Original Data

Bilirubin Increases the Expression of Glucose Transporter-1 and the Rate of Glucose Uptake in Vascular Endothelial Cells

Guy Cohen, Dan M. Livovsky, Jaime Kapitulnik, Shlomo Sasson

Abstract

BACKGROUND and OBJECTIVES: The close contact between the endothelial cell monolayer in blood vessels and blood plasma allows free diffusion of the hydrophobic unconjugated bilirubin (BR) into these cells. BR can exert both anti- and pro-oxidative effects in various types of cells in a dose-dependent manner. High glucose levels downregulate the expression of the glucose transporter-1 (GLUT-1) and the rate of glucose uptake in vascular endothelial cell (VEC). Pro-oxidants, on the other hand, up-regulate this system in VEC. We aimed to investigate potential effects of BR on the glucose transport system in VEC. METHODS: Primary cultures of bovine aortic endothelial cells were exposed to BR, and the rate of hexose transport, GLUT-1 expression and plasma membrane localization were determined. RESULTS: BR induced oxidative stress in VEC, and significantly augmented the rate of glucose transport and GLUT-1 expression and plasma membrane localization in these cells. BR also reversed the high glucose-induced downregulation of the glucose transport system in VEC. CONCLUSION: The pro-oxidative properties of BR are responsible for its effects on the regulation of glucose transport in vascular endothelium. Pathological concentrations of BR in the vascular compartment (jaundice) may influence the cellular handling of glucose in diabetes.

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Pregnancy Outcome in Type 2 Diabetes Mellitus: A Retrospective Analysis from the Netherlands

Harold W. de Valk¹, Nancy H.G. van Nieuwaal¹, Gerard H.A. Visser²

Abstract

MAIN OBJECTIVES: The objective was to describe pre-gestational history and the maternal, fetal and neonatal outcome in pregnancies in women with pre-gestational type 2 diabetes during the period between 1992 and 2006 from one center in the Netherlands. METHODS: Patients attending the obstetric-diabetology outpatient clinic of a tertiary referral center were studied. This center also has a regular diabetes clinic and a community midwifery service. Patients were identified from the database. Maternal outcome (pre-eclampsia, pre-term delivery, Cæsarean section) and fetal and neonatal outcome (macrosomia, congenital malformations, perinatal mortality, neonatal hypoglycemia) were analyzed as well HbA1c levels, planning of pregnancy, gestational age at first antenatal visit and ethnic background. RESULTS: Sixty-six singleton pregnancies from 48 women were analyzed. Their age was 34 ± 5 yr, the BMI 31.7 ± 7.4 and the median duration of diabetes was 3 yr. 52% were Caucasian and 35% were of Moroccan descent. 49% did not complete secondary school. Moroccan descent was associated with a lower educational level and a BMI comparable with the whole study group. The proportion of planned pregnancies was approximately 70%. The mean HbA1c in the first trimester was 6.4 ± 1.1% and the gestational age at first visit was 10 ± 5 wk, in one-quarter before 6 wk. The prevalences of variables related to maternal and neonatal outcome were as follows: spontaneous abortion 13.6%, pre-eclampsia 8.9%, pre-term delivery 21.4%, spontaneous labor 25.0%, induced labor 48.2%, Cæsarean section 42.9%, macrosomia (≥90th percentile) 41.1%, severe hypoglycemia 41.5% and major congenital malformations 5.1%. CONCLUSIONS: Pre-gestational type 2 diabetes is associated with an increased incidence of adverse pregnancy outcome despite reasonable mean HbA1c level and despite a high frequency of planned pregnancies. Many women report relatively late. Improvement in the outcome requires more active peri-gestational specialist care and a tailored approach is required towards migrant communities.

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