儿童糖尿病GH/IGF-1轴与血糖控制及胰岛β细胞的相关性研究

Correlation between GH/IGF-1 axis and blood glucose control and isletβcells in children with diabetes mellitus

目的探讨糖尿病患儿生长激素(GH)/胰岛素样生长因子1(IGF-1)轴与血糖控制及胰岛β细胞的相关性。方法选择2014年1月至2020年12月唐山市妇幼保健院收治的2~14岁糖尿病患儿136例,根据糖化血红蛋白(HbA1c)水平将其分为Ⅰ组(HbA1c<7%,42例)、Ⅱ组(HbA1c为7%~<9%,60例)、Ⅲ组(HbA1c≥9%,34例)。检测各组的血糖、血脂、胰岛β细胞分泌功能及血清GH和IGF-1水平;分析GH和IGF-1与血糖、血脂、胰岛β细胞分泌功能的相关性,采用多重线性回归分析影响儿童糖尿病GH/IGF-1轴的因素。结果Ⅲ组的胰岛β细胞功能指数(HOMA-β)、糖负荷30min净增C肽(C-P)与葡萄糖比值(△C-P30/△G30)、糖负荷30min净增胰岛素与葡萄糖比值(△I30/△G30)、120min血糖曲线下面积(AUC)校正后的C-P AUC(C-PAUC/GAUC)和120min血糖AUC校正后的胰岛素AUC(IAUC/GAUC)、载脂蛋白A1(ApoA1)、IGF-1均低于Ⅱ组和Ⅰ组(F=15.246~47.601,P<0.05),Ⅲ组的空腹血糖(FPG)、HbA1c、空腹C肽(FC-P)、餐后2hC肽(2hFC-P)、胰岛素抵抗指数(HOMA-IR)、甘油三酯(TG)、总胆固醇(TC)、载脂蛋白B(ApoB)、GH均高于Ⅱ组和Ⅰ组(F=17.390~285.565,P<0.05),Ⅲ组和Ⅱ组的餐后2h血糖(2hPG)、空腹胰岛素(FINS)均高于Ⅰ组(F值分别为4.687、4.152,P<0.05)。血清GH水平与FPG、2hPG、FINS、HbA1c、FC-P、2hFC-P、HOMA-IR、TG、TC、ApoB均呈正相关(r=0.229~0.534,P<0.05),与HOMA-β、△C-P30/△G30、△I30/△G30、C-PAUC/GAUC、IAUC/GAUC、ApoA1均呈负相关(r=-0.509~-0.243,P<0.05);血清IGF-1水平与HOMA-β、△C-P30/△G30、△I30/△G30、C-PAUC/GAUC、IAUC/GAUC、ApoA1均呈正相关(r=0.259~0.536,P<0.05),与FPG、2hPG、FINS、HbA1c、FC-P、2hFC-P、HOMA-IR、TG、TC、ApoB均呈负相关(r=-0.558~-0.242,P<0.05)。多重线性回归分析显示,HOMA-β、HOMA-IR、△C-P30/△G30、HbA1c均是影响GH/IGF-1轴的相关因素(t=2.259~25.064,P<0.05)。结论儿童糖尿病的血清GH水平增高、IGF-1水平降低,且与血糖控制不良和胰岛β细胞功能障碍有关。

Objective To investigate the relationship between growth hormone(GH)/insulin-like growth factor 1(IGF-1)axis and blood glucose control and isletβcells in children with diabetes mellitus.Methods A total of 136 children with diabetes and aged 2-14 years old,who were admitted to the Tangshan Maternal and Child Health Hospital from January 2014 to December 2020,were selected.According to the level of hemoglobin A1 c(HbA1 c),the children were divided into the groupⅠ(HbA1 c<7%,42 cases),the groupⅡ(7%≤HbA1 c<9%,60 cases),and the groupⅢ(HbA1 c≥9%,34 cases).Blood glucose,blood lipid,secretory function of isletβcells and serum GH and IGF-1 levels were detected in each group.The correlation of GH and IGF-1 with blood glucose,blood lipids and secretory function of isletβcells was analyzed.Multiple linear regression analysis was used to analyzed the factors affecting GH/IGF-1 axis in children with diabetes mellitus.Results Homeostasis model assessment ofβ-cell function(HOMA-β),glucose load 30 min net increased C-peptide(C-P)and glucose ratio(△C-P30/△G30),glucose load 30 min net increased insulin and glucose ratio(△I30/△G30),C-P AUC corrected by the area under the curve(AUC)of glucose at 120 min(C-PAUC/GAUC),insulin AUC corrected by the AUC of glucose at 120 min(IAUC/GAUc),apolipoprotein A1(ApoA1),and IGF-1 in the groupⅢwere lower than those in the groupⅡand the groupⅠ(F=15.246-47.601,respectively,P<0.05).Fasting plasma glucose(FPG),HbA1 c,fasting C-peptide(FC-P),2 h postprandial C-peptide(2 hFC-P),homeostatic model assessment of insulin resistance(HOMA-IR),triglyceride(TG),total cholesterol(TC),apolipoprotein B(ApoB)and GH in the groupⅢwere higher than those in the groupⅡand the groupⅠ(F=17.390-285.565,respectively,P<0.05).The 2 h postprandial plasma glucose(2 hPG)and fasting insulin(FINS)in the groupⅢand the groupⅡwere higher than those in the groupⅠ(F=4.687 and 4.152,respectively,P<0.05).Serum GH was positively correlated with FPG,2 hPG,FINS,HbA1 c,FC-P,2 hFC-P,HOMA-IR,TG,TC and ApoB(r=0.229-0.534,respectively,P<0.05),and negatively correlated with HOMA-β,△C-P30/△G30,△I30/△G30,C-PAUC/GAUC,IAUC/GAUC,and ApoA1(r=-0.509--0.243,respectively,P<0.05).Serum IGF-1 level was positively correlated with HOMA-β,△C-P30/△G30,△I30/△G30,C-PAUC/GAUC,IAUC/GAUC,ApoA1(r=0.259-0.536,respectively,P<0.05),and negatively correlated with FPG,2 hPG,FINS,HbA1 c,FC-P,2 hFC-P,HOMA-IR,TG,TC,ApoB(r=-0.558--0.242,respectively,P<0.05).The results of multiple linear regression analysis showed that HOMA-β,HOMA-IR,△C-P30/△G30and HbA1 c were the related factors affecting GH/IGF-1 axis(t=2.259-25.064,respectively,P<0.05).Conclusion In children with diabetes mellitus,the level of serum GH is increased and the level of IGF-1 is decreased,which are related to poor blood glucose control and isletβcell dysfunction.