Effect Of RhGH Treatment To Insulin Sensitivity In Patients With Short Stature

Objective: This study was designed to discuss the effect of recombinant human growth hormone(rh GH)on insulin sensitivity in patients with short stature as well as to analyze factors influencing insulin sensitivity.Methods: A total of 74 children with dwarfism treated by rh GH were recruited in this study.Growth parameters of subjects before and 3 months after treatment were recorded,including height(Ht),weight(Wt),body mass index(BMI),height standard deviation score(Ht SDS).Peripheral blood was collected to detect serological indicators including fasting blood glucose(FBG),fasting insulin(FINS),insulin-like growth factor 1,(IGF-1),insulin-like growth factor binding protein 3(IGFBP-3),total three iodide thyroidic acid(TT3),total four iodide thyroidic acid(TT4)and thyroid stimulating hormone(TSH)and so on.Insulin sensitivity(IS)of each subject was evaluated through FBG,FINS,QUICK and HOMA-IR and IS levels before and after rh GH treatment were compared.Furthermore,subjects were assigned into growth hormone deficiency(GHD)and idiopathic short stature(ISS)groups,low and high dose treatment groups respectively according to each patient's etiology and treatment dosage to observe the effect of rh GH treatment on IS in different cohorts.Pearson correlation coefficients between Ht,Wt,BMI,IGF-1,IGFBP-3,TT3,TT4,TSH and QUICK,HOMA-IR were measured to assess the strength of their correlation.Finally,to screen potential indicators envolving IS changes after rh GH treatment,a stepwise linear multi-variation regression model was constructed by using HOMA-IR and QUICK as dependent variables as well as Ht,Wt,BMI,IGF-1,TT3,TT4,TSH before treatment as independent variables.Results:1 Comparison of growth parameters and general serological parameters before and after rh GH treatmentPatients' Ht,Wt,Ht SDS,IGF-1,IGFBP-3 and TT3 levels were significantly increased after 3 months' rh GH treatment(P<0.05).No significant difference of BMI,TT4 and TSH was found before and after rh GH treatment(P>0.05).2 Effects of rh GH treatment on insulin sensitivity2.1 IS changes after rh GH treatment in all subjectsFBG and FINS of the patients were significantly increased after rh GH treatment(P<0.05).QUICK and HOMA-IR were significantly decreased and increased after rh GH treatment,respectively(P<0.05).2.2 IS changes after rh GH treatment in subjects from GHD and ISS groupBefore rh GH treatment,no significant difference of FBG,FINS and HOMA-IR could be observed between GHD and ISS patients,while ISS patients showed significantly lower QUICK than GHD patients(P<0.05).FBG,FINS,HOMA-IR of GHD and ISS patients were significantly increased after rh GH treatment,while QUICK was significantly decreased(P<0.05).After rh GH treatment,no statistically significant difference of FBG,FINS,HOMA-IR and QUICK could be found between GHD and ISS patients(P>0.05).2.3 IS changes after rh GH treatment in subjects from high-and low-dose groupIn patients from both high-(0.13?rh GH<0.18IU/(kg·d))and low-(0.09<rh GH<0.13IU/(kg·d))dose group,FBG,FINS,HOMA-IR were significantly increased after rh GH treatment,while QUICK was significantly decreased(P<0.05).No statistically significant difference of FBG,FINS,HOMA-IR and QUICK could be found between high-and low-dose group(P>0.05).3 Correlations of IS to growth parameters,serological indicators and rh GH dose1.1 Correlation between insulin sensitivity and indicators before treatmentBefore treatment,QUICK was negatively correlated with Ht(r=-0.291,P=0.012),Wt(r=-0.282,P=0.015),IGF-1(r=-0.242,P=0.037).No significant correlation was found between QUICK and indicators including BMI,IGFBP-3,TT3,TT4,TSH(P>0.05).HOMA-IR was positively correlated with Ht(r=0.299,P=0.010),Wt(r=0.327,P=0.004),IGF-1(r=0.235,P=0.044),No significant correlation was shown between HOMA-IR and indicators including BMI,IGFBP-3,TT3,TT4,TSH(P>0.05).1.2 Correlation between insulin sensitivity and indicators after treatmentAfter treatment,QUICK showed negative correlation with Ht(r=-0.434,P=0.000),Wt(r=-0.451,P=0.000),BMI(r=-0.328,P=0.004),IGF-1(r=-0.469,P=0.000)No significant correlation between QUICK and indicators including Ht SDS,IGFBP-3,TT3,TT4,TSH(P>0.05)was found.HOMA-IR was positively correlated with Ht(r=0.371,P=0.001),Wt(r=0.437,P=0.000),BMI(r=0.376,P=0.001),IGF-1(r=0.474,P=0.000),while not significantly correlated with Ht SDS,IGFBP-3,TT3,TT4,TSH(P>0.05).After treatment,QUICK and HOMA-IR showed no significant correlation with rh GH dose(P>0.05).3.3 Factors influencing ? QUICK and ? HOMA-IRMultiple linear stepwise regression analysis showed that BMI before treatment was an important influencing factor of ? QUICK and ? HOMA-IR.Conclusion:1.Short statured patients showed elevated FBG and FINS and decreased insulin sensitivity after short-term rh GH treatment,while dose is irrelevant.2.Insulin sensitivity of GHD patients before treatment was higher than that of ISS patients,which may be related to GH deficiency before treatment,and no significant difference of insulin sensitivity between GHD and ISS group was observed after treatment.3.During the rh GH treatment,the Ht and Wt,BMI,IGF-1 level was negatively correlated with insulin sensitivity.BMI before treatment was an important factor influencing the change of insulin sensitivity.