patients with tea drinking index ≥ 300 was 3.85(95% CI: 1.33-12.65);the risk of diabetes was increased in mild hypertension,moderate hypertension and severe hypertension;the ORs of diabetes in triglyceride increase group was 1.34(95% CI: 1.08-1.66);the ORs of overweight and obesity were 1.40(95% CI: 1.15-1.71)and 1.99(95% CI: 1.54-2.57)respectively.5.The multivariate Cox regression showed that blood pressure,total cholesterol,triglyceride,education level,overweight and obesity were the risk factors for the development of prediabetes into diabetes.In this population,mild hypertension and severe hypertension increased the risk of diabetes;the risk of diabetes increased by 1.25 times in marginal increase of total cholesterol group;the marginal increase and increase of triglyceride increased the risk of diabetes,which the HRs were 1.28(95% CI: 1.07-1.54)and 1.36(95% CI: 1.15-1.62)respectively,and BMI above 24 increased the risk of diabetes.There were dose-response relationships between systolic blood pressure,triglyceride,high-density lipoprotein cholesterol,BMI and the risk of diabetes(P < 0.05).6.There were dose-response relationships between BMI,total cholesterol,triglyceride,high-density lipoprotein cholesterol,systolic blood pressure,diastolic blood pressure and the risk of blood glucose increase in Jinchang cohort(P < 0.05).7.The expression level of pjak2tyr221 and pjak2tyr1007,the activators of pstat5 and JAK2,was the highest in prediabetes(P < 0.05).There was a positive correlation between pstat5 and pjak2tyr221,pjak2tyr1007 in prediabetes(P < 0.05);there were positive correlations between pstat5 and pjak2tyr221,pjak2tyr1007 in diabetes(P < 0.05).8.The expression levels of PIAS3,CISH,pjak2ty570 and PTP1 B were the highest in prediabetes compared to other groups(P < 0.05),while PTP1 B was the highest in diabetes(P < 0.05).There were positive correlations among CISH,pjak2ty570,PIAS3 and PTP1 B in prediabetes(P < 0.05),and there were positive correlations between CISH,pjak2ty570,PIAS3 and PTP1 B in diabetes(P < 0.05).Conclusions: 1.The prevalence of diabetes in Jinchang cohort was 8.17%,9.44% for men and 6.19% for women;The incidence of diabetes in patients with prediabetes was 15.65%,15.78% for males and 15.37% for females.2.High exposure to heavy metals,hypertension,elevated total cholesterol,elevated triglyceride,and overweight/obesity increased the risk of prediabetes,and there were dose-response relationships between BMI,total cholesterol,high-density lipoprotein cholesterol,systolic blood pressure,diastolic blood pressure and the risk of prediabetes.3.Hypertension,elevated triglyceride and overweight/obesity can promote the development of prediabetes into diabetes,and there were dose-response relationships between BMI,triglyceride,systolic blood pressure and the risk of diabetes.4.There were dose-response relationships between BMI,total cholesterol,triglyceride,high-density lipoprotein cholesterol,systolic blood pressure,diastolic blood pressure and blood glucose in Jinchang cohort.5.JAK2 / STAT5 signaling pathway in Jinchang cohort was related to the development of diabetes,and the phosphorylation of STAT5 mainly occurs in prediabetes.6.The expression of the activators of JAK2,pjak2tyr221 and pjak2tyr1007,mainly occured in prediabetes,and were positively related to the phosphorylation of STAT5.7.The expression of PIAS3,CISH and pjak2ty570,the negative regulators of pstat5,mainly occurred in prediabetes,and the expression of PTP1 B mainly occurred in diabetes,and these negative regulators were positively correlated with the phosphorylation of STAT5. |
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