The Effect Of Recombinant Human Growth Hormone Replacement Therapy On The Level Of Asymmetric Dimethylarginine In Short Stature Children

Objective: To assess the risk of arteriosclerosis and cardiovascular disease in short stature children,the levels of serum asymmetric dimethylarginine(ADMA)were observed.And to explore the effect of rh GH replacement therapy on arteriosclerosis and cardiovascular disease,the serum ADMA in short stature children after recombinant human growth hormone(rh GH)replacement therapy were observed.Methods: 63 short stature children who were diagnosed with growth hormone deficiency(GHD)or idiopathic short(ISS)(30 with GHD,33 with ISS)and 27 healthy children were selected as the research subjects.The therapeutic dose of rh GH was 0.10-0.20 IU/(kg·d).ADMA,height(Ht),weight(Wt),insulin-like growth factor-1(IGF-1),Thyroid function,fasting blood glucose(FBG),fasting insulin(FINS),glycosylated hemoglobin A1c(Hb A1c)and lipid profile of healthy children and short children at baseline,after 6 months and 12 months of rh GH treatment were assessed.And the standard deviation score of height(Ht SDS),body mass index(BMI),atherogenic index(Ai),homeostatic model assessment for insulin resistance index(HOMA-IR),quantitative insulin sensitivity check index(QUICKI)were calculated at the same time.Compared the difference of above indexes between short children and healthy children at baseline.Observed the changes of the above indexes in GHD and ISS children before and after rh GH treatment.The correlation between ADMA and metabolism parameters mentioned aboved were preliminarily analyzed at baseline and different treatment stages.Results:1.Comparison of clinical characteristics and serological indicators of short stature children and healthy children at baseline.At baseline,gender and age of each group were matched,and there were no significant differences in Wt and BMI(P > 0.05).The levels of Ht,Ht SDS,IGF-1 and Hb A1 c in GHD and ISS groups were significantly lower than those in healthy control group(P < 0.05),and Ai of GHD and ISS groups were significantly higher than healthy control group(P < 0.05).Only in GHD group,the level of LDL-C was significantly higher than that of healthy control group(P < 0.05).While there were no significant differences in the above indexes between GHD and ISS groups(P > 0.05).No significant differences in serum FBG,FINS,TG,TC,HDL-C,HOMA-IR and QUICKI among the three groups were observed(P > 0.05).2.Comparison of clinical characteristics and serological indicators of GHD children before and after treatment.In GHD group,there were no significant differences in BMI at baseline,6months and 12 months after treatment(P > 0.05).Ht SDS was significantly improved in GHD children after 6 months of treatment(P < 0.05),Ht,Ht SDS and Wt were significantly increased in GHD children after 12 months of treatment compared with those before treatment(P < 0.05).After 6 months of treatment,IGF-1 and Hb A1 c were significantly increased in GHD children(P< 0.05),while other glucose and lipid metabolism indexes including Ai,and thyroid function were not significantly changed compared with those before treatment(P > 0.05).After 12 months of treatment,IGF-1 and TG were significantly increased in GHD children compared with before treatment(P <0.05),while TC,LDL-C,HDL-C,Ai,glucose metabolism indexes and thyroid function were not significantly changed compared with those before treatment(P > 0.05).3.Comparison of clinical characteristics and serological indicators of ISS children before and after treatment.In ISS group,there were no significant differences in BMI at baseline,6months and 12 months after treatment(P > 0.05).Ht SDS were significantly improved after 6 months of treatment(P < 0.05),Ht,Ht SDS and Wt were significantly higher than those before treatment after 12 months of treatment in ISS group(P < 0.05).After 6 months of treatment,IGF-1 and Hb A1 c in ISS children were significantly increased(P < 0.05),while FBG,FINS and other glucose metabolism indexes,TC,TG,LDL-C,HDL-C,Ai and thyroid function were not significantly changed compared with those before treatment(P > 0.05).After 12 months of treatment,the level of IGF-1 was significantly higher than that before treatment in ISS children(P < 0.05),and no significant changes were found in thyroid function and other metabolism indexes including Ai(P > 0.05).4.Comparison of ADMA level.At baseline,ADMA in GHD group was significantly higher than that in healthy control group(P < 0.001).There was no statistical difference in ADMA between ISS group and healthy control group(P > 0.05),and between GHD and ISS group(P > 0.05).After rh GH replacement therapy,ADMA in GHD group showed a downward trend,and it was significantly lower after 12 months of treatment than that before treatment(P = 0.001).ADMA in ISS group showed no significant change after 6 months of treatment,but was significantly lower after 12 months of treatment than that before treatment(P =0.019).5.Correlation analysis between serum ADMA and metabolism indexes.There was a positive correlation between ADMA and FBG before treatment.No correlation between ADMA and the observed indexes was found after 6 months of treatment.While there was a positive correlation between ADMA and TC after 12 months of treatment.Conclusions:1.The level of ADMA in GHD children is significantly higher than that in healthy children,and the level of ADMA in ISS children also shows an increased trend.Suggesting that the risk of atherosclerosis and cardiovascular disease was increased in short stature children,especially in GHD children.2.rh GH replacement therapy for 12 months could effectively reduce the level of ADMA,blood glucose should be monitored dynamically.