Hypoglycemia in type 1 diabetic pregnancy: the role of pre-conception insulin aspart treatment in a randomized study

  1. Simon Heller, MD, FRCP (s.heller{at},
  2. Peter Damm, MD, DMSc2,
  3. Henriette Mersebach, MD, PhD3,
  4. Trine Vang Skjøth, MD3,
  5. Risto Kaaja, MD, PhD4,
  6. Moshe Hod, MD5,
  7. Santiago Durán-García, MD, PhD6,
  8. David McCance, MD7 and
  9. Elisabeth R. Mathiesen, MD, DMSc2
  1. 1Northern General Hospital, Sheffield, UK
  2. 2Rigshospitalet, University of Copenhagen, Denmark
  3. 3Novo Nordisk A/S, Soeborg, Denmark
  4. 4Helsinki University Central Hospital, Helsinki, Finland
  5. 5Rabin Medical Center, Tel-Aviv University, Petah-Tiqva, Israel
  6. 6University of Seville, Seville, Spain
  7. 7Royal Victoria Hospital, Belfast, UK


Objective: A recent randomized trial compared prandial insulin aspart (IAsp) with human insulin (HI) in type 1 diabetic pregnancy. The aim of this exploratory analysis was to investigate the incidence of severe hypoglycemia during pregnancy and compare women enrolled preconception with women enrolled during early pregnancy.

Research design and methods: IAsp administered immediately before each meal was compared with HI administered 30 minutes before each meal in 99 subjects (IAsp:44, HI:55) randomized pre-conception and in 223 subjects (IAsp:113, HI:110) randomized in early pregnancy (<10 weeks). NPH insulin was the basal insulin. Severe hypoglycemia (requiring third-party assistance) was recorded prospectively pre-conception (where possible), during pregnancy, and postpartum. Relative risk (RR) of severe hypoglycemia was evaluated with a gamma frailty model.

Results: 23% of patients experienced severe hypoglycemia during pregnancy with peak incidence in early pregnancy. In the first half of pregnancy the RR of severe hypoglycemia in women randomized in early pregnancy/pre-conception was 1.70 (95%CI: 0.91–3.18; P=0.097); the RR in the second half of pregnancy was 1.35 (0.38–4.77; P=0.640). In women randomized pre-conception, severe hypoglycemia rates occurring before, during first and second half of pregnancy and postpartum for IAsp vs. HI were 0.9 vs. 2.4, 0.9 vs. 2.4, 0.3 vs. 1.2, and 0.2 vs. 2.2 episodes/patient/year, respectively (NS).

Conclusion: These data suggest that initiation of insulin analog treatment pre-conception rather than during early pregnancy may result in a lower risk of severe hypoglycemia in women with type 1 diabetes.


    • Received August 27, 2009.
    • Accepted November 17, 2009.

This Article

  1. Diabetes Care
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