The Effects Of Short-term Insulin Intensive Treatment On The Expression Of IκB-α,COX-2 And INOS In Newly-diagnosed Type 2 Diabetic Patients

Objective:Type 2 diabetes mellitus (T2DM) is a group of metabolic disorder syndrome characterized by chronic hyperglycaemia resulting fromh the interaction of genetic and environmental factors .It is associated with the progressive decrease inβ-cell function and increase in insulin resistance.How- ever,the mechanism underline it still have not been explored clearly.Recent studies suggest that DM is in a state of oxidative-inflammatory cascade.Oxida- tive-inflammatory cascade participate in T2DM and complications developm- ent and progression. Early intervention with the positive feedback effect,will alleviate the illness and stabilize condition,researchers report that insulin still play a huge anti-inflammatory effect besides hypoglycemic.But comparing two different insulin therapies to the effect of proinflammatory factor is rare reported. This study through comparing the levels of oxidatie stress,inflammation between the newly-diagnosed T2DM and the normal,further proved the roles in T2DM onset of inhibitor of kappaB-α(IκB-α),cyclooxygen- ase-2(COX-2),inducible nitric oxide synthase(iNOS),and clinical significance of detection. Moreover,to evaluate the effects of Multiple-Daily Injection of Insulin(MDⅡ) or Twice-Daily Injection of Insulin(TDⅡ) on inflammatory factors(includingIκB-α,COX-2,iNOS)and insulin resistance as well asβ-cell function in newly diagnosed type 2 diabetic patients.Meanwhile to provide more definite data to support reasonable treatment for type 2 diabetes in clinic.Methods:After diabetes education according to the patient intend,eighty newly diagnosed T2DM subjects were divided into twogroups:(1)Multiple- Daily Injection of Insulin(MDⅡ)(n=41).(2)Twice-Daily Injection of Insulin (TDⅡ)(n=39).All the patients were admitted to the hospital and treated by MDⅡorTDⅡfor two weeks.Meanwhile,fourty subjects of NGT as normal control group(NC)(n=40). Serum levels of fasting insulin,fasting plasm glucose,in all subjects were measured before and after treatment.Using RT - PCR analysis the mRNA expression levels of SOD,COX-2 and iNOS in peripheral blood cells;using immunocell chemistry analysis the protein expression levels of IκB-α,COX-2,iNOS.HOMA-IR and HOMA-βwere calculated to evaluate insulin resistance(IR) status andβ-cell function respectively.Formula: body mass index (BMI) = weight / (height)~2 (kg/m~2), Homa-IR = FPG×FIN / 22.5,HOMA-β= 20×FIN / (FPG - 3.5).Results:(1)before therapy,the patients in MDⅡgroup andTDⅡgroup were no significantly difference in age,BMI,WC,FPG,2hPGand other laboratory data(P > 0.10).(2)Compared with healthy controls,the HOMA-IR,FBG,2hPG and HbA1C were obviously increased,the HOMA-βwas decreased in both T2DM groups(P<0.05);after 2 weeks insulin therapy,the HOMA-IR,HOMA-β,FBG and 2hPG were obviously improved in both T2DM groups(P<0.05). Compared with TDⅡgroup,the 2hPG decreased more significantly in MDⅡgroup (P<0.05).(3)Compared with healthy controls,the protein expression level of IκB-αwas decreased;the levels of COX - 2,iNOS were significantly increased in T2DM group(P<0.05);after 2weeks insulin therapy, the protein expression level of IκB-αwas increased,the levels of COX-2,iNOS were obviously decreased in both T2DM groups(P<0.05);Compared with TDⅡgroup,the alleviated degree of protein levels of IκB-α,COX - 2,iNOS were more significantly in MDⅡgroup (P<0.05).(4)Compared with healthy controls,the mRNA expression levels of SOD,COX-2,iNOS were significantly increased in T2DM group(P < 0.05);after 2weeks insulin therapy,the mRNA expression levels of SOD,COX - 2,iNOS were obviously decreased in both T2DM groups(P<0.05);Compared with TDⅡgroup,the alleviated degree of mRNA levels of SOD,COX - 2,iNOS were more significantly in MDⅡgroup (P<0.05).Conclusions: (1) Compared with healthy controls, there was oxidative st- ress inflammation imbalances in newly-diagnosed T2DM patients. ROS was increased, the expression of SOD was upregulated ,induced the degradation of IκB-αand activation of NF-κB,upregulation the gene expression of COX-2, iNOS,we could suppose that oxidative stress-NF-κB and downstream inflam- mation factors has played an important role in the development of type 2 diab- etes.(2)For newly diagnosed T2DM ,both Multiple-Daily Injection of Insulin (MDⅡ) and Twice-Daily Injection of Insulin(TDⅡ),could effectively impro- ved blood glucose,insulin secretion and insulin sensitivity.meanwhile,could significantly decrease oxidative stress and inflammation factors,we could sup- pose that insulin theapy improve insulin secretion and sensitivity by decreas- ing oxidative stress-inflammation passway.