Influence Of Maternal Diabetes Research Articles

The Influence of Maternal Diabetes on the Expression of Inflammatory Markers in the Offspring

Background and aims: Previous studies from our group have shown that maternal diabetes is an important cause of glomerular hypertrophy in the offpring (DO) and that hypertension linked to an impaiment in the vascular endothelium-dependent relaxation is early detected. The present study was designed to evaluate the expression of cytokines/chemokines in plasma and renal tissue from DO and the possible effect of L-arginine administration on those parameters.Methods: Diabetes mellitus was induced in Wistar female rats with a single dose of streptozotocyn, 50mg/kg, IP. Diabetic dams were caged overnight with a male. After birth, each litter was left with the mother for 28 days. Some of the offspring received a 2% L-Arg solution in drinking water (groups DA and CA, controls+ L-arg). Tumor necrosis factor-alpha (TNF-α), interleukin (IL) -6 and IL-1b were measured by real time PCR in the kidney from 2 and 6 month-old rats.Results: Serum expression of TNF-α, interleukin (IL)-1b, IL-2, IL-17, interferon (IFN)-g, macrophage inflammatory protein (MIP)-1and leptin enhanced in DO group and L-arg prevented this increase. TNF-α, interleukin (IL) -6 and IL-1b (measured by real time PCR) in the kidney from DO, 6 month-old, were also increased but returned to control values in DA.Conclusions: Renal and serum inflammatory pathways seem to be early activated in DO, contributing or being the triggering factor for the development of hypertension and renal injury in this model. Our results suggest that these inflammatory pathways can be attenuated by L-arginine.Supported by FAPESP and CNPq

Influence of maternal diabetes on serum leptinemic and insulinemic status of the offspring: A case study of selected patients in a tertiary care hospital in Bangladesh

Introduction Leptin is now known to be an important hormone affecting intrauterine fetal growth. Since growth of fetus is also affected by the glycemic status of the mother. Serum leptin of infant is influenced by the maternal diabetic state. Investigation of cord blood leptin in babies of DM (Diabetes Mellitus) and GDM (Gestational Diabetes Mellitus) mothers (controlled blood glucose levels) may provide some indication about involvement of genetic factor in the development of leptin abnormalities in fetus. Aim The study was taken to investigate whether cord blood insulin, c-peptide and leptin levels correlate with birth weight in offspring of DM mother. Methods Blood was drawn from umbilical cord of 30 babies from GDM mothers (GDM-babies), 45 babies from Type 2 DM Mothers (DM-babies), and 30 babies from ND (Nondiabetic) mothers (ND-babies) of term pregnancy. Weight, blood glucose, placenta, serum leptin and c-peptide of the babies were measured. Results Birth weight of GDM and DM babies were significantly higher compared to ND-babies. Glucose level in GDM babies was significantly higher than ND and DM babies. Leptin levels in GDM babies were significantly higher than that of ND and DM babies. Serum c-peptide in GDM babies was significantly higher than DM and ND babies. However, there was no significant difference in leptin–glucose ratio among the three groups. Irrespective of degree of hyperglycemia leptin is a major determinant of fetal growth. Conclusions DM mother produces different insulinemic and leptinemic responses in the fetus indicating a possible genetic involvement.

Influences of Pre- and Postnatal Nutritional Exposures on Vascular/Endocrine Systems in Animals

Human epidemiological and animal studies have revealed the long-term effects of malnutrition during gestation and early life on the health of the offspring. The aim of the current review is to survey the different means of achieving fetal malnutrition and its consequences, mainly in animals, and to identify key areas in which to direct future research. We address the impact of various models of a maternal protein-restricted diet and global maternal caloric restriction (either through the reduction of nutrient supply or through mechanic devices), the influence of maternal diabetes, and other maternal causes of fetal damage (maternal infections and toxic food components). More specifically, we enumerate data on how the different insults at different prenatal and early postnatal periods affect and program the development and the function of organs involved in diabetes, hypertension, and cardiovascular disease. Particular emphasis is given to the endocrine pancreas, but insulin-sensitive tissues, kidneys, and vasculature are also analyzed. Where available, the protective effects of maternal food supplementation for fetal organ development and function are discussed. Specific attention is paid to the amino acids profile, and the preventive role of taurine is discussed. Tentative indications about critical time windows for fetal development under different deleterious conditions are presented whenever possible. We also discuss future research and intervention.

Influences of pre- and postnatal nutritional exposures on vascular/endocrine systems in animals.

Human epidemiological and animal studies have revealed the long-term effects of malnutrition during gestation and early life on the health of the offspring. The aim of the current review is to survey the different means of achieving fetal malnutrition and its consequences, mainly in animals, and to identify key areas in which to direct future research. We address the impact of various models of a maternal protein-restricted diet and global maternal caloric restriction (either through the reduction of nutrient supply or through mechanic devices), the influence of maternal diabetes, and other maternal causes of fetal damage (maternal infections and toxic food components). More specifically, we enumerate data on how the different insults at different prenatal and early postnatal periods affect and program the development and the function of organs involved in diabetes, hypertension, and cardiovascular disease. Particular emphasis is given to the endocrine pancreas, but insulin-sensitive tissues, kidneys, and vasculature are also analyzed. Where available, the protective effects of maternal food supplementation for fetal organ development and function are discussed. Specific attention is paid to the amino acids profile, and the preventive role of taurine is discussed. Tentative indications about critical time windows for fetal development under different deleterious conditions are presented whenever possible. We also discuss future research and intervention.

Recto-vaginal colonization and urinary tract infection by group B Streptococcus in the pregnant diabetic patient.

The influence of maternal diabetes on Group B Streptococcus (GBS) colonization and GBS urinary infection was investigated. The population under study comprised 1,050 pregnant women (70 of them diabetics, the remaining 980 non-diabetics). A higher prevalence of GBS colonization was found among diabetics (20% versus 10.9%) (p less than 0.05). The rate of colonization was not correlated to the severity of the diabetes condition. Urinary infection was diagnosed on 8.6% of diabetic patients, versus 7.1% of non-diabetics (p greater than 0.05). Urinary infection by GBS occurred with similar frequency in both groups (0% in diabetics and 1% in non-diabetics). The possible etiological implications are commented on, and vaginal and rectal cultures are recommended for GBS screening in the pregnant diabetic patient.

Influence of maternal diabetes in rats on hemoglobin synthesis and uridine uptake by fetal liver cells.

The effect of streptozocin (STZ)-induced maternal diabetes in rats on fetal erythropoiesis was studied in short-term cultures of fetal liver cells at the time of switch from embryonic to adult hemoglobins. Liver erythroid cell functions were monitored by measuring the incorporation of [3H]-uridine in trichloroacetic acid (TCA)-soluble and -insoluble cell fractions and of [3H]-leucine in hemoglobin chains. Fetal liver cells of diabetic rats showed a higher incorporation of [3H]-uridine compared with controls when the cells were obtained from 14-day-old fetuses. However, there were no significant differences in the uptake of uridine when cells were obtained from 16-day-old fetuses. In parallel cell cultures, incorporation of [3H]-leucine into adult and embryonic globin chains was studied by separation of the globin chains by high-performance liquid chromatography (HPLC). The overall globin chain synthesis was higher in the fetuses of diabetic mothers compared with controls on day 14 of gestation. Erythropoietin had similar effects on the stimulation of globin chains in the two groups of fetuses. However, in the fetuses of diabetic mothers, erythropoietin had a specific stimulatory effect on embryonic-type globins that was significantly higher in the fetuses of diabetic mothers compared with controls. Differences between fetuses of control and diabetic mothers completely disappeared at 16 days of gestation. It is concluded that maternal diabetes has an effect on the cells synthesizing embryonic hemoglobins on day 14 of gestation, but by the time the switch from embryonic to adult-type hemoglobins is complete, these differences are abolished.

Influence of maternal diabetes in rats on hemoglobin synthesis and uridine uptake by fetal liver cells

Influence of maternal diabetes in rats on hemoglobin synthesis and uridine uptake by fetal liver cells

Influence of maternal diabetes on basement membranes, type 2 cells, and capillaries in the developing rat lung

To determine the effect of maternal diabetes on rat lung development, we studied the ultrastructure of the alveolar wall from the ninteenth day of gestation (term = 22 days) through the eighth postnatal day in fetal and neonatal rats of mothers with streptozotocin-induced diabetes. In normal fetal lung development, epithelial basement membranes develop large discontinuities beneath type 2 cells, through which cytoplasmic foot processes extend into the interstitium. Maternal diabetes delays the appearances of these epithelial basement membrane discontinuities and reduces the number of type 2 cell processes that penetrate it. These alterations in epithelial basement membrane are reversed after birth. There is no ultrastructural evidence of a delay in type 2 cell maturation as assessed by lamellar body volume density morphometry. Endothelial basement membranes, which are not present around the growing pulmonary capillary bed in the pseudoglandular lung, are seen late in normal gestation, primarily around capillaries forming the mature air-blood barrier. This development of endothelial basement membrane may be delayed in the fetuses of diabetic mothers and reflects a significant delay in the expansion of the pulmonary capillary network in these animals as assessed by morphometric volume density measurements. This effect on capillary growth is not reversed in the newborn animals through 8 days after birth. The summation of these effects indicates a generalized slowing of fetal lung development by maternal diabetes, some of which effects persist after birth and may continue to influence lung development during the period of postnatal alveolar septal growth.

Lung surfactant.

Aspects of pulmonary surfactant are reviewed from a biochemical perspective. The major emphasis is on the lipid components of surfactant. Topics reviewed include surfactant composition, cellular and subcellular sites as well as pathways of biosynthesis of phosphatidylcholine, disaturated phosphatidylcholine and phosphatidylglycerol. The surfactant system in the developing fetus and neonate is considered in terms of phospholipid content and composition, rates of precursor incorporation, activities of individual enzymes of phospholipid synthesis and glycogen content and metabolism. The influence of the following hormones and other factors on lung maturation and surfactant production is discussed: glucocorticoids, thyroid hormone, estrogen, prolactin, cyclic AMP, beta-adrenergic and cholinergic agonists, prostaglandins and growth factors. The influence of maternal diabetes, fetal sex, stress and labor are also considered. Nonphysiologic and toxic agents which influence surfactant in the fetus, newborn and adult are reviewed.

Influence of maternal diabetes on fetal rat development: alteration of insulin receptors in fetal liver and lung.

The influence of maternal diabetes on fetal development was studied in rats made diabetic by administration of streptozotocin on day 2 of gestation as well as in genetically diabetic BB Wistar rats. A dose of 65 mg streptozotocin/kg produced severe diabetes with plasma glucose levels of approximately 36 mmol/l, this was associated with fetal growth retardation but not fetal hyperinsulinaemia. In contrast, a smaller dose of streptozotocin (45 mg/kg) produced moderate diabetes with plasma glucose levels of approximately 20 mmol/l and was associated with fetal hyperinsulinaemia but only a marginal effect on fetal size. In both groups of diabetic animals, maternal body weight gain was decreased, maternal plasma insulin levels were low and fetal glucose levels were similar. In a small group of genetically diabetic BB rats on insulin therapy the fetuses were macrosomic and hyperinsulinaemic. The specific binding of 125I-labelled insulin to partially purified liver and lung membranes of fetuses of both groups of streptozotocin-induced diabetic rats was significantly lower than the binding to membranes from fetuses of control animals. The specific binding of 125I-labelled insulin to fetal liver and lung membranes from the diabetic BB Wistar rats also appeared to be reduced when compared to tissues from controls. Decreased insulin receptors in fetal lung and liver of diabetic rats suggest a role for insulin in the development of these organs during the fetal and neonatal period.

FOETAL-MATERNAL RELATIONSHIPS: ENDOCRINOLOGY

Although the growth and development of the fetus is hormonally modulated, there is little evidence to suggest that maternal hormones play a major role. Thus a relatively impermeable placenta preserves an autonomous status for the endocrine regulation of fetal growth. However indirect effects such as the influence of maternal diabetes upon fetal pancreatic function and of maternal thyrotoxicosis should not be overlooked.On the other hand, the intervention of chorionic hormones into the physiology of the mother is well established, varied, and in some species such as the human and rat, highly complex. It would seem that in gaining the advantages of a longer gestation mammals have faced greater evolutionary pressures to develop mechanisms to safeguard the endometrial-chorial relationship. Although in some species this has been accomplished by mechanisms which simply extend the life of the corpus luteum, in others, chorionic hormones themselves not only ensure the continuation of the progestational state, but actually marshall maternal intermediary metabolism for the benefit of the fetus.Luteotrophic responsibility resides in chorionic gonadotrophins such as hCG and PMSG. It may also be a property of placental lactogen, as for example in the rat where it replaces maternal pituitary hormones on about day 12, and possibly in the human female.More striking roles for placental lactogens are (1) in the alteration of maternal metabolism to fetal advantage and (2) in the stimulation of lobulo-alveolar growth in the mammary gland. In one species at least the subsequent lactational performance is dependent upon the intensity of this chorionic stimulus.Control of chorionic polypeptide hormone secretion is poorly understood. There is little doubt that it is influenced by fetal genotype as in the control of PMSG output in the mare, bPL in the cow and possibly hCG in man.The steroidogenic capability of the conceptus has permitted the fetus to participate in the control of birth. The influence is most complete in sheep where adrenal glucocorticoid induction of placental enzymes permits oestrogen synthesis to increase markedly at the expense of that of progesterone. In rats, where there is evidence of strong maternal influence on the onset of labour, the key event, namely the reduction of ovarian progesterone secretion, may again be determined by the conceptus. In man a fall in progesterone is not obligatory for labour but fetal adrenal participation in chorionic oestrogen biosynthesis may be important. The significance of oestrogen is not clear but may reside in actions on the myometrium and on the cervix, both of which may involve the participation of relaxin.

Influence of maternal diabetes on lipid metabolism in neonatal rat lung

The effect of maternal diabetes on tissue constituents, lipid metabolism and glucose utilization was examined in 1-day old rat lungs. Maternal diabetes was induced by intravenous injection of streptozotocin (50 mg/kg body weight) into pregnant Long-Evans hooded rats on the 10th day of gestation resulting in a maternal serum glucose concentration which was 3-fold higher than that of controls. Neonates from diabetic mothers showed a significant decrease in body weight (14%), lung weight (32%) and lung protein concentration (30%). Glycogen, DNA and lipid content of the lungs were significantly elevated in neonates from diabetic mothers. The percent of total phospholipid made up of phosphatidylcholine was not altered, but the percentage of disaturated phosphatidylcholine was decreased (25%). The activity of the CDPcholine pathway enzymes (choline kinase, cholinephosphate cytidylyltransferase and choline phosphotransferase) also showed a marked increase in lungs of neonates from diabetic mothers. Lung slices of neonates from diabetic mothers showed depressed in vitro incorporation of [U- 14C]glucose into neutral lipids and decreased oxidation to CO 2. The results of these investigations show that maternal diabetes interferes with the structural and metabolic processes by which the undifferentiated lung becomes functional at birth.

Influence of maternal diabetes on composition of plasma free fatty acids (FFA) and glucose in the newborn

Influence of maternal diabetes on composition of plasma free fatty acids (FFA) and glucose in the newborn

Influence of maternal diabetes on the inner ear of the foetus.

This is a report of histological changes found in the temporal bones of a full-term infant whose mother was suffering from severe diabetes mellitus. Pronounced degenerative changes were found throughout the labyrinth, engorgement throughout the blood vessels, and haemorrhages. These findings are in agreement with two cases reported by Kelemen and give reason to assume that the vascular changes so commonly present in diabetics may also involve the blood vessels of the inner ear, resulting in permanent damage of the acoustic-vestibular apparatus.