Pre-conception diabetes care in insulin-dependent diabetes mellitus. (1/228)

Prospective studies of pre-conception diabetes care have confirmed its positive impact on the incidence of malformations by improving glycaemic control. Less information is available on the impact of pre-conception care on maternal and neonatal morbidity. This audit addresses its impact on timing and mode of delivery, incidence of macrosomia and rate of admission to neonatal unit care in addition to sociodemographic factors which may influence attendance at such a service. Attenders were more likely to be in a stable relationship and be non-smokers. They were more likely to book for antenatal care earlier and with a lower glycated haemoglobin. There were no early deliveries (i.e. < 30 weeks) or small for gestational age (SGA) babies in those who attended for pre-conception care and no neonatal deaths. Admission to NNU care was reduced by 50% in those who attended for pre-conception care. Although the rate of macrosomia was reduced, there was no impact on the Caesarian section rate. A pre-conception diabetes clinic may have a positive impact on neonatal morbidity.  (+info)

Effects of overexpression of human GLUT4 gene on maternal diabetes and fetal growth in spontaneous gestational diabetic C57BLKS/J Lepr(db/+) mice. (2/228)

During gestation, heterozygous C57BLKS/J-Lepr(db/+) mice develop spontaneous gestational diabetes mellitus (GDM), and the newborn fetuses are macrosomic compared with offspring from wild-type (+/+) mothers. To investigate the effects of the leptin receptor mutation on maternal metabolism and fetal growth during pregnancy, we studied +/+, db/+, and db/+ transgenic mice that overexpress the human GLUT4 gene two- to three-fold (db/+TG6). During pregnancy, fasting plasma glucose and hepatic glucose production were twofold greater in db/+ than +/+ mice, despite similar insulin levels. In skeletal muscle, insulin-stimulated tyrosine phosphorylation was decreased in pregnant +/+ mice, and even more so in db/+ mice: insulin receptor beta (IR-beta), +/+ 34%, db/+ 57% decrease, P<0.05; insulin receptor substrate 1 (IRS-1), +/+ 44%, db/+ 61% decrease, P<0.05; and phosphoinositol (PI) 3-kinase (p85alpha), +/+ 33%, db/+ 65% decrease, P<0.05. Overexpression of GLUT4 in db/+TG6 mice markedly improved glucose-stimulated insulin secretion, by 250%, and increased IRbeta, IRS-1, and p85alpha phosphorylation twofold, despite no change in concentration of these proteins. Plasma leptin concentration increased 40-fold during pregnancy, from 2.2+/-0.5 to 92+/-11 ng/ml and 3.6+/-0.1 to 178+/-34 ng/ml in +/+ and db/+ mice, respectively (P<0.01), but was increased to only 23+/-3 ng/ml in pregnant db/+TG6 mice (P<0.001). Maternal fat mass and energy intake were greater in db/+ mice, and fat mass was reduced by GLUT4 overexpression, independent of food intake. Fetal body weight was increased by 8.1 and 7.9% in db/+ and db/+TG6 mothers, respectively (P<0.05), regardless of fetal genotype, whereas fetuses from db/+TG8 mothers (four- to fivefold overexpression) weighed significantly less compared with pups from +/+ or db/+ mothers (P<0.05). These results suggest that the single mutant db allele effects susceptibility to GDM through abnormalities in insulin receptor signaling, defective insulin secretion, and greater nutrient availability. GLUT4 overexpression markedly improves insulin-signaling in GDM, resulting in increased insulin secretion and improved glycemic control. However, maternal hyperglycemia appears not to be the sole cause of fetal macrosomia. These data suggest that GDM is associated with defects in insulin receptor signaling in maternal skeletal muscle, and this may be an important factor provoking maternal and fetal perinatal complications.  (+info)

Human placental nitric oxide synthase activity is not altered in diabetes. (3/228)

Endothelial nitric oxide synthase (NOS) protein and mRNA have been identified and calcium-dependent NOS activity has been measured in human placentae during normal pregnancy. Recently, mRNA and protein for the inducible isoform of NOS have been detected in placentae of women with gestational diabetes. The aim of this study was to determine whether calcium-independent (ciNOS) and/or total (tNOS) NOS activities were increased in placentae obtained after vaginal delivery or Caesarean section from women assigned to the following groups according to standard obstetric criteria: gestational diabetes, diabetes before pregnancy and non-diabetic controls. tNOS and ciNOS were assessed by measuring the conversion of [3H]L-arginine to [3H]L-citrulline in the three groups. Michaelis-Menten constants (Km) and maximum velocities of reaction (Vmax) were calculated using Lineweaver-Burk analysis for tNOS. There were no significant differences in either ciNOS, Vmax or Km values between any of the three groups (normal, ciNOS 12.7+/-1.6%, Vmax 16.6+/-3.3 pmol.min-1.mg-1 protein, Km 15.30+/-2.6 micromol/l; gestational diabetes, ciNOS 15.4+/-1.4%, Vmax 14.8+/-5.2 pmol.min-1. mg-1 protein, Km 10.5+/-1.7 micromol/l; diabetes before pregnancy, ciNOS 13.4+/-1.1%, Vmax 14.9+/-3.4 pmol.min-1.mg-1 protein, Km 17. 7+/-2.2 micromol/l). The presence of macrosomia did not affect tNOS activity in those with diabetes before pregnancy, and glycosylated haemoglobin levels measured between weeks 27 and 39 were not correlated with ciNOS activity. The results from the present study do not provide evidence for increased placental tNOS or ciNOS activities in pregnancies complicated by gestational diabetes or diabetes present before pregnancy.  (+info)

Screening efficacy of the subcutaneous tissue width/femur length ratio for fetal macrosomia in the non-diabetic pregnancy. (4/228)

BACKGROUND: Antenatal weight estimations have limited sensitivity and specificity for the detection of macrosomia. The objective of our study was to examine the screening efficacy of the subcutaneous tissue width/femur length ratio for the intrapartum detection of fetal macrosomia in a non-diabetic population at term. STUDY DESIGN: Intrapartum sonographic measurements were performed in 178 well-dated gravidas at 37-41 weeks' gestation with negative glucose tolerance screens. The biparietal diameter, femur length (FL), abdominal circumference and subcutaneous tissue width of the thigh (SCT) were determined. Subsequently, predictions for macrosomia (actual birth weights above the 90th centile) were made using varying cut-off points of the examined parameters or estimated fetal weights. RESULTS: Macrosomia occurred in 27 newborns (15.1%). The SCT/FL ratio was independent of gestational age (r = -0.017). Maternal age, gravidity, parity, gestational age and the ratio of male-to-female infants were similar in pregnancies resulting in appropriate-for-gestational-age and macrosomic infants (NS). There was no difference in the SCT/FL ratio between these groups (p = 0.067; 99% power to detect 2 standard deviation differences). Comparison of screening efficacy by the univariate z score for the area under receiver operating characteristic (ROC) curves (theta) revealed that the abdominal circumference had the best sensitivity-specificity trade-off (theta = 0.8843; p < 0.0001 for comparison with SCT/FL ROC curve), followed by weight estimations based on the Hadlock formula (theta = 0.8773; p < 0.0005), the Shepard formula (theta = 0.8606; p < 0.0001), subcutaneous tissue thickness alone (theta = 0.6872; p < 0.01) and the SCT/FL ratio (theta = 0.6303). CONCLUSIONS: We conclude that the SCT/FL ratio is a poor sonographic predictor of fetal macrosomia in the non-diabetic pregnancy and does not improve fetal weight estimations by conventional sonographic parameters.  (+info)

Early postpartum metabolic assessment in women with prior gestational diabetes. (5/228)

OBJECTIVE: To present the results of early postpartum metabolic assessment in women with gestational diabetes mellitus (GDM), to determine predictive factors for subsequent diabetes, and to investigate the association of postpartum glucose tolerance with other components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: A total of 788 women were evaluated 3-6 months after a GDM pregnancy. A 75-g oral glucose tolerance test (OGTT) was performed. Cholesterol, HDL cholesterol, triglycerides, blood pressure, BMI, and body fat distribution were assessed. Clinical and obstetric history, baseline variables at the diagnosis of GDM, metabolic control during pregnancy, and index pregnancy outcome were compared in women with diabetes and women without diabetes (American Diabetes Association [ADA] criteria) after pregnancy. Multivariate logistic regression analysis was used to ascertain independent predictors of subsequent diabetes. Correlation coefficients were assessed between postpartum glucose tolerance and lipid levels, blood pressure, BMI, and body fat distribution. RESULTS: According to ADA criteria, 588 (74.6%) women were normal, 46 (5.8%) had impaired fasting glucose, 82 (10.4%) had impaired glucose tolerance, 29 (3.7%) had both impaired fasting glucose and impaired glucose tolerance, and 43 (5.4%) had diabetes. Prepregnancy obesity, recurrence of GDM, gestational age at diagnosis of GDM, glucose values in the 100-g OGTT, number of abnormal values in the 100-g OGTT, fasting C-peptide levels in pregnancy, C-peptide/glucose score in pregnancy, insulin requirement in pregnancy, 3rd trimester HbA1c levels, and macrosomia differed significantly in women with subsequent diabetes. Independent predictors of postpartum diabetes were prepregnancy obesity, C-peptide/glucose score during pregnancy, and the number of abnormal values in the 100-g diagnostic OGTT. The area under the postpartum glucose curve was positively associated with BMI, waist circumference, waist-to-hip ratio, triglycerides, and systolic and diastolic blood pressures. CONCLUSIONS: Low C-peptide/glucose score during pregnancy together with prepregnancy obesity and severity of GDM (number of abnormal values in the 100-g diagnostic OGTT) are independent predictors of subsequent diabetes. Our data suggest that regardless of obesity and severity of GDM, a beta-cell defect increases the risk of postpartum diabetes. The association of postpartum glucose tolerance with triglyceride levels, blood pressure, obesity, and regional distribution of body fat suggests that postpartum glucose intolerance anticipates a high-risk cardiovascular profile that comprises other risk factors besides diabetes.  (+info)

What is the significance of macrosomia? (6/228)

This commentary/review briefly considers the diverse criteria recommended for classification of overweight infants. Macrosomia continues to be a vexing problem for both obstetricians and pediatricians. Among the various techniques possible for use in assessing body composition, none are more practical than body weight relative to gestational age. The criteria for normative data from large populations are reviewed. The stringent definition, i.e., exceeding +2 SD of an appropriate normative population, is reaffirmed. Using these criteria, infants of diabetic mothers showed a significant relationship of body weight to fetal hyperinsulinemia.  (+info)

Are conventional targets for metabolic control sufficient to prevent fetal macrosomia during diabetic pregnancy? (7/228)

We report the case of a 26 year-old woman, with an uncomplicated type 1 IDDM of 17 yr duration followed for her first pregnancy. At conception, HbA1c (measured by HPLC) was 6.5% and fructosamine was 280 u.mol.l (normal range below 285). During the follow-up, 15-days-interval frutosamine never exceeded the normal range and HbA1c values were under 6.5% excepted in the third trimester (7.0 +/- 0.8%) coinciding with a bad control of the 2 hours post-prandial blood glucose. A fetal macrosomy was discovered at 34 weeks of gestation and a heavy-for-date 4680 g baby was delivered by caesarean section at 38 weeks of gestation. Our case report outlines again the need to achieve the recommended target of metabolic control for the diabetic pregnant woman (blood preprandial glucose: 3.9-5.6 mM; post-prandial 2 h < 6.7 mM) specially during the third trimester of pregnancy. The use of computer databases might be helpful for precise monitoring during this narrow window period.  (+info)

Time course of changes in serum glucose, insulin, lipids and tissue lipase activities in macrosomic offspring of rats with streptozotocin-induced diabetes. (8/228)

The aim of this investigation was to determine the time course of changes in serum glucose, insulin and lipid levels, as well as lipid and protein content and lipolytic activities in insulin target organs (liver, adipose tissue and muscle), in macrosomic offspring of streptozotocin-induced mildly hyperglycaemic rats. Food intake and nutritional efficiency were also evaluated. Mild hyperglycaemia in pregnant rats was induced by intraperitoneal injection of streptozotocin (40 mg/kg body weight) on day 5 of gestation. Control pregnant rats were injected with citrate buffer. At birth, macrosomic pups (birth weight >1.7 S.D. greater than the mean value for the control pups) had higher serum insulin, glucose and lipid levels than control pups. These macrosomic rats maintained accelerated postnatal growth combined with high adipose tissue weight up to 12 weeks of age. These rats were not hyperphagic; however, they had higher food efficiency and fat storage capacity with higher adipocyte lipoprotein lipase activity, which contributed to persisting obesity. Hepatic lipase activity was increased in macrosomic rats at all ages. Moreover, macrosomia was associated with metabolic disturbances that varied according to age and sex. After 1 month, several alterations observed at birth had disappeared. Serum glucose, insulin and lipid levels in male and female macrosomic rats became similar to those of their respective controls. At 2 months of age, hepatic and serum triacylglycerol levels were higher in macrosomic females than in controls. By 3 months, macrosomic rats (both males and females) had developed insulin resistance with hyperinsulinaemia, hyperglycaemia, and higher serum and hepatic lipids. In conclusion, macrosomia was associated with alterations in glucose and lipid metabolism through to adulthood. It should be considered as an important potential risk factor for obesity and its metabolic complications.  (+info)

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