Karen Rossi

Glucose turnover and gluconeogenesis in human pregnancy.

The rate of appearance (Ra) of glucose in plasma and the contribution of gluconeogenesis were quantified in normal pregnant women early ( approximately 10 wk) and late ( approximately 34 wk) in gestation. Their data were compared with those of normal nonpregnant women. Glucose Ra was measured using the [U-13C]glucose tracer dilution method. Gluconeogenesis was quantified by the appearance of 2H on carbon 5 and 6 of glucose after deuterium labeling of body water pool. Weight-specific glucose Ra was unchanged during pregnancy (nonpregnant, 1.89+/-0.24; first trimester, 2.05+/-0.21; and third trimester 2.17+/-0.28 mg/kg.min, mean+/-SD), while total glucose Ra was significantly increased (early, 133.5+/-7.2; late, 162.6+/-16.4 mg/min; P = 0.005). The fractional contribution of gluconeogenesis via pyruvate measured by 2H enrichment on C-6 of glucose (45-61%), and of total gluconeogenesis quantified from 2H enrichment on C-5 of glucose (i.e. , including glycerol [68-85%]) was not significantly different between pregnant and nonpregnant women. Inasmuch as total glucose Ra was significantly increased, total gluconeogenesis was also increased in pregnancy (early pregnancy, 94.7+/-15.9 mg/min; late pregnancy, 122.7+/-9.3 mg/min; P = 0.003). These data demonstrate the ability of the mother to adapt to the increasing fetal demands for glucose with advancing gestation. The mechanism for this unique quantitative adjustment to the fetal demands remains undefined.

Management of pregnancies complicated by anti-E alloimmunization.

OBJECTIVE: To review cases of anti-c isoimmunization and determine the most appropriate management strategies. METHODS: We performed a review of 102 pregnancies managed at The Ohio State University from 1967 to 2001 for anti-c isoimmunization. Of these, 55 had complete data and are included in this report. Information collected included serum titers, ΔOD450 values, Liley zones, fetal and neonatal hemoglobin levels and antigen typing, neonatal direct antiglobulin test, and neonatal outcomes. The appropriateness of traditional management was then evaluated. RESULTS: Of the 55 pregnancies, 46 had fetuses with positive direct antiglobulin test, and nine pregnancies had unaffected fetuses. Of the affected neonates, 12 (26%) had serious hemolytic disease of the newborn. Of these 12, 8 required fetal transfusion, and the remaining 4 newborns had hemoglobin levels of less than 10 g/dL at the time of delivery. A titer of 1:32 or greater or the presence of hydrops fetalis identified all such fetuses. There were 58 amniocenteses performed for ΔOD450. When plotted on modified Liley graphs, ΔOD450 values corresponded to disease severity. There were no perinatal deaths attributable to anti-c hemolytic disease of the newborn. CONCLUSION: Anti-c isoimmunization might cause significant fetal and newborn hemolytic disease. A titer of 1:32 or greater or evidence of hydrops fetalis identified all the serious hemolytic disease at our institution. The significance of antibody titers and ΔOD450 values was similar to Rh-D sensitized pregnancies, and management by the same modalities is appropriate. LEVEL OF EVIDENCE: II-3

Relation between transamination of branched-chain amino acids and urea synthesis: evidence from human pregnancy

Protein and nitrogen (N) accretion by the mother is a major adaptive response to pregnancy in humans and animals to meet the demands of the growing conceptus. Quantitative changes in whole body N metabolism were examined during normal pregnancy by measuring the rates of leucine N (QN) and carbon (QC) kinetics with the use of [1-13C,15N]leucine. Rate of synthesis of urea was measured by [15N2]urea tracer. Pregnancy-related change in total body water was quantified by H2[18O] dilution, and respiratory calorimetry was performed to quantify substrate oxidation. A significant decrease in the rate of urea synthesis was evident in the 1st trimester (nonpregnant 4.69 +/- 1.14 vs. pregnant 3.44 +/- 1.11 micromol . kg-1 . min-1; means +/- SD, P < 0.05). The lower rate of urea synthesis was sustained through the 2nd and 3rd trimesters. QN was also lower in the 1st trimester during fasting; however, it reached a significant level only in the 3rd trimester (nonpregnant 166 +/- 35 vs. 3rd trimester 135 +/- 16 micromol . kg-1 . h-1; P < 0.05). There was no significant change in QC during pregnancy. A significant decrease in the rate of transamination of leucine was evident in the 3rd trimester both during fasting and in response to nutrient administration (P < 0.05). The rate of deamination of leucine was correlated with the rate of urea synthesis during fasting (r = 0.59, P = 0.001) and during feeding (r = 0.407, P = 0. 01). These data show that pregnancy-related adaptations in maternal N metabolism are evident early in gestation before any significant increase in fetal N accretion. It is speculated that the lower transamination of branched-chain amino acids may be due to decreased availability of N acceptors such as alpha-ketoglutarate as a consequence of resistance to insulin action evident in pregnancy.Protein and nitrogen (N) accretion by the mother is a major adaptive response to pregnancy in humans and animals to meet the demands of the growing conceptus. Quantitative changes in whole body N metabolism were examined during normal pregnancy by measuring the rates of leucine N ( Q N) and carbon ( Q C) kinetics with the use of [1-13C,15N]leucine. Rate of synthesis of urea was measured by [15N2]urea tracer. Pregnancy-related change in total body water was quantified by H2[18O] dilution, and respiratory calorimetry was performed to quantify substrate oxidation. A significant decrease in the rate of urea synthesis was evident in the 1st trimester (nonpregnant 4.69 ± 1.14 vs. pregnant 3.44 ± 1.11 μmol ⋅ kg-1 ⋅ min-1; means ± SD, P < 0.05). The lower rate of urea synthesis was sustained through the 2nd and 3rd trimesters. Q Nwas also lower in the 1st trimester during fasting; however, it reached a significant level only in the 3rd trimester (nonpregnant 166 ± 35 vs. 3rd trimester 135 ± 16 μmol ⋅ kg-1 ⋅ h-1; P < 0.05). There was no significant change in Q Cduring pregnancy. A significant decrease in the rate of transamination of leucine was evident in the 3rd trimester both during fasting and in response to nutrient administration ( P< 0.05). The rate of deamination of leucine was correlated with the rate of urea synthesis during fasting ( r = 0.59, P = 0.001) and during feeding ( r = 0.407, P = 0.01). These data show that pregnancy-related adaptations in maternal N metabolism are evident early in gestation before any significant increase in fetal N accretion. It is speculated that the lower transamination of branched-chain amino acids may be due to decreased availability of N acceptors such as α-ketoglutarate as a consequence of resistance to insulin action evident in pregnancy.

Glucose-alanine relationship in diabetes in human pregnancy☆

We have previously reported a decrease in gluconeogenesis from alanine in normal pregnant women at term gestation as compared with nonpregnant women. In the present study, the effect of diabetes on alanine metabolism was examined in five gestationally diabetic (GDM) women and seven women with type I (insulin-dependent) diabetes (IDDM) during the third trimester of pregnancy. The hemoglobin A1c (HbA1c) concentrations in all subjects were within normal range, indicating good metabolic control. After an overnight fast, each subject was infused simultaneously with L-[2,3, 13C2]alanine and D-[6,6,2H2]glucose tracers as prime constant rate infusion. Plasma alanine and glucose isotopic enrichments were measured by gas chromatography-mass spectrometry. Alanine and glucose turnover rates were quantified by tracer dilution. In five subjects, the contribution of alanine carbon to CO2 was quantified by respiratory calorimetry and by measurement of 13C enrichment of expired CO2. Data from 15 previously reported normal pregnant subjects were used for comparison. The rate of alanine turnover was similar in the GDM and IDDM subjects and was not different from the normal subjects (GDM, 4.6 +/- 1.9; IDDM, 5.4 +/- 2.5; normals, 4.4 +/- 0.8 mumol/kg.min, mean +/- SD). The rate of glucose turnover was significantly reduced (P less than .05) in IDDM as compared with GDM and normal subjects (IDDM, 8.1 +/- 0.8; GDM, 11.5 +/- 3.5; normals, 12.2 +/- 2.2 mumol/kg.min). The contribution of alanine C to glucose C and expired CO2 was similar in the three groups. These data demonstrate that rigorous metabolic control results in normal glucose and alanine metabolism in diabetic pregnancy during fasting.(ABSTRACT TRUNCATED AT 250 WORDS)