Correlation Between Serum Uric Acid And Diabetic Peripheral Neuropathy In T2DM Patients

BackgroundPeripheral neuropathy is the structural and functional disorder of the motor,sensory and autonomic nerve.Diabetic peripheral neuropathy(DPN),including sensory-motor diabetic peripheral neuropath and diabetic autonomic neuropathy(DAN),is one of the most common peripheral neuropathy.In recent years,the incidence of type 2 diabetes has increased in Clina[1,2].As one of the important complications of diabetes,diabetic peripheral neuropathy seriously affects human health and life.The prevalence of sensory-motor diabetic peripheral neuropath is as high as 30-40%in T2DM patients[3],while the prevalence of DAN is about 50%[4].Sensory-motor diabetic peripheral neuropath causes numbness and increases the risk of diabetic foot,which increases the disability and mortality in diabetes patients and brings great medical and economic burden to the society.DAN involves various systems,which seriously affects the quality of life of T2DM patients.There is still no effective treatment for diabetic peripheral neuropathy.Early diagnosis and effective intervention are of great importance.The pathogenesis of diabetic peripheral neuropathy is complicated,and many studies tend to be considered that the pathophysiological processes caused by multiple factors[5,6].Diabetes duration and long-term high glucose state were currently recognized as important pathological factors of diabetic neuropathy.In recent years,studies have found that hyperlipidemia,hypertension,hyperuriceimia,smoking,drinking,obesity,gene polymorphism and other factors may also contribute to the pathophysiology of diabetic neuropathy[7-1].Serum uric acid(SUA)is a final product of purine metabolism.The study showed that uric acid was related closely with cardiovascular and cerebrovascular diseases[12-14].The present studies of the correlation between DPN and serum uric acid were very limited.Studies[11]have shown that the T2DM patients with hyperuricemia were more likely to have cardiovascular diseases,cerebrovascular diseases,diabetic nephropathy,diabetic retinopathy and diabetic peripheral neuropathy compared with who didn't have hyperuricemia.Moreover,some researches[15]showed the level of SUA in DPN patients were higher than that in Non-DPN patients.The aim of our study is to explore the correlation between diabetic peripheral neuropathy and serum uric acid.The peripheral nerve fibers contained myelinated fibers and unmyelinated fibers.The sensory and motor nerve fibers are mainly myelinated nerve fibers,while the autonomic nerve fibers are mainly thin myelinated and unmyelinated nerve fibers.There were two parts in our studies.The first part was to investigate the correlation between sensory-motor diabetic peripheral neuropath and serum uric acid.The second part was to study the correlation between sudomotor dysfunction and serum uric acid in T2DM patients.Objective1.To investigate the correlation between diabetic peripheral neuropathy and serum uric acid.2.To investigate whether serum uric acid and other risk factors can be used as predictors of DPN.Subjects and MethodsSubjects:This study enrolled 200 T2DM inpatients aged 55.89 ±12.62 years(19-74 years old)old presenting at the Department of Endocrinology of Nanfang Hospital,Southern Medical University during January 2016 to November 2016.T2DM was diagnosed based on the 1999 World Health Organization criteria.All participants were screened for DPN.Patients were stratified into four groups according to SUA levels(<5 mg/dl,5.1-7 mg/dl,7.1-9 mg/dl,and>9 mg/dl).Exclusion criteria were as follows:other causes of peripheral nerve lesions(including chronic inflammatory demyelinating peripheral neuropathy,nutritional deficiency,poisoning,abnormal globulinemia,hypothyroidism,connective tissue disorder,heredity,trauma and so on),other causes of autonomic nerve lesions(including Parkinson,Parkinson's syndrome,multiple system atrophy,and other disorders that may lead to autonomic nerve dysfunction),alcohol abuse,vitamin B12 deficiency,peripheral arterial disease,malignant tumor,chronic rheumatic disease,acute or chronic infections or inflammation,history of hepatic dysfunction(transaminase>2-fold higher),history of renal dysfunction(serum creatinine>2.0 mg/dl or eGFR<30 ml.min-1/1.73m-2),acute attack of gouty arthritis(Joint redness or swelling pain within 2 weeks),and the use of any medication that might influence SUA within one month(benzbromarone,allopurinol,febuxostat,diuretics,losartan,fenofibrate,cyclosporin,salicylates,nicotinic acid,estrogens,ethambutol or pyrazinamide).Methods:1.The collection of clinical dataRecord sex,age,the course of diabetes,the history of smoking,the history of drinking,the height,weight,blood pressure,and calculate the BMI of the participants.2.MeasurementsSerum uric acid(SUA),total cholesterol(TC),triglycerides(TG),high-density lipoprotein(HDL),low-density lipoprotein(LDL)and Glycated hemoglobin(HbAlc)were measured.3.Electrophysiological assessments and quantitative sensory testsElectrophysiological assessments were performed using Viking Quest.The latency,compound muscle action potential(CMAP)amplitude and conduction velocity(CV)of motor nerve for the median,ulnar,posterior tibial,and peroneal nerves were measured and recorded.The measurements of sensory nerve action potential(SNAP)amplitude and CV were performed using the median,ulnar,and sural nerves.The quantitative sensory tests(QST)were performed using Semmes-Weinstein monofilament testing(SWMT)and vibration perception threshold(VPT)test.SWMT was used for detecting tactile sensation,while VPT was used for detecting vibration sensation.In the present study,sensory-motor DPN was defined as the presence of one or more abnormal nerve conduction results(latency,amplitude or CV)in at least two different peripheral nerves combined with an abnormality in SWMT or VPT test[17]4.Neuropad sweat testNeuropad is used to evaluate the sudomotor function,which were applied to both soles at the level of the first and second metatarsal heads.Record the time to the color started to change and completely changed respectively(from blue to pink).The time to the color changed completely more than 10min was considered as sudomotor dysfunction,which less than 10min was considered as normality.5.Statistical analysisThe IBM SPSS Statistics 2010(V.19.0,IBM Corp.,USA)was used for data analysis.Results1.The correlation between serum uric acid and sensory-motor diabetic peripheral neuropathy(1)The T2DM patients with higher SUA levels showed significant impairment in the NCS parameters.The mean of motor/sensory nerve latency was longer(P<0.05),while the mean amplitude/CV of motor/sensory nerve was lower in higher SUA group than that in lower SUA group(P<0.05).(2)The SUA levels were positively correlated to the means of motor nerve latency(r=0.397,P<0.05)and sensory nerve latency(r=0.320,P<0.05),The SUA levels were negatively correlated to the means of motor nerve amplitude(r=-0.142,P<0.05),motor nerve CV(r=-0.191,P<0.05),sensory nerve amplitude(r=-0.194,P<0.05)and sensory nerve CV(r=-0.191,P<0.05).(3)The result of multivariate logistic regression showed that the duration of>10 years(OR 3.26,95%CI 1.41-7.56,P<0.05),SUA>9 mg/dl(OR 7.98,95%CI 1.47-43.40,P<0.05)and TC>5.2mmol/L(OR 2.14,95%CI1.11-4.11,P<0.05)increased risk for sensory-motor DPN than the lower levels.(4)ROC analysis showed the cut-off points of T2DM duration combined SUA and TC values to predict sensory-motor DPN were revealed as:9 years,7.8 mg/dl,and 4.97 mmol/L,respectively(AUC=0.65;95%CI:0.53-0.77;sensitivity,70.6%;specificity,65.2%,P<0.05).2.The correlation between serum uric acid and sudomotor dysfunction in T2DM patients(1)The Neuropad test showed the time for the color that started to change and completely changed were prolonged with elevating of SUA level(P<0.05),which suggested higher SUA level impair the sudomotor function in T2DM patients.(2)Smoking and higher SUA level were risk factors for sudomotor dysfunction in T2DM.The history of smoking(OR 3.16,95%CI 1,29-7.74,P<0.05)was found to be significantly associated with sudomotor dysfunction in T2DM.SUA levels higher than 7 mg/dl(OR3.56,95%CI 1.17-10.89,P<0.05)and higher than 9 mg/dl(OR 9.68,95%CI 2.74-36.09,P<0.001)showed increased risk for sudomotor dysfunction in T2DM patients than the lower levels(?5 mg/dl).(3)ROC analysis showed the history of smoking combined with the level of SUA>7.57 mg/d could predict sudomotor dysfunction in T2DM patients(AUC=0.70;95%CI:0.60-0.80;sensitivity,76.9%;specificity,50.5%,P<0.05).Conclusion1.There are close correlations between serum uric acid and DPN.2.T2DM duration combined SUA and TC values could predict sensory-motor DPN.3.The history of smoking and hyperuricemia are risk factors for sudomotor dysfunction in T2DM patients.4.The history of smoking combined with SUA value could predict sudomotor dysfunction in T2DM patients.