Katra Pernilla, Dereke Jonatan, Nilsson Charlotta, Hillman Magnus
Department of Clinical Sciences, Diabetes Research Laboratory, Lund University, Lund, Sweden.
Department of Pediatrics, Helsingborg Hospital, Helsingborg, Sweden.
PLoS One. 2016 May 25;11(5):e0155701. doi: 10.1371/journal.pone.0155701. eCollection 2016.
Diabetes mellitus is a group of diseases characterized by chronic hyperglycemia. Women who develops hyperglycemia for the first time during pregnancy receive the diagnosis gestational diabetes mellitus (GDM). Presently, there is no consensus about the diagnostic criteria for GDM. A majority of these women subsequently develop postpartum overt diabetes making it important to identify these patients as early as possible. In this study we investigated if plasma levels of the interleukin-1 receptor antagonist (IL-1Ra), an endogenous inhibitor of IL-1 signaling, can be used as a complementary biomarker for diagnosing GDM and predicting postpartum development of overt diabetes mellitus. Patients participating in this study (n = 227) were diagnosed with their first GDM 2004-2013 at Lund University Hospital, Lund, Sweden. Healthy pregnant volunteers (n = 156) were recruited from women's welfare centers in the same region 2014-2015. Levels of IL-1Ra and C-peptide were analyzed in ethylenediaminetetraacetic acid (EDTA)-plasma or serum using enzyme linked immunosorbent assay (ELISA). GDM patients had significantly lower levels of IL-1Ra than the control group (p = 0.012). In addition, GDM patients that had developed impaired glucose tolerance (IGT) or type 2 diabetes mellitus postpartum had significantly lower levels of IL-1Ra, and significantly higher levels of C-peptide than GDM patients that had not developed diabetes mellitus postpartum (p = 0.023) and (p = 0.0011) respectively. An inverse correlation was found between IL-1Ra and serum C-peptide levels in the control group (rs = -0.31 p = 0.0001). Our results show that IL-1Ra might be included in a future panel of biomarkers, both for diagnosing GDM to complement blood glucose, and also identifying GDM patients that are at risk of developing type 2 diabetes mellitus postpartum. However, the ROC curve analysis provided a sensitivity of 52.2% and specificity of 67.1%, which nonetheless may not be sufficient enough to use IL-1Ra as a sole biomarker.
糖尿病是一组以慢性高血糖为特征的疾病。在孕期首次发生高血糖的女性被诊断为妊娠期糖尿病（GDM）。目前，关于GDM的诊断标准尚无共识。这些女性中的大多数随后会发展为产后显性糖尿病，因此尽早识别这些患者很重要。在本研究中，我们调查了白细胞介素-1受体拮抗剂（IL-1Ra）（IL-1信号的内源性抑制剂）的血浆水平是否可作为诊断GDM和预测产后显性糖尿病发生的补充生物标志物。参与本研究的患者（n = 227）于2004 - 2013年在瑞典隆德的隆德大学医院首次被诊断为GDM。健康怀孕志愿者（n = 156）于2014 - 2015年从同一地区的妇女福利中心招募。使用酶联免疫吸附测定（ELISA）分析乙二胺四乙酸（EDTA）血浆或血清中IL-1Ra和C肽的水平。GDM患者的IL-1Ra水平显著低于对照组（p = 0.012）。此外，产后出现糖耐量受损（IGT）或2型糖尿病的GDM患者的IL-1Ra水平显著更低，且C肽水平显著高于产后未发生糖尿病的GDM患者（分别为p = 0.023和p = 0.0011）。在对照组中发现IL-1Ra与血清C肽水平呈负相关（rs = -0.31，p = 0.0001）。我们的结果表明，IL-1Ra可能会被纳入未来的生物标志物组合中，既用于诊断GDM以补充血糖检测，也用于识别有产后发生2型糖尿病风险的GDM患者。然而，ROC曲线分析的敏感性为52.2%，特异性为67.1%，这可能不足以将IL-1Ra用作唯一的生物标志物。
