Human placental GLUT1 glucose transporter expression and the fetal insulin-like growth factor axis in pregnancies complicated by diabetes.

We have previously described regulation of syncytial GLUT1 glucose transporters by IGF-I. Despite this, it is not clear what signal regulates transplacental glucose transport. In this report we asked whether changes in GLUT1 expression and glucose transport activity in diabetic pregnancies were associated with alterations in the fetal IGF axis. Cord blood samples and paired syncytial microvillous and basal membranes were isolated from normal term pregnancies and pregnancies characterized by gestational diabetes type A2 (GDM A2) and pre-existing insulin-dependent diabetes mellitus (IDDM). Circulating IGF-I, basal membrane GLUT1 expression and glucose transporter activity were correlated with birth weight, but only in control, not diabetic groups. Basal membrane GLUT1 and transporter activity were correlated with IGF-I concentrations in control, but not diabetic groups. IGF binding protein (IGFBP) binding capacity showed a ≥50% reduction in the diabetic groups compared to control; both showed a higher level of free IGF-I. The absence of a correlation between birth weight and factors such as fetal IGF-I or GLUT1 expression in the diabetic groups suggests that IGF-I-stimulated effects may have reached a limiting threshold, such that further increases in IGF-I (or GLUT1) are without effect. These data support that fetal IGF-I acts as a fetal nutritional signal, modulating placental GLUT1 expression and birth weight via altered levels of fetal circulating IGFBPs. Diabetes appears to exert its effects on fetal and placental factors prior to the third trimester and, despite good glycemic control immediately prior to, and in the third trimester, these effects persist to term.

Integrated Practice Improvement Solutions-Practical Steps to Operating Room Management.

UNLABELLED: Perioperative productivity is a vital concern for surgeons, anesthesiologists, and administrators as the OR is a major source of hospital elective admissions and revenue. Based on elements of existing Practice Improvement Methodologies (PIMs), "Integrated Practice Improvement Solutions" (IPIS) is a practical and simple solution incorporating aspects of multiple management approaches into a single open source framework to increase OR efficiency and productivity by better utilization of existing resources. MATERIALS AND METHODS: OR efficiency was measured both before and after IPIS implementation using the total number of cases versus room utilization, OR/anesthesia revenue and staff overtime (OT) costs. Other parameters of efficiency, such as the first case on-time start and the turnover time (TOT) were measured in parallel. RESULTS: IPIS implementation resulted in increased numbers of surgical procedures performed by an average of 10.7%, and OR and anesthesia revenue increases of 18.5% and 6.9%, respectively, with a simultaneous decrease in TOT (15%) and OT for anesthesia staff (26%). The number of perioperative adverse events was stable during the two-year study period which involved a total of 20,378 patients. CONCLUSION: IPIS, an effective and flexible practice improvement model, was designed to quickly, significantly, and sustainably improve OR efficiency by better utilization of existing resources. Success of its implementation directly correlates with the involvement of and acceptance by the entire OR team and hospital administration.

Hypoglycemia and the origin of hypoxia-induced reduction in human fetal growth.

BACKGROUND: The most well known reproductive consequence of residence at high altitude (HA >2700 m) is reduction in fetal growth. Reduced fetoplacental oxygenation is an underlying cause of pregnancy pathologies, including intrauterine growth restriction and preeclampsia, which are more common at HA. Therefore, altitude is a natural experimental model to study the etiology of pregnancy pathophysiologies. We have shown that the proximate cause of decreased fetal growth is not reduced oxygen availability, delivery, or consumption. We therefore asked whether glucose, the primary substrate for fetal growth, might be decreased and/or whether altered fetoplacental glucose metabolism might account for reduced fetal growth at HA. METHODS: Doppler and ultrasound were used to measure maternal uterine and fetal umbilical blood flows in 69 and 58 residents of 400 vs 3600 m. Arterial and venous blood samples from mother and fetus were collected at elective cesarean delivery and analyzed for glucose, lactate and insulin. Maternal delivery and fetal uptakes for oxygen and glucose were calculated. PRINCIPAL FINDINGS: The maternal arterial - venous glucose concentration difference was greater at HA. However, umbilical venous and arterial glucose concentrations were markedly decreased, resulting in lower glucose delivery at 3600 m. Fetal glucose consumption was reduced by >28%, but strongly correlated with glucose delivery, highlighting the relevance of glucose concentration to fetal uptake. At altitude, fetal lactate levels were increased, insulin concentrations decreased, and the expression of GLUT1 glucose transporter protein in the placental basal membrane was reduced. CONCLUSION/SIGNIFICANCE: Our results support that preferential anaerobic consumption of glucose by the placenta at high altitude spares oxygen for fetal use, but limits glucose availability for fetal growth. Thus reduced fetal growth at high altitude is associated with fetal hypoglycemia, hypoinsulinemia and a trend towards lactacidemia. Our data support that placentally-mediated reduction in glucose transport is an initiating factor for reduced fetal growth under conditions of chronic hypoxemia.