Poster Presentation Australasian Diabetes in Pregnancy Society Annual Scientific Meeting 2019

Transient extreme insulin resistance in pregnancy following betamethasone administration managed with high-dose intravenous insulin: case series and literature review.  (#70)

Christopher W Rowe 1 2 , Andrew Woods 3 , Katie Wynne 1 2
  1. Department of Endocrinology and Diabetes, John Hunter Hospital, Newcastle, NSW, Australia
  2. School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
  3. Department of Maternity and Gynaecology, John Hunter Hospital, Newcastle, NSW, Australia

Background: Betamethasone, usually two doses separated by 24 hours, is administered for fetal lung maturation in the setting of threatened preterm labour.1  In women with gestational diabetes, resultant hyperglycaemia is effectively controlled using a pregnancy-specific intravenous insulin (P-IVI) algorithm,2 during which additional insulin doses of on average 93iu (IQR 32-142iu) are required over the first 48 hours.2  Extreme insulin resistance is rare, and is incompletely understood.   

Methods:  Electronic record search was performed to identify pregnant women receiving insulin using the P-IVI algorithm (n=776 uses) over 24 months at a tertiary maternity unit.  Two women were included who received >300iu intravenous insulin in the 48 hours following betamethasone.

Case 1: A 30-year-old woman had well-controlled Type 2 Diabetes using 54iu of subcutaneous insulin daily (NPH 30iu, Aspart 24iu) at 33 weeks gestation. She received two doses of betamethasone and required an additional 767iu of intravenous insulin over 48 hours (median IV rate in the second 24 hours of 23iu/hr, maximum rate of 50iu/hr).  Mean on-infusion BGL was 8.2±1.9mmol/L. 

Case 2: A 27-year-old woman with gestational diabetes was taking 18iu of subcutaneous insulin daily (NPH 6iu, Aspart 12iu) at 30 weeks gestation. She received one dose of betamethasone and required an additional 326 units of IV insulin over 24 hours (median IV rate 14iu/hour, maximum rate 50iu/hour).  Mean on-infusion BGL was 9.2±2.0mmol/L. The risk of a second betamethasone dose was felt to outweigh potential benefit.

In both women, extreme insulin resistance resolved within 24 hours without maternal hypoglycaemia or complications.

Discussion: Rapid insulin resistance may develop after glucocorticoid administration,3, 4 and high insulin doses (>20iu/hr) may be required to achieve optimal glycaemic targets.  This is uncommon in pregnant and non-pregnant adults.2, 5 Insulin requirements fall precipitously within 24 hours of the final dose of betamethasone.2, 6 The P-IVI algorithm was individualised and performed adequately in this challenging situation. Close observation is essential, as the pharmacology of high-dose IV insulin is not well studied.

  1. Gyamfi-Bannerman C, Thom EA, Blackwell SC, Tita AT, Reddy UM, Saade GR, et al. Antenatal Betamethasone for Women at Risk for Late Preterm Delivery. N Engl J Med. 2016;374(14):1311-20.
  2. Rowe CW, Putt E, Brentnall O, Gebuehr A, Allabyrne J, Woods A, et al. An intravenous insulin protocol designed for pregnancy reduces neonatal hypoglycaemia following betamethasone administration in women with gestational diabetes. Diabet Med. 2018.
  3. Zarkovic M, Beleslin B, Ciric J, Penezic Z, Stojkovic M, Trbojevic B, et al. Glucocorticoid effect on insulin sensitivity: a time frame. J Endocrinol Invest. 2008;31(3):238-42.
  4. van Raalte DH, Nofrate V, Bunck MC, van Iersel T, Elassaiss Schaap J, Nassander UK, et al. Acute and 2-week exposure to prednisolone impair different aspects of beta-cell function in healthy men. Eur J Endocrinol. 2010;162(4):729-35.
  5. Feleke AA, Fuller RC, Ismail R, Cadiz M. Characterization of Patients Requiring High-Dose Insulin Infusion for the Management of Hyperglycemia. Diabetes. 2018;67(Supplement 1):1269-P.
  6. Yuen KCJ, McDaniel PA, Riddle MC. Twenty-four-hour profiles of plasma glucose, insulin, C-peptide and free fatty acid in subjects with varying degrees of glucose tolerance following short-term, medium-dose prednisone (20 mg/day) treatment: evidence for differing effects on insulin secretion and action. Clin Endocrinol (Oxf). 2012;77(2):224-32.