Bhattacharya Saptarshi, Nagendra Lakshmi, Dutta Deep, Kamrul-Hasan A B M
Department of Endocrinology, Indraprastha Apollo Hospitals, New Delhi 110076, India.
Department of Endocrinology, JSS Medical College, JSS Academy of Higher Education and Research, Mysore 570004, India.
J Clin Endocrinol Metab. 2025 May 19;110(6):1781-1791. doi: 10.1210/clinem/dgae878.
Early gestational diabetes mellitus (eGDM) refers to elevated blood glucose levels not meeting the criteria for overt diabetes before 20 weeks gestation. Observational studies link eGDM to adverse outcomes, but randomized controlled trial (RCT) evidence on early intervention benefits remains inconclusive. To address this, we performed a systematic review and meta-analysis (SRM) of RCTs on this subject.
We searched electronic databases to identify RCTs comparing early treatment vs observation for eGDM. The primary neonatal outcomes analyzed were large-for-gestational age (LGA) and macrosomia. The primary maternal outcome was pregnancy-related hypertension. Secondary neonatal outcomes included neonatal respiratory distress (NRD), neonatal intensive-care unit admission, small-for-gestational age, cord-blood C-peptide ≥90th percentile, and neonatal hypoglycemia. Secondary maternal outcomes were cesarean section (CS), emergency CS, labor induction, preeclampsia, and preterm birth.
Seven RCTs involving 4427 pregnancies were analyzed. The studies differed in their timing and methods of inclusion. Six studies used a combination of lifestyle and pharmaceutical interventions, while 1 relied solely on lifestyle modifications. Early treatment did not reduce LGA [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.53-1.32; P = .44], macrosomia (OR 0.68; 95% CI: 0.43-1.06; P = .09), or pregnancy-related hypertension (OR 1.04; 95% CI: 0.68-1.57; P = .87). Among the secondary outcomes, only NRD was significantly reduced in the treatment arm (OR 0.52; 95% CI: 0.34-0.80; P = .003). However, sensitivity analysis, omitting the lifestyle-only study, demonstrated a lower risk of macrosomia with early intervention (OR 0.55; 95% CI: 0.34-0.91; P = .02).
The SRM demonstrates early intervention does not improve most pregnancy outcomes, except NRD. Sensitivity analysis, excluding the lifestyle-only study, additionally revealed a reduction in macrosomia. The findings must be interpreted cautiously due to the variability in study designs. Replication in well-designed multicenter trials is required before clinical application.
早期妊娠糖尿病（eGDM）是指妊娠20周前血糖水平升高但未达到显性糖尿病的标准。观察性研究将eGDM与不良结局联系起来，但关于早期干预益处的随机对照试验（RCT）证据仍不明确。为解决这一问题，我们对关于该主题的RCT进行了系统评价和荟萃分析（SRM）。
我们检索电子数据库以识别比较eGDM早期治疗与观察的RCT。分析的主要新生儿结局为大于胎龄儿（LGA）和巨大儿。主要母亲结局为妊娠相关高血压。次要新生儿结局包括新生儿呼吸窘迫（NRD）、新生儿重症监护病房入院、小于胎龄儿、脐血C肽≥第90百分位数和新生儿低血糖。次要母亲结局为剖宫产（CS）、急诊CS、引产、先兆子痫和早产。
分析了7项涉及4427例妊娠的RCT。这些研究在纳入时间和方法上存在差异。6项研究采用了生活方式和药物干预相结合的方法，而1项仅依靠生活方式改变。早期治疗并未降低LGA[比值比（OR）0.84；95%置信区间（CI）0.53 - 1.32；P = 0.44]、巨大儿（OR 0.68；95% CI：0.43 - 1.06；P = 0.09）或妊娠相关高血压（OR 1.04；95% CI：0.68 - 1.57；P = 0.87）。在次要结局中，仅治疗组的NRD显著降低（OR 0.52；95% CI：0.34 - 0.80；P = 0.003）。然而，敏感性分析排除仅采用生活方式干预的研究后，显示早期干预可降低巨大儿风险（OR 0.55；95% CI：0.34 - 0.91；P = 0.02）。
SRM表明，除NRD外，早期干预并不能改善大多数妊娠结局。排除仅采用生活方式干预的研究后的敏感性分析还显示巨大儿有所减少。由于研究设计的差异，这些结果必须谨慎解读。在临床应用前，需要在设计良好的多中心试验中进行重复验证。
