Oral Presentation Australasian Diabetes in Pregnancy Society Annual Scientific Meeting 2016

Falling insulin requirements in women with pre-existing diabetes during pregnancy – investigating the cause and consequences through a multicentre prospective study (#5)

Suja Padmanabhan 1 2 , Vincent Lee 2 3 , Mark Mclean 1 4 5 , Neil Athayde 6 , Valeria Lanzarone 7 , Qemer Khoshnow 7 , Michael J Peek 8 , Wah N Cheung 1 2
  1. Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW, Australia
  2. School of Medicine, University of Sydney, Sydney, NSW, Australia
  3. Renal Medicine, Westmead Hospital, Sydney, NSW, Australia
  4. Diabetes and Endocrinology, Blacktown Hospital, Sydney, NSW, Australia
  5. Western Sydney University, Sydney, NSW, Australia
  6. Obstetric Medicine, Westmead Hospital, Sydney, NSW, Australia
  7. Obstetric Medicine, Nepean Hospital, Sydney, NSW, Australia
  8. College of Medicine, Biology and Environment, The Australian National University, Canberra, Australia

Introduction: It is unclear whether falling insulin requirements (FIR), in late pregnancy, are a sign of placental dysfunction.

Objective: To investigate the association of FIR with maternal biomarkers and adverse obstetric outcomes, amongst women with pre-existing diabetes in pregnancy.

Methods: A multicentre prospective cohort study, including 41 women with Type 1 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 cases (n=32). The primary outcome was a composite of clinical markers of placental dysfunction (pre-eclampsia, small for gestational age (<5%), stillbirth (>20 weeks), premature delivery (<30 weeks) and placental abruption). Maternal circulating angiogenic markers (placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), placental hormones (human placental lactogen, progesterone, TNF-α) and HbA1c were studied serially during pregnancy.

Results: FIR ≥15% was associated with an increased risk of the composite primary outcome (OR:4.38,CI 1.9-10.3,p<0.001), pre-eclampsia (OR:6.76,CI 2.7-16.7,p<0.001) and was more common amongst women with type 1 diabetes (36.6 vs. 14.5%,p=0.002). There was no difference in HbA1c between groups. The ratio of sFlt-1:PlGF was significantly higher amongst women with FIR at 25, 30 and 36wks (p<0.01). To account for the effect of pre-eclampsia, the cohort was divided into subgroups: no pre-eclampsia and no FIR (1), no pre-eclampsia and FIR (2), pre-eclampsia and no FIR (3) and pre-eclampsia and FIR (4). There was a significant correlation between increasing sFlt-1:PlGF levels at 36 weeks as the subgroups increased from 1-4 respectively suggesting increasing underlying placental dysfunction (r=0.357,p<0.001). There was no difference in placental hormones between the groups.

Conclusion: This is the first prospective study to associate FIR with altered expression of placental anti-angiogenic factors and pre-eclampsia. FIR is an important clinical sign, amongst women with pre-existing diabetes, which should alert the clinician to investigate underlying placental dysfunction.