Enquobahrie Daniel A, Qiu Chun-Fang, Hevner Karin, Abetew Dejene, Williams Michelle A
Int J Mol Epidemiol Genet. 2011 Aug 30;2(3):292-9. Epub 2011 Aug 15.
Accumulating evidence documents the initiation of diverse physiologic and biochemical response subsequent to an oral glucose load. However, significant gaps in knowledge exist in the understanding of consequences of glucose load during pregnancy, a state of insulin resistance. Using high dimensional protein arrays, we conducted a pilot proof-of-concept and feasibility study to investigate profiles of 120 plasma proteins in pre- and post- 50-gram oral glucose challenge samples. Participants (N = 10) were selected from among women enrolled in a pregnancy cohort. Differences in plasma protein concentrations between pre- and post-glucose load challenge samples were evaluated using Student's T-test (paired) and mean fold change comparisons. Multiple testing adjusted p-values (i.e., false discovery rate q values) were computed using Benjamini-Hochberg (BH) corrections. Plasma haptoglobulin, epidermal growth factor, hemoglobin, thrombospondin-1, and S100 protein concentrations were two to five fold higher in post-glucose load compared with pre-glucose load samples (all q-values <0.05). Among women aged >31 years (above median), post-load S100 protein was elevated 9.92-fold above pre-load concentrations, while it was elevated 4.10-fold among women aged <31 years (below median). Similarly, among women with post-load glucose concentrations <101mg/dl (below median), S100 was elevated 8.26-fold while it was elevated 3.28 fold among women with post-load glucose concentrations >101mg/dl (above median). Our study findings suggest that post-glucose load changes in plasma biomarkers represent a diverse set of cellular responses including receptor for advanced glycation end products (RAGE), inflammation, oxidative stress and adipogenesis, during mid-pregnancy. Future studies of larger populations and longer periods of follow-up are warranted.
越来越多的证据表明，口服葡萄糖负荷后会引发多种生理和生化反应。然而，在理解孕期（一种胰岛素抵抗状态）葡萄糖负荷的后果方面，仍存在重大知识空白。我们使用高维蛋白质阵列进行了一项初步的概念验证和可行性研究，以调查50克口服葡萄糖耐量试验前后样本中120种血浆蛋白的谱。参与者（N = 10）从参加妊娠队列的女性中选取。使用配对学生t检验和平均倍数变化比较来评估葡萄糖负荷前后样本中血浆蛋白浓度的差异。使用Benjamini-Hochberg（BH）校正计算多重检验调整后的p值（即错误发现率q值）。与葡萄糖负荷前的样本相比，葡萄糖负荷后的血浆触珠蛋白、表皮生长因子、血红蛋白、血小板反应蛋白-1和S100蛋白浓度高出两到五倍（所有q值<0.05）。在年龄大于31岁（中位数以上）的女性中，负荷后S100蛋白比负荷前浓度升高了9.92倍，而在年龄小于31岁（中位数以下）的女性中升高了4.10倍。同样，在负荷后血糖浓度<101mg/dl（中位数以下）的女性中，S100升高了8.26倍，而在负荷后血糖浓度>101mg/dl（中位数以上）的女性中升高了3.28倍。我们的研究结果表明，孕期中期葡萄糖负荷后血浆生物标志物的变化代表了一系列不同的细胞反应，包括晚期糖基化终产物受体（RAGE）、炎症、氧化应激和脂肪生成。有必要对更大规模人群进行更长时间的随访研究。
