Dunseath Gareth, Atkinson Michael, Cheung Wai-Yee, Luzio Stephen, Peter Rajesh
Diabetes Research Group, Swansea University Faculty of Medicine Health and Life Science, Swansea, Wales, UK
Neath Port Talbot Hospital, Port Talbot, Wales, UK.
BMJ Open. 2025 Sep 5;15(9):e100039. doi: 10.1136/bmjopen-2025-100039.
Gestational diabetes mellitus (GDM) is common in pregnancy and is increasing in prevalence. It is associated with an increased risk of maternal and perinatal complications if not diagnosed and managed early. Most guidelines suggest making a diagnosis of GDM using an oral glucose tolerance test (OGTT) between 24 and 28 weeks of pregnancy at which stage there still is an increased risk of complications. Increased beta-cell secretory product concentrations have been observed prior to changes in glycaemia and can potentially be used as an early marker to diagnose and assess risk of developing GDM.
The study was a prospective, longitudinal cohort study. OGTTs were carried out at visit one: 16-18 weeks and visit two: 24-28 weeks gestation in pregnant women with at least one risk factor for GDM [Body Mass Index >30 kg/m, previous macrosomic baby (>4.5 kg), previous GDM, first degree relative with type 2 diabetes mellitus (T2DM)]. Blood sampling was performed at fasting, 30 min, 1 and 2 hours following a 75-g oral glucose load. Samples were analysed for glucose, total and intact proinsulin, insulin and C-peptide. Hormonal concentrations at visit 1 were compared between those that remained normal glucose tolerant (NGT) and those that progressed to GDM at visit 2 using receiver operator characteristic (ROC) area under the curve (AUC) to assess for discrimination between the two groups.
Unfortunately, a smaller than planned sample size was recruited due to the start of COVID-19 pandemic midway through the study. 83 pregnant women had OGTT at visit 1. Of these, 12 reached the threshold for GDM at visit 1 and were excluded. In total, data from 66 patients were included for analysis (5 Did Not Attend). Visit 1 hormone comparisons were carried out between 51 who remained NGT and 15 who progressed to GDM at visit 2. There were no significant differences at each time point in ROC AUC between the two groups for total and intact proinsulin and insulin. However, there were significant differences observed in C-peptide ROC AUC at 30 (p=0.041) and 60 min (p=0.003) between the two groups.
This study did not demonstrate significant increase in early proinsulin concentrations in patients that developed GDM. However, there were differences in C-peptide concentrations. The COVID-19 pandemic restricted the recruitment of patient numbers and further studies in a larger cohort will be needed to validate these findings.
ISRCTN16416602.
妊娠期糖尿病（GDM）在孕期较为常见，且患病率呈上升趋势。若不及早诊断和管理，其会增加孕产妇和围产期并发症的风险。大多数指南建议在妊娠24至28周期间采用口服葡萄糖耐量试验（OGTT）来诊断GDM，在此阶段并发症风险依然较高。在血糖变化之前就已观察到β细胞分泌产物浓度升高，其有可能作为诊断和评估发生GDM风险的早期标志物。
本研究为一项前瞻性纵向队列研究。对至少有一项GDM风险因素的孕妇[体重指数>30kg/m²、既往有巨大儿（>4.5kg）、既往有GDM、2型糖尿病（T2DM）一级亲属]在第一次就诊时（妊娠16 - 18周）和第二次就诊时（妊娠24 - 28周）进行OGTT。在口服75g葡萄糖负荷后，于空腹、30分钟、1小时和2小时进行采血。对样本进行葡萄糖、总胰岛素原和完整胰岛素原、胰岛素及C肽分析。使用受试者工作特征（ROC）曲线下面积（AUC）比较第一次就诊时糖耐量正常（NGT）者和第二次就诊时进展为GDM者的激素浓度，以评估两组之间的区分度。
遗憾的是，由于在研究进行到一半时新冠疫情爆发，招募的样本量小于计划。83名孕妇在第一次就诊时进行了OGTT。其中，12名在第一次就诊时达到GDM阈值并被排除。总共纳入66例患者的数据进行分析（5例未就诊）。对51名仍为NGT者和15名在第二次就诊时进展为GDM者进行了第一次就诊时激素比较。两组在总胰岛素原、完整胰岛素原和胰岛素的ROC AUC各时间点均无显著差异。然而，两组在30分钟（p = 0.041）和60分钟（p = 0.003）时C肽的ROC AUC存在显著差异。
本研究未证明发生GDM的患者早期胰岛素原浓度有显著升高。然而，C肽浓度存在差异。新冠疫情限制了患者数量的招募，需要在更大队列中进行进一步研究以验证这些发现。
ISRCTN16416602
