生长抑素类似物对不合并糖尿病的垂体生长激素瘤患者糖代谢的作用及相关因素分析

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目的:探讨长效生长抑素类似物(SSA)对正常糖耐量及糖尿病前期的垂体生长激素腺瘤患者糖代谢的影响及其影响因素。方法:回顾性分析2015年1月至2020年6月在复旦大学附属华山医院垂体瘤中心接受SSA治疗的垂体生长激素瘤患者用药前后的临床资料,根据糖代谢状态将患者分为正常糖耐量(NGT)组和糖尿病前期(preDM)组。分析用药前后糖代谢状态的变化、胰岛素抵抗和β细胞功能变化。患者使用SSA 3个月后复查口服葡萄糖耐量试验评估糖代谢状态,根据不同糖代谢状态的变化进行亚组分析(分为血糖恶化组、血糖稳定组和血糖好转组),采用Pearson分析法评估影响糖代谢变化的相关因素。使用SSA前、后各项指标的比较采用配对n t检验或Wilcoxon秩和检验。n 结果:最终纳入71例患者,其中NGT组36例、preDM组35例。所有患者采用SSA治疗后的空腹血糖明显上升,分别为(5.8±0.7)、(5.2±0.5)mmol/L,稳态模型评估β细胞功能指数下降,分别为4.2(2.1,6.3)和2.3(1.3,4.8),差异均有统计学意义(n P<0.05)。采用SSA治疗后,NGT组中41.7%(15/36)的患者糖代谢状态进展成preDM,preDM组22.9%(8/35)的患者进展成糖尿病。血糖恶化组(24例)患者的年龄为(37.4±11.8)岁,低于血糖稳定组(32例)的(45.7±12.5)岁。血糖恶化组的生长激素变化率为-30.3%(-70.5%,11.3%),低于血糖稳定组的-70.3%(-91.4%,-40.4%),差异有统计学意义(n P<0.05)。患者用药前后空腹血糖变化值、生长激素谷值变化率均与稳态模型评估胰岛素抵抗指数变化率呈正相关(n r值分别为0.318、0.251,n P值分别为0.013、0.030)。n 结论:SSA会使部分生长激素瘤患者血糖升高。年轻的、药物疗效不佳的患者用药后更容易发生糖代谢的恶化。“,”Objective:To investigate the effects of long-acting somatostatin analogues (SSA) on glucose metabolism in acromegalic patients without diabetes and the influence factors.Methods:Clinical information of patients with growth hormone (GH) secreting adenomas were collected at pretreatment and 3 months after initiation of treatment with long-acting SSA in Huashan Hospital from January 2015 to June 2020. The patients were divided into normal glucose tolerance (NGT) group and prediabetes (preDM) group according to glucose metabolism. Insulin resistance and β cell function were compared among different glucose tolerance groups; changes in the characteristics of glucose metabolism after SSA treatment were analyzed. Subgroup analysis was performed according to changes of glucose metabolism after SSA treatment and analysis the factors affecting the changes of glucose metabolism. The patients were divided into three subgroups: blood glucose deteriorated group, blood glucose stable group and blood glucose improved group. Pearson analysis was used to evaluate the related factors affecting glucose metabolism. Paired n t test or Wilcoxon rank sum test was conducted to compare the indexes before and after SSA treatment.n Results:A total of 71 patients were enrolled in this study. There were 36 patients in NGT group, and 35 in preDM group. The fasting blood glucose increased after SSA treatment [(5.8±0.7)n vs. (5.2±0.5) mmol/Ln P<0.05]. Homeostasis model assessment of insulin resistance declined [4.2(2.1, 6.3)n vs. 2.3(1.3, 4.8), n P<0.05] after SSA treatment. The glucose tolerance status deteriorated in 24 (33.8%) patients, including 16 patients in the NGT group and 8 patients in the preDM group. Deteriorated glucose tolerance status groups were younger than the stable glucose tolerance status groups [(37.4±11.8) and (45.7±12.5) years old, respectively]. The decrease of GH of deteriorated glucose tolerance status groups was significantly lower than the stable glucose tolerance status groups [-30.3% (-70.5%, 11.3%)n vs. -70.3% (-91.4%, -40.4%), n P<0.05]. The changes of fasting blood glucose and growth hormone before and after SSA treatment were positively correlated with the change rate of insulin resistance index evaluated by homeostasis model (n r=0.318 and 0.251, n P=0.013 and 0.030).n Conclusions:SSA can increase blood glucose in some patients with GH secreting adenomas. The outcome of glucose metabolism depends on the drug sensitivity. Moreover, young patients with poor drug efficacy are more likely to suffer from the deterioration of glucose metabolism after SSA treatment.
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