Maternal Glycemia Research Articles

Influence of Maternal Glycemia on Intrauterine Fetal Adiposity Distribution after a Normal Oral Glucose Tolerance Test at 28 Weeks Gestation

Objective. To examine the relationship between maternal glucose levels and intrauterine fetal adiposity distribution in women with a normal oral glucose tolerance test (OGTT) at 28 weeks gestation. Study Design. We recruited 231 women with a singleton pregnancy. At 28 and 37 weeks gestation, sonographic measurements of fetal body composition were performed. Multiple regression analysis was used to study the influence of different maternal variables on fetal adiposity distribution. Results. Maternal glucose levels correlated with the fetal abdominal subcutaneous tissue measurements (r = 0.2; P = 0.014) and with birth weight (r = 0.1; P = 0.04). Maternal glucose levels did not correlate with the fetal mid-thigh muscle thickness and mid-thigh subcutaneous tissue measurements. Conclusion. We found that in nondiabetic women maternal glucose levels not only influence fetal adiposity and birth weight, but also influence the distribution of fetal adiposity. This supports previous evidence that maternal glycemia is a key determinant of intrauterine fetal programming.

Synergistic effects of genetic beta cell dysfunction and maternal glucose intolerance on offspring metabolic phenotype in mice

Diabetes in pregnancy is linked to development of obesity in the offspring, but the mechanisms are not fully understood. Gestational diabetes mellitus (GDM) occurs when beta cells are unable to compensate for the normal insulin resistance of late pregnancy. In this study, we used a murine model of beta cell dysfunction to examine the effects of maternal GDM on phenotype in male offspring with and without an inherited predisposition for beta cell dysfunction. Beta cell-specific aryl-hydrocarbon receptor nuclear translocator-null (βArnt) mice develop GDM from beta cell dysfunction. βArnt and control female mice were used to induce GDM and non-diabetic pregnancies, respectively. Offspring from GDM pregnancies became spontaneously obese on a normal-chow diet. They were heavier than offspring from non-diabetic pregnancies, with increased body fat. Respiratory exchange ratio (RER) was higher, indicating decreased capacity to switch to lipid oxidation. Metabolic rate in GDM offspring was decreased prior to onset of obesity. The phenotype was more pronounced in βArnt GDM offspring than in GDM offspring of control genotype, demonstrating an interaction between genotype and pregnancy exposure. βArnt GDM offspring had increased hypothalamic neuropeptide Y (Npy) and decreased pro-opiomelanocortin (Pomc) expression. Weight, body fat, insulin sensitivity and RER in all mice, and hypothalamic Npy in βArnt mice were significantly correlated with AUC of maternal late pregnancy glucose tolerance tests (p < 0.01), but not with litter size, maternal weight, triacylglycerol or pre-pregnancy glycaemia. In βArnt mice, exposure to GDM and inheritance of genetic beta cell dysfunction had additive effects on male offspring obesity; severity of the offspring phenotype correlated with maternal glycaemia.

Hyperglycemia and Adverse Pregnancy Outcome Study: Neonatal Glycemia

The goal was to describe the temporal pattern of neonatal plasma glucose levels and associations with maternal glucose levels, cord serum C-peptide levels, and neonatal size and adiposity. A total of 17,094 mothers and infants were included in the Hyperglycemia and Adverse Pregnancy Outcome Study (15 centers in 9 countries). Mothers underwent a 75-g, 2-hour, oral glucose tolerance test (OGTT) at 24 to 32 weeks of gestation. Cord blood and neonatal blood samples were collected. Biochemical neonatal hypoglycemia was defined as glucose levels of <10th percentile (2.2 mmol/L). Clinically identified hypoglycemia was ascertained through medical record review and associations were assessed. Plasma glucose concentrations were stable during the first 5 hours after birth. Maternal glucose levels were weakly positively associated with biochemical neonatal hypoglycemia (odds ratios: 1.07-1.14 for 1-SD higher OGTT glucose levels). Frequency of neonatal hypoglycemia was higher with higher cord C-peptide levels (odds ratio: 11.6 for highest versus lowest C-peptide category). Larger and/or fatter infants were more likely to have hypoglycemia (P < .001), and infants with hypoglycemia tended to have a higher frequency of cord C-peptide levels of >90th percentile. Mean neonatal plasma glucose concentrations varied little in the first 5 hours after birth, which suggests normal postnatal adjustment. Biochemical and clinical hypoglycemia were weakly related to maternal OGTT glucose measurements but were strongly associated with elevated cord serum C-peptide levels. Larger and/or fatter infants were more likely to develop hypoglycemia and hyperinsulinemia. These relationships suggest physiologic relationships between maternal glycemia and fetal insulin production.

Conséquences à long terme d’une exposition fœtale au diabète gestationnel

To appreciate, in epidemiological studies, the impact of fetal exposure to gestational diabetes on the long term outcome of the offspring (type 2 diabetes, overweight and obesity, metabolic syndrome and neurological complications). A systematic search was conducted in Medline between January 1990 and April 2010. Prospective studies (follow-up of the offspring born of mothers with gestational diabetes) and retrospective studies (questionnaire about the parents'history of diabetes in diabetic patients) were searched and analysed. The fetal exposure to maternal gestational diabetes is a moderate risk factor for metabolic syndrome in the offspring. But some other perinatal risk factors of metabolic syndrome carry a bigger influence. The influence of genetic factors and maternal overweight may not be easily distinguished from the impact of fetal exposure to gestational diabetes. It remains uncertain if the control of maternal glycemia alone may be effective and sufficient to prevent the metabolic syndrome in the adult-aged offspring.

Long-term outcome in children of mothers with gestational diabetes

To assess the long-term outcomes (type 2 diabetes, overweight, cardiovascular disorders, metabolic syndrome and neurological manifestations) from human epidemiological studies of foetuses exposed to gestational diabetes. A literature search on Medline was performed for the period from 01 January 1990 to 01 April 2010. Prospective (follow-up of children born to diabetic mothers) and retrospective (investigation of parental history of diabetes in diabetic subjects) studies were analysed. Exposure to gestational diabetes moderately increases the risk of subsequent metabolic complications. It seems that this foetal exposure to maternal blood glucose is only one risk factor of metabolic syndrome among others. In particular, the role of maternal weight in the occurrence of the metabolic syndrome in the offspring is difficult to distinguish from that of gestational diabetes. According to the current state of knowledge, it is uncertain whether maternal glycaemia control alone during pregnancy is sufficient for the prevention of metabolic syndrome in the offspring.

Fetal growth trajectories in Type‐1 diabetic pregnancy

To describe the individual intrauterine growth patterns of fetuses of insulin-dependent (Type-1) diabetic women and to examine determinants of overgrowth (macrosomia) and its timing. This retrospective longitudinal study examined the developmental trajectories of fetal abdominal circumference (AC) and biparietal diameter in 76 Type-1 diabetic women with singleton pregnancies. Latent class analysis was used to identify subgroups of patients with a shared fetal AC growth trajectory. Subsequently, maternal factors, including glycemic control as assessed by glycosylated hemoglobin (HbA1c), were examined to see whether they had any effect on fetal growth. Four subgroups with different AC growth patterns were identified. Differences in birth weight between the distinct subgroups were related to the shape of the AC growth velocity curve over gestation. Acceleration of AC growth commencing before or after 25 weeks' gestation was associated with the birth of a heavy or large-for-dates baby in 94 and 56% of cases, respectively. Poor glycemic control (HbA1c > 7.0%) during the periconception period or before 12 weeks' gestation was a modest predictor of midtrimester growth in AC. Other diabetes-related factors, fetal sex, parity, or maternal weight/obesity were unrelated to the fetal growth pattern. The findings suggest that an individual fetus's growth trajectory is set early in gestation and that the contemporaneous degree of maternal glycemia plays a role in determining birth weight.

International Association of Diabetes and Pregnancy Study Groups Recommendations on the Diagnosis and Classification of Hyperglycemia in Pregnancy

In the accompanying comment letter (1), Weinert summarizes published data from the Brazilian Gestational Diabetes Study (2) and comments on applying International Association of Diabetes and Pregnancy Study Groups (IADPSG) Consensus Panel recommendations (3) for the diagnosis of gestational diabetes mellitus (GDM) to that cohort. The Brazilian study provided evidence that adverse perinatal outcomes are associated with levels of maternal glycemia below those diagnostic of GDM by American Diabetes Association or World Health Organization criteria. However, the results were potentially confounded by the treatment of GDM. It did find that women with GDM were at increased risk for some …

International Association of Diabetes and Pregnancy Study Groups Recommendations on the Diagnosis and Classification of Hyperglycemia in Pregnancy

Lack of international uniformity for the diagnosis of gestational diabetes mellitus (GDM) has been a clinical problem. The International Association of Diabetes and Pregnancy Study Groups (IADPSG) suggested new criteria for diagnosis and classification of diabetes in pregnancy (1) based on the association of maternal glycemia with perinatal outcomes reported in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study (2). Clinical outcomes are the best way to define diagnostic thresholds, and this approach to GDM diagnosis has already been reported in the Brazilian population. The study by Schmidt et al. (3) merits mentioning since it is one of the few large studies of unselected pregnant women universally evaluated with the …

Resistin in pregestational and gestational diabetic pregnancy

Resistin was originally postulated to be an essential link between obesity and diabetes. The aim of the study was to investigate resistin in diabetic pregnancy.Prospective cohort study where maternal and...

The role of the polycystic ovary syndrome susceptibility locus D19S884 allele 8 in maternal glycemia and fetal size.

The high incidence of insulin resistance, type 2 diabetes, and metabolic syndrome in Western societies and their impact on quality of life emphasize the importance of identifying underlying susceptibility loci for metabolic diseases. The polycystic ovary syndrome (PCOS) susceptibility locus D19S884 allele 8 (A8) is associated with measures of insulin resistance, beta-cell dysfunction, and other metabolic phenotypes in PCOS families. We now investigate the role of D19S884 A8 in pregnancy. Using the multiethnic Hyperglycemia and Adverse Pregnancy Outcome cohort, we assessed the associations of D19S884 A8 with measures of maternal glycemia and fetal size. We tested for association of maternal D19S884 A8 with maternal outcomes (fasting, 1-h, and 2-h plasma glucose, and fasting and 1-h C-peptide from an oral glucose tolerance test) and fetal and maternal D19S884 A8 with fetal outcomes (birth weight, length, head circumference, sum of skin folds, fat mass, cord C-peptide, and 2-h neonatal plasma glucose). We analyzed 4424 Caucasian mothers and 3347 offspring of northern European ancestry, 1957 Thai mothers and 2089 offspring from Bangkok, 1208 Afro-Caribbean mothers and 1209 offspring from Barbados, and 774 Hispanic mothers and 762 offspring from Bellflower, California. After adjusting for confounding variables and multiple testing, neither maternal nor fetal D19S884 A8 showed significant evidence for association with any of the outcomes tested. The PCOS susceptibility locus, D19S884 A8, is not a major factor contributing to glycemia during pregnancy or fetal size in a general obstetric population.

Evaluation of placental glycogen storage in mild diabetic rats

To evaluate the placental glycogen storage and fetal development in the pregnancy of neonatally streptozocin-induced diabetic rats and to establish relation with glycemia and insulin levels. At the birth day, 147 female rats were randomly distributed in two experimental groups: 1) Non-diabetic Group (Control, n=45) - received the vehicle; 2) Diabetic Group (STZ, n=102) - received 100 mg streptozocin/kg in neonatal period. At day 0 of pregnancy, adult female rats were included in the control group when presented glycemia below 120 mg/dL and, in the group STZ with glycemia between 120 and 300 mg/dL. At day 21 of pregnancy, blood samples were collected for glycemia and insulin determination, and placentas withdrawn for placental glycogen determination. The newborns (NB) were classified in small (SGA), appropriate (AGA) and large (LGA) for gestational age. Rats STZ presented higher glycemia at days 0 and 14 of pregnancy. At end of pregnancy, rats STZ showed higher proportion of NB SGA and LGA; reduced rate of NB AGA and unaltered glycemia, insulin and placental glycogen determinations. Mild diabetes altered the maternal glycemia in the early pregnancy, impairing future fetal development, but it caused no alteration on insulin and placental glycogen determination, confirming that this glycemic intensity was insufficient to change glycogen metabolism.

The influence of maternal glycaemia and dietary glycaemic index on pregnancy outcome in healthy mothers

Infant birth weight has increased in Ireland in recent years along with levels of childhood overweight and obesity. The present article reviews the current literature on maternal glycaemia and the role of the dietary glycaemic index (GI) and its impact on pregnancy outcomes. It is known that maternal weight and weight gain significantly influence infant birth weight. Fetal macrosomia (birth weight >4000 g) is associated with an increased risk of perinatal trauma to both mother and infant. Furthermore, macrosomic infants have greater risk of being obese in childhood, adolescence and adulthood compared to normal-sized infants. There is evidence that there is a direct relationship between maternal blood glucose levels during pregnancy and fetal growth and size at birth, even when maternal blood glucose levels are within their normal range. Thus, maintaining blood glucose concentrations within normal parameters during pregnancy may reduce the incidence of fetal macrosomia. Maternal diet, and particularly its carbohydrate (CHO) type and content, influences maternal blood glucose concentrations. However, different CHO foods produce different glycaemic responses. The GI was conceived by Jenkins in 1981 as a method for assessing the glycaemic responses of different CHO. Data from clinical studies in healthy pregnant women have documented that consuming a low-GI diet during pregnancy reduces peaks in postprandial glucose levels and normalises infant birth weight. Pregnancy is a physiological condition where the GI may be of particular relevance as glucose is the primary fuel for fetal growth.

Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) Study: associations with maternal body mass index

To determine whether higher maternal body mass index (BMI), independent of maternal glycaemia, is associated with adverse pregnancy outcomes. Observational cohort study. Fifteen centres in nine countries. Eligible pregnant women. A 75-g 2-hour oral glucose tolerance test (OGTT) was performed between 24 and 32 weeks of gestation in all participants. Maternal BMI was calculated from height and weight measured at the OGTT. Fetal adiposity was assessed using skinfold measurements and percentage of body fat was calculated. Associations between maternal BMI and pregnancy outcomes were assessed using multiple logistic regression analyses, with adjustment for potential confounders. Predefined primary outcomes were birthweight >90th percentile, primary caesarean section, clinical neonatal hypoglycaemia and cord serum C-peptide >90th percentile. Secondary outcomes included pre-eclampsia, preterm delivery (before 37 weeks) and percentage of body fat >90th percentile. Among 23 316 blinded participants, with control for maternal glycaemia and other potential confounders, higher maternal BMI was associated (odds ratio [95% confidence interval] for highest {> or =42.0 kg/m(2)} versus lowest {<22.6 kg/m(2)} BMI categories) with increased frequency of birthweight >90th percentile (3.52 [2.48-5.00]) and percentage of body fat >90th percentile (3.28 [2.28-4.71]), caesarean section (2.23 [1.66-2.99]), cord C-peptide >90th percentile (2.33 [1.58-3.43]) and pre-eclampsia (14.14 [9.44-21.17]). Preterm delivery was less frequent with higher BMI (0.48 [0.31-0.74]). Associations with fetal size tended to plateau in the highest maternal BMI categories. Higher maternal BMI, independent of maternal glycaemia, is strongly associated with increased frequency of pregnancy complications, in particular those related to excess fetal growth and adiposity and to pre-eclampsia.

International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy.

In the accompanying comment letter (1), Weinert summarizes published data from the Brazilian Gestational Diabetes Study (2) and comments on applying International Association of Diabetes and Pregnancy Study Groups (IADPSG) Consensus Panel recommendations (3) for the diagnosis of gestational diabetes mellitus (GDM) to that cohort. The Brazilian study provided evidence that adverse perinatal outcomes are associated with levels of maternal glycemia below those diagnostic of GDM by American Diabetes Association or World Health Organization criteria. However, the results were potentially confounded by the treatment of GDM. It did find that women with GDM were at increased risk for some …

Clinical assessment of insulin action during late pregnancy in women at risk for gestational diabetes: Association of maternal glycemia with perinatal outcome

ObjectiveWe prospectively evaluated differences in fasting- and oral glucose tolerance test (OGTT)-derived indices of insulin action in Caucasian (Cau) and African-American (AA) pregnant women and compared them with obstetric outcomes. Study designIRB-approved prospective study in 171 pregnant women undergoing a 3-h OGTT. Mathematical modeling was used to evaluate insulin response, insulin activity and glucose tolerance in fasting and postglucose ingestion state. Insulin sensitivity indices derived from fasting (HOMA-IR) and glucose-stimulated values (SIOGTT) were compared. An insulin sensitivity-secretion index (IS-SI) was calculated from the product of the SIOGTT and early-phase insulin secretion. ResultsForty-nine patients had gestational diabetes (GDM), 28 had gestational impaired glucose tolerance (GIGT) and 94 had normal glucose tolerance after an abnormal glucose challenge test (NGT-abnGCT). Insulin sensitivity was lowest in women with GDM. In all groups, pregnant AA women were significantly more insulin resistant than Cau women, based on both HOMA-IR and SIOGTT, but had enhanced insulin secretion compared to their Cau counterparts. The mean IS-SI progressively improved for all women from GDM to GIGT to NGT-abnGCT. Women with NGT-abnGCT had a higher prevalence of large-for-gestational age (LGA) newborns and significantly higher cesarean section rate. DiscussionInsulin measures along with glucose determinations during OGTT testing in pregnant women at risk for diabetes provide valuable information that varies according to race. We observed that pregnant women with a lesser degree of glucose tolerance abnormality during pregnancy who receive no intervention have a higher risk for LGA infants and significantly increased C-section rate (ClinicalTrials.gov number, NCT006874791).

52: The relationship between maternal glycemia and perinatal outcome

52: The relationship between maternal glycemia and perinatal outcome

Hesperidin, a natural citrus flavanone, alleviates hyperglycaemic state and attenuates embryopathies in pregnant diabetic mice

In this study, we attempted to investigate the effect of hesperidin, a natural antioxidant citrus flavanone, on diabetes-induced embryopathies in mice. Streptozotocin (STZ) was injected intraperitoneally in 60 mg/kg bw/day for 3 consecutive days to induce diabetes in virgin females. 72 h later, mating was applied and hesperidin was orally given to pregnant diabetic mice in 20 ppm from the 1st to the 18th day of approximately 19 days-gestational length. Maternal body weight and glycaemia were measured throughout pregnancy. Mice were euthanized on day 18 in order to evaluate the teratological parameters. The results showed a considerable decrease of maternal body weight at the last week of pregnancy in hesperidin-treated diabetic mice. Maternal glycaemia was slowly attenuated by hesperidin with a significantly manifest effect on days 11 and 18. This flavanone enhanced the number of implantations per litter, the overall number of foetuses and the absolute and relative foetal weights while reducing malformations and resorptions rates. The red alizarin-staining procedure for foetal skeleton demonstrated a full protective role of hesperidin since, as in controls, no skeletal defects were found in treated diabetic group. These findings suggest that hesperidin may have a prophylactic effect against diabetic embryopathies in mice. Key words: Hesperidin, citrus fruits, diabetic embryopathy, mice.

Association of existing diabetes, gestational diabetes and glycosuria in pregnancy with macrosomia and offspring body mass index, waist and fat mass in later childhood: findings from a prospective pregnancy cohort

The aim of the study was to examine the association of existing diabetes (i.e. already diagnosed prior to pregnancy), gestational diabetes and glycosuria (both diagnosed and ascertained during pregnancy) with birthweight and future offspring BMI, waist circumference and fat mass (assessed by dual x-ray emission absorptiometry). A prospective pregnancy/birth cohort study was performed using data from the Avon Longitudinal Study of Parents and Children. Among 10,591 mother-offspring pairs included in analyses with birth size, women with existing diabetes (n = 40), those diagnosed with gestational diabetes (n = 53) and those with at least two episodes of ++ glycosuria (n = 372) had greater mean birthweight and odds for macrosomia (birthweight > 4,000 g) than women with none of these. Adjusted odds ratios for macrosomia were 3.56 (95% CI 1.53-8.28), 5.50 (95% CI 1.18-10.30) and 1.58 (95% CI 1.18-2.12) for existing diabetes, gestational diabetes and glycosuria, respectively. Among 6,842 mother-offspring pairs with anthropometric measurements at age 9-11 years, maternal gestational diabetes and glycosuria (but not existing diabetes) were associated with increased offspring odds of general or central overweight/obesity. For gestational diabetes, these associations attenuated towards the null with adjustment for maternal prepregnancy BMI, but independent associations remained for glycosuria. The adjusted odds ratio for general overweight/obesity when comparing women with at least two episodes of ++ glycosuria with those with no evidence of diabetes or glycosuria was 1.35 (95% CI 1.00-1.82) and that for central obesity (top 10% waist circumference vs all others) was 1.31 (95% CI 1.00-1.72). These results provide some evidence for a long-term effect of maternal glycaemia in pregnancy on offspring obesity risk.

Animal models for clinical and gestational diabetes: maternal and fetal outcomes

BackgroundDiabetes in pregnant women is associated with an increased risk of maternal and neonatal morbidity and remains a significant medical challenge. Diabetes during pregnancy may be divided into clinical diabetes and gestational diabetes. Experimental models are developed with the purpose of enhancing understanding of the pathophysiological mechanisms of diseases that affect humans. With regard to diabetes in pregnancy, experimental findings from models will lead to the development of treatment strategies to maintain a normal metabolic intrauterine milieu, improving perinatal development by preventing fetal growth restriction or macrosomia. Based on animal models of diabetes during pregnancy previously reported in the medical literature, the present study aimed to compare the impact of streptozotocin-induced severe (glycemia >300 mg/dl) and mild diabetes (glycemia between 120 and 300 mg/dl) on glycemia and maternal reproductive and fetal outcomes of Wistar rats to evaluate whether the animal model reproduces the maternal and perinatal results of clinical and gestational diabetes in humans.MethodsOn day 5 of life, 96 female Wistar rats were assigned to three experimental groups: control (n = 16), severe (n = 50) and mild diabetes (n = 30). At day 90 of life, rats were mated. On day 21 of pregnancy, rats were killed and their uterine horns were exposed to count implantation and fetus numbers to determine pre- and post-implantation loss rates. The fetuses were classified according to their birth weight.ResultsSevere and mild diabetic dams showed different glycemic responses during pregnancy, impairing fetal glycemia and weight, confirming that maternal glycemia is directly associated with fetal development. Newborns from severe diabetic mothers presented growth restriction, but mild diabetic mothers were not associated with an increased rate of macrosomic fetuses.ConclusionExperimental models of severe diabetes during pregnancy reproduced maternal and fetal outcomes of pregnant women presenting uncontrolled clinical diabetes. On the other hand, the mild diabetes model caused mild hyperglycemia during pregnancy, although it was not enough to reproduce the increased rate of macrosomic fetuses seen in women with gestational diabetes.

Maternal Glycemia and Risk of Large-for-Gestational-Age Babies in a Population-Based Screening

OBJECTIVEGestational diabetes is a risk factor for large-for-gestational-age (LGA) newborns, but many LGA babies are born to mothers with normal glucose tolerance. We aimed to clarify the association of maternal glycemia across the whole distribution with birth weight and risk of LGA births in mothers with normal glucose tolerance.RESEARCH DESIGN AND METHODSWe undertook a population-based gestational diabetes screening in an urban area of Hungary in 2002–2005. All singleton pregnancies of mothers ≥18 years of age, without known diabetes or gestational diabetes (World Health Organization criteria) and data on a 75-g oral glucose tolerance test at 22–30 weeks of gestation, were included (n = 3,787, 78.9% of the target population). LGA was determined as birth weight greater than the 90th percentile using national sex- and gestational age–specific charts.RESULTSMean ± SD maternal age was 30 ± 4 years, BMI was 22.6 ± 4.0 kg/m2, fasting blood glucose was 4.5 ± 0.5 mmol/l, and postload glucose was 5.5 ± 1.0 mmol/l. The mean birth weight was 3,450 ± 476 g at 39.2 ± 1.2 weeks of gestation. There was a U-shaped association of maternal fasting glucose with birth weight (Pcurve = 0.004) and risk of having an LGA baby (lowest values between 4 and 4.5 mmol/l, Pcurve = 0.0004) with little change after adjustments for clinical characteristics. The association of postload glucose with birth weight (P = 0.03) and the risk of an LGA baby (P = 0.09) was weaker and linear.CONCLUSIONSBoth low and high fasting glucose values at 22–30 weeks of gestation are associated with increased risk of an LGA newborn. We suggest that the excess risk related to low glucose reflects the increased use of nutrients by LGA fetuses that also affects the mothers' fasting glucose.