Padmanabhan S, et al. – The aim of this study was to evaluate the correlation of falling insulin requirements (FIR) among women with pre–existing diabetes with adverse obstetric outcomes and maternal biomarkers longitudinally in pregnancy. This is the first prospective study to correlate FIR with altered expression of placental antiangiogenic factors and pre–eclampsia. The outcomes highlighted falling insulin requirements is an important clinical sign, among women with pre–existing diabetes, that should alert the clinician to investigate underlying placental dysfunction.

Methods

• Researchers conducted a multicenter prospective cohort study including a total 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 (n = 32).
• The preliminary endpoint was a composite of clinical markers of placental dysfunction (pre-eclampsia, small for gestational age [≤5th centile], stillbirth, premature delivery [<30 weeks], and placental abruption).
• They studied 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-≥), HbA1c, and creatinine during pregnancy.

Results

• The evidence showed that FIR ≥15% was correlated with an increased risk of the composite primary outcome (odds ratio [OR] 4.38 [95% CI 1.9-10.3]; P < 0.001), pre-eclampsia (OR 6.76 [95% CI 2.7-16.7]; P < 0.001), and was more common among women with type 1 diabetes (36.6 vs. 14.5%; P = 0.002).
• They observed that creatinine was modestly elevated among women with FIR ≥15%; however, there was no difference in HbA1c.
• The results showed that 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 pre-eclampsia.
• No difference was observed in placental hormones between the groups.