Relationship Between Serum Uric Acid And Blood Glucose In Normal Glucose Tolerance Population

Objective:Uric acid and blood glucose are inherently biologically linked.There have been some epidemiological studies to assess the relationship between fasting glucose（FBG）and serum uric acid（SUA）levels,Perhaps because they are more likely to choose diabetes or abnormal blood glucose regulation,maybe also be due to race,gender,statistical methods or other factors,the results are not consistent,but for normal glucose tolerance in normal human body blood glucose and uric acid relationship research is still blank,Therefore,from the perspective of clinical research,this study is divided into two parts.In the first part,we conducted a cross-sectional study of normal population with impaired glucose tolerance,to determine the relationship between uric acid and blood glucose before the occurrence of abnormal glucose metabolism,and analysis of related factors,for the early intervention of uric acid and blood glucose metabolism to provide a clinical basis。The use of continuous blood glucose monitoring system（CGMS）has led us to recognize that there are different fluctuations in blood glucose in both pre-diabetes and diabetes conditions,even in people with normal glucose tolerance,blood glucose fluctuates differently,in addition,many other related diseases,including metabolic syndrome,also have fluctuations in blood glucose.So in the second part,we selected a newly diagnosed gout group with hyperuricemia of normal glucose tolerance as a subject to which wo do continuous blood glucose monitoring and treatment by short-term uric acid,And further explore the relationship between serum uric acid level and blood glucose and its fluctuation in patients with normal glucose tolerance and hyperuricemia,and to provide clinical basis and theoretical basis for the prevention or the intervention of abnormal glucose metabolism of gout patients.Methods:We conducted an epidemiological survey of 16572 people aged 20 to 80 years in the coastal areas of Shandong Province from August 2004 to December 2014,we use a method of stratified random cluster sampling,of which 14,361 individuals（8123women and 6238 men）completed the investigation。In addition to the abnormal glucose metabolism and compliance with the rejection criteria,we included a total of5726 women and 5457 men with normal glucose tolerance as subjects of this study。Epidemiological survey was approved by the Qingdao University Affiliated Hospital Ethics Committee.For all completed investigators,we give physical examination,OGTT and blood samples were taken,biochemical markers were measured,CKD-EPI calculated glomerular filtration rate（eGFR）,and insulin resistance index（HOMA-IR）were assessed by steady-state model.Finally,Subjects had normal glucose tolerance of5726 women and 5457 men,excluding impaired glucose tolerance.Statistical analysis was performed using R software（version 3.2.2）and SPSS 16.0 statistical software,the data were described using mean±standard deviation or median（quartile）。Normal distribution of data between the two groups was compared using an independent t-test,otherwise the line Mann-Whitney U test。The Chow test^[30]is used to evaluate the difference between the hierarchical regression coefficients R。The t-test was used to compare the differences in the regression coefficients between models.The relationship between blood glucose and uric acid was evaluated by the generalized additive model and two segmented linear regression models.The correlation of univariate was analyzed by Spearman rank correlation test.P values less than 0.05 were considered statistically significant（bilateral）。In the scond part,30 cases of male patients from our gout and endocrine clinics of our hospital newly diagnosed gout with normal glucose tolerance and hyperuricemia were enrolled in our study。Normal glucose tolerance according to the 2003 American Diabetes Association（ADA）diabetes diagnostic criteria;gout in accordance with the American College of Rheumatology recommended diagnostic criteria in 1977;hyperuricemia is reference tothe 8th edition of"internal medicine"diagnostic criteria。The clinical data,physical examination,oral glucose tolerance test（OGTT）and blood test were performed.The blood glucose monitoring（CGM）were carried out for 72 hours,after 2 weeks of allopurinol treatment,72 hours of blood glucose monitoring and blood-testing performed again。Blood glucose fluctuation parameters were analyzed by CGMS Software 3.0 and SPSS 16.0 software package.The continuous blood glucose test parameters MAGE and MODD were calculated according to the MAGE self programming program.P values less than 0.05were considered statistically significant（bilateral）。Results:1.Cross-sectional study of the clinical characteristics of the study showed that the levels of serum uric acid and blood glucose were significantly higher in men than in women,but there was no significant difference in age.The prevalence of smokers and daily drinkers was significantly higher in male than that of females.Waist circumference,hip circumference,waist-to-hip ratio,blood pressure,triglyceride,creatinine and eGFR were significantly higher in men than in women,but male’s OGTT 2h blood glucose and high density lipoprotein cholesterol were significantly lower than women.Male and female body mass index,glycosylated hemoglobin,total cholesterol,low density lipoprotein cholesterol,fasting serum insulin have no difference.2.Fasting blood glucose and uric acid levels in normal glucose tolerance patients showed a smooth U-shaped curve.Blood uric acid levels were associated with fasting blood glucose levels at 4.6（female）/4.7（male）mmol/L,and elevated levels of uric acid after the crossing inflection point.In the female population,the regression coefficients of fasting blood glucose<4.6mmol/L were-38.8 and the regression coefficient of FPG≥4.6 mmol/L was 36.5,and the difference was significant.In the male population,fasting blood glucose<4.7 mmol/L regression coefficient of-35.2,FPG≥4.7mmol/L of the regression coefficient of 35.4,significant differences between the layers.The adjusted age and body mass index,systolic blood pressure,diastolic blood pressure,total cholesterol,triglyceride,alcohol,smoking status,estimated glomerular filtration rate,insulin,the inflection point remains and remains unchanged,but the regression coefficient is reduced.3.Serum uric acid and blood glucose correlation analysis showed that serum insulin levels and uric acid and fasting blood glucose was significantly positively correlated.HOMA-IR was positively correlated with uric acid and fasting blood glucose.4.In newly developed normal glucose tolerance gout with hyperuricemia patients,uric acid and triglyceride levels decreased significantly by 15%and 25%（P=0.005,P<0.001）after uric acid treatment,and fasting insulin and 2 hours postprandial insulin and HOMA-IR decreased significantly（P<0.001）,respectively,about 24%,27%,27%.（P>0.05）.The HOMB-βindex did not change significantly（P>0.05）,but there was no significant difference between the two groups（P>0.05）。5.There was a significant difference between Mean Amplitude of Glucose Excursions（MAGE）and standard deviations of blood glucose（SDBG）in blood glucose fluctuation parameters after urate lowering treatment,and the difference was statistically significant（P<0.001）;the mean blood glucose（MBG）also decreased（P>0.05）.There was no significant difference between the largest amplitude of blood glucose Excursions（LAGE）and the Absolute Mean of Daily Difference（MODD）。6.There was a significant correlation between MAGE and uric acid before and after urate lowering treatment（r=0.63,P=0.004;r=0.51,P=0.02）.The 24h MBG was significantly associated with postprandial 2-hour insulin（r=0.59,P=0.006）,and the correlation disappeared after urate lowering treatment.MAGE was associated with HOMA-IR（r=0.47,P=0.03）before treatment,and the correlation disappeared after treatment.The association between SDBG and MODD and TG disappeared after treatment with uric acid.There was a significant correlation between MBG and MODD after urate lowering treatment（r=0.51,P=0.02）.The correlation analysis found that there was a significant correlation between TG and uric acid before and after treatment（r=0.51,P=0.02;r=0.61,P=0.005）。7.Linear correlation analysis showed that MAGE was significantly associated with TG,MAGE and uric acid both before and after intervention,whereas MAGE was not associated with other blood glucose fluctuation parameters in this study before and after urate lowering treatment.Conclusions:1.For the first time at home and abroad found that people with normal glucose tolerance,uric acid changes with fasting blood glucose curvely,the inflection point in4.6（female）/4.7（male）mmol/L,before the inflection point uric acid with the increase in blood glucose decreased,the mechanism is glucose and uric acid reabsorption competition may play a leading role.After the inflection point uric acid with the increase in blood glucose decreased,the mechanism is elevated insulin caused by elevated blood glucose levels may lead to increased uric acid reabsorption.2.For people with normal glucose tolerance,the relationship between fasting blood glucose and serum uric acid concentration is partly mediated by serum insulin levels.3.At home and abroad,CGMS was used to observe the change of blood glucose for the first time in patients with gout,and we found that even in the normal stage of fasting glucose<5.6 mmol/L,the blood glucose fluctuation in the body with gout and hyperuricemia was increased,and the blood glucose fluctuation amplitude increased during-one-day and the average blood glucose level and day-to-day blood glucose drift were normal.5.First observed at home and abroad,after urate lowering treatment with allopurinol,gout patients with normal glucose tolerance and hyperuricemia were associated with a decrease in serum uric acid,triglyceride and insulin levels,and reduced blood glucose fluctuation.6.Blood glucose fluctuations in gout patients of hyperuricemia with normal glucose tolerance are associated with uric acid,insulin resistance,and TG levels.