Effect Of Vitamin A And Vitamin D Deficiency On Insulin Resistance And Oxidative Stress In Gestational Diabetes Mellitus

Part?Correlation between maternal and fetal insulin resistance in pregnant women with gestational diabetes mellitusObjective:Offspring of mothers with gestational diabetes mellitus(GDM)are far more likely to develop type 2 diabetes.The aim of this study was to investigate the effect of the insulin metabolism of pregnant women with GDM in late pregnancy on the insulin metabolism of the fetuses and their correlation.Methods:This study enrolled 55 pregnant woment with GDM and 87control subjects.Fasting venous blood samples and umbilical venous blood samples(reflecting fetal metabolism)were collected from the study subjects.All blood samples were used to evaluate the blood glucose and insulin concentrations.The blood glucose and insulin concentrations were measuredusinganautomaticbiochemicalanalyserand radioimmunoassays,respectively.The homeostasis model assessment(HOMA)was performed to assess the insulin resistance of maternal blood and umbilical venous blood.Results:(1)Compared with the control group,the age of pregnant women(32.81�0.62 vs.29.18�0.52 years,p<0.001),pre pregnancy weight(58.52�0.92 vs.53.89�0.75 kg,p=0.0002),pre pregnancy BMI(23.39�0.39 vs.18.84�0.24 kg/m~2,p<0.0001),family history of diabetes(34.5%vs.17.4%,p=0.019),percentage of multipara(64.3%vs.44.5%,p=0.024)and cesarean section rate(80%vs.45%,P=0.001)in GDM group were significantly higher than those in control group.(2)The results of logistic regression analyses showed that maternal age,prepregnancy body mass index(BMI),and family history of diabetes were high-risk factors for the development of GDM in pregnant women.(3)The fasting blood glucose,fasting insulin,and HOMA-IR of pregnant women in the late pregnancy GDM group were all significantly higher than those in the control group(fasting blood glucose:4.70�0.11vs.4.11�0.05mmol/L,P<0.001;fasting insulin:44.1�6.76 vs.25.1�3.58?U/mL,p=0.013;HOMA-IR:8.92�1.25 vs.5.39�0.83,p=0.012);(4)The insulin level and HOMA-IR in the umbilical venous blood of the late pregnancy GDM group were both significantly higher than those in the control group(insulin:10.1�1.41 vs.6.38�0.49?U/mL,p=0.035;HOMA-IR:1.60�0.22vs.1.07�0.08,p=0.006).(5)The umbilical venous blood HOMA-IR in the GDM group positively correlated with the maternal HOMA-IR and fasting insulin level.The neonatal ponderal index(PI)in the GDM group positively correlated with the umbilical venous blood HOMA-IR and insulin level.Conclusion:The HOMA-IR was significantly higher in the late pregnancy GDM women and their fetuses than in the control group.In addition,fetal HOMA-IR positively correlated to maternal HOMA-IR in late pregnancy GDM women.Part ? Effects of vitamin A and D deficiency on insulin resistancc in pregnant women with gestational diabetes mellitusObjective: This study was designed to investigate the vitamin A(VA)and vitamin D(VD)levels in women with gestational diabetes mellitus(GDM)and to explore the effect of co-deficiency of VA and VD on the insulin metabolism in women with gestational diabetes mellitus and their fetus.Methods: A total of 159 pregnant women in the late pregnancy(72 GDM and 87 healthy pregnant women)and 55 newborns born by women with GDM were included in this study.The fasting venous blood samples before birth of all pregnant women and 55 cases of umbilical vein blood(reflecting the fetal metabolism)were collected for the following measurements.The serum retinol levels were detected with high-performance liquid chromatography(HPLC).The serum levels of 25-OH vitamin D were measured with an immunoassay method(CMIA).The blood glucose and insulin concentrations were measured using an automatic biochemical analyser and radioimmunoassays,respectively.The homeostasis model assessment(HOMA)was performed to assess the insulin resistance of maternal blood and umbilical venous blood.Results:(1)Comparison of serum VA level in two groups of pregnant women: The serum VA level in GDM group was lower than that in the control group(1.102�0.062 vs.1.20�0.048 ?mol/L,p=0.2112).VA subgroup analysis found that VA levels in vitamin A deficiency(VAD)subgroup,vitamin A(VAI)subgroup and vitamin A(VAN)subgroup of GDM group were all lower than those in the control group and the level of the VA levels in VAI subgroup of GDM group was significantly lower than the control group(0.839 + 0.023 vs.0.920 + 0.022 mol/L.p= 0.0165),and the difference was statistically significant.(2)Comparison of serum VD level in two groups of pregnant women: The serum VD level in GDM group was significantly lower than that in the control group(25.09 + 1.439 vs.31.6 + 1.75 nmol/L,p=0.0058).VD subgroup analysis found that VD levels in vitamin D deficiency(VDD)subgroup was significantly lower than that of the control group(19.31 + 0.781 vs.21.72 + 0.768 nmol/ L,p=0.0303),and the difference was statistically significant.(3)The serum VA level of pregnant women with GDM is negatively correlated with their HOMA-IR(r=-0.271,p= 0.029;The serum VD level of pregnant women with GDM was negatively correlated with their insulin and HOMA-IR(insulin: r=-0.411,p=0.0003;HOMA-IR:r=-0.36,p=0.002).(4)The effect of VA and VD co-deficiency on insulin metabolism in GDM is greater than that of a single VAD or VDD.(5)No significant correlation was found between VAD and VDD in pregnant women with GDM and insulin metabolism parameters of umbilical vein blood.Conclusion:(1)The VD levels is generally low in late pregnant women,which is more obvious in GDM patients;(2)The VA levels in late pregnant women with GDM was negatively correlated with their own HOM-IR and the VD levels in late pregnant women with GDM was negatively correlated with their own HOM-IR and insulin,suggesting that GDM patients with VA or VD deficiency can aggravate insulin resistance;(3)VA and VD co-deficiency may aggravate insulin resistance in pregnant women with GDM;(4)There was no significant correlation between VAD and VDD in pregnant women with GDM and insulin metabolism parameters of umbilical vein blood.Part ? Effects of vitamin A and D deficiency on oxidative stress in pregnant women with gestational diabetes mellitusObjective: To evaluate oxidative and antioxidative status and the effect of VA and VD deficiency on oxidative stress in late pregnancy GDM women.Methods: A total of 159 pregnant women in the late pregnancy(72 GDM and 87 healthy pregnant women)were included in this study.The fasting venous blood samples before birth of all pregnant women were collected for the following measurements.The serum retinol levels were detected with high-performance liquid chromatography(HPLC).The serum levels of 25-OH vitamin D were measured with an immunoassay method(CMIA).The serum superoxide dismutase(SOD)activity was detected by xanthine oxidase detection.The serum catalase(CAT)activity was detected by visible light method.The concentration of the reduced glutathione(GSH)in serum was detected by microenzyme labeling.The level of malondialdehyde(MDA)in serum was detected by thiobarbital acid method(TBA).Results:(1)Compared with the control group,the age of pregnant women(33.41 � 1.53 vs.29.18�0.52 years,p<0.001),pre pregnancy weight(56.72�1.73 vs.53.89�0.75 kg,p = 0.0002),pre pregnancy BMI (23.59 � 0.39 vs.18.84 � 0.24 kg/m~2,p<0.0001),family history of diabetes(35.6% vs.17.4%,p=0.017),percentage of multipara(64.3% vs.44.5%,p=0.024)and cesarean section rate(83% vs.47%,p=0.001)in GDM group were significantly higher than those in control group;(2)Comparison of serum VA and VD levels in two groups of pregnant women: Although there was no statistical difference in the level of VA between the two groups of pregnant women,the trend of GDM was decreasing(1.102�0.062 vs.1.20�0.048 ?mol/L,p=0.2112).The serum VD level in GDM group was significantly lower than that in the control group(25.09� 1.439 vs.31.6�1.75 nmol/L,p=0.0058);(3)Comparison of serum indexes of oxidative stress in two groups of pregnant women: Compared with the control group,the activity of SOD and the activity of CAT were significantly lower than that of the healthy control group(SOD: 71.5 � 5.91 vs.84.92� 6.54U/m L,p<0.01;CAT: 1.89 � 0.075 vs.2.57�0.158 U/m L,p<0.01).The concentration of GSH and MDA was significantly higher than that of the control group(GSH: 39.51 � 1.42 vs.33.65 �1.83umol/L,p<0.05;MDA:5.94 � 0.263 vs.4.027� 0.206 nmol/m L,p<0.001);(4)Analysis of oxidative stress in VA subgroup of GDM pregnant women: The activity of serum SOD in the VAD subgroup was significantly lower than that of the VAN subgroup(58.83�5.806 vs.82.78�4.18 U/m L,p<0.01)and the VAI subgroup(58.83�5.806 vs.71.53�4.846 U/m L,p<0.05),at the same time,the VAI subgroup was significantly lower than the VAN subgroup(71.53�4.846 vs.82.78�4.18 U/m L,p<0.05).The serum concentration of GSH in the VAD subgroup was significantly lower than that in the VAN subgroup(39.87�4.59 vs.53.64�6.63 umol/l,p<0.05).The serum concentration of MDA in the VAD subgroup was significantly higher than that in the VAN subgroup(8.47�1.22 vs.5.26�0.54 nmol/ml,p<0.01).The serum CAT activity was equal between the three subgroups(The CAT activities of VAD,VAI and VAN are respectively:1.01�0.0198,1.201�0.0775,1.245�0.0594 U/ml,p>0.05);(5)Analysis of oxidative stress in VD subgroup of GDM pregnant women: The activity of serum SOD in the VDD subgroup was significantly lower than that of the VDN subgroup(63.42�4.231 vs.80.42�5.231 U/m L,p<0.01).The activity of serum CAT in VDD subgroup was significantly lower than that in VDN subgroup(0.860�0.119 vs.1.49 � 0.0506 U/m L,p < 0.01)and VDI subgroup(0.860�0.119 vs.1.36�0.1035 U/m L,p<0.05).The serum concentration of GSH in the VDD subgroup was significantly lower than that in the VDN subgroup(38.53�4.185 vs.58.59�6.31 umol/l,p<0.01).The serum MDA concentration in VDD subgroup was significantly higher than that in VDN subgroup(9.83� 1.35 vs.4.41� 0.97 nmol/ml,p< 0.01)and VDI subgroup(9.83�1.35 vs.6.42�0.76 nmol/ml,p<0.05);(6)Comparison of the oxidative stress levels of different vitamin A levels in GDM pregnant women with deficiency and lack of VD: The VAD,VAI and VAN subgroups were 11,29 and 28,respectively.The activity of SOD in the three subgroups was 52.87 �5.33,64.4 � 4.52 and 73.2 �6.78 U/m L respectively,and the SOD activity in the VAD subgroup was significantly lower than that in the VAN subgroup(p=0.002).The activity of CAT in the three subgroups was 0.87� 0.112,1.16 �0.13 and 1.338 � 0.16 U/m L respectively,and the CAT activity in the VAD subgroup was significantly lower than that in the VAN subgroup(p=0.017).The concentrations of serum GSH in the three subgroups were 37.29 � 5.23,46.9� 4.33 and 51.13 5.19umol/L respectively,and the GSH concentration in the VAD subgroup was significantly lower than that in the VAN subgroup(p=0.023).The concentrations of MDA in serum of three subgroups were 9.46 � 1.18,7.08 � 0.93 and 6.18 � 0.84nmol/m L,respectively,and the MDA concentration in serum of VAD subgroup was significantly higher than that of VAI subgroup(p=0.027)and VAD(p=0.0032).Conclusion:(1)The serum VD levels in pregnant women with GDM were significantly lower than those of healthy pregnant women;(2)The antioxidant capacity of pregnant women with GDM was significantly lower than that of healthy pregnant women,and the oxidative stress injury was significantly increased;(3)VA and VD co-deficiency may aggravate oxidative stress in pregnant women with GDM.