title: Impaired hormonal counterregulation to biochemical hypoglycaemia does not explain the high incidence of severe hypoglycaemia during pregnancy in women with type 1 diabetes.
abstract: OBJECTIVE
  To explore hormonal counterregulation to biochemical hypoglycaemia during pregnancy.
  
  
  METHODS
  Observational study of 107 consecutive pregnant women with type 1 diabetes (median duration 16 years (range 1-36), HbA1c 6.6% (4.9-10.5) in early pregnancy) and 22 healthy pregnant women. At 8, 14, 21, 27 and 33 weeks (women with diabetes) and 15, 28 and 34 weeks (healthy women) blood was sampled for measurements of glucose, adrenaline, noradrenaline, cortisol and glucagon. Each woman's measurement of serum glucose was matched with her corresponding hormone concentrations. Severe hypoglycaemia (requiring help from another person) was recorded prospectively.
  
  
  RESULTS
  During normoglycaemia (serum glucose > 3.9 mmol/L), adrenaline concentrations were higher in early pregnancy compared with late pregnancy in women with diabetes (21 (7-111) pg/ml vs. 17 (2-131), p = 0.02) and healthy women (21 (10-37) pg/ml vs. 13 (5-49), p = 0.046). Biochemical hypoglycaemia (serum glucose ≤ 3.9 mmol/L) occurred in 70 women with diabetes (65%) in at least one of the five samplings. At 8 and 33 weeks, adrenaline concentrations at biochemical hypoglycaemia were similar (30 (5-164) pg/ml and 29 (9-152), p = 0.79). Adrenaline concentrations at biochemical hypoglycaemia increased from normoglycaemia at diabetes duration < 16 years (p = 0.03). In first trimester, adrenaline concentrations were comparable in women with or without severe hypoglycaemia (24 (14-164) pg/ml vs. 33 (5-86), p = 0.35). Noradrenaline, glucagon and cortisol concentrations did not increase during biochemical hypoglycaemia.
  
  
  CONCLUSIONS
  Adrenaline response to biochemical hypoglycaemia was present at similar levels in early and late pregnancy, particularly in shorter diabetes duration, and was not associated with severe hypoglycaemia in early pregnancy.
authors.affiliation: Center for Pregnant Women with Diabetes, Rigshospitalet, University of Copenhagen, Denmark. enel@dadlnet.dk
authors.forename: Lene
authors.initials: L
authors.lastname: Ringholm
authors.forename: Ulrik
authors.initials: U
authors.lastname: Pedersen-Bjergaard
authors.forename: Birger
authors.initials: B
authors.lastname: Thorsteinsson
authors.forename: Frans
authors.initials: F
authors.lastname: Boomsma
authors.forename: Jens F
authors.initials: JF
authors.lastname: Rehfeld
authors.forename: Peter
authors.initials: P
authors.lastname: Damm
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Mathiesen
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000503:physiopathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006728:Hormones / Q000502:physiology*; D006801:Humans; D007003:Hypoglycemia / Q000150:complications / Q000503:physiopathology*; D015994:Incidence; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000503:physiopathology*
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D006728:Hormones; C517652:hemoglobin A1c protein, human