Clinical Features Of Type 1 Diabetes Patients With Neuropathy And The Therapeutic Effects Of Hydrogen Sulfide On Diabetic Neuropahty Rats

AimsThe prevalence of Type 1 diabetes（T1DM）is increasing year by year,Chinese T1DM patients have unique demographic and clinical presentations.Diabetic peripheral neuropathy（DPN）is one of the most seen diabetic complications and one of the main causes of disablement and death among diabetic patients.Early recognition of the risk factors for DPN is of great importance,it may reduce complications.Also,the underlying mechanism of DPN are not completed understood.To the date,there’re still no adequate treatments for DPN.Our study is divided into two parts,in clinical study,we aim to find out the potential risk factors for DPN among T1DM patients,especially the effect of TIR and blood glucose fluctuation on neuropathy and patient’s gait.In basic research,we aim to find out whether H₂S can improve DPN and to explore its possible mechanism.MethodsIn clinical research,a total of 326 Type 1 Diabetes inpatients were recruited.All patients were screened for DPN and then divided into 2 groups,DPN and non-DPN group.A 3-day CGMs was conducted on each patient.Information regarding BMI,smoking and drinking habits,medical history,glycemic control,insulin function parameters were collected from the patients’medical record book.Furthermore,a group of type 1 diabetes patients further went through a gait analysis to investigate the spectral content of gait in patients with DMIn fundamental research,experimental diabetic rats were induced by intraperitoneal injection of streptozotocin（STZ）at dose of 60 mg/kg,all rats were randomly assigned to 3 groups:non-diabetic control group（NC）,diabetic control group（DM）,H₂S treatment group（H₂S）.We use Na HS as exogenous sulfur donors to treat the experimental animals for 14 days in row.At the end of the experiment,the rats went through an electromyography,then serum and tissues were processed for serologic test,histological examination and analysis of western blot.We hope to look into the effects of H₂S on DPN and the possible mechanism.Results1.Among the 326 type 1 diabetes patients enrolled in our study,37.11%presented with DPN.Compared with the control group,DPN patients are older,have longer duration,higher BMI,waist circumstance,Hb A1c,mean blood glucose,and lower TIR（P<0.05）.The prevalence of hypertension,stroke,current drinking and smoking were higher in DPN group（P<0.05）.Meanwhile,glucose variability,insulin function,max BG,min BG and lipid profiles are comparable between two groups（P>0.05）.In general,most of the T1DM patients don’t meet the glucose control target,mean TIR is only 54.75%among all enrolled subjects,and DPN group has a mean TIR of 48.24%.Logistic regression analysis showed that TIR,age,duration,and smoking habit were significantly correlating with DPN in T1DM patients.The gait spectral analysis revealed T1DM patients have more unstable gait and underlying mobility limitations compared with health control.2.Treating with H₂S improved the pathological damage of DPN by HE staining,transmission electron microscope results also showed H₂S repaired nerve fiber lesions.In both serum and sciatic nerve,the MDA of DM group increased significantly,and decreased significantly in H₂S treatment group.While the SOD of DM group dropped significantly,and raise back to almost normal level in H₂S treatment group.Analysis of Western Blot indicated that H₂S inhibited the expression of AR compared with the upregulated expression in DM group（P<0.05）. Additionally,no difference was found in the level of serum ALT,AST,BUN,TC,TG,LDL-C,HDL-C among H₂S group and DM group（P>0.05）.Treating with H₂S can improve DPN nerve conduction velocity with no statistical difference（P>0.05）.Conclusion1.The blood glucose control situation of T1DM patients in China is not ideal,only a small percent of patients reached the recommended targets.In T1DM patients, glycemic variability is not a risk factor for DPN.Age,duration,smoking,HTN and TIR are significantly independent risk factors for DPN.The gait spectral analysis revealed T1DM patients have underlying mobility limitations.2.In our study,H₂S has a positive treating effect on the pathological and ultrastructure damage of the peripheral nerve in diabetic rats.Treating with H₂S by abdominal injection has no obvious side effect on DM rats.The results presented here indicate that may H₂S may have the potential to be a therapeutic option for treating DPN.Its mechanism maybe related to the inhibition of the oxidative stress injury and th polyol signaling pathway.