Diabetes and Endocrinology, Westmead Hospital, Sydney, New South Wales, Australia
Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Diabetes Care. 2017 Oct;40(10):1323-1330. doi: 10.2337/dc17-0391. Epub 2017 Aug 10.
To investigate the association of falling insulin requirements (FIR) among women with preexisting diabetes with adverse obstetric outcomes and maternal biomarkers longitudinally in pregnancy.
A multicenter prospective cohort study of 158 women (41 with type 1 diabetes and 117 with type 2 diabetes) was conducted. Women with FIR of ≥15% from the peak total daily dose after 20 weeks' gestation were considered case subjects ( = 32). The primary outcome was a composite of clinical markers of placental dysfunction (preeclampsia, small for gestational age [≤5th centile], stillbirth, premature delivery [<30 weeks], and placental abruption). Maternal circulating angiogenic markers (placental growth factor [PlGF] and soluble fms-like tyrosine kinase 1 [sFlt-1]), placental hormones (human placental lactogen, progesterone, and tumor necrosis factor-α), HbA, and creatinine were studied serially during pregnancy.
FIR ≥15% were associated with an increased risk of the composite primary outcome (odds ratio [OR] 4.38 [95% CI 1.9-10.3]; < 0.001), preeclampsia (OR 6.76 [95% CI 2.7-16.7]; < 0.001), and was more common among women with type 1 diabetes (36.6 vs. 14.5%; = 0.002). Creatinine was modestly elevated among women with FIR ≥15%; however, there was no difference in HbA. The ratio of sFlt-1 to PlGF was significantly higher among women with FIR at 25, 30, and 36 weeks, with differences maintained in the subgroup that developed preeclampsia. There was no difference in placental hormones between the groups.
This is the first prospective study to associate FIR with altered expression of placental antiangiogenic factors and preeclampsia. FIR are an important clinical sign, among women with preexisting diabetes, that should alert the clinician to investigate underlying placental dysfunction.
研究患有糖尿病的女性胰岛素需求量下降（FIR）与不良产科结局和母婴生物标志物之间的纵向关系。
对 158 名女性（41 名 1 型糖尿病患者和 117 名 2 型糖尿病患者）进行了一项多中心前瞻性队列研究。20 周后，从总日剂量峰值下降≥15%的女性被认为是病例组（=32 例）。主要结局是胎盘功能障碍的临床标志物（子痫前期、小于胎龄儿[≤第 5 百分位数]、死胎、早产[<30 周]和胎盘早剥）的复合指标。在妊娠期间，连续研究了母体循环血管生成标志物（胎盘生长因子[PlGF]和可溶性 fms 样酪氨酸激酶 1[sFlt-1]）、胎盘激素（人胎盘催乳素、孕酮和肿瘤坏死因子-α）、HbA 和肌酐。
FIR≥15%与复合主要结局的风险增加相关（比值比[OR]4.38[95%CI 1.9-10.3]；<0.001），子痫前期（OR 6.76[95%CI 2.7-16.7]；<0.001），1 型糖尿病患者中更为常见（36.6%比 14.5%；=0.002）。FIR≥15%的女性肌酐略有升高，但 HbA 无差异。25、30 和 36 周时，FIR 较高的女性 sFlt-1/PlGF 比值明显较高，在发生子痫前期的亚组中差异仍存在。两组之间胎盘激素无差异。
这是首例前瞻性研究将 FIR 与胎盘抗血管生成因子表达改变和子痫前期相关联。在患有糖尿病的女性中，FIR 是一个重要的临床标志，应该引起临床医生的注意，以调查潜在的胎盘功能障碍。
