RBP-4 Levels And Significance In Short Stature Children With Recombinant Human Growth Hormone Therapy

Objective:To observe the changes of levels of retinol-binding protein-4(RBP-4)in children with short stature before and after treatment with recombinant human growth hormone(rhGH).The correlation of RBP-4 with growth parameters,hematological indexes and glucose and lipid metabolism indexes were analyzed.The effect of rhGH treatment on RBP-4 level and glucose and lipid metabolism were further investigated.Methods:In this study,63 patients with growth hormone deficiency(GHD)or idiopathic short(ISS)were selected,among which 30 patients with GHD and 33 patients with ISS were given rhGH by subcutaneous injection before bedtime.The growth parameters,including height(Ht),weight(Wt),body mass index(BMI),height standard deviation of points(Ht SDS)were recorded.Fasting blood glucose(FBG),fasting insulin(FINS),free fatty acid(FFA),blood lipid,insulin-like growth factor-1(IGF-1),total three iodine thyroidic acid(TT3),total four iodine thyroidic acid(TT4)and thyroid-stimulating hormone(TSH)were also measured.Evaluated RBP-4levels by enzyme-linked immunosorbent assay.Quantitative insulin sensitivity check index(QUICKI)and homeostasis model assessment for insulin resistance(HOMA-IR)were calculated at baseline and after treatment of 6months and 12 months.We estimated the changes of the above indexes after treatment,and the correlation of RBP-4 with growth-related parameters,hematological parameters and insulin sensitivity parameters were analyzed.Results:1.Comparison of general characteristics,growth parameters and hematological indexes in GHD and ISS children before rhGH treatmentBefore treatment,there were no significant differences in Ht,Ht SDS,Wt and BMI between GHD group and ISS group(P>0.05).There were no significant differences in seruml evels of IGF-1,TT3,TT4,TSH,FBG,FINS,lipid,FFA and RBP-4 between GHD group and ISS group(P>0.05).2.Comparison of growth parameters and hematological indexes in patients between baseline and after rhGH treatmentAfter 6 months of rhGH treatment,the Ht SDS of GHD patients were higher than baseline(P<0.05).After 12 months of rhGH treatment,the Ht,Wt and Ht SDS of GHD patients were significantly higher than baseline(P<0.05).After 6 months of treatment,the Ht SDS of ISS group was higher than baseline(P<0.001),and the growth parameters of Ht,Wt and Ht SDS were higher than baseline during 12 months of rhGH treatment(P<0.05),and the Ht SDS were also higher than that after 6 months of treatment(P=0.038).There was no significant difference in BMI(P>0.05).In GHD and ISS group,serum IGF-1 levels were higher after 6 or 12 months of rhGH treatment than baseline(P<0.001).There were no significant differences in serum levels of TT3,TT4,TSH and FBG before and after rhGH treatment in GHD and ISS group(P>0.05).3.Changes of serum lipids,insulin and insulin resistance parameters after rhGH treatmentAfter 12 months of rhGH treatment,the serum level of triglycerides(TG)of GHD patients was decreased(P=0.035).Serum total cholesterol(TC),high density lipoprotein(HDL-C)and low density lipoprotein(LDL-C)levels were not altered in GHD group.There were no alternations in serum TC,TG,LDL-C and HDL-C levels in ISS group after rhGH treatment(P>0.05).In GHD patients,there was no significant difference in the serum level of FFA after 6 months and 12 months of rhGH treatment compared with baseline(P>0.05),while the serum level of FFA after 12 months of rhGH treatment was higher than that after 6 months of treatment(P=0.010).The level of FFA after 6 months of rhGH treatment in ISS group was lower than baseline(P=0.032),the difference was statistically significant.After 12 months of rhGH treatment,there was no significant change in the level of FFA compared with before treatment(P>0.05),while it was increased compared with after 6months of treatment in ISS group(P=0.014).In patients with GHD,FINS levels was higher after 6 months of treatment(P=0.032)compared to before treatment,HOMA-IR is also higher than before treatment(P=0.034),QUICKI reduced(P=0.034).After 12 months of treatment,the FINS and HOMA-IR were higher than before treatment,and QUICKI reduced,but there were no obvious significance.In patients with ISS,FINS levels were elevated after treatment,but without statistically difference,HOMA-IR levels after 6 and 12 months of treatment were higher than that before treatment,and the significance were P=0.048 and P=0.034 respectively.QUICKI levels showed a decreasing trend after treatment,and the difference was statistically significant at 12 months compared with that before treatment(P=0.035).There was no significant difference in FINS,HOMA-IR and QUICKI between GHD and ISS groups after 6 months of rhGH treatment and 12 months of rhGH treatment(P>0.05).4.Changes in retinol-binding protein-4 levels before and after rhGH treatmentIn GHD patients,there was no significant difference in serum RBP-4levels between baseline and after 6 months or 12 months treatment(P>0.05).In ISS group,the level of RBP-4 increased after 12 months of rhGH treatment compared with before treatment(P=0.009),and there was no statistically significant change in RBP-4 levels after 6 months of rhGH treatment compared with before treatment and 12 months after treatment(P>0.05).5.Correlation analysis of serum RBP-4 with growth parameters,clinical hematologic indexes and insulin resistance index before and after rhGH treatmentIn GHD patients,RBP-4 was not correlated with age,Ht,Ht SDS,Wt,BMI,IGF-1,TT3,TT4,TSH,FBG,FINS,HOMA-IR,QUICKI,lipid,FFA at baseline;after 6 months of rhGH treatment,there was a positive correlation between serum RBP-4 level and FFA in GHD patients(correlation coefficient r=0.384,P=0.033),but no correlation with other indexes;after 12 months of rhGH treatment,serum RBP-4 level in GHD patients was positively correlated with Ht SDS(correlation coefficient r=0.355,P=0.046)and HOMA-IR(correlation coefficient r=0.355,P=0.046).However,RBP-4 was positively correlated with Ht,BMI,and IGF-1 in ISS patients before treatment.After 6 months of rhGH treatment,there was a negative correlation between RBP-4 and TT3 in ISS patients(correlation coefficient r=-0.508,P=0.003).After 12 months of rhGH treatment,RBP-4 in ISS patients was negatively correlated with TT3(r=-0.427,P=0.021),positively correlated with TT4(r=0.374,P=0.046),and positively correlated with FFA(r=0.412,P=0.001).Conclusion:1.After rhGH treatment,the insulin level and HOMA-IR were increased,but the blood glucose level had no significant change.2.RBP-4 level was increased in ISS patients after 12 months of rhGH treatment,and RBP-4 level was correlated with BMI,FFA,IGF-1,HOMA-IR and thyroid hormone.