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Biomedical subjects

B E Metzger

Publications and source records attributed to B E Metzger.

At least 37 records · Page 2Linked to original sources
PubMed1995

Impaired glucose tolerance in adolescent offspring of diabetic mothers. Relationship to fetal hyperinsulinism.

OBJECTIVE: To test the hypothesis that long-term postnatal development may be modified by metabolic experiences in utero. RESEARCH DESIGN AND METHODS: We enrolled offspring of women with pregestational diabetes (this included insulin-dependent diabetes mellitus [IDDM] and non-insulin-dependent diabetes mellitus [NIDDM]) and gestational diabetes in a prospective study from 1977 through 1983. Fetal beta-cell function was assessed by measurement of amniotic fluid insulin (AFI) at 32-38 weeks gestation. Postnatally, plasma glucose and insulin were measured yearly from 1.5 years of age after fasting and 2 h after 1.75 g/kg oral glucose. Control subjects had a single oral glucose challenge at 10-16 years. RESULTS: In offspring of diabetic mothers, the prevalence of impaired glucose tolerance (IGT) (2-h glucose concentration > 7.8 mmol/l) was: 1.2% at < 5 years, 5.4% at 5-9 years, and 19.3% at 10-16 years. The 88 offspring of diabetic mothers (12.3 +/- 1.7 years), when compared with 80 control subjects of the same age and pubertal stage, had higher 2-h glucose (6.8 +/- 1.4 vs. 5.7 +/- 0.9 mmol/l, P < 0.001) and insulin (660 +/- 720 vs. 455 +/- 285 pmol/l, P < 0.03) concentrations. The 17 subjects with IGT at > 10 years of age (9 boys and 8 girls) include one girl with NIDDM. IGT was not associated with the etiology of the mother's diabetes (gestational versus pregestational) or macrosomia at birth. IGT was found in only 3.7% (1 of 27) of adolescents whose AFI was normal ( < or = 100 pmol/l) and 33.3% (12 of 36) of those with elevated AFI (P < 0.001). Although most of the children with IGT are obese, AFI and obesity are independently associated with IGT by multiple logistic analysis. CONCLUSIONS: In confirmation of our original hypothesis, IGT in the offspring is a long-term complication of maternal diabetes. Excessive insulin secretion in utero, as assessed by AFI concentration, is a strong predictor of IGT in childhood.

Adolescent↗
PubMed1995

Metabolic control and progression of retinopathy. The Diabetes in Early Pregnancy Study. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study.

OBJECTIVE: To evaluate the role of metabolic control in the progression of diabetic retinopathy during pregnancy. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study of 155 diabetic women in the Diabetes in Early Pregnancy Study followed from the periconceptional period to 1 month postpartum. Fundus photographs were obtained shortly after conception (95% within 5 weeks of conception) and within 1 month postpartum. Glycosylated hemoglobin was measured weekly during the 1st trimester and monthly thereafter. RESULTS: In the 140 patients who did not have proliferative retinopathy at baseline, progression of retinopathy was seen in 10.3, 21.1, 18.8, and 54.8% of patients with no retinopathy, microaneurysms only, mild nonproliferative retinopathy, and moderate-to-severe nonproliferative retinopathy at baseline, respectively. Proliferative retinopathy developed in 6.3% with mild and 29% with moderate-to-severe baseline retinopathy. Elevated glycosylated hemoglobin at baseline and the magnitude of improvement of glucose control through week 14 were associated with a higher risk of progression of retinopathy (adjusted odds ratio for progression in those with glycohemoglobin > or = 6 SD above the control mean versus those within 2 SD was 2.7; 95% confidence interval was 1.1-7.2; P = 0.039). CONCLUSIONS: The risk for progression of diabetic retinopathy was increased by initial glycosylated hemoglobin elevations as low as 6 SD above the control mean. This increased risk may be due to suboptimal control itself or to the rapid improvement in metabolic control that occurred in early pregnancy. Excellent metabolic control before conception may be required to avoid this increase in risk. Those with moderate-to-severe retinopathy at conception need more careful ophthalmic monitoring, particularly if their diabetes was suboptimally controlled at conception.

Adult↗
PubMed1994

Perinatal complications and cognitive development in 2- to 5-year-old children of diabetic mothers.

OBJECTIVE: Our purpose was to assess whether perinatal complications contribute to lower intellectual attainment in offspring of diabetic mothers, independent of antepartum metabolic disregulation. STUDY DESIGN: Subjects were 223 pregnant women and their singleton offspring. Eighty-nine women had pregestational diabetes mellitus, 99 had gestational diabetes mellitus, and 35 had normal gestational glucose metabolism. Perinatal complications were prospectively recorded on an examination checklist. The intelligence quotient of the child was assessed with the Bayley Scales of Infant Development at age 2 years and the Stanford-Binet Intelligence Scale at age 3 to 5 years. RESULTS: No significant correlations emerged between either measure of child's intelligence quotient and any prevalent perinatal complication, after statistical correction for socioeconomic status, race or ethnic origin, patient group, and antepartum metabolic control. CONCLUSIONS: Given prevailing practices in diabetes management and obstetric and neonatal care, the effects of prevalent perinatal complications on the intellectual development of offspring of diabetic mothers appear minimal.

Adult↗
PubMed1994

Glucose metabolism in separated embryos and investing membranes during organogenesis in the rat.

Glucose metabolism provides an essential energy source in the mammalian embryo. We used the rat embryo culture system to investigate the activity of several critical pathways for glucose metabolism during early organogenesis, before (day 10 of gestation) and during (day 11) the establishment of the chorioallantoic circulation and closure of the neural tube. We studied glucose metabolism in the intact conceptus, the separated embryo, and its investing membranes, including the visceral yolk sac, allantois, and amnion. Short-term incubations were performed for 4 hours in culture media containing U-14C-, 14C-1-, or 14C-6-labeled D-glucose on day 10 and day 11 of gestation, and the rates of glucose utilization by glycolysis and oxidative metabolism, including the pentose phosphate pathway (PPP), were measured. Glycolytic metabolism, estimated by the accumulation of lactate, was high on day 10 in the intact conceptus, embryo, and membranes (92 +/- 6, 63 +/- 5, and 99 +/- 8 nmol/micrograms protein/4 h, respectively) and decreased by two thirds by day 11 in each tissue. Of note, the rate of glycolysis was greater in membranes than in the embryo on both days (P < .01). On the other hand, oxidative metabolism, reflected in the production of 14CO2, was relatively low on day 10 (0.78 +/- 0.04, 0.73 +/- 0.05, and 0.6 +/- 0.06 nmol/micrograms protein/4 h for intact conceptus, embryo, and membranes, respectively) and increased significantly in each tissue by day 11 (P < .01 for each).

Animals↗
PubMed1993

Moderate caffeine use and the risk of spontaneous abortion and intrauterine growth retardation.

OBJECTIVE: To examine the relationship between caffeine consumption during pregnancy and the occurrence of spontaneous abortion and intrauterine growth retardation. DESIGN, SETTING, AND PATIENTS: A cohort of 431 women, enrolled in a multicenter study within 21 days of conception, was monitored throughout pregnancy to determine (1) caffeine exposure, (2) exposure to other risk factors, (3) fetal growth as assessed by ultrasonography, and (4) pregnancy outcome. OUTCOME MEASURES: Spontaneous abortion, intrauterine growth, birth weight, and head circumference. RESULTS: The mean (+/- SD) first-trimester caffeine consumption was not significantly higher in women who aborted (125.9 +/- 123.1 mg) than in women who delivered liveborn infants (111.6 +/- 107.0 mg) (P = 34). The adjusted odds ratio (OR) for spontaneous abortion was 1.15 (95% confidence interval [CI], 0.89 to 1.49). Early fetal growth, assessed by crown-rump length on ultrasonographic examination, was not affected by caffeine. Although the group consuming the most caffeine (> 300 mg/d) had a significantly higher proportion of babies with birth weights and head circumferences below the 10th percentile in the crude analysis, the association with caffeine was no longer significant when other risk factors (notably smoking) were taken into account. The adjusted ORs were 1.11 (95% CI, 0.88 to 1.40) for decreased birth weight and 1.09 (95% CI, 0.86 to 1.37) for smaller head circumference. CONCLUSIONS: Close monitoring of a cohort identified very soon after conception enabled us to identify all abortions after 21 days postconception, monitor intrauterine growth prospectively, and track caffeine use. Despite this intensive surveillance, we found no evidence that moderate caffeine use increased the risk of spontaneous abortion, intrauterine growth retardation, or microcephaly after accounting for other risk factors.

Abortion, Spontaneous↗
PubMed1993

Glucose and scyllo-inositol impair phosphoinositide hydrolysis in the 10.5-day cultured rat conceptus: a role in dysmorphogenesis?

Culture of the postimplantation rat conceptus from gestational day 9.5-10.5 in media supplemented with d-glucose or scyllo-inositol decreases tissue myo-inositol and phosphoinositides with a concomitant increase in dysmorphogenesis. A number of mitogenic agents initiate cellular proliferation and differentiation through receptors coupled to phosphoinositide hydrolysis. To test whether the decrease in conceptus phosphoinositides is associated with a reduced phosphoinositide hydrolytic response, we developed a protocol to stimulate phosphoinositide hydrolysis. Phosphoinositide hydrolysis was monitored by measurement of [3H]inositol phosphates after preincubation in serum free media. We examined the ability of serum, platelet-derived growth factor (PDGF), epidermal-derived growth factor (EGF), insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2), endothelin-1 (ET-1), and endothelin-2 (ET-2), to stimulate phosphoinositide hydrolysis. As measured by [3H]inositol monophosphate ([3H]InsP1) accumulation, normal rat seru, ET-1, and ET-2 stimulated phosphoinositide hydrolysis 47%, 420%, and 154% above the basal rate observed in serum free controls. EGF stimulated a statistically insignificant 15% increase while PDGF, IGF-1, or IGF-2 were without effect. We further characterized ET-1 stimulated phosphoinositide hydrolysis. Dose-response studies disclosed that incremental increases in [3H]InsP1 (129-420%) are observed over a concentration range of 10-1,000 nM. Maximal stimulation was not reached even at 1,000 nM. Temporally [3H]InsP1 and [3H]InsP3 levels increased linearly during incubation periods of 15-60 min. We further analyzed ET-1 stimulated phosphoinositide hydrolysis in 10.5-day conceptuses cultured for 24 hr in media containing high concentrations of glucose (23.3-56.6 mM) or scyllo-inositol (0.55, 5.5 mM). Under these dysmorphogenic conditions that concomitantly decrease the phosphoinositide precursor pool the response to ET-1 was blunted 28-76% for glucose and 29-65% for scyllo-inositol. This suggests that the effect of glucose and scyllo-inositol on lowering phosphoinositide precursor pools also results in a decrease in the response to agonists using the inositol/lipid intracellular pathway. This impaired signaling response may contribute to initiating dysmorphogenic events in diabetic embryopathy.

Animals↗
PubMed1993

Insulin-like growth factors and binding proteins in the fetal rat: alterations during maternal starvation and effects in fetal brain cell culture.

Maternal malnutrition adversely affects fetal body and brain growth during late gestation. We utilized a fetal brain cell culture model to examine whether alternations in circulating factors may contribute to reduce brain growth during maternal starvation; we then used specific immunoassay and western blotting techniques, and purified peptides to investigate the potential role that altered levels of insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) may play in impaired growth during maternal nutritional restriction. Fetal, body, liver, and brain weight were reduced after 72 hr maternal starvation, and plasma from starved fetuses were less potent than fed fetal plasma in stimulating brain cell growth. Circulating levels of IGF-I were reduced in starved compared to fed fetuses, while levels of IGF-II were similar in both groups. In contrast, [125I]-IGF-I binding assay demonstrated an increase in the availability of plasma IGFBPs following starvation. Western ligand blotting and densitometry indicated that levels of 32 Kd IGFBPs were 2-fold higher in starved compared to fed fetal plasma. Immunoblotting and immunoprecipitation with antiserum against rat IGFBP-1 confirmed that heightened levels of immunoreactive IGFBP-1 accounted for the increase in 32 Kd IGFBPs in starved plasma. Levels of 34 Kd BPs, representing IGFBP-2, were unaffected by starvation. Reconstitution experiments in cell culture showed that IGF-I promoted fetal brain cell growth, and that when they were supplemented with IGF-I, the growth promoting activity of starved fetal plasma was restored to fed levels. These changes were measured using MTT to assess mitochondrial reductase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Prepregnancy weight and antepartum insulin secretion predict glucose tolerance five years after gestational diabetes mellitus.

OBJECTIVE: To identify phenotypic, genotypic, and metabolic parameters measured at the time of antepartum diagnosis of gestational diabetes mellitus that can indicate the risk of diabetes mellitus at early postpartum (< or = 6 mo after delivery) and at a 5-yr follow-up. RESEARCH DESIGN AND METHODS: The recommendations from the National Diabetes Data Group and International Workshop Conferences on Gestational Diabetes Mellitus were used for screening, diagnosing, and subclassifying gestational diabetes mellitus. National Diabetes Data Group criteria were also used for classification of glucose tolerance postpartum. Plasma glucose, insulin, and free fatty acids were measured after an overnight fast. Plasma glucose and insulin were measured 15, 30, 60, 120, and 180 min after the 100-g oral glucose load. Postpartum glucose tolerance was evaluated at 3-6 mo (early), 1 yr, and annually thereafter. RESULTS: The 5-yr cumulative incidence of diabetes during follow-up after gestational diabetes mellitus was nearly 50%. Among those who had diabetes within 5 yr, a history of diabetes in only the mother was nearly threefold more common than a history of diabetes in only the father (30 vs. 11%, P < 0.01). Those who displayed diabetes at early postpartum (< or = 6 mo) testing had significantly higher antepartum glucose levels at 60, 120, and 180 min compared with those whose early postpartum results were normal. They were also relatively insulinopenic at antepartum testing. Their fasting, acutely stimulated (15 and 30 min), and integrated 3-h response to oral glucose were all significantly lower relative to women who remained normal or had impaired glucose tolerance at early postpartum testing. Women who developed diabetes between 6 mo and 5 yr postpartum were more obese before the index pregnancy, and they had lower fasting, acutely stimulated (15 and 30 min), and integrated (1-3 h) insulin levels compared with women who remained normal or displayed impaired glucose tolerance at 5 yr postpartum. A multiple logistic regression model showed that diabetes present at early postpartum testing was independently associated with higher 2-h glucose and lower basal and total integrated insulin level. Later (> or = 6 mo-5 yr postpartum) development of diabetes was independently associated with prepregnancy weight and impaired insulin secretion at diagnosis of gestational diabetes mellitus. CONCLUSIONS: Impaired beta-cell function and obesity at diagnosis of GDM were associated with the development of diabetes during a 5-yr, follow-up period. Studies designed to prevent diabetes in this high-risk group should examine strategies to maintain both optimal beta-cell function and maximum insulin sensitivity.

Adult↗
PubMed1992

Retardation of fetal brain cell growth during maternal starvation: circulating factors versus altered cellular response.

Maternal starvation inhibits fetal brain development during late gestation in the rat. To determine whether intrinsic or extrinsic factors might be the principal contributor to altered growth, brain cells from 20 day fetuses were cultured in a 96 well plate with MEM and 10% adult rat serum. Tissue growth was monitored by spectrophotometric measurement of the mitochondrial reduction of a chromagen 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT). After 1, 4 or 6 days incubation, MTT activity in non confluent cultures was shown to be directly related to tissue mass. When fetal brain cell cultures were incubated with 1% and 10% concentrations of adult rat serum, an 11-fold increase in MTT activity paralleled a 15-fold increase in tritiated thymidine incorporation. The impact of maternal starvation on fetal brain cell growth was examined by measuring MTT activity in fetal brain cells from fed and starved mothers. When cultures were incubated for 6 days with graded concentrations of fed adult serum (1.25-10%), the MTT response was slightly but consistently lower in cells from starved when compared with cells from fed mothers. By contrast, a marked difference in MTT activity which was paralleled by a lower DNA content became apparent when fetal rat brain cells were incubated with starved adult serum. Fetal serum and adult male serum were found to support growth equally well, while incubation of fetal brain cells with maternal sera resulted in lower MTT values than with the corresponding fetal sera. When cells were incubated with fetal sera pooled from starved mothers, MTT activity was decreased by 42 to 45%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Caloric restriction in gestational diabetes mellitus: when and how much?

Variations in nutritional intake during pregnancy have measurable effects on the circulating levels of maternal nutrients, maternal weight gain, and birth weight of the offspring. A growing body of evidence indicates that alterations in maternal metabolism can also have long-term consequences in the offspring in relation to adult adiposity, glucose tolerance, and perhaps intellectual development. Therefore, recommendations for diet during pregnancy must be made with great care, and with as much scientific understanding as possible. Nutritional advice traditionally given to all pregnant women, including those with gestational diabetes mellitus (GDM) or noninsulin-dependent diabetes, does not allow for individual differences in caloric needs as a function of the degree of maternal obesity and thus, may encourage excessive weight gain. Evidence reviewed below suggests that adjusting caloric intake to meet new guidelines for weight gain during pregnancy may be advantageous in reducing maternal blood sugar and insulin levels, without producing abnormalities in other metabolic variables. Modest caloric reduction which limits excessive weight gain in the mother may also be associated with a small reduction of fetal weight. However, more stringent dietary manipulations in obese gravida should be discouraged as a routine measure until more knowledge is available from large-scale clinical trials about their effects on the entire panoply of maternal nutrients and their impact on the offspring.

Body Weight↗
PubMed1992

Phosphoinositide metabolism in the developing conceptus. Effects of hyperglycemia and scyllo-inositol in rat embryo culture.

Culture of the postimplantation rat conceptus in hyperglycemic medium causes developmental abnormalities and is associated with a diminished water-soluble myo-inositol content. We investigated the effect myo-inositol depletion has on lipid-soluble phosphoinositides, precursors, and water-soluble inositol phosphates. Rat conceptuses were cultured from gestational day 9.5 (presomite, early head fold) to day 10.5 (7-15 somites) in 6.7-73.3 mM D-glucose. Significant decreases in the phosphoinositides of the embryo were observed with increased culture D-glucose concentrations. PI was reduced 15-34%, PIP 18-46%, and PIP2 26-46%. Yolk sac phosphoinositides also were reduced but to a lesser degree. Culture in hyperglycemic media also mediated significant reductions of conceptus inositol phosphates. To investigate whether effects similar to those induced by D-glucose could be mediated by another agent capable of decreasing myo-inositol content, we used scyllo-inositol, a transported but nonmetabolized isomer of myo-inositol. Conceptuses cultured in medium containing scyllo-inositol (0.06-16.7 mM) had dose-dependent decreases of myo-[3H]inositol in water-soluble and lipid-soluble fractions. Incorporation of myo-[3H]inositol into phosphoinositides and inositol phosphates was decreased concomitantly. Developmental effects of D-glucose and scyllo-inositol were assessed in rat conceptuses cultured from day 9.5 (presomite, early head fold) to day 11.5 (22-28 somites). Culture in 40.0-73.3 mM glucose and 0.06-33.3 mM scyllo-inositol impaired growth while increasing dysmorphogenesis in a dose-dependent manner. The results suggest that decreases in conceptus myo-inositol and associated diminution of phosphoinositides, which are the inositol/lipid cycle precursors, are dysmorphogenic and may contribute to the etiology of diabetic embryopathy.

Analysis of Variance↗
PubMed1992

Early sonographic evaluation for fetal growth delay and congenital malformations in pregnancies complicated by insulin-requiring diabetes. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study.

OBJECTIVE: It has been reported that early fetal growth retardation may be a useful marker for congenital malformations in diabetic pregnancies. To test this hypothesis, diabetic and nondiabetic women were sonographically evaluated during the first trimester. RESEARCH DESIGN AND METHODS: Fetal crown-rump lengths were measured sonographically at least once during the first 15 wk of pregnancy in 329 nondiabetic and 312 diabetic women. Of these, 289 nondiabetic and 269 diabetic women had sonograms before 10 wk of gestation and 283 nondiabetic and 269 diabetic women had sonograms between 10 and 15 wk of gestation. Early fetal growth delay was defined as a sonographic gestational age of greater than or equal to 6 days less than menstrual gestational age. RESULTS: The mean crown-rump lengths at 8 wk were 17.9 +/- 4.6 mm in the diabetic and 18.7 +/- 4.9 mm in the nondiabetic groups (P = 0.13). At 12 wk, the mean fetal crown-rump length was 58.5 +/- 8.8 mm for diabetic subjects and 60.6 +/- 8.7 mm for nondiabetic subjects (P = 0.04). Between 5 and 9 wk, 28 of 289 (9.7%) fetuses of nondiabetic subjects, 34 of 259 (13.1%) normal fetuses of diabetic subjects, and 2 of 10 (20%) malformed fetuses of diabetic subjects demonstrated growth delay (P = 0.31, normal vs. malformed diabetic). Between 10 and 15 wk of gestation, 28 of 283 (9.9%) fetuses of nondiabetic subjects, 32 of 256 (12.5%) normal fetuses of diabetic subjects, and 4 of 13 (30.8%) malformed fetuses of diabetic subjects demonstrated growth delay (P = 0.06, normal vs. malformed diabetic). Early fetal growth delay did not predict a reduced birth weight at term. CONCLUSIONS: Among insulin-dependent diabetic subjects who were moderately well controlled at conception, statistically significant but mild early fetal growth delay was present but did not appear to be useful clinically in predicting congenital malformations. Recommendations that growth delay demonstrated on early ultrasound be used as a predictor of congenital malformation require careful reexamination.

Adult↗
PubMed1991

Correlations between antepartum maternal metabolism and intelligence of offspring.

BACKGROUND: It is not clear to what extent maternal metabolism during pregnancy affects the cognitive and behavioral function of the offspring by altering brain development in utero. To investigate this question, we correlated measures of metabolism in pregnant diabetic and nondiabetic women with the intellectual development of their offspring. METHODS: The study included 223 pregnant women and their singleton offspring: 89 women had diabetes before pregnancy (pregestational diabetes mellitus), 99 had the onset of diabetes during pregnancy (gestational diabetes mellitus), and 35 had normal carbohydrate metabolism during their pregnancy. We correlated measures of maternal glucose and lipid metabolism (fasting plasma glucose levels, hemoglobin A1c levels, episodes of hypoglycemia, episodes of acetonuria, and plasma beta-hydroxybutyrate and free fatty acid levels) with two measures of intellectual development in the offspring--the mental development index of the Bayley Scales of Infant Development, given at the age of two years, and the Stanford--Binet Intelligence Scale, given at the ages of three, four, and five years and expressed as an average of the three scores. RESULTS: After correction for socioeconomic status, race or ethnic origin, and patient group, the children's mental-development-index scores at the age of two years correlated inversely with the mothers' third-trimester plasma beta-hydroxybutyrate levels (r = -0.21, P less than 0.01); the average Stanford-Binet scores correlated inversely with third-trimester plasma beta-hydroxybutyrate (r = -0.20, P less than 0.02) and free fatty acid (r = -0.27, P less than 0.002) levels. No other correlations were significant. Including various perinatal events (e.g., prematurity and acidemia) in the analyses did not alter the results. CONCLUSIONS: Maternal diabetes during pregnancy may affect behavioral and intellectual development in the offspring. The associations between gestational ketonemia in the mother and a lower IQ in the child warrant continued efforts to avoid ketoacidosis and accelerated starvation in all pregnant women.

3-Hydroxybutyric Acid↗
PubMed1991

Maternal postprandial glucose levels and infant birth weight: the Diabetes in Early Pregnancy Study. The National Institute of Child Health and Human Development--Diabetes in Early Pregnancy Study.

The cause of macrosomia in the infant of the diabetic woman is still not completely defined. The National Institute of Child Health and Human Development--Diabetes in Early Pregnancy Study, which recruited insulin-dependent diabetic and control women before conception, provided an opportunity to address the relationship between maternal glycemia and percentile birth weight. Data were analyzed from 323 diabetic and 361 control women. Fasting and nonfasting venous plasma glucose were measured on alternate weeks in the first trimester and monthly thereafter. Glycosylated hemoglobin was measured weekly in the first trimester and monthly thereafter. More infants of the diabetic women were at or above the 90th percentile for birth weight than infants of control women (28.5% versus 13.1%, p less than 0.001). Although first-trimester nonfasting glucose and glycosylated hemoglobin levels were positively correlated with infant birth weight (p less than 0.001 and p = 0.008), when the analyses were adjusted for the variables of the subsequent trimesters the values became insignificant, whereas the third-trimester nonfasting glucose levels adjusted for values in prior trimesters emerged as the stronger predictor of percentile birth weight (p = 0.001). After adjusting for maternal hypertension, smoking, and ponderal index, the above relationships remained. In conclusion, monitoring of nonfasting glucose levels rather than the fasting levels, which are more commonly monitored in clinical practice, are necessary to prevent macrosomia.

Blood Glucose↗
PubMed1991

The influence of demographic and phenotypic heterogeneity on the prevalence of gestational diabetes mellitus.

In order to explore the influence of demographic and phenotypic characteristics on the prevalence of gestational diabetes mellitus (GDM), data were analyzed from 3744 consecutive patients who underwent universal screening with a 50 g glucose load at 24-28 weeks gestational age. Those with a 1-h plasma glucose greater than or equal to 130 mg/dl underwent a 3-h, 100-g oral glucose tolerance test following dietary preparation. The population was 39.1% White, 37.7% Black, 19.8% Hispanic and 3.4% Oriental/other. The overall prevalence of GDM was 3.5 cases/100. Significant inter-racial differences in maternal age and prepregnant percent ideal body weight (PIBW) were observed, with White patients being older and leaner than Blacks and Hispanics. By multiple logistic regression, Black and Hispanic race, maternal age and PIBW were found to have significant independent effects on the prevalence of GDM. Controlling for age and PIBW, the adjusted relative risk of GDM was significantly higher in Black (1.81, 95% CI 1.13-2.89) and Hispanic (2.45, 95% CI 1.48-4.04) patients compared to White. We conclude that demographic and phenotypic characteristics of populations need to be taken into consideration in future studies of prevalence of GDM, perinatal implications and therapeutic approaches to the disease.

Adult↗
PubMed1991

Long-term prospective evaluation of offspring of diabetic mothers.

We have suggested that altered maternal metabolism may affect the subsequent anthropometric and neuropsychological development of children who were in utero during disturbances in maternal fuel economy. This study reports the physical growth through 8 yr of age and the neuropsychological development through 4 yr of age in offspring of diabetic mothers (ODM). At birth, 50% of infants had weights greater than 90th percentile for gestational age. By 12 mo, length and weight were similar to the general population. Height remained normal until 7 yr of age, when it became slightly greater than average. After 5 yr of age, relative weight increased dramatically, and by 8 yr of age, half of the ODM had weights greater than 90th percentile. This childhood obesity in ODM is correlated with maternal prepregnant weight and independently with amniotic fluid insulin at 32-38 wk gestation. The Brazelton Neonatal Behavioral Assessment Scale (BNBAS) was administered to 185 newborn ODM. Significant correlations were found between poorer second- and third-trimester glycemic regulation and lower scores in three of four newborn BNBAS dimensions. The Stanford-Binet Intelligence Scale was measured in 102 ODM at 4 yr of age. We found an inverse correlation between childhood IQ and second- and third-trimester maternal lipid metabolism (serum free fatty acids and beta-hydroxybutyrate). This correlation is not explained by adverse perinatal events, socioeconomic status, maternal IQ, ethnicity, or diabetes type. These long-range associations between altered maternal metabolism and childhood growth and development continue to support Freinkel's hypothesis of fuel-mediated teratogenesis.

Aging↗