2型糖尿病患者黎明现象发生机制的初步研究

A preliminary study of pathogenesis of dawn phenomenon in patients with type 2 diabetes mellitus

目的：初步研究2型糖尿病患者黎明现象的发生机制。方法将2012年1月至2014年7月行动态血糖监测、资料完整的264例2型糖尿病患者分为无黎明现象组和黎明现象组,检测两组肝肾功能、血脂、HbA1C、果糖胺（FMN）、促肾上腺皮质激素和皮质醇等生化指标,行口服葡萄糖耐量试验及胰岛素、胰升糖素释放试验,比较两组生化指标、血糖水平、空腹和糖负荷后胰岛α和β细胞功能,对黎明现象行相关及回归分析。结果黎明现象组促肾上腺皮质激素为（6.6±2.4） pmol/ L,皮质醇为（523.8±84.2） nmol/ L,HbA1C为（8.1±2.0）%,FMN 为（0.32±0.09）mmol/ L,空腹血糖与夜间最低点血糖净增值（BG1）、早餐后与早餐前血糖净增值（BG2）、24 h 平均血糖分别为（26.2±5.8）、（39.6±8.3）和（188.5±36.2） mg/ dl,高血糖持续时间为29：31（41%）,稳态模型评估的胰岛素抵抗指数（HOMA-IR）为4.18±0.94,均高于无黎明现象组[分别为（4.8±1.9） pmol/ L、（448.2±76.9） nmol/ L、（7.5±1.8）%、（0.29±0.08） mmol/ L,（18.0±4.9） mg/ dl,（28.8±7.4） mg/ dl,（164.5±31.2） mg/ dl,20：10（28%）,3.82±0.82]（均 P〈0.05）。黎明现象组胰岛素敏感指数（ISI）为-4.28±0.62、血糖曲线下面积/胰岛素曲线下面积（AUCG /AUCI ）为-0.74±0.48,低于无黎明现象组的-4.04±0.54和-0.63±0.30（均 P〈0.05）。黎明现象组各时间点胰升糖素水平及胰升糖素曲线下面积明显高于无黎明现象组（均 P〈0.05）,黎明现象组0、60、180 min 胰升糖素/胰岛素比值及0、30、120、180 min 胰升糖素/血糖比值明显高于无黎明现象组（均 P〈0.05）。Logistic 回归分析显示黎明现象与 HOMA-IR、胰升糖素/胰岛素比值、BG2、BG1和皮质醇呈正相关（均 P〈0.05）,与 ISI 呈负相关（P〈0.05）。结论黎明现象可能与皮质醇分泌增多及胰岛α和β细胞功能异常有关。

Objective To study the preliminary pathogenesis of dawn phenomenon in patients with type 2 diabetes mellitus. Methods Two-hundred and sixty-four patients with type 2 diabetes had performed continuous glucose monitoring since Jan 2012 to July 2014. They were divided into two groups： patients without dawn phenomenon and patients with dawn phenomenon. Biochemical indicators including liver and kidney function, blood lipids, HbA1C , fructosamine（FMN）, adrenocorticotropic hormone and cortisol were detected in the two groups. Oral glucose tolerance test, insulin releasing test and glucagon releasing test were performed. The differences in biochemical indicators, glucose level and α-cell and β-cell function after fasting and glucose-load were compared. The correlation and regression analysis were performed between dawn phenomenon and other indicators. Results The level of adrenocorticotropic hormone, cortisol, HbA1C , FMN, the increment of fasting glucose and nocturnal nadir glucose （BG1 ）, the glucose increment before and after breakfast（BG2 ）, 24-hour mean glucose, duration above high limit, and HOMA-IR were significantly higher in patients with dawn phenomenon compared to those in patients without dawn phenomenon[（6. 6 ± 2. 4） vs（4. 8 ± 1. 9） pmol/ L, （523. 8 ± 84. 2） vs （448. 2 ± 76. 9） nmol/ L, （8. 1 ± 2. 0）% vs （7. 5 ± 1. 8）% ,（0. 32 ± 0. 09） vs（0. 29 ± 0. 08） mmol/ L, （26. 2 ± 5. 8） vs （18. 0 ± 4. 9） mg/ dl, （39. 6 ± 8. 3） vs （28. 8 ± 7. 4） mg/ dl,（188. 5 ± 36. 2） vs（164. 5 ± 31. 2） mg/ dl, 29 ： 31（41% ） vs 20 ： 10（28% ）, 4. 18 ± 0. 94 vs 3. 82 ± 0. 82]（all P〈0. 05）. ISI and AUCG / AUCI were lower in patients with dawn phenomenon than those in patients without dawn phenomenon（-4. 28±0. 62 vs -4. 04±0. 54, -0. 74±0. 48 vs -0. 63±0. 30） （all P〈0. 05）. The level of glucagon at each time point and area under curve of glucagon were significantly higher in patients with dawn＆nbsp;phenomenon than those in patients without. 0, 60, 180 min glucagon/ insulin ratio and 0, 30, 120, 180 min glucagon / glucose ratio were significantly higher in patients with dawn phenomenon（all P〈0. 05）. Logistic regression analysis showed that dawn phenomenon was positively related to HOMA-IR, glucagon/ insulin ratio, BG2 , BG1 and cortisol（all P〈0. 05）, and negatively related to ISI（P〈0. 05）. Conclusion Dawn phenomenon may be associated with increased secretion of cortisol and dysfunction of islet α-cell and β-cell.