Non-diabetic Mothers Research Articles

Gestational diabetes and offspring body disproportion

It has been demonstrated that females born large for gestational age (LGA) in weight but not length are at increased risk of being obese at childbearing age. We addressed the question whether women with gestational diabetes mellitus (GDM) are at increased risk of giving birth to such infants. Birth characteristics of 884,267 infants of non-diabetic mothers and 7817 of mothers with GDM were analysed. LGA was defined as birth weight or birth length >2 standard deviation scores for gestational age. Multiple logistic regression analysis was performed. The odds ratio (OR) for a woman with GDM to give birth to an LGA infant that was heavy alone was four times increased (OR: 3.71, 95% CI: 3.41-4.04). Furthermore, in the population of mothers giving birth to LGA infants, the proportion heavy alone was 68% in the group of women with GDM compared with 64.4% in the group of non-diabetic women. The risks were independent of gender of the foetus. Women with GDM have an almost four times higher risk of delivering an LGA infant that is heavy alone. The noted disproportion between weight and length in infants of such mothers may have an impact on the risk of later obesity.

Is there a Relationship between Metabolic Control and Glucose Concentration in Breast Milk of Type 1 (Insulin-Dependent) Diabetic Mothers?

We studied glucose concentration of breast milk of nursing diabetic mothers and its possible relationship to the quality of metabolic control. Eleven Type 1 (insulin-dependent) diabetic mothers and 11 age-matched control subjects were included in the study. Although a near-normoglycemic control of diabetic mothers was accomplished by intensified insulin treatment, the HbA1 value was significantly higher in comparison to non-diabetic mothers (8.1 +/- 0.9% versus 6.2 +/- 0.5%; p less than 0.01). Regardless of this, the glucose concentration of breast milk did not differ between diabetic mothers and that of non-diabetic women (0.68 +/- 0.50 mmol/l versus 0.66 +/- 0.55 mmol/l). No correlation exists between glucose concentration of breast milk and relevant blood glucose concentration as well as glycosylated haemoglobin A1 of the mother. In conclusion, our data support the view that breast-feeding of infants of diabetic mothers is not associated with an increased offer of glucose and thus not being of importance as a possible mechanism to sustain a hyperinsulinemic state in the newborns.

Neonatal outcomes of macrosomic births in diabetic and non-diabetic women

Objective:To compare the neonatal outcomes and birth injuries of macrosomic infants born to diabetic mothers (IDM) and non-diabetic mothers (non-IDM).Study design:This is a retrospective survey of all live born, singleton...

Impact of maternal body mass index on neonatal outcome

IntroductionMaternal body mass index has an impact on maternal and fetal pregnancy outcome. An increased maternal BMI is known to be associated with admission of the newborn to a neonatal care unit. The reasons and impact of this admission on fetal outcome, however, are unknown so far.ObjectiveThe aim of our study was to investigate the impact of maternal BMI on maternal and fetal pregnancy outcome with special focus on the children admitted to a neonatal care unit.MethodsA cohort of 2049 non-diabetic mothers giving birth in the Charite university hospital was prospectively studied. The impact of maternal BMI on maternal and fetal outcome parameters was tested using multivariate regression analysis. Outcome of children admitted to a neonatal ward (n = 505) was analysed.ResultsIncreased maternal BMI was associated with an increased risk for hypertensive complications, peripheral edema, caesarean section, fetal macrosomia and admission of the newborn to a neonatal care unit, whereas decreased BMI was associated with preterm birth and lower birthweight. In the neonatal ward children from obese mothers are characterized by hypoglycaemia. They need less oxygen, and exhibit a shorter stay on the neonatal ward compared to children from normal weight mothers, whereas children from underweight mothers are characterized by lower umbilical blood pH and increased incidence of death corresponding to increased prevalence of preterm birth.ConclusionPregnancy outcome is worst in babies from mothers with low body mass index as compared to healthy weight mothers with respect to increased incidence of preterm birth, lower birth weight and increased neonate mortality on the neonatal ward. We demonstrate that the increased risk for neonatal admission in children from obese mothers does not necessarily indicate severe fetal impairment.

The type 1 diabetes protective HLA DQB1*0602 allele is less frequent in gestational diabetes mellitus

We tested whether gestational diabetes mellitus (GDM) is associated with HLA-DQ genotypes. A total of 764 mothers with non-autoimmune (GAD65, insulinoma-associated protein 2 [IA-2] and insulin autoantibody-negative) GDM were ascertained between September 2000 and August 2004 in the population-based Diabetes Prediction in Skåne (DiPiS) study. HLA-DQB1 genotypes were determined in these mothers and in 1191 randomly selected non-diabetic control mothers also negative for islet autoantibodies. The data were analysed in relation to maternal age, country of birth, number of pregnancies/siblings and pregnancy weight gain. The frequency of type 1 diabetes high-risk HLA-DQ alleles (DQB1*0201, DQB1*0302) did not differ between GDM mothers and controls. In contrast, the low-risk DQB1*0602 allele was less prevalent (OR 0.64, 95% CI = 0.51-0.80, p = 0.0006) in GDM than in control mothers. The difference in DQB1*0602 frequency between GDM mothers and controls remained after multiple logistic regression analysis correcting for maternal age, country of birth, number of pregnancies/siblings and weight gain during pregnancy (OR 0.67, 95% CI 0.51-0.88, p = 0.009). The negative association between mothers who have non-autoimmune GDM and HLA-DQ*0602 suggest that this allele may protect not only from type 1 diabetes but also from GDM.

Status of essential trace metals in biological samples of diabetic mother and their neonates

There is accumulating facts that the metabolism of essential trace elements is altered in diabetic patients. The aim of present study was to compare the status of essential trace elements, chromium (Cr), manganese (Mn), and zinc (Zn) in biological samples (whole blood, urine and scalp hair) of insulin dependent diabetic mothers (age ranged 30-40) and their newly born infants (n = 76). An age matched 68 non-diabetic mothers and their infants, residing in the same locality, were selected as referents. For a comparative study, the biological samples of non-diabetic and diabetic pregnant and non pregnant of same age group and socio-economics status were also analysed. The biological samples (scalp hair, blood and urine) were collected from study and referent groups. The Cr, Mn and Zn concentrations in all three biological samples were determined by a flame/electrothermal atomic absorption spectrometer, prior to microwave assisted acid digestion. The validity and accuracy of the methodology was checked by certified reference materials (CRMs) and using conventional wet acid digestion method on same CRMs. The mean values of Cr, Mn and Zn in scalp hair and blood samples of diabetic mothers and their infants were significantly lower as compared to the referent mothers-infants pairs (p < 0.01), while urinary excretion of all these elements were high in diabetic mother-infant pair samples. The deficiencies of essential trace elements, Cr, Mn and Zn in biological samples of diabetic women, may play role in the pathogenesis of diabetes mellitus and impacts on their neonates.

Fetal macrosomia in non-diabetic mothers: Antenatal diagnosis and delivery outcome

SummaryThis is a retrospective study of 74 non-diabetic women that delivered babies in excess of 4,500 g. The women were divided into two groups, depending on whether there had been suspected macrosomia antenatally or not. Mode of delivery and rates of induction of labour were examined. Women diagnosed with a macrosomic fetus were more likely to have elective caesarean sections or premature induction of labour. Those women in whom macrosomia was not suspected had higher rates of vaginal deliveries without any increase in neonatal morbidity.

An investigation into genetic contribution to the relationship between insulin resistance and birth weight

BACKGROUND:Insulin resistance has been proposed to be the most likely phenotypic trait that could represent a genetic link between low birth weight and type 2 diabetes, especially in Southeast Asia. Insulin resistance can persist for many years, even decades, before the manifestation of overt diabetes. There have been many studies suggesting a strong genetic basis in the etiology of type 2 diabetes mellitus. There is also ample evidence providing a link with low birth weight and type 2 diabetes in later life. Hence, parental insulin sensitivity could well serve as a representation of the offspring's future insulin resistance state. Association between maternal insulin sensitivity and the incidence of type 2 diabetes mellitus in low birth weight babies is confounded by many factors and hence, has limited value in the determination of any genetic origin of the disease. Therefore, the present study was done to investigate the relationship between paternal insulin sensitivity and the growth parameters of the foetus to determine a genetic link between poor early growth and the increased risk of type 2 diabetes mellitus in later life.MATERIALS AND METHODS:The study was performed on 30 healthy fathers and their babies born from nondiabetic mothers. Each father underwent a low-dose short insulin tolerance test (ITT) as a measure of insulin sensitivity. Placental weight was recorded and a blood sample was collected from the placental side of the umbilical cord at birth for measurement of insulin. Measurement of birth weight, length, and head circumference were recorded and ponderal index was calculated from the formula: weight (kg)/ length (cm)3. Individual parameters of insulin resistance syndrome were measured in the fathers.RESULTS:The degree of insulin sensitivity, Km (constant for insulin tolerance test) did not correlate with the fetal growth parameters (Ponderal Index r = 0.031, P = 0.870; weight of baby r = 0.010, P = 0.959; length of baby r = 0.087, P = 0.464; head circumference r = 0.280, P = 0.142) or with the fathers' anthropometric measures: body mass index (BMI), blood pressure, fasting glucose, insulin, and lipid profiles.CONCLUSION:The data suggest that the mechanism linking insulin resistance with low birth weight is not a genetically determined defect.

Gender differences in serum leptin concentrations from umbilical cord blood of newborn infants born to nondiabetic, gestational diabetic and type-2 diabetic mothers

To investigate gender differences, if any, in leptin concentrations from umbilical cord blood of new born infants of mothers with type 2 diabetes mellitus (DM), gestational diabetes mellitus (GDM), and Non diabetic (ND) at delivery. Serum leptin concentrations were measured in 105 newborns (53 males and 52 females in the three groups). Blood was taken from the umbilical cord of the babies at delivery. Maternal anthropometric measurements were recorded within 48 hours after delivery. Pearson correlation coefficient was used to explore the relationship between serum leptin concentrations and anthropometric measures of the fetus and their mother. Both Serum leptin level and serum C-peptide was measured by chemiluminescence based ELISA. The median range of leptin concentration in cord blood was ND group: Male [13.91 (3.22 – 47.63)], Female [16.88 (2 – 43.65)]; GDM group: Male [32 (7 – 76.00)], Female [36.73 (4.80 – 81.20)]; DM group: Male [20.90 (2 –76.00)], Female [32 {2.58 – 80.67)]. Cord serum leptin levels correlated with birth weight(r=0.587, p=0.0001), ponderal index (PI) (r=.319, p=0.024)of the babies and body mass index (BMI) (r=−0.299, p=0.035) of their mothers but did not correlate with gestational age, cord serum C-peptide concentration or placental weight at delivery. Leptin concentrations were higher in the female fetus in comparison to the male fetus. Birth weight of the female fetuses were also higher than that of male fetus. We found that there are very strong associations between cord leptin concentrations at delivery and birth weight, ponderal index of the baby, body mass index of the mothers with Type 2 DM. We also found that high leptin levels could represent an important feedback modulator of substrate supply and subsequently for adipose tissue status during late gestation or adipose tissue is the major determinant of circulating leptin levels.

Determining a cutoff for fetal lung maturity with lamellar body count testing

Objective. A lamellar body count (LBC) ≥50,000/μl is suggested to document fetal lung maturity (FLM). We sought to determine the LBC threshold for FLM with the Cell-dyn 4000 hematology analyser.Methods. We queried our database for patients who underwent LBC testing from 2001 to 2007. Included were deliveries between 35 and 38 weeks gestation with testing ≤7 days from delivery. We excluded twins, anomalies and cases of ruptured membranes. Data were analysed for sensitivity and specificity of predicting respiratory distress syndrome (RDS) and plotted on a receiver operating characteristic curve.Results. There were 209 patients meeting study criteria. Of these, 120 had diabetes. Five neonates experienced RDS, all born to non-diabetic mothers with LBC values ≤72,000/μl. At this value the sensitivity is 100%, false positive rate 18% and the p value is 0.0146.Conclusion. Our results question the 50,000/μl threshold and demonstrate the need for hematology analyser specific thresholds.

Risk for developing gestational diabetes in women with twin pregnancies

Objective. To examine the risk of developing gestational diabetes mellitus (GDM) in women with twin compared with singleton pregnancies.Research design and methods. We examined a cohort of 23,056 pregnant women who gave birth to a live infant between 1 September 1998 and 31 December 2006, 553 of whom had twin pregnancy. The primary exposure was twin versus singleton pregnancy, and the primary outcome was the development of GDM. Standard univariate analyses were performed, as were multivariable analysis with logistic regression to control for potential confounding variables. GDM was diagnosed using criteria of the National Diabetes Data Group.Results. Patients with twin pregnancies had a higher rate of GDM when compared with singleton pregnancies (3.98%vs. 2.32%; p = 0.01). In a multiple regression analysis after adjusting for age, race/ethnicity, body mass index, maximal systolic and diastolic blood pressure, smoking and parity, twin pregnancy was associated with an approximately two-fold increase in risk for developing GDM (OR 2.2, 95% CI 1.4–3.6). In a stratified analysis, women between the ages of 25 and 30 years and African-American women had the highest risk of developing GDM in twin pregnancies. When compared with twins of non-diabetic mothers, twins of gestational diabetics had a higher rate of admission to the neonatal intensive care unit (37%vs. 52%; p = 0.05), had longer hospitalisation (8 ± 0.5 vs. 16 ± 4 days; p = 0.01) and higher rate for respiratory distress syndrome (7%vs. 27%; p = 0.001).Conclusion. There is a significant increase in the incidence of GDM in twin pregnancies versus singleton pregnancies. The risk is highest in African-American and young women.

Left atrial shortening fraction in fetuses with and without myocardial hypertrophy in diabetic pregnancies

To test the hypothesis that, in diabetic pregnancies, left atrial shortening fraction (LASF) is decreased in fetuses with myocardial hypertrophy, compared to those without hypertrophy and to fetuses of non-diabetic mothers. Fetal echocardiography was performed in women with pre-existing or gestational diabetes and in non-diabetic controls between 25 weeks' gestation and term. LASF was calculated using the formula: (end-systolic diameter-end-diastolic diameter)/end-systolic diameter, and data were compared between diabetic women with and without fetal myocardial hypertrophy and controls. The study population comprised 53 diabetic women and 45 controls. Out of the 53 fetuses of diabetic women, 14 had myocardial hypertrophy and 39 had normal septal thickness. Gestational age at the time of examination did not differ significantly between the control group and the two diabetic subgroups (P = 0.57). Fetuses with myocardial hypertrophy presented a mean ( +/- SD) LASF of 0.32 +/- 0.11, those without myocardial hypertrophy 0.46 +/- 0.12, and those of normal mothers 0.53 +/- 0.09 (P < 0.001). A significant inverse linear correlation was observed between LASF and septal thickness (r = - 0.51, P < 0.001). In diabetic pregnancies, LASF is lower in fetuses with myocardial hypertrophy than it is in those without hypertrophy and in fetuses of non-diabetic women, suggesting that LASF could be a useful alternative parameter in the assessment of fetal diastolic function.

Pregnancy insulin, glucose, and BMI contribute to birth outcomes in nondiabetic mothers.

OBJECTIVE—We investigated the effects of normal variations in maternal glycemia on birth size and other birth outcomes.RESEARCH DESIGN AND METHODS—Women in two unselected birth cohorts, one retrospective (n = 3,158) and one prospective (n = 668), underwent an oral glucose challenge at 28 weeks of gestation. In the retrospective study, glycemia was linked to routine birth records. In the prospective study, offspring adiposity was assessed by skinfold thickness from birth to age 24 months.RESULTS—In the retrospective study, within the nondiabetic range (2.1–7.8 mmol/l), each 1 mmol/l rise in the mother's 60-min glucose level was associated with a (mean ± SEM) 2.1 ± 0.8% (P = 0.006) rise in absolute risk of assisted vaginal delivery, a 3.4 ± 0.8% (P < 0.0001) rise in emergency cesarean delivery, a 3.1 ± 0.7% (P < 0.0001) rise in elective cesarean delivery, and a 46 ± 8 g (P < 0.0001) increase in offspring birth weight. In the prospective study, fetal macrosomia (birth weight >90th centile) was independently related to the mother's fasting glucose (odds ratio 2.61 per +1 mmol/l [95% CI 1.15–5.93]) and prepregnancy BMI (1.10 per +1 kg/m2 [1.04–1.18]). The mother's higher fasting glycemia (P = 0.004), lower insulin sensitivity (P = 0.01), and lower insulin secretion (P = 0.02) were independently related to greater offspring adiposity at birth. During postnatal follow-up, the correlation between the mother's glycemia and offspring adiposity disappeared by 3 months, whereas prepregnancy BMI was associated with offspring adiposity that was only apparent at 12 and 24 months (both P < 0.05).CONCLUSIONS—Prepregnancy BMI, pregnancy glycemia, insulin sensitivity, and insulin secretion all contribute to offspring adiposity and macrosomia and may be separate targets for intervention to optimize birth outcomes and later offspring health.

Disease-associated autoantibodies during pregnancy and at birth in families affected by type 1 diabetes.

We studied the pattern of type 1 diabetes-associated autoantibodies during pregnancy and the transplacental transfer of these autoantibodies to the fetal circulation and searched for possible signs of prenatal induction of beta-cell autoimmunity in newborn infants. The population comprised 208 mothers and their newborn infants. Seventy-four of the mothers (36%) had type 1 diabetes and 134 (64%) of the infants had an affected father or sibling. Blood samples were obtained from the mother at the end of the first trimester and at delivery, and from the cord blood of the newborn infant. Close to 40% of the mothers with type 1 diabetes had antibodies to islet cells (ICA), 55% to glutamic acid decarboxylase (GADA) and 54% to the IA-2 protein (IA-2A) in early pregnancy, whereas the corresponding frequencies in the nonaffected mothers were 5.2%, 5.2% and 3.0%. No significant changes could be seen in autoantibody levels during pregnancy, and there was a close correlation between the two maternal samples. One third of the infants of mothers with type 1 diabetes tested positive for ICA, 50% for GADA and 51% for IA-2A. Six percent of the infants of nondiabetic mothers had ICA, 2.2% GADA and none had IA-2A. None of the infants of the antibody negative mothers had antibodies in their cord blood. These observations indicate that the immunomodulatory effect of pregnancy on signs of beta-cell autoimmunity is weak, but if diabetes-associated autoantibodies are present in the mother, most of them are transferred to the fetal circulation. Our data do not provide any support for fetal induction of beta-cell autoimmunity.

Effectiveness of sucrose analgesia in newborns undergoing painful medical procedures.

Sucrose is widely used to manage procedural pain in term newborns despite a lack of evidence of its effectiveness for different procedures and infant populations. Our objectives were to evaluate the effectiveness and safety of sucrose in newborns undergoing various medical procedures within 2 days of birth. We performed a double-blind, randomized controlled trial. We included newborns (>or= 36 weeks gestation) of diabetic mothers and nondiabetic mothers. Each newborn received 2 mL of a 24%-sucrose or placebo solution before all procedures. We used the Premature Infant Pain Profile to assess pain during intramuscular injection of vitamin K, venipuncture for the newborn screening test and the first 3 heel lances for glucose monitoring (newborns of diabetic mothers only). Scores ranged from from 0 (no pain) to 18 (maximum pain). We included 240 newborns (120 from diabetic mothers, 120 from nondiabetic mothers). The overall mean pain score was lower among newborns who received sucrose than among those who received a placebo (mean difference -1.3, 95% confidence interval [CI] -2.0 to -0.6). We found that pain scores during intramuscular injection did not differ significantly between the sucrose and placebo groups for newborns of diabetic or nondiabetic mothers (newborns of nondiabetic mothers: mean difference -1.1, 95% CI -2.4 to 0.2; newborns of diabetic mothers: mean difference -1.0, 95% CI -2.4 to 0.4). During venipuncture, newborns who received sucrose had lower pain scores compared with those who received a placebo (newborns of nondiabetic mothers: mean difference -3.2, 95% CI -4.6 to -1.8; newborns of diabetic mothers: mean difference -2.4, 95% CI -3.8 to -1.0). Among newborns of diabetic mothers, there was no difference in pain during the first 3 heel lances or mean glucose levels between the sucrose and placebo groups (p = 0.94 and p = 0.29 respectively). We found a modest reduction of pain in newborns of both diabetic and nondiabetic mothers when sucrose was used for all medical procedures performed in the first 2 days after birth. However, when each procedure was analyzed separately, we found that the effectiveness of sucrose was limited to venipuncture for the newborn screening test. (http://Clinicaltrials.gov trial register no. NCT00213213.).

Assessment of diastolic ventricular function in fetuses of diabetic mothers using tissue Doppler

To identify the presence of ventricular diastolic dysfunction by tissue Doppler in fetuses of diabetic mothers, with or without septal hypertrophy, in comparison to fetuses of nondiabetic mothers. A contemporary transverse study in fetuses with a gestational age between 25 weeks to term, studying diastolic function by assessment using tissue Doppler and pulsed wave Doppler of the atrioventricular diastolic flow. The mothers of the fetuses all had previous or gestational diabetes, and were referred to the Fetal Cardiology Unit of the Institute of Cardiology in Porto Alegre, Brazil. We analysed variance with the Student-Neumann-Keuls post hoc test. An alfa of 0.05 was considered significant for statistical analysis. The mean myocardial velocities of the E'and A' waves at the mural mitral annulus, in fetuses of diabetic mothers with myocardial hypertrophy, were, respectively, 7.00 plus or minus 1.6 centimetres per second, and 10.24 plus or minus 3.3 centimetres per second. In the fetuses of diabetic mothers group without myocardial hypertrophy, the comparable values were 7.19 plus or minus 2.4 centimetres per second and 10.77 plus or minus 3.77 centimetres per second, respectively. In the control group, they were 4.81 plus or minus 0.85 centimetres per second and 8.01 plus or minus 2.2 centimetres per second. The difference between the velocities in fetuses of diabetic mothers and in fetal normal mothers was statistically significant (p less than 0.05). Statistically significant differences were also observed in E' and A' diastolic waves at the aortic mitral annulus, as well as for the tricuspid annulus when tissue Doppler assessment was carried out in the same sample. The mean ratio between the E and E' of mitral and tricuspid waves in the control fetuses of normal mothers was significantly higher than in fetuses of diabetic mothers. Pulsed tissue Doppler, when used in fetuses of diabetic mothers and compared with fetuses of nondiabetic mothers, shows evidence of impaired diastolic function, independently of the presence of myocardial hypertrophy.

Maternal diabetes causes coordinated down-regulation of genes involved with lipid metabolism in the murine fetal heart

Maternal diabetes is associated with increased transport of lipids to the fetus and increased risk of hypertrophic cardiomyopathy in the fetus. During fetal life, the heart normally has limited capacity to use lipids as fuel; and, at least in adults, cardiac lipid accumulation may lead to cardiomyopathy. Postnatally, lipid supply is increased when the offspring begins to suckle. We examined offspring from hypoinsulinemic Ins2 Akita mice to assess whether maternal diabetes results in fetal myocardial hypertrophy and triglyceride accumulation and compared these with fetal hearts collected postnatally. On embryonic days 16 to 19, the fetal heart weight and triglyceride content were similar in offspring from Ins2 Akita and nondiabetic wild-type mothers. The heart expression of lipid-metabolizing genes (peroxisomal proliferator-activated receptor α, lipoprotein lipase, fatty acid translocase, and fatty acid transport protein 1) was reduced in offspring from Ins2 Akita mothers with high blood glucose levels and were closely intercorrelated, suggesting coordinated down-regulation. In contrast, on day 1 postnatally where the lipid availability to the heart is markedly increased, heart triglycerides and expression of several lipid-metabolizing genes (including lipoprotein lipase and fatty acid transport protein 1) were increased in offspring from wild-type mice. The results suggest that maternal type 1 diabetes mellitus in Ins2 Akita mice does not cause cardiac hypertrophy or triglycerides accumulation in the fetal heart, possibly because of a coordinated down-regulation of genes controlling fatty acid uptake.

Maternal type 1 and gestational diabetes: postnatal differences in insulin secretion in offspring at preschool age

It is well known that children born to mothers with diabetes in pregnancy are more likely to develop metabolic abnormalities in later life. Most prior studies have not differentiated between offspring of mothers with type 1 diabetes (T1DM) and gestational diabetes (GDM) or lack a control group of non-exposed offspring. Offspring of T1DM (n = 16), GDM (n = 22) and mothers without diabetes (n = 25) born at Oulu University Hospital. To assess insulin secretion and insulin resistance in the offspring of T1DM and GDM at preschool age in comparison with offspring of non-diabetic mothers. Anthropometric measurements and intravenous glucose tolerance testing were performed. First-phase insulin response (FPIR) and homoeostasis model assessment (HOMA) values were calculated. Pregnancy and birth data were analysed in relation to later metabolic parameters in all three groups using one-way analysis of variance (ANOVA) and analysis of covariance (ANCOVA). At a mean age of 4.9 yr, offspring of T1DM had increased fasting serum insulin concentrations (p = 0.044), FPIR (p = 0.034) and HOMA-B values (p = 0.008) compared with offspring of GDM or with offspring of healthy controls (statistically non-significant). The GDM gained least weight during pregnancy, and when adjusted for maternal weight gain during pregnancy, there were no statistically significant differences between study groups. Prenatal exposures to maternal type 1 and gestational diabetes may have different effects on postnatal glucose metabolism in the offspring assessed at a mean age close to 5 yr. Maternal weight gain in pregnancy may affect the postnatal glucose metabolism in the offspring.

Caudal dysgenesis, sirenomelia, and situs inversus totalis: A primitive defect in blastogenesis

Caudal dysgenesis (CD) constitutes a heterogeneous spectrum of congenital caudal anomalies, including varying degrees of agenesis of the vertebral column, as well as anorectal and genitourinary anomalies. Sirenomelia, characterized by a fusion of the lower limbs, could represent the most severe end of this spectrum. The two main debated pathogenic hypotheses are an aberrant vascular supply versus a primary axial mesoderm defect. We present the autopsy findings of two fetuses of non-diabetic mothers, with normal karyotype. Both fetuses presented situs inversus associated with a CD, in one case consisting of sirenomelia, establishing a very rare association profile that might be random. This association also suggests the occurrence of a common pathogenic mechanism, in accordance to recent genetic data, such as displayed in the Kif3A murine mutation phenotype. Some cases of sirenomelia and CD could represent developmental field defects of blastogenesis involving the caudal mesoderm, rather than being related to vascular insufficiency.

Novel De Novo Mutation in Sulfonylurea Receptor 1 Presenting as Hyperinsulinism in Infancy Followed by Overt Diabetes in Early Adolescence

OBJECTIVE—Congenital hyperinsulinism, usually associated with severe neonatal hypoglycemia, may progress to diabetes, typically during the 4th decade of life in nonpancreatectomized patients. We aimed to genotype the ATP-sensitive K+ channel in a 10.5-year-old girl presenting with overt diabetes following hyperinsulinism in infancy.RESEARCH DESIGN AND METHODS—A female aged 10.5 years presented with new-onset, antibody-negative diabetes (A1C 10.6%). She was born large for gestational age (5 kg) to a nondiabetic mother and developed frequent hypoglycemic episodes, which persisted until age 3 years and responded initially to intravenous glucose and later to oral sweets. Currently, she is fully pubertal and obese (BMI 30.2 kg/m2), with a partially controlled convulsive disorder (since age 1 year) and poor school performance. Glucose levels were >11.1 mmol/l throughout 72 h of continuous glucose monitoring, with low insulin secretion during intravenous glucose tolerance testing. KCNJ11 and ABCC8 mutation analysis was performed, and the mutation identified was characterized in COSm6 cells.RESULTS—A novel, de novo heterozygous ABCC8 sulfonylurea receptor (SUR)1 mutation (R370S) was identified in the patient's DNA but not in that of either parent. Cotransfection of Kir6.2 and mutant SUR1 demonstrate that the mutated protein is expressed efficiently at the cell surface but fails to respond to MgADP, resulting in minimal channel activity. Interestingly, the heterozygous channel (WT:R370S) responded well to glibenclamide, a finding that lead to the successful initiation of sulfonylurea therapy.CONCLUSIONS—This new ABCC8 mutation is associated with neonatal hyperinsulinism progressing within 10 years to insulinopenic diabetes. Consistent with in vitro findings, the patient responded to sulfonylurea treatment. The mechanism causing the relatively rapid loss in β-cell function is not clear, but it may involve mutation-induced increased β-cell apoptosis related to increased metabolic demand.