Offspring Of Gestational Diabetic Mothers Research Articles

Gestational diabetes induces behavioral and brain gene transcription dysregulation in adult offspring

The etiology of Autism Spectrum Disorders (ASD) includes a strong genetic component and a complicated environmental component. Recent evidence indicates that maternal diabetes, including gestational diabetes, is associated with an increased prevalence of ASD. While previous studies have looked into possible roles for maternal diabetes in neurodevelopment, there are few studies into how gestational diabetes, with no previous diabetic or metabolic phenotype, may affect neurodevelopment. In this study, we have specifically induced gestational diabetes in mice, followed by behavioral and molecular phenotyping of the mice offspring. Pregnant mice were injected with STZ a day after initiation of pregnancy. Glucose levels increased to diabetic levels between E7 and E14 in pregnancy in a subset of the pregnant animals. Male offspring of Gestational Diabetic mothers displayed increased repetitive behaviors with no dysregulation in the three-chambered social interaction test. RNA-seq analysis revealed a dysregulation in genes related to forebrain development in the frontal cortex and a dysregulation of a network of neurodevelopment and immune related genes in the striatum. Together, these results give evidence that gestational diabetes can induce changes in adulthood behavior and gene transcription in the brain.

Exposure to maternal gestational diabetes is associated with higher cardiovascular responses to stress in adolescent indians.

Context:Altered endocrinal and autonomic nervous system responses to stress may link impaired intra-uterine growth with later cardiovascular disease.Objective:To test the hypothesis that offspring of gestational diabetic mothers (OGDM) have high cortisol and cardiosympathetic responses during the Trier Social Stress Test for Children (TSST-C).Design:Adolescents from a birth cohort in India (n = 213; mean age, 13.5 y), including 26 OGDM, 22 offspring of diabetic fathers (ODF), and 165 offspring of nondiabetic parents (controls) completed 5 minutes each of public speaking and mental arithmetic tasks in front of two unfamiliar “evaluators” (TSST-C). Salivary cortisol concentrations were measured at baseline and at regular intervals after the TSST-C. Heart rate, blood pressure (BP), stroke volume, cardiac output, and total peripheral resistance were measured continuously at baseline, during the TSST-C, and for 10 minutes after the test using a finger cuff; the beat-to-beat values were averaged for these periods.Results:Cortisol and cardiosympathetic parameters increased from baseline during stress (P < .001). OGDM had greater systolic BP (mean difference, 5.6 mm Hg), cardiac output (0.5 L/min), and stroke volume (4.0 mL) increases and a lower total peripheral resistance rise (125 dyn · s/cm5) than controls during stress. ODF had greater systolic BP responses than controls (difference, 4.1 mm Hg); there was no difference in other cardiosympathetic parameters. Cortisol responses were similar in all three groups.Conclusions:Maternal diabetes during pregnancy is associated with higher cardiosympathetic stress responses in the offspring, which may contribute to their higher cardiovascular disease risk. Further research may confirm stress-response programming as a predictor of cardiovascular risk in OGDM.

Circulating Docosahexaenoic Acid Levels Are Associated with Fetal Insulin Sensitivity

BackgroundArachidonic acid (AA; C20∶4 n-6) and docosahexaenoic acid (DHA; C22∶6 n-3) are important long-chain polyunsaturated fatty acids (LC-PUFA) in maintaining pancreatic beta-cell structure and function. Newborns of gestational diabetic mothers are more susceptible to the development of type 2 diabetes in adulthood. It is not known whether low circulating AA or DHA is involved in perinatally “programming” this susceptibility. This study aimed to assess whether circulating concentrations of AA, DHA and other fatty acids are associated with fetal insulin sensitivity or beta-cell function, and whether low circulating concentrations of AA or DHA are involved in compromised fetal insulin sensitivity in gestational diabetic pregnancies.Methods and Principal FindingsIn a prospective singleton pregnancy cohort, maternal (32-35 weeks gestation) and cord plasma fatty acids were assessed in relation to surrogate indicators of fetal insulin sensitivity (cord plasma glucose-to-insulin ratio, proinsulin concentration) and beta-cell function (proinsulin-to-insulin ratio) in 108 mother-newborn pairs. Cord plasma DHA levels (in percentage of total fatty acids) were lower comparing newborns of gestational diabetic (n = 24) vs. non-diabetic pregnancies (2.9% vs. 3.5%, P = 0.01). Adjusting for gestational age at blood sampling, lower cord plasma DHA levels were associated with lower fetal insulin sensitivity (lower glucose-to-insulin ratio, r = 0.20, P = 0.036; higher proinsulin concentration, r = −0.37, P <0.0001). The associations remained after adjustment for maternal and newborn characteristics. Cord plasma saturated fatty acids C18∶0 and C20∶0 were negatively correlated with fetal insulin sensitivity, but their levels were not different between gestational diabetic and non-diabetic pregnancies. Cord plasma AA levels were not correlated with fetal insulin sensitivity.ConclusionLow circulating DHA levels are associated with compromised fetal insulin sensitivity, and may be involved in perinatally “programming” the susceptibility to type 2 diabetes in the offspring of gestational diabetic mothers.

266: The risk of childhood obesity in toddler offspring of gestational diabetic mothers

266: The risk of childhood obesity in toddler offspring of gestational diabetic mothers

The Fetal Origins of Disease and Associations With Low Birthweight

After completing this article, readers should be able to: 1. Explain the fetal insulin hypothesis. 2. Explain the thrifty phenotype hypothesis. The importance of the early environment for long-term health has been recognized for many years. Seventy years ago, observations in England, Scotland, and Sweden showed that death rates decreased between 1751 and 1930 due to improved childhood living conditions. Death rates in specific age groups at any time depended more on the date of birth of the individuals than the year under consideration. A relationship between infant mortality and ischemic heart disease in the same geographic cohort of Norwegians was reported in the 1970s. There was a positive correlation between death rates from heart disease and geographic variations in past infant mortality rates. A study in the United Kingdom by Williams and colleagues showed similar findings. These relationships were linked to events in childhood and adolescence. A study by Wadsworth and associates in 1985 revealed that adult blood pressure was inversely related to birthweight in British men and women, which was linked to “social and familial factors, smoking, and body mass.” In 1986, Barker and Osmond examined mortality rates from stroke and cardiovascular diseases in different areas of England and Wales. They noticed a parallel relationship between neonatal mortality in the 1920s and 1930s and the mortality rates from strokes and cardiovascular diseases in the 1960s and 1970s from the same geographic areas. In the early 20th century, a high neonatal mortality rate was an indication of a high occurrence of low-birthweight babies and of poor nutrition and health of the mothers. Barker and Osmond concluded that the health of the mothers was important in determining the risk of stroke in their offspring and proposed that cardiovascular diseases might originate during fetal life or early childhood. To follow up these findings, …

Antecedents of Childhood Adiposity in the Offspring of Gestational Diabetic Mothers (OGDM)

Antecedents of Childhood Adiposity in the Offspring of Gestational Diabetic Mothers (OGDM)

THE EFFECTS OF GESTATIONAL DIABETES AND GENDER ON ATTENTION, BEHAVIOR, AND COGNITION AT 4 AND 5 YEARS OF AGE. † 87

Male gender has been linked to ↑ behavior and attention problems. Offspring of gestational diabetic mothers (OGDM) have also been found to be at increased risk for cognitive and behavior problems. The purpose of this study is to examine the effects of gestational diabetes and gender on behavior and cognition at 4 and 5 yrs of age. It was hypothesized that OGDM would be at↑ risk of attention, behavior, and cognitive problems and that OGDM boys would be at the greatest risk. 105 OGDM (58 boys, 47 girls) and 104 controls(C) (54 boys, 50 girls) were studied at 4 yrs. 80% were also seen at 5 yrs. The children were videotaped during a 15 min free play session, which was coded for attention (switches, longest, average) by a blind observer. The mothers completed the Eyberg Child Behavior Inventory and the EAS Temperament Survey (to assess activity). A Test Behavior Checklist rating attention during WPPSI-R testing was completed. Results: Table At 4 yrs, OGDM and C girls performed better than OGDM or C boys on the WPPSI-R(p<0.04). At 4 and 5 yrs, both OGDM and C boys were rated as being more active than OGDM or C girls (p<0.04). At 5 yrs, OGDM boys and girls had better attending skills [longer average time spent per toy] than C boys or girls (p<0.02). No other group differences [OGDM-control] were identified. At 4 yrs, ↓ attention correlated with ↓ IQ, and ↑ switches correlated with ↓ IQ (p<0.02); for OGDM boys but no other group. In summary, although both OGDM and control boys were ↑ active, had ↑ behavior problems and ↓ IQ scores; for OGDM boys ↓ attending ability impacted negatively on behavior and cognition, suggesting ↑ vulnerability.