Effects Of Pioglitazone/metformin Fixed-dose Combination Therapy And Metformin Monotherapy On Serum Vaspin,Adiponectin And IL-6 Levels In Patients With Type 2diabetes

Adipose tissue is not only an energy storage organ,but also is an endocrine organ.The secretion of fat factors play a role in various complex metabolism process by autocrine,paracrine and endocrine.Diabetes,central obesity,high blood pressure,blood coagulation dysfunction etc are related to fat factors.Adipose tissue can secrete many fat factors to adjust the function of itself and other organizations.Hundreds of kinds of adipocytokines have been known such as leptin,adiponectin,resistin,tumor necrosis factor alpha(TNF alpha),il-6,angiotensin,PAI-1,etc.Representative factors associated with type 2 diabetes are adiponectin,visceral adipose tissue origin of serine protease inhibitors,interleukin-6.Adiponectin,interleukin 6,has been closely related to insulin resistance,type 2 diabetes.Visceral adipose tissue origin of serine protease inhibitors is a relatively new adipocytokines.Domestic and foreign studies proved that their level and obesity,insulin resistance,type 2 diabetes were positively correlated.Pioglitazone as an anti-diabetes drugs can improve insulin sensitivity.Metformin also has the role of reducing insulin resistance.This experiment study the change of serum ADP,il-6 and vaspin through theraping type 2 diabetes with new drug pioglitazone/metformin fixed-dose combination or metformin,comparing the two kinds of hypoglycemic drugs on serum ADP,IL-6 and vaspin.[AIM]To investigate the effects of pioglitazone/metformin fixed-dose combination therapy and metformin monotherapy on serum vaspin,adiponectin and IL-6 levels in patients with type 2 diabetes.The change of the adipocytokines with different sex after treatment and the internal relations between the adipo-cytokines and change of weight and blood glucose are discussed.And thereby we can get the difference in treating the type 2 diabetes between pioglitazone/metformin and metformin.[METHODS]From May 2011 to November 2012,130 eases was randomly chosed from with newly diagnosed type2 diabetes from 10 hospitals(Zhuhai People’s Hospital,Foshan Hospital of Traditional Chinese Medicine,Affiliated Hospital of Guangdong Medical College,The First Affiliated Hospital of Shantou University Medical College,The Third Affiliated Hospital of Sun Yat-sen University,The Second People’s Hospital of Shenzhen).130 patients was then randomly divided into two groups.the metformin group(65 patients)and the pioglitazone/group(65 patients).80 patients in accord with standard of this experiment was chosed in two groups and then they were randomly divided into two groups.38 patients in metformin group were given metformin(500mg twice daily),42 patients in pioglitazone/metformin group were given pioglitazone/metformin(15/500mg twice daily).The treatment lasted for 12 weeks.The glycosylated hemoglobin(HbA1c)、blood Lipid、body mass index(BMI)、the ratio of waist to hip(W/H)、assessmentβ-cell secretion index(HOMA-β)、blood pressure(BP),fasting blood glucose(FBG),2h plasma glucose(2hPG)、fasting insulin(FINS),insulin resistance index(IRI)and serum dipocytokine levels(including IL-6、vaspin,adiponectin)before and after the treatment of two groups were observed.GOD-PAP method was adopted to detect venous glueose,Oxidase method was adopted to deteet TG,cholesterol oxidative enzymic method to deteet TC,Enzyme-colorimetrie method to deteet HDL-C and homogeneous Enzyme-eolorimetrie method to detect LD L-C,The instrument:;are Produced by Roehe Roehe P Module biochemic alanalyzer Modular P800.HPLC method to deteet HbAle,the instruments are Produced by JaPan Tosoh Corporatiozo HLC-723GHb G7(inier-bateh coefficienis of variation were 3.66% and 4.76%).Urinary albumin Were measured by immune turbidimetry,The instruments are Produced by BN ProsPeet of German SIEMENS Instruments Corporation.[RESULTS]一.Before thetreatment:There is no significant statistic difference of Sex、Age、HbA1C、FPG、2hPG、FINS、HOMA-IR、BMI、W/H、TG、TC、HDL-L、LDL-L、SBP、DBP、MS、ADP、VaspinIL-6 between pioglitazone/metformin group and metformin group(P>0.05);There is significant statistic difference of HOMA-β and 2hFINS between pioglitazone/metformin group and metformin group(P<0.05).二.After thetreatment:1.After metformin treatment,the level of FPG,2hPG,HbA1C,2hFINS,HOMA-IR,BMI、TC decreased significantly,compared with the level of these before treatment,the statistic difference is significant(p<0.01 or p<0.05).HOMA-β was increased,the difference is significant(P<0.01);2.After pioglitazone/metformin treatment,the level of FPG,2hPG,HbA1C,HOMA-IR,HOMA-β,BMI、W/H、TG decreased significantly,compared with the level of these before treatment,the statistic difference is significant(p<0.01 or p<0.05).HOMA-βwas increased,the difference is significant(P<0.01);3.The level of vaspin decreased significantly compared with these before the treatment in two groups(p<0.05).The level of serum IL-6 and adiponectin had no significant statistic difference compared with these before the treatment in metformin group(p>0.05).The level of IL-6 decreased significantly in pioglitazone/metformin group,compared with these before the treatment,the statistic difference is significant(p<0.05);The level of adiponectin rised significantly in pioglitazone/metformin group,compared with these before the treatment,the statistic difference is significant(p<0.01);4.The level of insulin and blood glucose decreased significantly and the ADP rised significantly in pioglitazone/metformin group as compared with these in metformin group(P<0.01 or P<0.05).The comparison of indexes difference of FPG、HOMA-IR、BMI(kg/m2)、TG(mmol/L)、TC(mmol/L)、HDL-L(mmol/L)、LDL-L(mmol/L)、Vaspin、IL-6、had no significant statistic difference compared with these in metformin group(p>0.05).Metformin group:Changes of adipocytokines between man and women before and after metformin treatment:Based on the difference of sex,patients in metformin group was divided into two groups,women:20 patients;man:18 patients.There is no significant statistic difference of the level of vaspin and IL-6 before and after treatment in two groups(P>0.05).The level of vaspin had significant statistic difference before and after treatment in female group(P<0.05).But there is no significant statistic difference of adipocytokines in male group(P>0.05).pioglitazone/metformin group:Changes of adipocytokines between man and women before and after pioglitazone/metformin treatment:Based on the difference of sex,patients in pioglitazone/metformin group was divided into two groups,women:16 patients;man:26 patients.The level of vaspin、IL-6 and adiponectin had significant statistic difference before and after treatment in female group(P<0.05).There is no significant statistic difference of the level of vaspin、IL-6 and adiponectin before and after treatment in male group(P>0.05).CorrelationAnalysiMetformin group:1.Correlation Analysis of △HbA1C(rate of change of HbA1C)with rate of change of clinical indicatorsThere were no significant correlation between △HbA1C and△BMI、△FBG、△2hPG、△FINS、△2hFINS、△HOMA-IR、△HOMA-β、△TG、△TC、△HDL-L、△LDL-L、△W/H、△SBP、△DBP、△ADP、△Vaspin、△IL-6(P>0.05).2.Correlation Analysis ofABMI(rate of change of BMI)with rate of change of clinical indicatorsThere were significant positive correlation betweenABMI andADBP(P<0.05).There were no significant correlation between △BMI and △HbA1C、△FBG、△2hPG、△FINS、△2hFINS、△HOMA-IR、△HOMA-β、△TG、△TC、△HDL-L、△LDL-L、△W/H、△SBP、△AOP、△Vaspin、△IL-6(P>0.05).Pioglitazone/metformin group:1.Correlation Analysis of △HbA1 C with rate of change of clinical indicatorsThere were significant positive correlation between △HbA1C and △HDL-L(p<0.05).There were no significant correlation between △HbA1C and △BMI、△FBG、△2hPG、△FINS、△2h FINS、△HOMA-IR、△HOMA-β、△TG、△TC、△LDL-L、△W/H、△SBP、△DBP、△ADP、△Vaspin、△IL-6(P>0.05).2.Correlation Analysis of ABMI with rate of change of clinical indicatorsThere were significant positive correlation between △BMI and △W/H、△SBP(p<0.05).There were no significant correlation between △BMI and △HbA1C、△FBG、△2hPG、△FINS、△2h FINS、△HOMA-IR、△HOMA-β、△TG、△TC、△HDL-L、△LDL-L、△DBP、△ADP、△Vaspin、△IL-6(P>0.05).[Conclusion]1.The level of insulin and blood glucose decreased significant in Pioglitazone/metformin as compared with metformin.They can decrease the level of serum vaspin while pioglitazone/metformin can also improve the level of adiponectin and IL-6,but metformin can not.Metformin can only improve Vaspin.ADP rised significantly in pioglitazone/metformin group than that in metformin group.2.The two drugs,effects on adipocytokines also had difference in patients with different sex.Whether male or female patients,ADP and IL-6 is different before and after metformin treatment.But metformin can significantly reduce female serum vaspin.In female group,adipocytokines had significant difference before and after the pioglitazone/metformin treatment,but not in male group.Pioglitazone/metformin’s effect on adipocytokines is more significant for women;Female adipocytokines may be more sensitive to drug treatment.3.There were no significant correlation between rate of change of adipocytokines and rate of change of BMI.rate of change of HbA1C in two groups.Pioglitazone/metformin’s and metformin’s effects on adipocytokines did not depend to its decreased glucose and weight.