Maternal Glucose Concentrations Research Articles

Maternal arachidonic acid supplementation improves neurodevelopment in young adult offspring from rat dams with and without diabetes

Maternal diabetes may compromise infant arachidonic acid (AA) status and development. This study tested if maternal AA supplementation improves neurodevelopment in adult offspring. Rat dams were randomized into 6 groups: Saline-Placebo, streptozotocin-induced diabetes with glucose controlled at <13 mmol/L, or poorly controlled at 13–20 mmol/L using insulin; and fed either a Control or AA (0.5% fat) diet throughout reproduction. Weaned-offspring were fed regular chow to 12 weeks of age. Testing included exploratory behavior, rota rod and water maze (WM). Poorly controlled offspring showed longer ( p≤0.018) escape-latency on testing-day 1 WM but not thereafter ( p>0.05). Maternal glucose concentration positively correlated with ( p=0.006) male offspring testing-day 1 WM latency. The AA-diet offspring performed better in WM and rota rod ( p≤0.032) and showed higher exploratory behavior ( p=0.008) than Control-diet offspring. These data suggest maternal hyperglycemia has longstanding consequences to initial stages of learning in the offspring. Maternal AA supplementation and training positively influence learning outcomes.

Diabetes in pregnancy: Effect on glycation and acetylation of the different chains of fetal and maternal hemoglobin

Background Measurement of glycated fetal hemoglobin to assess maternal glycemic control is unreliable. Electrospray ionization–mass spectrometry (ESI-MS) has been suggested as a definitive procedure. Objective This study aimed to evaluate glycation and acetylation by ESI-MS of the separate chains of neonatal fetal hemoglobin in comparison with glycation of maternal hemoglobin, to assess the impact of maternal diabetes. Methods Twenty-nine non-diabetic (31 neonates) and 15 diabetic women (15 neonates) were recruited. Whole blood was collected at delivery from the mothers and cord blood from their respective neonate. The blood samples were diluted in acetonitrile:water (50:50) and treated with a cation exchange resin to remove sodium and potassium adducts on the hemoglobin. The α- and β-chain glycated maternal hemoglobin and α- and γ-chain glycated and acetylated hemoglobin of the neonate were measured by ESI-MS. HbA1c was measured on the Menarini 8160. Results Mean α- and γ-chain and overall glycated hemoglobin and acetylated fetal hemoglobin were 1.23 ± 0.41%, 1.62 ± 0.47%, 1.24 ± 0.37%, and 8.56 ± 0.84% in the infant of the non-diabetic mother (INDM) and 1.39 ± 0.21%, 1.92 ± 0.61%, 1.64 ± 0.59%, and 8.44 ± 0.63% in the infant of the diabetic mother (IDM). Mean maternal α- and β-chain, overall glycated hemoglobin and HbA1c were 1.98 ± 0.38%, 4.28 ± 0.76%, 3.13 ± 0.51%, 5.39 ± 0.39% (non-diabetic) and 2.40 ± 0.83%, 4.71 ± 0.90%, 3.58 ± 0.83%, 6.15 ± 0.71% (diabetic). Overall glycated hemoglobin levels were significantly higher in the IDM ( p = 0.006) compared to the INDM. Maternal glycated hemoglobin was significantly higher than neonatal glycated hemoglobin in the control ( p < 0.0001) and diabetic group ( p < 0.0001). A significant correlation was observed between maternal glucose concentration and overall glycated fetal hemoglobin in the IDM ( p = 0.02). Glucose concentrations in the diabetic mother and the IDM were not significantly different ( p = 0.5) and were significantly correlated ( p < 0.0001). HbA1c was not significantly different in the two maternal groups. No significant difference was observed between AcHbF in IDM or INDM ( p = 0.61). Conclusions Measurement of overall glycated fetal hemoglobin, incorporating α- and γ-chain glycations, seems best to assess abnormal glucose homeostasis during pregnancy. Accurate assay of this parameter is critical for stratification of risk of possible post birth developmental complications.

Prepartum Maternal Plasma Glucose Concentrations and Placental Glucose Transporter mRNA Expression in Cows Carrying Somatic Cell Clone Fetuses

In this study, the plasma glucose concentrations of cows carrying a somatic cell clone fetus during late pregnancy and placental glucose transporter (GLUT) mRNA levels at parturition were examined. Parturition was induced using dexamethasone, prostaglandin F(2α) and estriol in cows bearing a clone (Clone) or a fetus fertilized in vivo as a control (DEX). Plasma glucose concentrations were measured in the cows (days 257 and 271 of pregnancy and at parturition) and newborn calves. Cotyledon and caruncle tissues removed just after parturition were used for mRNA extraction. Expression of mRNA was also analyzed in control cows that were induced to undergo parturition without dexamethasone (PG) or that spontaneously delivered (SP). The glucose concentrations of the Clone group were significantly low at all points examined, but those of the calves were normal. The increase in the maternal glucose concentration from day 257 to parturition was significantly lower in the Clone group. Glucose concentrations were negatively correlated with birth weight for clones (day 257; r=-0.584, day 271; r=-0.286, parturition; r=-0.549). There was no difference in mRNA levels in the cotyledons among the animals examined. In the caruncles, the Clone and PG groups showed significantly higher GLUT1 and GLUT3 mRNA levels than the SP group, and the GLUT3 mRNA level was significantly higher in the Clone group than in the DEX group. The glucocorticoid receptor α mRNA level was significantly lower in the SP group than in the DEX group. Although spontaneous parturition and administration of dexamethasone suppressed the placental GLUT mRNA levels, the action was not observed in clone pregnancy. These results raise the possibility of facilitation of glucose transportation through the placenta to meet increased nutritional requirements of overgrown clone fetuses.

Determinants of early ponderal and statural growth in full-term infants in the EDEN mother-child cohort study

Growth velocity in the first months of postnatal life has been associated with later overweight and obesity. We analyzed prenatal and postnatal factors in association with weight, length, and growth velocities in the first 3 mo of life. We estimated weight, length, and instantaneous weight- and length-growth velocities (in g/d and mm/d) in 1418 term infants at 1 and 3 mo of age and evaluated the following potential determinants: maternal prepregnancy body mass index (BMI), 1-h plasma glucose concentrations during pregnancy, smoking, socioeconomic status, parity, paternal BMI, parental heights, and infant feeding, gestational age, and sex. Maternal obesity and plasma glucose concentrations were associated with the weights and lengths of offspring at birth but not at 1 and 3 mo after birth. In contrast, there was no association between paternal BMI and anthropometric measures of offspring at birth, but by 3 mo of age infants of obese fathers had significantly higher weights and weight-growth velocities than did infants of fathers with a normal BMI. Maternal weight gain was a significant predictor of weight at birth and 3 mo of age. Exclusively breastfed infants had a slower weight-growth velocity as early as 1 mo of age compared with exclusively formula-fed infants. In the first 3 mo of life, the positive associations between maternal obesity, plasma glucose concentrations, and infant anthropometric measures at birth seem to progressively fade away, whereas the emerging association with paternal BMI may indicate an early postnatal influence of paternal genetics. Among the determinants we evaluated, some are potentially modifiable, such as maternal gestational weight gain and infant feeding. The identification of optimal patterns of growth remains crucial before providing any clinical recommendations.

Gestational diabetes: risk factors and recent advances in its genetics and treatment.

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study of over 23000 diabetes-free pregnancies has shown that at a population level an unequivocal linear relationship exists between maternal glucose concentrations around the beginning of the third trimester of pregnancy and the risk of their baby being born above the ninetieth centile for weight. With the rising incidence of gestational diabetes (GDM) across the developed world, largely paralleling the increased prevalence of obesity, there has been a sharp increase in the risk of pregnancy complications developing related to the birth of macrosomic babies. The associated additional long-term complications of GDM pregnancies means that in the future there is likely to be a large increase in the incidence of type 2 diabetes and associated conditions in both the mothers and their affected offspring. The present review seeks to highlight recent advances and remaining gaps in knowledge about GDM in terms of its genetics (where some of the recently discovered polymorphic risk factors for type 2 diabetes have also proved to be risk factors for GDM) and its treatment by diet, exercise and drugs.

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.

High Fat Programming Induces Glucose Intolerance in Weanling Wistar Rats

We sought to determine whether maintenance on a high fat diet during defined periods of gestation and lactation induced glucose intolerance in weanling Wistar rats or affected food intake, weight, and glucose concentrations in mothers. Experimental groups comprised mothers and their weanling offspring maintained on a high fat diet during gestation and lactation (HFGL), during gestation only (HFG), or during lactation only (HFL). Maternal food intake, body weight, and fasting blood glucose concentrations were determined during lactation. Glucose tolerance was measured in the three-week-old weanling offspring. After overnight fasting, oral glucose tolerance tests were performed in the weanlings. Glucose was collected at (0), 10, 15, 30 and 60 min. HFGL and HFL weanlings had greater glucose concentrations compared to control weanlings at 10, 15, 30 and 60 min. For HFG weanlings, greater glucose concentrations were only found at 30 min, which normalized at 60 min. In all of the experimental groups, the highest glucose concentrations were demonstrated at 30 min, whereas the peak was achieved at 15 min in the control weanlings. Overt glucose intolerance was induced in weanlings maintained on a high fat diet throughout both gestation and lactation or throughout lactation only. Further, weanlings maintained on a high fat diet solely throughout gestation displayed milder glucose intolerance. Developmental programming with a high fat diet during defined periods of gestation and lactation induces glucose intolerance in weanling rats.

Thioredoxin Binding Protein-2 Inhibits Excessive Fetal Hypoglycemia During Maternal Starvation by Suppressing Insulin Secretion in Mice

Glucose is a major fuel for fetal development. Fetal blood glucose level is mainly dependent on maternal blood glucose concentration, though it is also regulated by fetal insulin level. Thioredoxin binding protein-2 (TBP-2), which is identical to vitamin D3 up-regulated protein (VDUP1) and thioredoxin interacting protein (Txnip), was recently reported to be a key transcriptional factor controlling glucose metabolism. Here, we elucidated the functions of TBP-2 in maintaining blood glucose homeostasis during the fetal period. TBP-2(+/-) female mice were mated with TBP-2(+/-) male mice; beginning 16.5-d post coitum, pregnant mice were fed or fasted for 24 h. Under conditions of maternal starvation, the blood glucose levels of TBP-2(-/-) fetuses were significantly lower than those of TBP-2(+/+) fetuses, corresponding to the elevated plasma insulin levels of TBP-2(-/-) fetuses compared with those of TBP-2(+/+) fetuses. There was no difference between TBP-2(+/+) and TBP-2(-/-) fetuses in terms of their pancreatic beta-cell masses or the expression of placental glucose transporters under conditions of either maternal feeding or fasting. Thus, during maternal fasting, fetal TBP-2 suppresses excessive insulin secretion to maintain the fetus's glucose levels, implying that TBP-2 is a critical molecule in mediating fetal glucose homeostasis depending on nutrient availability.

Raised late pregnancy glucose concentrations in mice carrying pups with targeted disruption of H19delta13.

OBJECTIVEWe have hypothesized that variation in imprinted growth-promoting fetal genes may affect maternal glucose concentrations in pregnancy. To test this hypothesis we evaluated the effects of fetal disruption of murine H19Δ13 on maternal glucose concentrations in pregnancy.RESEARCH DESIGN AND METHODSExperimental mice were pregnant females that had inherited the disrupted H19Δ13 from their fathers and were therefore phenotypically wild type due to imprinting; approximately half of their litters were null for H19Δ13 through maternal inheritance of the disrupted gene. In control mice approximately half the litter paternally inherited the disrupted H19Δ13, so the pups were either genetically wild type or phenotypically wild type due to imprinting. Blood glucose concentrations were assessed by intraperitoneal glucose tolerance tests on days 1, 16, and 18 of pregnancy.RESULTSThere were no differences in the glucose concentrations of control and experimental pregnant mice at day 1. However, at day 16 mothers carrying H19Δ13-null pups had a significantly higher area under the glucose tolerance test curves than controls (1,845 ± 378 vs. 1,386 ± 107 mmol · min · l−1 [P = 0.01]) in association with increasing pregnancy-related insulin resistance. Although this difference lessened toward term, overall, mothers of maternally inherited H19Δ13 mutants had significantly higher glucose concentrations during the last trimester (1,602 ± 321 [n = 17] vs. 1,359 ± 147 [n = 18] mmol · min · l−1 [P = 0.009]).CONCLUSIONSThis study provides evidence that maternal glucose concentrations in pregnant mice can be affected by targeted disruption of fetal H19Δ13. This implies that variable fetal IGF2 expression could affect risk for gestational diabetes.

The prolonged effect of repeated maternal glucocorticoid exposure on the maternal and fetal leptin/insulin-like growth factor axis in Papio species.

Maternal obesity represents a risk factor for pregnancy-related complications. Glucocorticoids are known to promote obesity in adults. We evaluated maternal and fetal metabolic changes during and after 3 weekly courses of betamethasone administered to pregnant baboons (Papio subspecies) at doses equivalent to those given to pregnant women. Betamethasone administration during the second half of pregnancy increased maternal weight but neither maternal food intake nor fetal weight, as assessed at the end of gestation. Betamethasone increased maternal serum glucose concentration, the ratio of insulin-like growth factor-I and insulin-like growth factor binding protein-3, and serum leptin during treatment (normalized by 17, 35, and 45 days posttreatment, respectively, for each parameter). Maternal and fetal serum leptin concentrations did not differ between groups at the end of gestation. Prolonged maternal hyperleptinemia caused by betamethasone administration in the second half of gestation did not change fetal metabolic parameters measured and placental leptin distribution at the end of gestation.

Offspring of diabetic pregnancy: Short-term outcomes

In spite of clinicians apparently appreciating the risks of maternal diabetes to the baby, babies of mothers with diabetes are still at increased risk compared to those of non-diabetic women. The rate of prematurity in infants of diabetic mothers is five times that of the general population. Women with pre-gestational diabetes give birth to larger babies. In a recent study, half were above the 90th centile for weight. The postnatal management of these babies continues to give cause for concern. In a recent UK study, over half of all infants of diabetic mothers were admitted to a neonatal unit. One-third of these were at term. This admission rate is three times the UK average and examination of cases showed that two-thirds of admissions were unnecessary. It is likely that a high maternal blood glucose concentration is the most important factor causing this increased risk. Babies of women with type 1 and type 2 DM have similar complication rates. Tighter preconceptional glycaemic control as well as during the pregnancy is likely to be important in improving outcome for the babies of diabetic mothers.

Interaction of PDGFRA promoter haplotypes and maternal environmental exposures in the risk of spina bifida

Neural tube defects are multifactorial malformations involving both environmental exposures, such as maternal nutrition, and genetic factors. Aberrant expression of the platelet-derived growth factor alpha-receptor (PDGFRA) gene has been implicated in neural-tube-defect etiology in both mice and humans. We investigated possible interactions between the PDGFRA promoter haplotype of mother and child, as well as maternal glucose, myo-inositol, and zinc levels, in relation to spina bifida offspring. Distributions were determined of the PDGFRA promoter haplotypes H1 and H2 in a Dutch cohort, consisting of 88 spina bifida children with 56 of their mothers, and 74 control children with 72 of their mothers, as well as maternal plasma glucose, myo-inositol, and red blood cell zinc concentrations. A significantly higher frequency of H1 was observed in children with spina bifida than in controls (30.1 vs. 20.3%; OR = 1.69, 95% CI 1.02-2.83). High maternal body mass index (BMI) and glucose were significant risk factors for both H1 and H2 children, whereas low myo-inositol and zinc were risk factors for H2 but not for H1 children. Stepwise multiple logistic regression analysis showed that high maternal glucose and low myo-inositol are the main risk factors for H2 spina bifida children, whereas for H1 spina bifida children, maternal BMI was the main risk factor. Interestingly, H1 mothers (median 165.5 cm) showed a significantly lower body height than H2 mothers (median 169.1 cm; p = 0.003). These data suggest that the child's PDGFRA promoter haplotype is differentially sensitive for periconceptional exposure to glucose, myo-inositol, and zinc in the risk of spina bifida.

The effects of maternal health and body condition on the endocrine responses of neonatal foals

Chronic and acute alterations in maternal nutrient intake during pregnancy alter pancreatic and hypothalamo-pituitary-adrenal (HPA) axis function in the offspring, before and after birth. Little is known about these effects. To determine whether maternal nutrient restriction caused by natural infection with Streptococcus equi altered endocrine function in neonatal foals born from mares fed a maintenance or high plane of nutrition throughout pregnancy. Ten primiparous mares received either a diet to maintain moderate body condition score (Moderate, n = 5) or a near ad libitum feeding regime to maintain a high body condition score (High, n = 5) throughout pregnancy. All mares inadvertently became infected with Streptococcus equi in mid gestation and lost approximately 10% body mass. Maternal insulin and glucose concentrations decreased (P < 0.05) during, and one month following, the weight loss period. High mares weighed more (P < 0.05) at parturition than Moderate mares; all foals were healthy. Gestational age, foal bodyweights, placental and clinical parameters after birth were no different between the 2 groups. Foal plasma cortisol and glucose responses to exogenous adrenocorticotrophic hormone and insulin, respectively, were similar for both groups. Insulin concentrations during glucose tolerance test were significantly higher (P < 0.05) in foals from Moderate than High mares and compared with foals studied previously from healthy, well-fed mares, suggesting that the beta cell sensitivity to glucose was enhanced in Moderate. Acute nutrient restriction in mid gestation caused by maternal illness and inappetence, superimposed on a maintenance feed intake throughout pregnancy, enhanced insulin secretion to glucose in foals. Nutritional programming of pancreatic beta cells, but not the HPA axis, appeared to depend on the level of nutrition before and after the weight loss period. Disturbances in neonatal pancreatic beta cell function programmed during pregnancy may predispose foals to metabolic problems in later life.

Maternal Blood Glucose Levels Determine the Severity of Diabetic Embryopathy in Mice with Different Expression of Copper-Zinc Superoxide Dismutase (CuZnSOD)

Excess oxygen radical formation is suggested to be involved in the etiology of diabetic embryopathy. We aimed to investigate the effects of altered maternal antioxidative status in conjunction with a varied severity of the maternal diabetic state on embryonic development by using mice with different gene expression of CuZn superoxide dismutase (CuZnSOD). The mice were wild-type (WT), transgenic (TG), or knockout (KO) with regard to CuZnSOD. Alloxan was used to induce diabetes (DWT, DTG, DKO) in female mice before pregnancy and, noninjected mice served as controls (NWT, NTG, NKO). The minimum alloxan dose required to induce diabetes was 80 mg/kg for WT, 100 mg/kg for TG, and 65 mg/kg for KO mice. When KO mice were made diabetic with 80 mg/kg alloxan, they produced no living offspring. The pregnancies were interrupted on gestational day 18, when maternal diabetic state, that is, blood glucose concentration, as well as fetal outcome, genotype and hepatic isoprostane levels were assessed. The mean maternal blood glucose levels were positively associated with the alloxan dose, that is, the DWT and DTG groups had higher blood glucose concentration than the DKO group, and the DWT and DTG fetuses increased their hepatic isoprostane levels, whereas the DKO fetuses did not. However, in all diabetic groups, increased maternal blood glucose concentration was associated with higher resorption and malformation rates as well as lowered fetal and placental weight. Furthermore, diabetes increased the fraction of WT offspring in the TG and KO groups. We conclude that both fetal antioxidative capacity and maternal diabetic state affect the development of the offspring. However, the maternal diabetic state is the major teratogenic factor and overrides the influence of fetal antioxidative capacity.

Continuous Subcutaneous Glucose Monitoring System in diabetic mothers during labour and postnatal glucose adaptation of their infants

To assess a new technique for continuous monitoring of glucose concentration during labour in diabetic mothers. A second objective was to study maternal glucose levels in relation to postnatal glucose adaptation and the need for intravenous (IV) glucose treatment in the newborn infant. Fifteen pregnant women with insulin-treated diabetes mellitus participated in this prospective pilot study. To measure their glucose control during labour we used the Continuous Subcutaneous Glucose Monitoring System (CGMS; Medtronic, Minneapolis, MN, USA) to calculate the mean glucose concentration and the area under the curve (AUC) in the last 120 min before delivery. All infants of these women were transferred to the neonatal care unit for early oral feeding and blood glucose measurements up to 14 h after delivery. Infants received IV glucose if blood glucose values were repeatedly < 2.2 mmol/l. All women coped well with the CGMS monitoring. AUC 0-120 min before delivery, mean glucose concentration 0-120 min before delivery and cord plasma insulin level were all significantly associated with the need for IV glucose in the newborn children. In this study we found an association between maternal glucose concentrations during labour and postnatal glucose adaptation and need for IV glucose treatment in the infants. Online monitoring of glucose levels during delivery might help us to achieve maternal normoglycaemia and further reduce the risk of postnatal hypoglycaemia in the offspring.

Vitamin D insufficiency is common in Indian mothers but is not associated with gestational diabetes or variation in newborn size

Vitamin D is required for bone growth and normal insulin secretion. Maternal hypovitaminosis D may impair fetal growth and increase the risk of gestational diabetes. We have related maternal vitamin D status in pregnancy to maternal and newborn glucose and insulin concentrations, and newborn size, in a South Indian population. Serum 25 hydroxy vitamin D (25(OH)D) concentrations, glucose tolerance, and plasma insulin, proinsulin and 32-33 split proinsulin concentrations were measured at 30 weeks gestation in 559 women who delivered at the Holdsworth Memorial Hospital, Mysore. The babies' anthropometry and cord plasma glucose, insulin and insulin precursor concentrations were measured. In total 66% of women had hypovitaminosis D (25(OH)D concentrations <50 nmol l(-1)) and 31% were below 28 nmol l(-1). There was seasonal variation in 25(OH)D concentrations (P<0.0001). There was no association between maternal 25(OH)D and gestational diabetes (incidence 7% in women with and without hypovitaminosis D). Maternal 25(OH)D concentrations were unrelated to newborn anthropometry or cord plasma variables. In mothers with hypovitaminosis D, higher 25(OH)D concentrations were associated with lower 30-min glucose concentrations (P=0.03) and higher fasting proinsulin concentrations (P=0.04). Hypovitaminosis D at 30 weeks gestation is common in Mysore mothers. It is not associated with an increased risk of gestational diabetes, impaired fetal growth or altered neonatal cord plasma insulin secretory profile.

Mutations in the Glucokinase Gene of the Fetus Result in Reduced Placental Weight

In human pregnancy, placental weight is strongly associated with birth weight. It is uncertain whether there is regulation of the placenta by the fetus or vice versa. We aimed to test the hypothesis that placental growth is mediated, either directly or indirectly, by fetal insulin. Birth weight and placental weight were measured in 43 offspring of 21 parents with mutations in the glucokinase (GCK) gene (25 had inherited the mutation and 18 had not), which results in reduced fetal insulin secretion. Birth weight, placental weight, umbilical cord insulin, and maternal glucose and insulin concentrations were measured in 573 nondiabetic, healthy, term pregnancies. GCK mutation carriers were lighter and also had smaller placentas (610 vs. 720 g, P = 0.042). This difference was also seen in 17 discordant sibling pairs (600 vs. 720 g, P = 0.003). GCK mRNA was not detected in the placenta by RT-PCR. In the normal pregnancies, placental weight was strongly correlated with birth weight (r = 0.61, P < 0.001). Cord insulin concentrations were directly related to placental weight (r = 0.28) and birth weight (r = 0.36) (P < 0.001 for both). These results suggest that insulin, directly or indirectly, plays a role in placental growth, especially as a mutation in the GCK gene, which is known to only alter fetal insulin secretion, results in altered placental weight. This finding is consistent with the preferential localization of the insulin receptors in the fetal endothelium of the placenta in the last trimester of pregnancy.

Metabolic Changes in Pregnancy

Maternal metabolism changes substantially during pregnancy. Early gestation can be viewed as an anabolic state in the mother with an increase in maternal fat stores and small increases in insulin sensitivity. Hence, nutrients are stored in early pregnancy to meet the feto-placental and maternal demands of late gestation and lactation. In contrast, late pregnancy is better characterized as a catabolic state with decreased insulin sensitivity (increased insulin resistance). An increase in insulin resistance results in increases in maternal glucose and free fatty acid concentrations, allowing for greater substrate availability for fetal growth.

Gestational diabetes: aetiology and management

It is well known that raised glucose levels in women with established diabetes increase both morbidity and mortality among their offspring due mainly to an increased incidence of congenital abnormalities and excessive fetal growth in the third trimester. Whether milder elevations of maternal glucose are clinically relevant in pregnancy has been controversial. However, emerging evidence points to a linear increase in fetal risk as maternal glucose concentrations rise. Much of this morbidity can be prevented with aggressive treatment of hyperglycaemia, often with insulin. Furthermore, transient glucose intolerance in pregnancy has major implications for the women affected, since it confers a risk of type 2 diabetes in later life which exceeds 50%. It is therefore now established that gestational diabetes mellitus is of considerable clinical relevance. Obstetric units should establish clear policies to ensure that those at risk are reliably identified, appropriately treated during pregnancy and then equipped to make the necessary lifestyle changes to try and prevent them developing diabetes in later life.

Point: Oral Hypoglycemic Agents Should Not Be Used to Treat Diabetic Pregnant Women

Studies in pregnancy indicate that the most important glucose concentration throughout the day is the peak postprandial glucose response; i.e., it is the highest blood glucose of the day, not the average, that predicts risk of untoward effects. The Diabetes in Early Pregnancy (DIEP) Study was a multicenter, case-controlled trial of type 1 diabetic women compared with healthy control women throughout pregnancy. Along with the primary objective of relating maternal glucose to risk of spontaneous abortions and malformations, they also studied the relationship between maternal postprandial glucose concentrations and risk of neonatal macrosomia (1). The DIEP Study identified 28.5% of infants from diabetic mothers who were above the 90th percentile of infant birth weight. Birth weight correlated positively with first-trimester maternal fasting blood glucose and A1C. When adjusted for fasting blood glucose and A1C, the 1-h postprandial maternal blood glucose concentration in the third trimester was an even stronger predictor of infant birth weight and fetal macrosomia. In addition, they reported that the risk of macrosomia is a continuum. They showed that any postprandial glucose peak was associated with an increased risk of macrosomia above the 10% risk seen in the general population. Combs et al. (2) confirmed the findings of the DIEP Study and added the observation that elevated postprandial glucose was associated with an increased rate of macrosomia when higher maternal postprandial glucose concentrations were observed between weeks 29 and 32 of gestation. In a study of gestational diabetic women who failed a trial of diet and thus required insulin therapy, De Veciana et al. (3) described improved fetal outcome with less risk of neonatal hypoglycemia, macrosomia, and Caesarean delivery in women with gestational diabetes mellitus (GDM) when the women were managed by controlling 1-h postprandial glucose concentrations as opposed to action only based on preprandial glucose concentrations. …