Study On The Effect Of Triglycerides In The Relationship Between High Uric Acid Levels And Glucose Abnormality

Part 1 Current status analysis of association between high serum uric acid levels and diabetesObjective: To explore the role of uric acid(UA)in the onset of diabetes by investigating the prevalence of diabetes(diabetes mellitus,DM)and pre-diabetes in Fuzhou City’s residents over 18 years old.Methods: In our cross-sectional survey,using multi-stage cluster sampling method randomly selects 5796 residents of Fuzhou City’s permanent residents over the age of 18 as the survey and research objects.The survey content mainly includes questionnaire survey,physical examination,laboratory test and oral glucose tolerance test(OGTT).Then,Logistic regression model was used to analyze the relationship between uric acid and blood glucose levels.Results: A total of 5796 of 6000 subjects completed the survey(response rate:96.6%).21%(1216/5786)of respondents were diagnosed with diabetes.19.24%(1118/5796)of respondents showed impaired glucose tolerance.And Few(1.4%,82/5796)respondents described impaired fasting blood glucose.Ordered multi-class logistic regression analysis showed high uric acid levels would increase the risk of diabetes(P<0.05).The high level of uric acid is also concerned as a risk factor for abnormal blood glucose levels 2 hours after the glucose tolerance test(P<0.05).However,there was no relationship between high uric acid and the risk of abnormal fasting blood glucose(FBG)(P>0.05).Conclusion: The High level of uric acid is associated with abnormal blood glucose risk and is a risk factor for impaired glucose tolerance.Part 2 Current status analysis of association between high serum uric acid levels and diabetesObjective: To explore the role of lipid metabolism in the association of hyperuricemia and diabetes risk.Methods: the mediation effect of lipid metabolism on the relationship between hyperuricemia and diabetes risk was analyzed by Vander Weele mediation analysis based on part one Population.Results: The results showed that the direct effect of the high level of uric acid on the risk of abnormal blood glucose was 1.353(95%CI: 1.199-1.539),the indirect effect through TG was 1.110(95%CI: 1.081-1.143),the indirect effect through HDL-c was1.029(95%CI: 1.015-1.044),and the indirect effect through LDL-c was 1.011(95%CI:1.001-1.024).The proportion mediated(PM)were 29.65%,10.08% and 4.12%,respectively.Conclusion: TG,HDL-c and LDL-c played a mediating role in the relationship between hyperuricemia and the abnormal blood glucose risk.Part 3 Study on the effect of serum triglycerides on diabetes mellitus complicated with hyperuricemiaObjective: To investigate the relationship between serum triglyceride(TG)and the risk of hyperuricemia and abnormal blood glucose and its possible mechanism.Methods: A case-control study was conducted based on the first part of the population.Strictly according to the case-control study inclusion criteria and exclusion criteria to select healthy group(Normal glucose tolerance and Normal uric acid,NGT+NUA),hyperuricemia group(Normal glucose tolerance and hyperuricemia,NGT+HUA)group,diabetes group(Diabetes and normal uric acid,DM+NUA)and diabetes complicated with hyperuricemia group(Diabetes+ hyperuricemia,DM+HUA),each group number for 428 cases.The unconditioned Logistic regression model and a smooth curve fitting to explore the association between TG level and risk of DM+HUA.Meanwhile,q RT-PCR was used to detect the transcriptional expression levels of TG biosynthesis related factors(GPAT1,GPAT2,GPAT3,GPAT4,ACC1,DPAT1 and FASN)in peripheral blood leukocytes.Results:(1)Logistic regression was used to analyze the relationship between TG level and DM+HUA.After adjust for potential confounding variables such as age,gender was conducted,Per 1mmol/L TG level increment was associated with increased risk of DM+HUA [NGT+NUA: OR(95%CI)=1.737(1.405-2.148);NGT+HUA: OR(95%CI)=1.226(1.068-1.409);DM+NUA: OR(95%CI)=1.082(0.973-1.204)].We also converted TG from a continuous variable to a categorical variable(quartile).and compared to participants in Q1.The results showed that there was a significantly increased risk of DM+HUA compared to NGT+HUA [Q3: OR(95%CI)=2.355(1.453-3.817),Q4: OR(95%)=4.233(2.498-7.175)].when NGT+HUA was control group,TG Q4 group significantly increased the risk of DM+HUA [OR(95%CI)= 1.598(1.045-2.441)],and DM+NUA is control group,Q4 group significantly increased the risk of DM+HUA [OR(95%)=1.758(1.092-2.829)].The smoothing curve results showed that the associations between TG and DM+HUA was linear.(2)Compared with NGT+NUA group,the m RNA level of GPAT2 in peripheral blood leukocytes in DM+NUA group and DM+HUA group was significantly increased(P<0.05);The expression level of GPAT3 m RNA showed a downward trend in all groups,but the difference was statistically significant only in DM+HUA group(P<0.05).The GPAT4 m RNA expression levels in NGT+HUA,DM+NUA and DM+HUA groups was increased,and were all higher than those in NGT+NUA group(P<0.05).The m RNA expression level of ACC1 in DM+HUA and DM+NUA groups was significantly higher than that in NGT+NUA group(P<0.05).The m RNA expression level of DPAT1 in DM+NUA group was significantly higher than that in NGT+NUA group(P<0.05).The m RNA expression level of FASN in DM+HUA and DM+ NUA groups was higher than that in NGT+ NUA groups(P<0.05).Conclusion: Diabetes is related to changes in the transcription levels of factors related to the triglyceride synthesis pathway.The High level of uric acid may cause abnormal changes in blood glucose by affecting the transcription levels of GPAT4 factors.