Fetal Hyperinsulinemia Research Articles

Placental Vascular Dysfunction in Diabetic Pregnancies: Intimations of Fetal Cardiovascular Disease?

In the human placenta, the angioarchitecture of fetal vessels lying in maternal blood is useful for nutrient uptake, but it makes the synthesis, maturation and functioning of placental vessels vulnerable to any alterations in the fetal and maternal environment. This review discusses how the maternal diabetic milieu, and the resultant fetal hyperglycemia and hyperinsulinemia, may act together to produce an altered placental vascular phenotype, which includes increased angiogenesis, altered junctional maturity, increased vascular endothelial-like growth factor (VEGF), altered VEGF and insulin receptor profiles, and upregulation of genes involved in signal transduction, transcription and mitosis in placental endothelial cells. The placental vascular dysfunction does extend to other fetal vascular beds including endothelial cells from umbilical vessels, where there are reports of elevated basal iNOS activity and altered sensitivity to insulin. There is emerging evidence of epigenetic modulation of fetal endothelial genes in diabetes and long-term vascular consequences of this. Thus, placental vascular dysfunction in diabetes may be contributing to and describing disturbances in the fetal vasculature, which may produce an overt pathological response in later life if challenged with additional cardiovascular stresses.

Technology and pregnancy

The World Health Organisation projects that the number of diabetes-related deaths will double between the years 2005 and 2030. An important method for reducing the number of new cases of diabetes is by screening for and controlling glucose in women with gestational diabetes, the form of diabetes that afflicts up to 10% of the pregnant population. Uncontrolled gestational diabetes mellitus results in an increased risk of complications due to maternal hyperglycaemia and the resultant fetal hyperinsulinaemia. These complications include macrosomia and an increased risk of metabolic disorders including diabetes later in the child's life. Advances in the treatment of gestational diabetes have shown promising results in minimising fetal complications; they have also helped to slow the vicious cycle of women who contract gestational diabetes mellitus producing children with a high risk of developing diabetes later in life. A comprehensive literature review with an emphasis on technology has resulted in the following collection of papers relating to pregnancy and diabetes. Last year there were several technological advances in glucose monitoring. This year the applications of telemedicine in the treatment of gestational diabetes and the use of ultrasound for early detection of the disease have been at the forefront. The authors aimed to include articles that were not only relevant to the field of diabetes technology in pregnancy, but that also improved treatment and advanced understanding. The study design and results were also carefully examined in considering the articles. The selected articles contain findings that provide new techniques for diagnosing gestational diabetes mellitus as well as provide additional treatment methods for those affected by the disease.

Evaluation of Glycemic and Lipid Profile of Offspring of Diabetic Wistar Rats Treated withMalpighia emarginataJuice

Knowing that maternal diabetes is related to hyperglycemia and fetal hyperinsulinemia, which affect the lipid metabolism, the aim of this study was to evaluate the effects of Malpighia emarginata (acerola) juice on the glycemic and lipid profile of offspring of diabetic and nondiabetic Wistar rats. The adult offspring of non-diabetic dams and of dams with severe streptozotocin-induced diabetes were divided into groups: G1, offspring (of control dams) treated with water, G2, offspring (of diabetic dams) treated with water, G3, male offspring (of control dams) treated with acerola juice, and G4, male offspring (of diabetic dams) treated with acerola juice. The offspring of diabetic dams treated with acerola juice showed significantly decreased levels of glucose, cholesterol, triglycerides, and increased HDL-c. The use of acerola juice is a potential strategy to aid in the prevention of DM and dyslipidemia and its complications or to act as an auxiliary in the treatment of these diseases.

Critères diagnostiques du diabète gestationnel

To answer two questions: is there a threshold for pathological hyperglycemia after 24 weeks of gestation? What are the diagnostic criteria for gestational diabetes mellitus? Review of the literature considering the relationships between glucose values and complications during pregnancy in women without specific care for this condition. Only the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study meets sufficient quality criteria. Increasing glucose values during pregnancy, either at fasting and after a 75-g oral glucose-tolerance test, are independently associated with adverse pregnancy outcomes, especially birth weight above the 90th percentile for gestational age, caesarian delivery and fetal hyperinsulinemia. There is no obvious threshold at which risks increase. The International Association of Diabetes Pregnancy Study Group has proposed, considering the glycemic values associated with a 1.75-fold increased risk of macrosomia, fetal hyperinsulinism and adiposity in the HAPO study, the following criteria: fasting plasma glucose ≥ 0.92 g/L (5.1 mmol/L) and/or 1-hour plasma glucose value ≥ 1.80 g/L (10.0 mmol/L) and/or 2-hour plasma glucose value ≥ 1.53 g/L (8.5 mmol/L). Choosing glycemic threshold to define gestational diabetes mellitus is necessarily arbitrary because of a continuum. Only experts may propose definition criteria.

Technology and pregnancy

In the USA, depending upon the diagnosis criteria used, 135,000-200,000 women annually develop gestational diabetes mellitus, adding to the number of pregnant women already suffering from either type 1 or type 2 diabetes. Maternal hyperglycaemia and the resultant fetal hyperinsulinaemia are central to the pathophysiology of diabetic complications of pregnancy. These complications include congenital malformations and an increase in neonatal intensive care unit admission and birth trauma. In addition, there is an increased rate of accelerated fetal growth, neonatal metabolic complications and risk for stillbirth. Importantly, during the last century there were two breakthroughs in diabetes management and monitoring that changed the course of treatment: the discovery of insulin and the progress in the understanding of glucose monitoring. As technology has evolved, both glucose monitoring and insulin administration can now be achieved in a continuous fashion. In this review of the literature we focus on the utility of new technologies in the management and monitoring of diabetes in pregnancy.

Insulin Action on the Human Placental Endothelium in Normal and Diabetic Pregnancy

The placental endothelium is unique among the entire human vasculature. The blood enriched in oxygen and nutrients is transported in the veins, whereas the arteries contain deoxygenated blood coming from the fetus. The placental vasculature has to develop rapidly to ensure adequate supply of the fetus. Therefore, factors present in the fetal circulation will stimulate placental angiogenesis. In the third trimester of pregnancy the placental endothelium is richly endowed with insulin receptors. In a pregnancy complicated by maternal diabetes, fetal hyperinsulinemia resulting from maternal and, hence, fetal hyperglycaemia induces changes in the placental vasculature such as increased growth and angiogenesis. This review will discuss general effects of insulin on endothelial cells and further focus on insulin effects on the placental endothelium. Isolation and culture of placental endothelial cells has allowed the identification of insulin effects in vitro. These include metabolic effects of insulin i.e. stimulation of glycogen synthesis, and modulation of angiogenesis on the placental arterial endothelium i.e. regulation of ephrin-B2 expression, an arterial specific signalling molecule implicated in sprouting. The effect of insulin on ephrin-B2 in placental arterial endothelial cells as well as their particularly high expression levels of insulin receptors and receptors for vascular endothelial growth factors indicate that placental angiogenesis is likely to emanate from the arterial compartment and is stimulated by insulin.

Vascular dysfunction in the diabetic placenta: causes and consequences

The development and functioning of the human fetoplacental vascular system are vulnerable to the maternal diabetic milieu. These vessels are in direct continuum with the fetal vascular system and are therefore also vulnerable to fetal endocrine derangements. Increased angiogenesis, altered junctional maturity and molecular occupancy, together with increased leakiness, constitute a well-described phenotype of vessels in the Type 1 diabetic human placenta and can be related to increased levels of placental vascular endothelial growth factor. The causes of these observed changes, whether maternal hyperglycaemia or fetal hyperinsulinaemia, still remain to be shown in the human placenta. Mechanistic studies using different vascular systems have shown high glucose and insulin to have profound vascular effects, with elevations in vascular endothelial growth factor, nitric oxide and protein kinase C being behind alterations in junctional adhesion molecules such as occludin and vascular endothelial-cadherin and vascular leakage of albumin. The role of advanced glycation products and oxidative stress in this vascular pathology is also discussed. The altered molecular mechanisms underlying the vascular changes in the diabetic human placenta may reflect similar consequences of high glucose and hyperinsulinaemia.

Maternal mid-pregnancy serum triglyceride levels and neonatal birth weight

Although disturbances in maternal glucose metabolism and resultant fetal hyperinsulinemia are known to significantly impact fetal overgrowth, it has been suggested that other fuels such as lipids and amino acids may be the determinants of fetal growth in nondiabetics. Maternal serum lipid levels increase in mid to late pregnancy; and in women with gestational diabetes, elevated triglycerides were significantly associated with birth weight corrected for gestational age. Although the role of maternal hyperlipidemia in fetal growth is not known, maternal fasting serum triglyceride levels at 24 to 32 weeks of Pregnancy were shown to be significantly and positively associated with neonatal weight at term,independent of maternal prepregnancy obesity, weight gain during pregnancy, or mid-pregnancy plasma glucose levels (either fasting or postprandial) in Japanese and white women. The aim of the present study was to determine the relationship between maternal mid-pregnancy serum lipid levels and neonatal birth weight in our region. Fasting levels of serum triglycerides and total cholesterol were evaluated in 108 consenting consecutive women who attended for prenatal care with a singleton pregnancy between 24 to 34 weeks and who had abnormal results on the glucose challenge test (plasma glucoseN140 mg/dL) and normal results from the oral 100 g 3-hour glucose tolerance test. Women with antiphospholipid antibody syndrome, hypertension, or thyroid disorder were excluded. The relationship between mid-pregnancy triglyceride and total cholesterol values and neonatal birth weight was determined according to fasting glucose, body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) and pregnancy weight gain—with 95 mg/dL, 25, and 10 kg as the cut-off values, respectively. The relative risk of having heavier babiesweighing 3.5 kg or greater was 2 (95% CI, 0.9–4.2) for women with hypertriglyceridemia and 2.6 (95% CI, 0.78–8.4) when controlled for fasting glucose, BMI, and pregnancy weight gain. When studied together, the combination of hypertriglyceridemia, fasting hyperglycemia, and higher BMI was a significant predictor of heavier neonates. It is important to note that the higher relative risk for heavier babies in women with hypertriglyceridemia persisted even when the variables such as greater BMI, greater pregnancy weight gain, and hyperglycemia were accounted for. With a combination of greater BMI and fasting hyperglycemia, women with hypertriglyceridemia had a much higher relative risk for heavier babies (RR 9.7; 95% CI, 1.7–62.6).

Environmental rather than genetic fetal overgrowth: defining the difference and hints for diagnosis and management

Environmental rather than genetic fetal overgrowth: defining the difference and hints for diagnosis and management

Neonatal glucose metabolism in offspring of mothers with varying degrees of hyperglycemia during pregnancy

The definition of neonatal hypoglycemia is controversial. Operational thresholds of blood glucose values at which intervention should be considered have been proposed. IDM and GDM infants frequently exhibit a pronounced drop of plasma glucose immediately after birth. This exaggerated physiological decline of glucose is transient and is seldom accompanied by suppressed lipolysis or clinical symptoms. It is generally attributed to hyperinsulinism elicited by maternal hyperglycemia. Alternative substrates for CNS i.e. lactate and astrocyte glycogen may explain lack of symptoms. Similarly low glucose values later on may cause clinical symptoms. Glucose production rates vary from attenuated to normal likely reflecting differences in maternal glycemic control. The HAPO study of around 25,000 non-diabetic pregnancies revealed strong associations between glucose values (75g OGTT) and increased fetal size and hyperinsulinemia at birth - findings adding strong support to the maternal hyperglycemia - fetal hypinsulinism theory. Mothers with the highest fasting glucose had infants with the highest frequency of clinical neonatal hypoglycaemia (4,6%).

Normal Pregnancy and Healthy Child After Continued Exposure to Gliclazide and Ramipril During Pregnancy

To report a case of exposure to gliclazide and ramipril during pregnancy in a patient with diabetes mellitus and hypertension. A 42-year-old female with type 2 diabetes mellitus and hypertension who had been taking gliclazide 30 mg/day and ramipril 10 mg/day for 2 years was admitted in the 16th week of gestation. The following week, gliclazide and ramipril were discontinued and methyldopa 500 mg 4 times daily and intensive insulin therapy were instituted. Blood glucose concentrations and blood pressure remained within acceptable levels throughout the pregnancy. The patient gave birth to a healthy child (3200 g) by cesarean section after completing an uneventful gestation period. Oral antidiabetic drug use in pregnancy is not recommended secondary to known effects on the fetus such as congenital abnormalities, fetal hyperinsulinemia, macrosomia, and neonatal hypoglycemia. Although this infant had no abnormalities after being exposed to gliclazide and ramipril during the first 16 weeks of gestation, this case is not an unconditionally acceptable indication for safety of these medications in pregnancy. Angiotensin-converting enzyme inhibitors increase fetal risks and therefore should not be used during pregnancy, according to data from animals and humans. There are few data available on use of sulfonylureas; thus, their use should also be avoided during pregnancy. Although the normal pregnancy outcome in our patient does not indicate that use of gliclazide and ramipril is safe during gestation, these data contribute to limited information regarding human exposure to these drugs.

Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study

OBJECTIVE—To examine associations of neonatal adiposity with maternal glucose levels and cord serum C-peptide in a multicenter multinational study, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, thereby assessing the Pederson hypothesis linking maternal glycemia and fetal hyperinsulinemia to neonatal adiposity.RESEARCH DESIGN AND METHODS—Eligible pregnant women underwent a standard 75-g oral glucose tolerance test between 24 and 32 weeks gestation (as close to 28 weeks as possible). Neonatal anthropometrics and cord serum C-peptide were measured. Associations of maternal glucose and cord serum C-peptide with neonatal adiposity (sum of skin folds >90th percentile or percent body fat >90th percentile) were assessed using multiple logistic regression analyses, with adjustment for potential confounders, including maternal age, parity, BMI, mean arterial pressure, height, gestational age at delivery, and the baby's sex.RESULTS—Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, cord serum C-peptide results were available for 19,885 babies and skin fold measurements for 19,389. For measures of neonatal adiposity, there were strong statistically significant gradients across increasing levels of maternal glucose and cord serum C-peptide, which persisted after adjustment for potential confounders. In fully adjusted continuous variable models, odds ratios ranged from 1.35 to 1.44 for the two measures of adiposity for fasting, 1-h, and 2-h plasma glucose higher by 1 SD.CONCLUSIONS—These findings confirm the link between maternal glucose and neonatal adiposity and suggest that the relationship is mediated by fetal insulin production and that the Pedersen hypothesis describes a basic biological relationship influencing fetal growth.

Developmental programming of adult hyperinsulinemia, increased proinflammatory cytokine production, and altered skeletal muscle expression of SLC2A4 (GLUT4) and uncoupling protein 3

Fetal glucocorticoid excess programs detrimental effects in the adult phenotype including hyperleptinemia and aberrant glycemic control. In this study, we determined the interactive effects of maternal dexamethasone (Dex) treatment and postnatal dietary omega-3 (n-3) fatty acids on adult proinflammatory cytokine production and skeletal muscle expression of genes central to glucose handling and fatty acid metabolism. Dex acetate was administered to pregnant rats (0.75 microg/ml drinking water) from day 13 to term. Offspring of treated and control mothers were cross-fostered to mothers on either a standard (Std) or high n-3 (Hn3) diet, and remained on these diets postweaning. Adult offspring exposed to Dex in utero exhibited fasting hyperinsulinemia when raised on the Std diet but not when raised on the Hn3 diet. Dex also programmed increased plasma tumour necrosis factor alpha and interleukin 1 beta (IL-1 beta), but the increase in IL-1 beta was also prevented by the Hn3 diet. In skeletal muscle, expression of insulin regulated Slc2a4 (formerly known as GLUT4) was elevated (up to 15-fold) after Dex in utero, and this resulted in elevated intracellular, but not membrane-associated, SLC2A4 protein. Fetal glucocorticoid excess also reduced adult skeletal muscle Ucp3 expression in all offspring, whereas skeletal muscle expression of both Ppard and Ppargc1a were increased in females but not males. In conclusion, our data show that fetal glucocorticoid excess programs adult hyperinsulinemia and increased proinflammatory cytokine production. Related changes in the skeletal muscle Slc2a4, Ucp3, and Ppard indicate that fetal glucocorticoid excess disturbs adult glucose/fatty acid transport and metabolism.

Fetal growth in women managed with insulin pump therapy compared to conventional insulin

Objective Fetal hyperinsulinaemia secondary to maternal hyperglycaemia is considered to be the driving force behind excessive fetal growth. We hypothesised that insulin pump therapy (continuous subcutaneous insulin infusion, CSII) would improve maternal glycaemic control and normalise fetal growth parameters. To this end, this study compares maternal glycaemic control and fetal growth of women receiving insulin pump therapy with those receiving conventional insulin therapy. Study design Prospective non-randomised study of 42 women with pre-existing diabetes attending a joint obstetric diabetic clinic. Each woman was offered the choice of commencing insulin pump therapy or remaining on a conventional insulin regime. Estimated fetal weight and fetal growth velocity were calculated from routinely collected third trimester ultrasound biometry and expressed as standard deviation ( Z) scores. Results Eighteen women commenced insulin pump therapy. There was no difference in pre-conception glycosylated haemoglobin A1c concentrations (HbA1c) between pump and conventional therapy groups (mean HbA1c 7.62 versus 8.01; p = 0.49) or third trimester glycaemic control (mean HbA1c 6.63 versus 6.44; p = 0.51). Women using pump therapy had similar mean growth velocity Z scores (1.5 versus 1.36; p = 0.83), similar mean estimated fetal weight Z scores prior to delivery (2.80 versus 2.16; p = 0.16) and similar mean birthweight Z scores (2.09 versus 2.00; p = 0.86) compared to women using conventional insulin therapy. Conclusion This small, non-randomised study suggests that the use of insulin pump therapy offers no benefit in terms of normalising fetal growth velocity, fetal size, birthweight or improving maternal glycaemic control compared to conventional insulin therapy.

Treatment With Insulin and Its Analogs in Pregnancies Complicated by Diabetes

Before the advent of insulin in 1922, 90% infant mortality rate and a 30% maternal mortality rate. As late as 1980, physicians were still counseling diabetic women to avoid pregnancy. This philosophy was justified because of the poor obstetric history in 30–50% of diabetic women. Improved infant mortality rates finally occurred after 1980, when treatment strategies stressed better control of maternal plasma glucose levels, once self-monitoring of blood glucose and A1C became available. As the pathophysiology of pregnancy complicated by diabetes has been elucidated and as management programs have achieved and maintained near-normoglycemia throughout pregnancy complicated by diabetes, perinatal mortality rates have decreased to levels seen in the general population (2–5). This review reports the literature on the safety and efficacy of insulin analogs in pregnancy and thereby enables the clinician to choose the optimal insulin treatment protocol to achieve and maintain normoglycemia throughout pregnancies complicated by diabetes. Maternal glucose freely crosses the placenta. Maternal insulin does not cross the placenta unless it is bound to IgG antibody, which carries it through the placenta or insulin is forced through the placenta by high perfusion (6,7). Diabetic fetopathy is thought to be the result of fetal hyperinsulinemia (1–9). Thus, our treatment must be designed to normalize maternal blood glucose concentrations without the use of exogenous insulins that cross the placenta. Placental transfer of insulin complexed with immunoglobulin has also been associated with fetal macrosomia in mothers with near-normal glycemic control during gestation. Menon et al. (8) reported that antibody-bound insulin transferred to the fetus was proportional to the concentration of antibody-bound …

Role of lipids and fatty acids in macrosomic offspring of diabetic pregnancy

Diabetic pregnancy frequently results in macrosomia or fetal obesity. It seems that the anomalies in carbohydrate and lipid metabolism in macrosomic infants of diabetic mothers are due to maternal hyperglycemia, which leads to fetal hyperinsulinemia. We have developed a rat model of macrosomic offspring and assessed the onset of obesity in these animals. The macrosomic offspring born to diabetic mothers are prone to the development of glucose intolerance and obesity as a function of age. It seems that in utero programming during diabetic pregnancy creates a "metabolic memory" which is responsible for the development of obesity in macrosomic offspring. We have demonstrated that the metabolism of lipids, and altered anti-oxidant status and immune system are implicated in the etiopathology of obesity in these animals. We have reported beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) in obese animals, born to diabetic dams.

Increased farnesylation of p21-Ras and neonatal macrosomia in women with gestational diabetes

Six of 22 mothers with gestational diabetes mellitus had infants with macrosomia, cord blood hyperinsulinemia, and increased amounts of a key mitogenic intermediate, farnesylated p21-Ras. The ability of fetal hyperinsulinemia to increase the availability of farnesylated p21-Ras may represent one mechanism of the growth-promoting action of insulin during fetal development.

Can ultrasound fetal biometry predict fetal hyperinsulinaemia at delivery in pregnancy complicated by maternal diabetes?

Objective The aim of this study was to determine whether there is an association between ultrasound fetal biometry and amniotic fluid insulin levels at delivery in women with pre-existing diabetes or impaired glucose tolerance in pregnancy. Study design This retrospective cohort study identified 93 women who had amniotic fluid insulin levels measured at time of delivery. Standardised estimated fetal weight and fetal growth velocity were calculated from serial third trimester fetal ultrasound measurements. Results Women with pre-existing diabetes had significantly greater mean growth velocity [1.39 (95% CI: 0.43–2.23) versus 0.39 (95% CI: −01.7–0.95); p = 0.04], significantly greater mean estimated fetal weight (EFW) Z score prior to delivery [2.36 (95% CI: 1.82–2.9) versus 1.38 (95% CI: 1.02–1.74); p = 0.002] and greater mean birthweight centile [82 (95% CI: 0.74–0.89) versus 67 (95% CI: 58–76); p = 0.02] than those with GDM/IGT. Amniotic fluid insulin levels demonstrated a similar significant difference between the pre-existing and GDM/IGT groups [20.5 (95% CI: 12.9–28.1) versus 8.5 (95% CI: 5.4–11.7); p = 0.001]. An association between fetal growth and size and amniotic fluid insulin was observed in women with pre-existing diabetes. Positive likelihood ratios were 1.67 and 2.08, respectively, for the prediction of liquor insulin greater than the 95th centile in women with pre-existing diabetes. Conclusion Ultrasound measures of fetal size and growth used in this study are not sufficiently accurate to predict those infants likely to be at risk from the adverse effects of fetal hyperinsulinaemia.

The importance of postprandial glucose concentration: lessons learned from diabetes and pregnancy

AbstractPregnancy may be considered as a model for the importance of postprandial hyperglycemia on the risk of complications in diabetic subjects in the non‐pregnant state. Although pregnancy is only 9 months, the accelerated growth of the fetus is very sensitive to glucose variability and may be similar to a “life time” of struggle for survival. The toxicity due to hyperglycemia during pregnancy manifests itself by fetal overgrowth secondary to maternal overnourishment to the fetus. Glucose is the main nutrient that passes to the fetus by facilitated diffusion. Thus, maternal hyperglycemia results in a big baby who is also sick secondary to fetal hyperinsulinemia and the resultant metabolic aberrancy. In addition, if the fetus has inherited the type 2 diabetes gene or genes, then the fetal adiposity tends to be accrual of visceral fat, an abnormal distribution of fat in utero that increases the risk of subsequent type 2 diabetes in the child if the baby survives the insult. Studies have shown that the maternal postprandial glucose concentration is the most important variable associated with fetal overgrowth. The studies that support the importance of maternal postprandial glucose concentrations as the primary risk factor in fetopathy and this discussion suggests that these observations may extrapolate to the non‐pregnant person with diabetes and are presented in this review. Drug Dev. Res. 67:591–594, 2006. © 2006 Wiley‐Liss, Inc.

Diabetes in pregnancy

Diabetes occurs in approximately 2–5% of all pregnancies. As the UK antenatal population becomes older, more obese and more ethnically diverse the number of pregnant women with pre-existing type 2 diabetes and gestational diabetes will increase. Whether diabetes precedes the pregnancy or arises within it, the risk of accelerated fetal growth, stillbirth and neonatal hypoglycaemia are all increased. As a generalization, adverse pregnancy outcomes increase with increasing maternal glycaemia. Hyperglycaemic-mediated oxidative stress has been implicated as a cause for the increased congenital malformation rates and early fetal loss associated with diabetic pregnancies. While fetal hyperinsulinaemia, secondary to maternal hyperglycaemia, is the cause of accelerated fetal growth and neonatal hypoglycaemia. Achieving optimal maternal glycaemic control prior to and throughout pregnancy is a pivotal goal in the management of all diabetic pregnancies. This degree of control requires all diabetic women contemplating a pregnancy to have access to preconception counselling and being managed with intensive insulin regimens throughout pregnancy. The medical and obstetric surveillance of pregnant diabetic women should be undertaken in a specialized multidisciplinary clinic, where diabetic complications, such as retinopathy and nephropathy, can be regularly assessed, as can fetal growth and development. As birth trauma and stillbirth are all more frequent in diabetic pregnancies elective delivery between 38–39 weeks is usually advised. At birth there is an increased risk of transient metabolic disturbances and in later life an increased risk of adolescent obesity, the metabolic syndrome and type 2 diabetes in young adulthood.