title: A high concentration of prorenin in early pregnancy is associated with development of pre-eclampsia in women with type 1 diabetes.
abstract: OBJECTIVE
  The aim of this study was to investigate whether components of the renin-angiotensin system and semicarbazide-sensitive amine oxidase (SSAO) are associated with the development of pre-eclampsia in women with type 1 diabetes.
  
  
  METHODS
  This was an observational study of 107 consecutive pregnant women with type 1 diabetes (median duration 16 years [range 1-36 years], HbA(1c) 6.6% [range 4.9-10.5%]) in early pregnancy. At 8, 14, 21, 27 and 33 weeks and once within 5 days postpartum, blood was sampled for measurements of prorenin, renin, angiotensinogen, ACE and SSAO. HbA(1c), blood pressure and urinary albumin excretion were recorded. Pre-eclampsia was defined as blood pressure >140/90 mmHg and proteinuria ≥300 mg/24 h after 20 weeks.
  
  
  RESULTS
  Pre-eclampsia developed in nine women (8%) with longer diabetes duration (median 20 [range 10-32] vs 16 [range 1-36] years, p = 0.04), higher SSAO concentrations (592 [range 372-914] vs 522 [range 264-872] mU/l, p = 0.04) and a tendency towards higher prorenin levels (136 [range 50-296] vs 101 [range 21-316] ng angiotensin I ml(-1) h(-1), p = 0.06) at 8 weeks compared with women without pre-eclampsia. Levels of renin, angiotensinogen and ACE did not differ in the two groups. Throughout pregnancy, prorenin and SSAO levels were 30% (p = 0.004) and 16% (p = 0.04) higher, respectively, in women developing pre-eclampsia. Using multivariate logistic regression analysis, prorenin concentration at 8 weeks was associated with pre-eclampsia (OR 4.4 [95% CI 1.5-13.0], p = 0.007), i.e. an increase of prorenin of 100 ng angiotensin I ml(-1) h(-1) implies a 4.4 times higher risk of subsequent pre-eclampsia.
  
  
  CONCLUSIONS
  In type 1 diabetic women with pre-eclampsia, a higher concentration of prorenin in early pregnancy and higher levels of prorenin and SSAO throughout pregnancy were seen.
authors.affiliation: Center for Pregnant Women with Diabetes, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark. enel@dadlnet.dk
authors.forename: L
authors.initials: L
authors.lastname: Ringholm
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; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications* / Q000453:epidemiology; D005260:Female; D006801:Humans; D011225:Pre-Eclampsia / Q000097:blood* / Q000453:epidemiology / Q000209:etiology*; D011247:Pregnancy; D011446:Prospective Studies; D012083:Renin / Q000097:blood*; D055815:Young Adult
chemical_list: D012083:Renin