Study Of Blood Glucose Fluctuations On Diabetic Nerve Conduction Function And MitoQ Improve Nerve Cellular Oxidative Stress

AimsIn this study,we analyzed the correlation between glucose variability parameter time in range(TIR)and nerve conduction function in patients with type 2 diabetes.In addition,the effect of MitoQ on the oxidative stress of rat Schwann Cell(RSC96)under different high glucose conditions was studied.MethodsThe 740 patients with type 2 diabetes mellitus(T2DM)included in the study were grouped according to the TIR tertiles,and their basic clinical characteristics,biochemical results,and nerve conduction function data were compared.In order to comprehensively evaluate patients’ peripheral nerve conduction function,a composite Z-score model of nerve conduction function parameters: conduction velocity,latency,and amplitude was constructed,respectively.The correlation between TIR and Z-score of each parameter of nerve conduction function was analyzed by regression analysis.At the same time,an in vitro cell model of blood glucose fluctuations was constructed to study MitoQ intervention on cell proliferation and reactive oxygen species.Furthermore,the effects of MitoQ intervention on Nrf2 / HO-1 signaling pathway were investigated by quantitative PCR and western blot.Compared with the low TIR group and the medium TIR group,patients in the high TIR group had shorter diabetic duration,younger age,and better control of blood glucose and lipids.With the increased of TIR level,the composite Z-score of conduction velocity and amplitude were increased,while the composite Z-score of latency was decreased significantly(P <0.05).Linear regression analysis showed that after adjusting for other confounding factors such as age and duration of diabetes,TIR level was positively related to composite Z-score of conduction velocity(β = 0.230,P <0.001),and composite Z-score of amplitude(β = 0.099,P = 0.010),but was negatively associated with composite Z-score of latency(β =-0.172,P <0.001).After further correction of glycated hemoglobin(Hb A1c),the correlation between TIR and velocity composite Z-score was still significant(β = 0.098,P =0.023).In addition,after adjusting for confounding factors in Logistic regression analysis,the higher the TIR,the lower the risk of a slower conduction velocity(medium TIR group: OR = 0.44,P <0.001;high TIR group: OR = 0.27,P <0.001);the greater the risk of shortened latency(medium TIR group : OR = 1.55,P = 0.022;high TIR group: OR = 1.69,P = 0.008);the lower the risk of lowered amplitude(medium TIR group:OR = 0.97,P = 0.875;high TIR group: OR = 0.61,P = 0.011).After readjusting Hb A1 c,the risk of slowing the conduction velocity of patients in each TIR group was still significantly reduced(medium TIR group:OR = 0.48,P = 0.001;high TIR group: OR = 0.41,P <0.001).In vitro cell experiments showed that MitoQ can inhibit the production of reactive oxygen species in cells caused by high glucose and fluctuating high glucose(P <0.05)and improve cell proliferation(P<0.05).In addition,MitoQ can cause increased expression of Nrf2 and downstream HO-1 genes and proteins(P <0.05).ConclusionsIn T2 DM,TIR was positively correlated with conduction velocity and amplitude,and negatively related to latency.The correlation between TIR and conduction velocity was independent of Hb A1 c.TIR was expected to be a blood glucose control predictor of diabetic peripheral neuropathy(DPN).MitoQ can activate the Nrf2/HO-1 signaling pathway and improve oxidative stress in cells under high glucose and fluctuating high glucose conditions.