Study design and participants
Participants in the current study are a subset of the “Markers And Mechanisms for PreEclampsia in Type 1 Diabetes” (MAMPED) cohort. MAMPED design, participant characteristics, and inclusion/exclusion criteria have been described previously.24-30 The overall goal of MAMPED was to identify early markers and potential mechanisms for PE in the context of pregnancy complicated by maternal T1DM. Briefly, it was a longitudinal, prospective pregnancy study of 151 women with T1DM and 24 non-diabetic women enrolled in the first trimester and followed until delivery. The study was conducted in Norway, Australia, and the United States, and participants were predominantly Caucasian (86%). All were free of hypertension, proteinuria and microalbuminuria at enrolment (urinary albumin:creatinine ratio <30mg/g at the first study visit when gestational age was 9-16 weeks)). PE was defined as new-onset hypertension (>140/90 mmHg) and proteinuria (>300 mg/24 h) after 20 weeks’ gestation. Clinical data and specimens (plasma, urine) were collected at three visits: first trimester (V1: gestation 12.2 ± 1.9 wks (mean±SD)), mid-second trimester (V2: 21.6 ± 1.5 wks), and early third trimester (V3: 31.5±1.7 wks). Samples were stored at -80°C until analysis. The study was conducted according to Declaration of Helsinki guidelines and approved by the Institutional Review Boards at all participating institutions. Written informed consent was obtained from all participants.
In accordance with the original MAMPED design, type 1 diabetic women with PE were compared with a matched group (by age, diabetes duration, and parity) without PE. For this report, these subsets comprised 23 (of the original 26) who developed PE (DM+PE+; three were unavailable through sample attrition), and 24 who remained normotensive (DM+PE-; from an original matched subset of 26). We also included 19 non-diabetic, non-PE women (DM-) as ‘reference controls’. All study visits occurred prior to the onset of PE.
Medication usage was recorded at V1. All with diabetes were taking insulin. A majority were taking folic acid at V1 (DM+PE+: 70%; DM+PE-: 71%; DM-: 42%, p>0.05), but overall, a minority took vitamin supplements (DM+PE+: 39%; DM+PE-: 50%; DM-: 32%, p>0.05). Use of vitamin supplements did not differ by presence of diabetes, PE outcome, or vitamin D deficiency.