title: Severe hypoglycaemia during pregnancy in women with type 1 diabetes: possible role of renin-angiotensin system activity?
abstract: OBJECTIVE
  To investigate whether increased risk of severe hypoglycaemia in early pregnancy is related to pregnancy-induced changes in renin-angiotensin system (RAS) activity in women with type 1 diabetes (T1DM).
  
  
  METHODS
  Severe hypoglycaemic events the year preceding pregnancy were recorded retrospectively in 107 consecutive pregnant women with T1DM. Events during pregnancy were recorded prospectively. Measurements of ACE, renin and angiotensinogen were determined at 8, 14, 21, 27 and 33 weeks and postpartum.
  
  
  RESULTS
  The rate of severe hypoglycaemia was 1.1 and 5.3 events/patient-year the year preceding pregnancy and in first trimester, respectively (p<0.0001). Levels of ACE, renin or angiotensinogen did not differ between women with and without severe hypoglycaemia during pregnancy. Multivariate regression analysis identified a positive association between rate of severe hypoglycaemia the year preceding pregnancy and postpartum ACE activity (relative rate of severe hypoglycaemia above versus below median ACE activity: 4.4 (CI: 1.7-11.9), p=0.003). No association was found between severe hypoglycaemia during pregnancy and renin angiotensin system activity at 8 weeks.
  
  
  CONCLUSIONS
  In early pregnancy increased RAS activity does not explain the 5-fold increase in severe hypoglycaemia in women with T1DM. A positive association between occurrence of severe hypoglycaemia and ACE activity outside pregnancy was demonstrated.
authors.affiliation: Center for Pregnant Women with Diabetes, Rigshospitalet, Denmark. enel@dadlnet.dk
authors.forename: L Ringholm
authors.initials: LR
authors.lastname: Nielsen
authors.forename: U
authors.initials: U
authors.lastname: Pedersen-Bjergaard
authors.forename: B
authors.initials: B
authors.lastname: Thorsteinsson
authors.forename: F
authors.initials: F
authors.lastname: Boomsma
authors.forename: P
authors.initials: P
authors.lastname: Damm
authors.forename: E R
authors.initials: ER
authors.lastname: Mathiesen
mesh_terms: D000328:Adult; D000808:Angiotensinogen / Q000378:metabolism; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism*; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D000808:Angiotensinogen; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; D012083:Renin