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Biomedical subjects

B E Metzger

Publications and source records attributed to B E Metzger.

At least 19 recordsLinked to original sources

Declining insulin requirement in the late first trimester of diabetic pregnancy.

OBJECTIVE: To investigate whether pregnancies complicated by type 1 diabetes are associated with a decrease in first-trimester insulin requirement. RESEARCH DESIGN AND METHODS: We examined the weekly insulin requirement (as units per kilogram per day) during the first trimester of pregnancy in diabetic women in the Diabetes in Early Pregnancy Study (DIEP) with accurate gestational dating, regular glucose monitoring, daily insulin-dose recording, and monthly glycohemoglobin measurements. RESULTS: In pregnancies that resulted in live-born full-term singleton infants, a significant 18% increase in mean weekly dosage was observed between weeks 3 and 7 (P = 0.000), followed by a significant 9% decline from week 7 through week 15 (P = 0.000). Further testing localized a significant change in insulin dose in the interval beginning weeks 7-8 and ending weeks 11-12 (P = 0.014). Within this interval, the maximum decrease was between weeks 9 and 10 (mean), 10 and 11 (median), and 8 and 9 (most frequent maximal decrease). To determine whether prior poor glucose control exaggerated these trends, we categorized the women based on their glycohemoglobin values: <2 SDs above the mean of a normal population (subgroup 1), 2-4 SDs (subgroup 2), and >4 SDs (subgroup 3) at baseline. Late first-trimester declines in dosage were statistically significant in subgroup 2 (P = 0.002) and subgroups 2 and 3 together (P = 0.003). Similarly, women with BMI >27.0 had a greater initial insulin rise and then fall compared with leaner women. CONCLUSIONS: Observations in the DIEP cohort disclose a mid-first-trimester decline in insulin requirement in type 1 diabetic pregnant women. Possible explanations include overinsulinization of previously poorly controlled diabetes, a transient decline in progesterone secretion during the late first-trimester luteo-placental shift in progesterone secretion, or other hormonal shifts. Clinicians should anticipate a clinically meaningful reduction in insulin requirement in the 5-week interval between weeks 7 and 12 of gestation.

Adolescent↗

Correlations between the intrauterine metabolic environment and blood pressure in adolescent offspring of diabetic mothers.

OBJECTIVE: To investigate associations between maternal diabetes and blood pressure (BP), obesity, impaired glucose tolerance, and serum lipids in offspring and whether these parameters correlate with metabolism during pregnancy. STUDY DESIGN: Body mass index, BP, serum glucose, and insulin during an oral glucose tolerance test, and lipid concentrations were measured in 99 offspring of diabetic mothers (ODM) and 80 members of a control group. RESULTS: ODM were more obese (body mass index 22.5 +/- 5.6 vs 20.3 +/- 4.0 kg/m(2)) and had higher systolic (8 mm Hg) and mean arterial BP (4 mm Hg) but similar diastolic BP compared with the control group. ODM had higher 2-hour glucose (6.6 +/- 1.3 vs 5.7 +/- 0.9 mmol/L) and insulin (580 +/- 544 vs 377 +/- 239 pmol/L) concentrations but lower fasting concentrations of low-density lipoprotein (2.54 +/- 0.67 vs 2.82 +/- 0.70 mmol/L) and total cholesterol (4.01 +/- 0.80 vs 4.40 +/- 0.78 mmol/L). In both groups body mass index, triglycerides, and fasting and 2-hour glucose concentrations showed correlations with BP measurements. Fasting insulin was correlated with BP readings only in the ODM. Correlations were found between second- and third-trimester maternal free fatty acid concentrations and diastolic and mean arterial BP. Third-trimester beta-hydroxybutyrate was correlated with mean arterial BP. CONCLUSIONS: In ODM, abnormalities in weight and glucose tolerance are associated with abnormal maternal metabolism. Higher BP is an additional abnormality associated with fetal overnutrition.

Adolescent↗

Short stature in Korean women: a contribution to the multifactorial predisposition to gestational diabetes mellitus.

We examined the associations between demographic characteristics including short stature and the prevalence of gestational diabetes mellitus (GDM) in Korean women. In this study, a total of 9005 pregnant women underwent universal screening for GDM. Oral glucose tolerance tests (100 g OGTT) were performed in positive screenees (1 h plasma glucose > or = 7.2 mmol/l) and GDM was diagnosed using National Diabetes Data Group criteria. Women with GDM were older and heavier than those with a positive screen and normal OGTT, as well as those with a negative screen. However, height of women with GDM was significantly shorter than those with a positive screen and normal OGTT, and a negative screen. When the study subjects were stratified according to height quartiles, the plasma glucose at the screening test decreased as height increased. Furthermore, the prevalence of GDM was highest in the shortest quartile (< or = 157 cm) group; the odds ratio for GDM was two times greater compared with the highest quartile (> or = 163 cm) group, even after controlling for age and body mass index (BMI). In addition, multiple logistic regression analysis revealed that greater prepregnancy BMI, age, weight gain, a parental history of diabetes mellitus, and shorter maternal height were directly and independently associated with the prevalence of GDM. We have found that short stature is an independent risk factor for GDM in the racially homogeneous population of Seoul, Korea. It is suggested that this propensity may be conveyed primarily by environmental influences. However, genetic factors may also modify the response to the environmental insult. Our findings also emphasize the heterogeneity of factors which predispose to GDM.

Adult↗

The Diabetes in Early Pregnancy Study: beta-hydroxybutyrate levels in type 1 diabetic pregnancy compared with normal pregnancy. NICHD-Diabetes in Early Pregnancy Study Group (DIEP). National Institute of Child Health and Development.

OBJECTIVE: The objective was to assess relationships between beta-hydroxybutyrate (beta-OHB) level and pregnancy outcome in human pregnancy in light of the fact that high levels of beta-OHB cause malformations and growth retardation in in vitro studies. RESEARCH DESIGN AND METHODS: We analyzed beta-OHB in prospectively collected specimens from the National Institute of Child Health and Human Development-Diabetes in Early Pregnancy Study, in gestational weeks 6-12 in diabetic (n = 204-239) and nondiabetic (n = 316-332) pregnant women. RESULTS: Levels of beta-OHB in diabetic women were 2.5-fold higher than in nondiabetic pregnant women at 6 weeks' gestation and declined to 1.6-fold above nondiabetic women by 12 weeks' gestation (P < 0.0001 at all times). beta-OHB was positively correlated with glucose levels (P < 0.0001) in diabetic mothers, probably reflecting degree of diabetic control. beta-OHB correlated inversely with glucose (P < 0.0003) (gestational week 6 only) in nondiabetic mothers, possibly reflecting caloric intake. beta-OHB tended to be lower (not higher) in diabetic and nondiabetic mothers with malformed infants or pregnancy losses, but the difference was not statistically significant. beta-OHB in diabetic mothers at 8, 10, and 12 weeks correlated inversely with birth weight (P = 0.004-0.02), even after adjusting for maternal glucose levels. beta-OHB levels were also generally lower in diabetic mothers of macrosomic infants, and week 12 ultrasound crown-rump measurements were inversely related to beta-OHB levels. CONCLUSIONS: The lst trimester beta-OHB is significantly higher in diabetic than nondiabetic pregnant women. In both groups, beta-OHB tended to be lower, not higher, in mothers who had a malformed infant or pregnancy loss. beta-OHB was inversely related to crown-rump length and birth weight. The modest beta-OHB elevation in the 1st trimester of reasonably well-controlled diabetic pregnancy is not associated with malformations, probably because beta-OHB levels causing malformations in embryo culture models are 20- to 40-fold higher. The mechanism of the beta-OHB association with impaired fetal growth is unknown.

3-Hydroxybutyric Acid↗

Long-term effects of the intrauterine environment. The Northwestern University Diabetes in Pregnancy Center.

We sought to test the hypothesis that long-term postnatal development may be modified by metabolic experiences in utero. We enrolled offspring of women with pregestational diabetes (this included type 1 and type 2 diabetes) and gestational diabetes in a prospective study from 1977 to 1983. Fetal beta-cell function was assessed by measurement of amniotic fluid insulin (AFI) concentration at 32-38 weeks' gestation. Postnatally, offspring were seen yearly for neuropsychological testing, measurement of anthropometrics, and modified glucose tolerance testing. Neuropsychological control subjects were followed longitudinally. Additional control subjects had anthropometrics measured once, and a random subset of these had a single oral glucose challenge at 10-16 years. The rates of major neuropsychological disturbances in our cohort did not differ significantly from national estimates. However, aberrant maternal metabolism was associated with poorer intellectual performance and psychomotor development. The macrosomia observed at birth in offspring of diabetic mothers (ODM) resolves by 1 year of age. Obesity recurs in childhood; and by 14-17 years, the mean BMI is 24.6 +/- 5.8 kg/m2 in ODM versus 20.9 +/- 3.4 kg/m2 in control subjects. Obesity in adolescence is associated with sex, mother's weight, and AFI concentration. Impaired glucose tolerance (IGT) is found in 36% of ODM and is also associated with elevated amniotic fluid insulin in utero. In confirmation of our original hypothesis, aberrant maternal metabolism is associated with poorer intellectual and psychomotor development, obesity, and IGT in offspring. Excessive insulin secretion in utero, as assessed by AFI concentration, is a predictor of both obesity and IGT in adolescence. This study is a long-term prospective evaluation of the effects of maternal diabetes on pregnant women and their offspring. In this article, we report the results of the correlations between indexes of maternal and fetal metabolism during pregnancy and the offspring's subsequent physical, metabolic, and psychological development from birth through adolescence.

Adolescent↗

Behavioral adjustment in children of diabetic mothers.

The aim of this study was to evaluate whether maternal diabetes in pregnancy may adversely affect the children's behavioral adjustment, in a sample of 201 mothers (68 with pre-gestational diabetes, 50 with gestational diabetes, and 83 with non-diabetic pregnancies) and their singleton offspring. After accounting for socioeconomic status, ethnicity and maternal attitudes, none of the Child Behavior Checklist ratings correlated significantly with maternal patient group or several indices of antepartum maternal metabolism. Child obesity, a common sequela of diabetic pregnancies, correlated positively with Internalizing Behavior problems and three narrow-band sub-scales: Somatic Complaints, Anxious/Depressed, and Social Problems. Results suggest that children of diabetic mothers are at increased risk for a variety of developmental disturbances. Screening for learning and behavioral difficulties should be made at regular pediatric visits, with follow-up evaluations warranted by positive indications, excessive weight gain, or other evolving medical concerns.

Adaptation, Psychological↗

Increased macrosomia and perinatal morbidity independent of maternal obesity and advanced age in Korean women with GDM.

OBJECTIVE: To examine the impact of gestational diabetes mellitus(GDM) on perinatal outcome in a setting where influences of maternal age and obesity would be minimal. RESEARCH DESIGN AND METHODS: A case-control study was done to compare the outcome of pregnancy in 65 women with GDM and 153 women with normal carbohydrate metabolism matched for age, height, and prepregnancy weight. RESULTS: The frequencies of preeclampsia and primary cesarean sections were higher and delivery was earlier in pregnancies complicated by GDM. Birth weight, symmetry index, and chest circumference were greater, and macrosomia and need for phototherapy were more common in offspring of mothers with GDM. Cord-serum C-peptide and insulin concentrations were higher in the infants of mothers with GDM and were strongly correlated with birth weight and symmetry index. However, maternal age, prepregnancy weight, and prepregnancy BMI were not correlated with birth weight. Postprandial glucose levels during the first 2 weeks after diagnosis of GDM had associations with the infants' birth weight, symmetry index, and cord insulin concentration in the diet-treated patients with GDM. CONCLUSIONS: Antepartum maternal glucose metabolism was significantly associated with fetal hyperinsulinemia and excessive fetal growth in relatively nonobese Korean women. These findings support a direct role for metabolic factors in the adverse outcomes in pregnancies complicated by GDM.

Adult↗

Diabetes, asymptomatic hyperglycemia, and 22-year mortality in black and white men. The Chicago Heart Association Detection Project in Industry Study.

OBJECTIVE: To assess relationships of diabetes and asymptomatic hyperglycemia at baseline to the risk of cardiovascular disease (CVD) and all-cause (ALL) mortality in employed, white and black middle-aged men. RESEARCH DESIGN AND METHODS: A prospective cohort study of 11,554 white men and 666 black men between the ages 35 and 64 from 1967 to 1973 was conducted using data from the Chicago Heart Association (CHA) Detection Project in Industry 22-year mortality follow-up. cox proportional hazards models, adjusted fro age and other CVD risk factors, were used to estimate the relative risk (RR) and the 95% CI of mortality associated with baseline glycemic status. RESULTS: Age-adjusted baseline prevalence of clinical diabetes was similar in white (3.7%) and black (4.3%) men; asymptomatic hyperglycemia (glucose post-50-g load > or = 11.1 mmol/l) was present in 11.1% of whites and 7.8% of blacks. After controlling for age, lifestyle, and other CVD risk factors, mortality risk was increased among white men with clinical diabetes (CVD: RR 2.51, CI 2.08-3.02; ALL: RR 1.88, CI 1.63-2.17) and asymptomatic hyperglycemia (CVD: RR 1.18, CI 1.01-1.37; ALL: RR 1.24, CI 1.11-1.37), compared with men with postload glucose < 8.9 mmol/l. Risks were similarly, though nonsignificantly (owing to low statistical power), increased among black men with clinical diabetes (CVD: RR 1.60, CI 0.60-4.29; ALL: RR 1.78, CI 0.97-3.25) and asymptomatic hyperglycemia (CVD: RR 1.29, CI 0.61-2.72; ALL: RR 1.37, CI 0.85-2.20). CONCLUSIONS: Asymptomatic hyperglycemia and clinical diabetes appear to confer increased mortality risk in both white and black men. In addition, mortality risk is increased with increased severity of glycemia. These findings indicate the importance of applying efforts to reduce risk factors and prevent diabetes in both blacks and whites.

Administration, Oral↗

Early malnutrition and child neurobehavioral development: insights from the study of children of diabetic mothers.

In this study we sought to discern whether disturbances in mothers' metabolism during pregnancy may exert long-range effects on the neurobehavioral development of the progeny. Participants were 139 women with diabetes in pregnancy and their singleton offspring. Serial estimates of circulating maternal fuels were obtained for each pregnancy, along with detailed records of perinatal course and outcome. Offspring were administered the Wechsler Intelligence Scale for Children--Revised (WISC-R) and Kaufman Test of Educational Achievement: Short Form (KTEA) at ages 7 to 11 years. The rate of WISC-R full-scale IQ scores below 70 in our cohort did not differ significantly from national estimates. Nonetheless, after statistically controlling for other influences, WISC-R verbal, performance, and full-scale IQ scores, and Bannatyne's indices of Verbal Conceptualization Ability, Acquired knowledge, Spatial Ability, and Sequencing Ability were inversely correlated with measures of maternal lipid and glucose metabolism in the second and third trimesters. KTEA Arithmetic scores were similarly correlated with measures of maternal lipids in the third trimester. All correlations indicate that poorer maternal metabolic regulation was attended by poorer child performance. The effects of maternal metabolism on fetal brain and neurobehavioral development are discussed as potential intermediary factors.

Child↗

The size of subcortical ischemic infarction in patients with and without diabetes mellitus.

Diabetes mellitus is associated with a higher frequency and poorer outcome of ischemic stroke. Determinants of the poorer prognosis of stroke in patients with diabetes are not well defined. We investigated whether size of cerebral infarction differs in patients with and without diabetes mellitus. We compared ischemic lesions in 41 consecutive stroke patients with subcortical infarction-22 with and 19 without diabetes mellitus. The location and size of the ischemic infarct were derived from magnetic resonance images obtained on day 3 or 4 post stroke onset. Cross-sectional infarct area was determined by direct measurement from film. The age of patients was similar in both groups. Patients with diabetes had higher prevalence of arterial hypertension, and previous stroke, and higher admission triglyceride and glucose levels compared to patients without diabetes. We found no significant difference in the size of ischemic lesions in patients with and without diabetes mellitus (1.87 vs. 1.72 cm2, respectively). We conclude that among patients with subcortical ischemic stroke the size of infarction is not different between patients with and without diabetes mellitus.

Aged↗

Metabolic response to meal eating and extended overnight fast in twin gestation.

OBJECTIVE: Our purpose was to compare the metabolic response to normal meal eating and the vulnerability to starvation ketosis in twin versus singleton gestation. STUDY DESIGN: Data are reported on 10 twin and 10 singleton nondiabetic gestations enrolled in a 40-hour metabolic study. Singletons were age (+/- 5 years) and prepregnancy weight (+/- 10% ideal body weight) matched with twins. The diet (35 kcal/kg ideal body weight for singletons, 40 kcal/kg ideal body weight for twins) was distributed as one fifth at 8 AM, two fifths at 1 PM, and two fifths at 6 PM. An overnight fast was extended until noon the following day. Glucose and beta-hydroxybutyrate measurements were made hourly except at night, when they were made every 2 hours. Insulin values were obtained before and after dinner and on the day when breakfast was delayed. RESULTS: The glucose, beta-hydroxybutyrate, and insulin excursions in response to meal eating from 8 AM to 12:00 noon on day 1 were similar in twin and singleton pregnancies (analysis of variance for repeated measures, p < 0.05). On day 2, when breakfast was delayed, a progressive decrement in glucose was observed in both twins and singletons (p = 0.4682). Concurrently, there was a progressive rise in beta-hydroxybutyrate in both twins and singletons, which was significantly greater for twins compared with singletons (p = 0.002). CONCLUSIONS: These data indicate that twin gestations are more vulnerable to the accelerated starvation of late normal pregnancy than singletons are in spite of additional caloric intake. We speculate that the observed difference may be the result of the increased metabolic demands of twin gestation.

3-Hydroxybutyric Acid↗

Effect of pregnancy on renal function in patients with moderate-to-severe diabetic renal insufficiency.

OBJECTIVE: Previous studies of patients with diabetic nephropathy and mild renal impairment have suggested no determination in renal function as a result of pregnancy. The objective of this study was to determine whether pregnancy may permanently worsen renal function in women with diabetic nephropathy and moderate-to-severe renal insufficiency. RESEARCH DESIGN AND METHODS: Eleven patients were identified with diabetic nephropathy and moderate-to-severe renal dysfunction (creatinine [Cr] > or = 124 mumol/l [1.4 mg/dl]) at pregnancy onset by retrospective chart review. Alterations in glomerular filtration rate were estimated by using linear regression of the reciprocal of Cr over time. An equal number of nonpregnant premenopausal type 1 diabetic women with similar degrees of renal dysfunction served as a comparison group for nonpregnant rate of decline of renal function and potential contributing factors. RESULTS: Mean serum Cr rose from 159 mumol/l (1.8 mg/dl) prepregnancy to 221 mumol/l (2.5 mg/dl) in the third trimester. Renal function was stable in 27%, showed transient worsening in pregnancy in 27%, and demonstrated a permanent decline in 45%. Proteinuria increased in pregnancy in 79%. Exacerbation of hypertension or preeclampsia occurred in 73%. Seven patients progressed to dialysis 6-57 months postpartum, with 71% (five of seven) of these cases attributed to acceleration of disease during the pregnancy. Student's tests and repeated-measures analysis of variance support a pregnancy-induced acceleration in the rate of decline of renal function. CONCLUSIONS: In this series, patients with diabetic nephropathy and moderate-to-severe renal insufficiency were found to have a > 40% chance of accelerated progression of their disease as a result of pregnancy.

Adult↗

Prenatal and perinatal influences on long-term psychomotor development in offspring of diabetic mothers.

OBJECTIVE: Our purpose was to assess to what extent disturbances in antepartum maternal metabolism and perinatal complications and morbidities contribute to poorer psychomotor development in offspring of diabetic mothers. STUDY DESIGN: One hundred ninety-six pregnant women and their singleton offspring participated in this prospective cohort-analytic study. Ninety-five women had pregestational diabetes mellitus, and 101 women had gestational diabetes mellitus. Serial estimates of circulating maternal fuels were obtained throughout each index pregnancy along with detailed records of the perinatal course and outcome. Offspring were administered the psychomotor development index of the Bayley Scales of Infant Development at age 2 years and the Bruininks-Oseretsky Test Of Motor Proficiency at ages 6, 8, and 9 years. Tests were performed blinded to the mother's antepartum metabolic status, and perinatal history, and the child's previous test scores. Partial correlations and analyses of covariance were used to control for other influences and confounds, such as family socioeconomic status, racial or ethnic origin, patient group (i.e., pregestational or gestational diabetes mellitus), and sex of child. RESULTS: Children's average score on the Bruininks-Oseretsky test at ages 6 to 9 years correlated significantly with maternal second (p < 0.02) and third trimester (p < 0.001) beta-hydroxybutyrate. There was also a borderline association between the children's scores on the psychomotor development index at age 2 years and maternal third-trimester beta-hydroxybutyrate levels (p = 0.06). No other correlations approached significance. CONCLUSIONS: Intrauterine metabolic experiences continue to influence the neurodevelopmental course in offspring of diabetic mothers. Prevailing practices in diabetes management and obstetric and neonatal care appear to effectively mitigate the potential long-term effects of most perinatal complications and morbidities. Management and obstetric and neonatal care appear to effectively miltigate the potential long-term effects of most perinatal complications and morbidities.

Child↗

Screening for gestational diabetes mellitus in Korea.

OBJECTIVES: To examine the effect of clinical characteristics on the prevalence of gestational diabetes mellitus (GDM) and to find the most effective screening program for GDM in Korea. METHODS: Universal screening with a 50-g glucose load at 24-28 weeks' gestation, as recommended by the Third International Workshop-Conference on Gestational Diabetes Mellitus, was carried out among 3581 consecutive Korean women. Women with a 1-h plasma glucose > or = 130 mg/dl underwent a 3-h 100-g oral glucose tolerance test. The women's clinical characteristics and risk factors for GDM were recorded at the time of the screening test. RESULTS: The overall prevalence of GDM in Korean women was 2.2 cases/100. Although only 1.3% of this population was obese, the prevalence of GDM was found to be significantly increased with increasing body mass index. When 135 mg/dl is used as a threshold, the number of women requiring a diagnostic test decreases to 19.5%, enabling identification of 98.8% of women with GDM. CONCLUSION: Universal screening using 135 mg/dl as a threshold and early screening of those with two or more risk factors represent the most effective paradigm for Korea.

Adult↗