Shen Ming, Wang Meng, He Wenqiang, He Min, Qiao Nidan, Ma Zengyi, Ye Zhao, Zhang Qilin, Zhang Yichao, Yang Yeping, Cai Yanjiao, ABuDuoReYiMu Yakupujiang, Lu Yun, Lu Bin, Shou Xuefei, Wang Yongfei, Ye Hongying, Li Yiming, Li Shiqi, Zhao Yao, Cao Xiaoyun, Zhang Zhaoyun
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai 200040, China.
Int J Endocrinol. 2018 Apr 26;2018:3015854. doi: 10.1155/2018/3015854. eCollection 2018.
To evaluate the change in glucose tolerance in treatment-naïve patients with acromegaly after administration of SSA and to identify predictive factors of glucose impairment during SSA therapy.
Oral glucose tolerance testing (OGTT) was performed on 64 newly diagnosed and treatment-naïve patients with acromegaly both at pretreatment and 3 months after initiation of treatment with long-acting SSA. Insulin resistance (IR) was assessed by homeostatic model assessment- (HOMA-) IR and IS. Insulin secretion was assessed by HOMA-, INS/BG, IGI (insulinogenic index), IGI/IR, ISSI2, and AUC/AUC. Receiver-operating characteristic (ROC) curves were generated to determine the optimal cutoffs to predict the impact of SSA on glucose metabolism.
Pretreatment, 19, 24, and 21 patients were categorized as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM), respectively. Posttreatment, IR, represented by IS, was significantly improved in all 3 groups. Insulin secretion, represented by HOMA-, declined in the NGT and IGT groups, but was unaltered in the DM group. The glucose tolerance status deteriorated in 18 (28.1%) patients, including 13 patients in the NGT group and 5 patients in the IGT group. Deterioration was associated with lower baseline BG (plasma glucose 120 min post-OGTT), less reduction of growth hormone (GH), and greater reduction of insulin secretion after SSA therapy. BG greater than 8.1 mmol/l provided the greatest sensitivity and specificity in predicting the stabilization and/or improvement of glucose tolerance status after SSA treatment (PPV 90.7%, NPV 66.7%, < 0.001).
The deterioration of glucose metabolism induced by SSA treatment is caused by the less reduction of GH and the more inhibition of insulin secretion, which can be predicted by the baseline BG during OGTT.
评估初治肢端肥大症患者使用生长抑素类似物（SSA）治疗后糖耐量的变化，并确定SSA治疗期间糖耐量受损的预测因素。
对64例新诊断且初治的肢端肥大症患者在治疗前及开始长效SSA治疗3个月后进行口服葡萄糖耐量试验（OGTT）。通过稳态模型评估胰岛素抵抗（HOMA-IR）和胰岛素敏感性指数（IS）评估胰岛素抵抗。通过HOMA-胰岛素分泌指数（HOMA-IS）、胰岛素与血糖比值（INS/BG）、胰岛素生成指数（IGI）、IGI/IR、胰岛素分泌敏感性指数2（ISSI2）和曲线下面积比值（AUC/AUC）评估胰岛素分泌。绘制受试者操作特征（ROC）曲线以确定预测SSA对糖代谢影响的最佳临界值。
治疗前，分别有19例、24例和21例患者被分类为糖耐量正常（NGT）、糖耐量受损（IGT）和糖尿病（DM）。治疗后，以IS表示的胰岛素抵抗在所有3组中均显著改善。以HOMA-表示的胰岛素分泌在NGT组和IGT组中下降，但在DM组中未改变。18例（28.1%）患者的糖耐量状态恶化，包括NGT组中的13例患者和IGT组中的5例患者。恶化与较低的基线血糖（OGTT后120分钟血浆葡萄糖）、生长激素（GH）降低较少以及SSA治疗后胰岛素分泌降低较多有关。血糖大于8.1 mmol/l在预测SSA治疗后糖耐量状态的稳定和/或改善方面具有最高的敏感性和特异性（阳性预测值90.7%，阴性预测值66.7%，P<0.001）。
SSA治疗引起的糖代谢恶化是由GH降低较少和胰岛素分泌抑制较多所致，这可通过OGTT期间的基线血糖进行预测。
