Association Between Serum Uric Acid And β-cell Function As Well As Insulin Resistance In Gout Patients

Part1:The association between serum uric acid and β-cell function as well as insulin resistance in the patients with goutObjective To evaluate the relationship between serum uric acid (sUA) level and two critical sides in the pathogenesis of type2diabetes, that is, insulin resistance and P-cell dysfunction, and the interrelationship between sUA and blood glucose, serum lipid, blood pressure and the risk factors of metabolic syndrome.Methods We enrolled96patients with gout and80healthy subjects. Gout patients were divided into6groups according to serum uric acid levels:<7mg/dL;7-7.9mg/d;8-8.9mg/d;9-9.9mg/dL;10-10.9mg/dL;≥11mg/dL(lmg/dL=59.5μ mol/L). Insulin resistance was evaluated by HOMA-IR and ISI, and Insulin secretion was evaluated by HOMA-B. Fasting glucose, fasting insulin, glycosylated hemoglobin (HbAlc), serum uric acid, C-reactive protein, cholesterol and triglycerides were investigated in all subjects. Oral glucose tolerance tests (OGTT) were performed in two subjects. The multiple step regression analyses were conducted between serum uric acid level and these indexes respectively. All statistical analyses were conducted with the Statistical Package for Social Science for Windows (SPSS, version12.0).Results1.There was no significant difference in the average age between gout patients and healthy controls(mean age47.5±18.21vs50.7±8.64). The serum uric acid levels were higher in the patents with gout than those in the healthy subjects(521.5±48.56μ mol/L vs318.2±80.3μ mol/L)(P<0.001). Patients with gout had higher prevalence of metabolic syndrome, hypertention, diabetes mellitus than controls(42.9%vs11.7%;53.1%vs19.5%;35.4%vs9.2%, respectively). Patients with gout had higher levels of BMI, SBP, Scr, fasting insulin, TG, TC, and LDL, but the HDL were lower than controls.2.Patients with gout had higher HOMA-IR and lower ISI than controls. And their β-cell function seems to have no statistical difference.3.The serum uric acid level in the patents with gout was positively correlated with fasting insulin, HOMA-IR, and negatively correlated with HOMA-B. Morever, there was significantly association between serum uric acid (sUA) level and BMI, TG, TC and SBP, but negatively association with DBP.4.After multiple step regression analysis, sUA was significantly associated with HOMA-IR but negatively associated with HOMA-B.Conclusion Our cross-sectional study suggest that patients with gout frequently suffer from a number of comorbid conditions including diabetes mellitus,hypertension and metabolic syndrome. Patients with gout have severe insulin resistance but their β-cell dysfunction is not obvious. Gout comorbid type2diabetes may owing to isullin resistance and multiple component of metabolic syndrome aggregation. The serum uric acid levels in gout patients is associated with insulin resistance, but negatively association with β-cell function. The level of serum uric acid is independent association with insulin resistance in gout patients. It has been suggested that TG、 TC、 BMI、 blood pressure may be factors affecting Homa-IR. SUA was found to be associated with the component of metabolic syndrome (such as blood pressure,cholesterol,triglycerides,BMI). Tight control of uric acid may decrease the incidence of insulin resistance and the risks of metabolic syndrome. Part2:Function of islet β cell in gout patients with different status of glucose metabolismObjective To investigate the changes of insulin resistance(IR) and function of islet P-cell function in gout patients with different status of glucose metabolism. To analysis metabolic features in gout patients with hyperglycemia.Methods Ninety-six patients with gout were consecutively enrolled into the study. According to75g oral glucose tolerance test results,patients were divided into normal glucose tolerance group (NGT, n=34), impaired glucose regulation group (IGR, n=27) and diabetic group (DM, n=35).Height, weight, blood pressure, fasting glucose, fasting insulin, glycosylated hemoglobin (HbAlc), serum uric acid, C-reactive protein,cholesterol and triglycerides were investigated in all subjects.Body mass index (BMI), homeostasis model insulin resistance index (HOMA-IR), pancreatic β-cell function index (HOMA-B) and insulin sensitivity index (ISI) were calculated.Results Among three groups of DM，IGR and NGT, BMI ((27.36±4.10)、(25.52±3.87) and (23.64±3.19) kg/m2]、2hPG ((18.25±7.03),(10.12±0.85) and (6.75±0.45) mmol/L]. fasting insulin ((17.58±6.35)、(14.92±5.72) and (8.51±4.56) IU/ml]、glycosylated hemoglobin ((10.18±3.24)、(6.54±3.28) and (5.12±2.21)%]、 cholesterol ((5.84±1.09)、(5.23±0.97)and(4.62±1.08)mmol/L]、 triglycerides ((3.93±1.23)、(3.09±1.01) and (2.37±0.95) mmol/L]、 C-reactive protein [(4.98±2.02)、(3.79±1.29)and(3.07±1.26)mg/L].HOMA——IR((1.80±0.06).(1.72±0.20)and(0.93±0.14))were increased in the DM and IGR groups,although ISI was significantly decreased. HOMA-B ((87.6±25.1)、(126.46±34.2) and (173.75±32.1)) was significantly different between the three groups.Logistic analysis showed that age, BMI, SBP, triglyceride, ISI is independently associated with diabetes, but no correlation with uric acid.Conclusion The Gout patients with IGR mainly showed defect of insulin resistance. The subjects with DM have more severe insulin resistance and defect of insulin secretion. Sever insulin resistance,β-cell dysfunction, increased BMI and C-reactive protein, lipid disorders, and hereditary susceptibility may be the main metabolic features of gout with hyperglycemia. Part3:Febuxostat treatments on blood glucose, insulin resistance, B-cell function and uric acid in gouty patientsObjective The aim of this study was to observe the effects of urate-lowering therapy (UALT), febuxostat, on blood glucose, and serum uric acid level. To investigate the changes of insulin resistance(IR) and function of islet β-cell function in gout patients after febuxostat treatment2months.Methods Gouty patients were randomized1:1to group A and group B. Group A received daily febuxostat80mg, while Group B received febuxostat40mg. Throughout the2-month treatment period, all patients received prophylaxis for gout flares, with either colchicine0.5mg daily, or diclofenac sodium0.1daily. Patients with eGFR<50ml/min were permitted only colchicine prophylaxis. All patients received75g oral glucose tolerance test before receiving urate-lowering therapy and after2months’treatment, Blood glucose and serum creatinine level were measured at baseline and at month2. Height, weight, blood pressure, fasting glucose, fasting insulin, glycosylated hemoglobin (HbAlc), serum uric acid, C-reactive protein, cholesterol and triglycerides were investigated in all subjects. Body mass index (BMI), homeostasis model insulin resistance index (HOMA-IR), pancreatic β-cell function index (HOMA-B) and insulin sensitivity index (ISI) were calculated.Results The group A completed20gouty man, average age53.3±12.5, average sUA635±127μ mol/L, the group B completed21gouty man, average age56.1±11.4, average sUA624±116μ mol/L. At baseline, the age, sex, course of disease, BMI, blood pressure, renal function have no significant difference between the two groups(P>0.05). The SUA levels, fasting insulin, and serum creatinine concentration had decreased significantly after treatment compared to baseline. Patients with gout had higher ISI and lower HOMA-IR after febuxostat treatment. But their β-cell function seems to have no statistical difference. There were no statistically significant differences in fasting glucose,2hPQ HbAlc, AST, ALT when compared with the distribution of baseline. Analysis was performed to determine associations between the change in uric acid and changes in HOMA-IR, ISI, and HOMA-B. Lower target uric acid levels tended to be associated with decreased HOMA-IR and higher ISI. Serum uric acid level were significantly associated with HOMA-IR(P<0.0001) and ISI(P=0.017), but not associated with HOMA-B(P=0.025).Conclusion Gout patients with urate lowering drugs febuxostat intervention, fasting insulin levels decrease, insulin sensitivity improved, HOMA-IR decreased, alleviated insulin resistance, while HOMA-B and fasting blood glucose,2hPG, glycosylated hemoglobin had no significant difference compare to basline. Indicating that the urate lowering treatment have no effect on blood sugar. Correlation analysis also showed that uric acid level is positive associated with HOMA-IR, negative associated with ISI, but not associated with HOMA-B. Moreover, lower uric acid may improve patient’s renal function. Therefore, lowering uric acid levels can improve insulin resistance in patients with gout, and prevention of type2diabetes mellitus.