Urine-plasminogen as a Predictor for Development Of Preeclampsia in Pregnant Women With Type 1 Diabetes Mellitus
A tonic active epithelial Na+ channel (ENaC) in pre-eclampsia (PE) escaped normal hormonal control may offer an attractive explanatory model for the pathophysiology of established PE. The channel is activated by plasmin. Because microalbuminuria in pregnant pregestational diabetes patients predicts the development of preeclampsia, we believe that it is caused by plasmin(plasminogen) lose from plasma to the urine. The investigators want to test the correlation between measurable plasmin/plasminogen in the urine early in pregnancy and the development of preeclampsia in patients with type 1 diabetes.
Type 1 Diabetes
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Urine-plasminogen as a Predictor for Development Of Preeclampsia in Pregnant Women With Type 1 Diabetes Mellitus|
- preeclampsia [ Time Frame: 3 years ] [ Designated as safety issue: No ]The development of preeclampsia, defined by hypertension ( > 140/90 mmHg) and proteinuria ( >0,3 g/24 hour).
- preterm delivery [ Time Frame: 3 years ] [ Designated as safety issue: No ]post-partum registration of preterm delivery
- light for gestational age [ Time Frame: 3 years ] [ Designated as safety issue: No ]post-partum registration of "light for gestational age"
Biospecimen Retention: Samples With DNA
whole blood serum plasma urine
|Study Start Date:||June 2013|
|Estimated Study Completion Date:||February 2016|
|Estimated Primary Completion Date:||April 2015 (Final data collection date for primary outcome measure)|
pregestational type 1 diabetes
It is an observational study. No intervention is made.
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Study aim and hypothesis:
To test if there is a measurable correlation between plasmin/plasminogen abnormally excreted by the kidneys to the urine and the development of preeclampsia at pregnant women with Type 1 diabetes.
1. The amount of proteases ( plasmin/plasminogen ) excreted in urine predicts the development of preeclampsia at pregnant patients with type 1 diabetes.
If we see a correlation between the excretion of plasmin/plasminogen in urine in patients with type 1 diabetes and the development of preeclampsia, the proteases might be used as a marker for these patients in the diabetes group that develop the disease and eventually also as a marker for the severity.
In these high risk groups it is possible that we would be able to optimize their outpatient visits even more in trying to lower the amount of preterm births.
The study is an observational, longitudinal - prospective study. Women with pregestational type 1 diabetes are included when they show up for their first outpatient pregnancy visit around the 9th weeks gestation.
Selection of patients:
The selection of patients is based on pregnant outpatients with Type 1 diabetes, over 18 years, from Gynecological- obstetric department, Aarhus University hospital - Skejby, and Gynecological- Obstetric department, Odense University Hospital.
Registration of date of birth, sex, weight, height, hip-waist ratio, and smoking status will be noted.
Furthermore, we will register current medical treatment, duration of diabetes, pregestational bloodpressure, parity and HbA1c.
Also post-partum registration of length of gestation, weight of placenta, way of delivery (natural birth or cesarean section), umbilical cord pH, apgar score and the infant weight will be noted.
Weight, height, BMI, smoking status, microalbuminuria/proteinuria . Blood pressure (systolic, diastolic, mean arterial pressure). Weight of placenta
Measurements in blood tests:
Se-creatinine, p-Na+, p-K+. P-plasminogen, P-albumin, Aldosterone.
Measurements in 50 ml newly "spot urine":
Plasmin, plasminogen, ENaC peptide fragment (analyses in location of development,) Proteolytic activity, Prostatin, Creatinine, Na+, K+, Aldosterone, Albumin
Visits, including bloodsampels and spoturine collection:
Women with pregestational type 1 diabetes are included. In first trimester, around pregnancy week 9-14 an urinesampel is collected. Blood pressure is measured and urine plasmin/plasminogen, albumin and aldosterone are analyzed. After that urine- and blood samples are collected in pregnancyweek 20, 28,32, 36 and perhaps 38. Plasmin/plasminogen analyses, regarding to detect the excretion compared to the development in PE, are made. Around pregnancy week 28 a single 24 hour blood pressure measurement are done according to observe the daily variation.
Following outcomes are observed: The development of preeclampsia, defined by hypertension ( > 140/90 mmHg), and proteinuria ( >0,3 g/24 hour). Preterm delivery and light for gestational age.
Data- analysis methods:
This is an observational longitudinal-prospective study which includes approximately 130 pregnant patients with Type 1 diabetes. Patients are included from Skejby and Odense University Hospitals in cooperation.
Results are evaluated statistically by uni - and multivariate logistic regression analysis.
Population size evaluation:
Similar (Danish) observational prospective studies of urine- biomarkers (including albumin) ability to predict preeclampsia/preterm delivery in patients with pregestational type 1 diabetes have achieved high significance data with spotsamples at 130 -170 patients. With the participation of two centers it seems realistic and adequately to include 130 patients within the settings of a Ph. D. study. Every year an amount of 50-60 patients are seen in the outpatient ward at Skejby- and Odense Universityhospitals (in all approximately 100-120 patients).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01821053
|Gynelogical Obstetrical Department||Recruiting|
|Skejby, Aarhus N, Denmark, 8200|
|Contact: Lise H. Nielsen, doctor +4553347735 firstname.lastname@example.org|
|Contact: Per Ovesen, doctor +4561669728 Per.Ovesen@dadlnet.dk|
|Principal Investigator: Lise H. Nielsen, Doctor|
|Study Director:||Boye L. Jensen, Professor||cardiovascular and renal research department, Odense University Hospital|