Social and economic factors, maternal behaviours in pregnancy and neonatal adiposity in the PANDORA cohort.

BACKGROUND: Australian Indigenous women experience high rates of social disadvantage and type 2 diabetes (T2D) in pregnancy, but it is not known how social factors and maternal behaviours impact neonatal adiposity in offspring of women with hyperglycaemia in pregnancy. METHODS: Participants were Indigenous (n = 404) and Europid (n = 240) women with gestational diabetes mellitus (GDM) or T2D in pregnancy and their offspring in the Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) study. Social, economic factors, and maternal behaviours were measured in pregnancy and six neonatal anthropometric outcomes were examined after birth. RESULTS: On univariate analysis, maternal education < 12 years (p = 0.03), unemployment (p = 0.001), welfare income vs no welfare income (p = 0.001), lower area based socio-economic score (p < 0.001), and fast food intake > 2 times/week (p = 0.002) were associated with increased sum of skinfolds (SSF) in offspring. Smoking was significantly associated with a reduction in anthropometric measures, except SSF. In multivariable models adjusted for ethnicity, BMI and hyperglycaemia, social and economic factors were no longer significant predictors of neonatal outcomes. Smoking was independently associated with a reduction in length, head circumference and fat free mass. Frequent fast food intake remained independently associated with SSF (ß-coefficient 1.08 mm, p = 0.02). CONCLUSION: In women with hyperglycaemia in pregnancy, social factors were associated with neonatal adiposity, particularly skinfold measures. Promoting smoking cessation and limited intake of energy-dense, nutrient-poor foods in pregnancy are important to improve neonatal adiposity and lean mass outcomes. Addressing inequities in social and economic factors are likely to be important, particularly for Indigenous women or women experiencing social disadvantage.

Assessment of resting energy expenditure and body composition in Japanese pregnant women with diabetes.

AIMS/INTRODUCTION: To measure longitudinal changes in resting energy expenditure and body composition of Japanese pregnant women with or without diabetes. MATERIALS AND METHODS: The study population consisted of women who had delivered a live singleton neonate after 22 weeks' gestation at Okayama University Hospital from July 2013 to June 2017. Resting energy expenditure and body composition were measured in the first trimester, second trimester, third trimester and postpartum. RESULTS: A total of 144 women participated in this study: 103 with normal glucose tolerance and 41 with diabetes. The resting energy expenditure (kcal/day) of pregnant women with normal glucose tolerance was significantly higher in the third trimester (1,644 ± 234) than in the first (1,461 ± 215) and second trimesters (1,491 ± 219), and postpartum (1,419 ± 254), whereas that of pregnant women with diabetes did not significantly change during all periods (1,568 ± 404, 1,710 ± 332, 1,716 ± 251, 1,567 ± 249). The resting energy expenditure of women with good glycemic control was lower than that of women with poor control. Fat-free mass was closely correlated with resting energy expenditure. CONCLUSIONS: The resting energy expenditure of Japanese pregnant women with normal glucose tolerance was significantly increased in the third trimester. The resting energy expenditure of women with good glycemic control was lower than that of women with poor control. Resting energy expenditure and fat-free mass are potential indexes for medical nutrition therapy in pregnant women with diabetes.

Embryopathy in experimental diabetic gestation: assessment of oxidative stress and antioxidant defence.

Maternal diabetes is associated with an increased rate of congenital fetal anomaly. In the present study, diabetes was induced by streptozotocin in female rats one week prior to conception and the embryos were examined during organogenesis. Experimental diabetes is associated with over-production of free radicals and disturbed antioxidant defence, particularly in malformed embryos. Oxidative stress is demonstrated by increased MDA accumulation and reduced glutathione levels. Despite large differences in the reduced/oxidised glutathione ratios during organogenesis in the control, diabetic non-malformed and malformed embryo groups, the half-cell redox potential was constant for each group during the experimental period. Calculated redox potentials indicated that although embryo cells from the control and diabetic mother groups were of the same chronological age, the stages of development were different. Increased oxidative stress in rat embryos was associated with increased glutathione peroxidases and glutathione-S-transferase activity. This may, in part, provide an explanation for the observed accumulation of oxidised glutathione in malformed embryos. Moreover, decreased levels of vitamin C and selenium were observed. Increased oxidative stress and perturbations in antioxidant defence contribute to the high incidence of congenital anomalies in experimental diabetic gestation.

Embryopathy in experimental diabetic gestation: assessment of PGE2 level, gene expression of cyclooxygenases and apoptosis.

The causes of, and predisposing conditions for, increased congenital anomalies in embryos of experimental diabetic gestation are not fully identified. In the present study, some possible factors involved in diabetes-induced embryopathy are explored. The concentration of PGE2, the gene expression of cyclooxygenases (COX-1 and COX-2) and level of apoptosis (measured by caspase-3 activity) are assessed during organogenesis in the embryos of streptozotocin-induced diabetic rats. The concentrations of PGE2 in the embryos of diabetic rats were lower than controls, with the lowest values in malformed embryos and their associated membranes (yolk sacs). The pattern of change in PGE2 was similar in the embryos of the control and diabetic groups, which showed a steady decline between days 9 and 11 of gestation. These changes in PGE2 were accompanied by a small decrease in COX-1 expression in all embryos and associated membranes during the same gestational period. Expression of COX-2, which was below normal in diabetic embryos, decreased between days 9 and 11 of gestation in all groups. In the membranes of non-malformed embryos, COX-2 expression peaked on day 10 of gestation. It was found that there was little or no detectable COX-2 expression in the membranes of malformed embryos on day 9 of gestation and although its expression was detectable on the following days it was much lower than in the other groups. Caspase-3 activity increased substantially between days 9 and 11 of gestation. Embryos from the experimentally diabetic group showed higher activity than did controls, with the largest increases in the malformed embryos. It would appear that COX-2 expression and PGE2 concentration (in both embryo and associated membranes) play a significant role in organ formation. The data presented here suggest that an unhealthy placenta may be instrumental in the development of malformed embryos.

Non-parametric test of ordered alternatives in incomplete blocks.

Often in medical studies, study subjects become a natural block of observations repeated over a time period. Some subjects miss observations, thus becoming incomplete blocks of observations. We are interested in testing an ordered alternative (or time trend), and propose a non-parametric method to detect a trend in incomplete blocks. Our approach is to estimate the trend by the linear regression method within each block and apply the one-sample Wilcoxon test to the estimated linear trends. The one-sample Wilcoxon test will be sensitive to the trend if it exists. The proposed test statistic is asymptotically normal and consistent. We can also estimate the overall magnitude of the linear trend and its confidence interval by a proper non-parametric method. By Monte Carlo studies, we compare the performance of the proposed test against extended Page and Jonckheere tests. Published in 2000 by John Wiley & Sons, Ltd.

Dietary myo-inositol therapy in hyperglycemia-induced embryopathy.

Dysmorphogenesis in diabetic mothers occurs more frequently than in the general population. This phenomenon is believed to be caused by the teratogenic effects of metabolic fuel mixtures with associated membrane injury and aberrations in the biochemical constituents. The present experiment was designed to determine: 1) if hyperglycemia-induced membrane injury is associated with intracellular and/or extracellular lipid disturbances; 2) if supplemental myo-inositol therapy prevents hyperglycemia-induced embryopathy; 3) if a correlation exists between dietary myo-inositol, serum and tissue levels of myo-inositol, and conceptus development; and 4) the cellular content of arachidonic acid following myo-inositol supplementation. Sixty-five female Sprague-Dawley rats were mated, and divided into three groups. One group was nondiabetic normal controls, and two groups had diabetes experimentally induced with streptozotocin. Of the diabetic groups, one received a normal diet, while the other received a myo-inositol-supplemented diet during the period of organogenesis. Blood samples were collected on days 0 and 12 of pregnancy. Embryos and yolk sacs were analyzed for myo-inositol and arachidonic acid levels, using mass spectrochromatography. Dietary myo-inositol supplementation of diabetic mothers resulted in a significant decrease in the incidence of neural tube defects when compared with diabetics not receiving supplements (9.5 vs. 20.4%; P < 0.05). This protective effect was incomplete, based on the incidence observed in the nondiabetic controls (9.5 vs. 3.8%; P < 0.05). The myo-inositol embryonic tissue levels in the diabetic group which had been fed a regular diet without supplementation were significantly lower than in the nondiabetic group. Dietary therapy successfully restored myo-inositol levels in the yolk sacs, as suggested by similar tissue levels in diabetics receiving myo-inositol supplementation and normal controls (18.7 +/- 1.3 vs. 19.1 +/- 2.0 ng/mg; P = ns). Dietary therapy, however, failed to restore myo-inositol levels in the embryos, suggesting hyperglycemia-induced faulty transport of nutrients from the yolk sac to the embryo. No correlation was noted between maternal blood levels of myo-inositol, with or without supplementation, and the clinical outcome. Tissue arachidonic acid levels were markedly reduced in the conceptuses of diabetic mothers with (0.4 +/- 0.1 micrograms/mg) or without (0.25 +/- 0.08 micrograms/mg) myo-inositol supplementation when compared to the nondiabetic controls (3.33 +/- 0.24 micrograms/mg). These data demonstrate that diabetes-induced embryopathy is associated with a deficiency state in both myo-inositol and arachidonic acid. The myo-inositol deficiency is not demonstrated at the serum level, but rather at the tissue level, suggesting a paracrine action. Dietary supplementation of myo-inositol is associated with an increase in tissue myo-inositol levels and a decrease in malformations. This therapy holds promise for use as a dietary prophylaxis against diabetic embryopathy.

Assessment and management of pregnancies complicated by pregestational and gestational diabetes mellitus.

Diabetes mellitus is a commonly encountered medical complication of pregnancy that affects more than 100,000 pregnancies annually. The discovery of insulin and numerous scientific advances, including both fetal heart rate and glucose monitoring, dramatically improved the outlook for women with diabetes and their offspring. However, despite these recent advances, women with diabetes and their infants still remain at higher risk for a number of complications. Pregnancy has frequently been characterized as having a diabetogenic effect on normal carbohydrate metabolism, as evidenced by hyperglycemia and hyperinsulinemia in response to feeding. This leads to gestational diabetes in 2% to 3% of women and a worsened metabolic state in women with insulin-dependent diabetes mellitus. Since the availability of nutrients for the fetus is primarily dependent on the maternal metabolic state, these aberrations in fuel metabolism are believed to result in a host of perinatal complications, including diabetic embryopathy. In fact, the frequency of congenital anomalies is increased among infants of women with diabetes; they are responsible for approximately 40% of all perinatal deaths. Recent evidence suggests that normalization of blood glucose levels coupled with contemporary management strategies can reduce the frequency of congenital anomalies as well as improve maternal and neonatal outcomes. However, to impact on the congenital anomalies, euglycemia must begin in the preconceptual period and continue throughout organogenesis. Preconception counseling and intensive therapy regimens remain the focus of management programs targeted at women with diabetes.

[Results of 5-year activity in a program for pregnant diabetics in south-eastern Poland. I. Methodology of a unified program and evaluation of the degree of diabetes compensation in pregnant women]. / Wyniki 5-letniej dzialalnosci programu dla ciezarnych z cukrzyca w Polsce poludniowo-wschodniej. I. Metodyka ujednoliconego programu i ocena stopnia wyrównania cukrzycy u ciezarnych.

A model of diabetic-obstetrical management in pregnant diabetics from the south-eastern Poland realized in Cracow has been described. It consists in education, intensive insulin therapy and self-control with borrowed glucose meters. The study included 102 pregnant women enrolled from 1987-1991. It was found that the patients in general with poorly normalized diabetes mellitus referred late to a special unit. It was shown that with experience normoglycemia was achieved with lower insulin doses in four injections. A characteristic feature was a very small number (4) of the patients who had thought of diabetes normalization before pregnancy. Coordinated care provides a possibility of reducing failures in pregnancy, nevertheless it is necessary to develop comprehensive care both before and during pregnancy in diabetic women.

[Study on insulin resistance in rats treated with estrogen and progesterone--assessment with the euglycemic glucose clamp technic].

To clarify the mechanism of insulin resistance in pregnancy, we have used the euglycemic glucose clamp technique in estradiol(E) treatment(n = 6), progesterone(P) treatment (n = 28), and Control(n = 29) female rats. E(10 micrograms/day) and P(10 mg/day) were injected subcutaneously into female rats for 14 days, to increase E and P concentrations to pregnant levels. Glucose production and glucose utilization were measured by using [3-3H]-glucose. The results were as follows, 1) Glucose production was almost suppressed at hyperinsulinemia(11,000 microU/ml) both Control and P treatment rats. Then at hyperinsulinemia, glucose utilization rate was almost equal to glucose infusion rate. 2) In P treatment rats glucose utilization was significantly lower (p less than 0.05) than in Control rats at hyperinsulinemia (11,000 microU/ml). 3) In P treatment rats glucose infusion rate was significantly lower than in Control rats at plasma insulin concentrations of 1,000 microU/ml(p less than 0.02), and 11,000 microU/ml(p less than 0.01), and lower than in E treatment rats at plasma insulin concentrations of 11,000 microU/ml(p less than 0.05). 4) In a dose-response curve for the effects of four different concentrations of insulin on glucose infusion rate, the insulin resistance induced by progesterone is characterized by a decreased responsiveness to insulin. The results suggest that progesterone may play an important role in inducing insulin resistance in pregnancy.

[Significance of amniotic fluid phosphatidylglycerol for the assessment of fetal lung maturity during diabetic pregnancy].

In diabetic pregnancy, a high rate of postnatal development of RDS has been observed even with a mature lecithin/sphingomyelin (L/S) ratio, and the efficacy of phosphatidylglycerol (PG), a second major surfactant phospholipid, in predicting fetal lung maturity remains to be established. In this communication, we determined PG and phosphatidylcholine (PC) in 59 samples of amniotic fluid obtained from 46 pregnant diabetic patients, based on an enzymatic method reported previously. 35 infants who had more than critical PG concentrations (0.36 mumoles/dl) were all associated with normal postnatal respiratory function. 9 out of 10 infants with a PG value lower than this level developed RDS. PG values in patients with mild and severe type diabetes were compared with those of uneventful pregnant women. The appearance of PG was delayed in mild diabetes (Class A, B and C), while it appeared earlier in severe type diabetes (Class D, F and R). Determination of catecholamines together with PG in amniotic fluids of four pregnant women with diabetes indicated that PG values were closely associated with the activities of the fetal adrenergic system. Since an increase in adrenergic activity occurs as a response to fetal distress, amniotic fluid PG is important not only in assessing fetal lung maturity, but also in managing high-risk pregnancies such as diabetic patients.

Fast fraction haemoglobin (HbA1) in the assessment of diabetes control.

The degree of control of 132 diabetic patients was assessed using historical data, urine glucose and blood glucose measurements. These were then related to HbA1, taken as the final arbiter of glycaemic control. Symptoms of hyperglycaemia and glycosuria were found to be not sensitive or specific indices of control, though symptomatic glycosuric patients tended to have higher HbA1. Fasting blood glucose correlated modestly with HbA1 (r = 0.60, p less than 0.001) but if used alone to determine degree of control, 21% and 9% of patients could be expected to be over or under assessed respectively. The assessment value of timed post-breakfast blood glucose applied only to 120 and 150 minutes post-breakfast blood glucose as they correlated well with HbA1 (r = 0.73, p less than 0.001 and r = 0.96, p less than 0.001 respectively). Clinically impression of degree of control based on a combination of historical data, urine glucose and blood glucose led to "undertreatment" in 41% and "overtreatment" in 27% of patients. The complementary value of a knowledge of HbA1 was thus highlighted.

Endocrine assessment of high-risk pregnancies.

For critical obstetrical judgment, no single laboratory test or biophysical technique has proved completely effective in preventing fetal deaths. Endocrine assessment of high-risk pregnancies has proved helpful in managing pregnancies with diabetes, hypertension, third trimester bleeding, suspected IUGR, and postdate pregnancies. No single endocrine test has proved to be effective in all cases, and much research remains to be done. Of the current endocrine factors being evaluated when all factors are considered, serum unconjugated estriol would appear to be the best predictor of fetal distress or well-being. However, it must be remembered that interpretation of laboratory values is difficult, and that there are many false positives and false negatives. Perhaps the greatest problem with estriol interpretation is short-term and daily fluctuations. If the estriol values are used as the only indicator for following high-risk pregnancies, there is a very likely possibility of delivering a normal premature infant that was wrongly diagnosed as having fetal distress. In the following high-risk pregnancies with estriols, the delivery decision should not be based on a single factor. Rather, the decision to deliver should be based on the estriol values, monitoring of the fetal heart rate (rhythm strip or OCT), amniotic fluid evaluation for fetal lung maturity, and clinical judgment.

Amniotic fluid palmitic acid/stearic acid ratios. Lecithin/sphingomyelin ratios and palmitic acid concentrations in the assessment of fetal lung maturity in diabetic pregnancies.

The lecithin/sphingomyelin (L/S) ratio, palmitic acid concentration and palmitic to stearic acid (P/S) ratio were estimated on samples of amniotic fluid obtained from 66 patients with diabetes. These were compared with similar estimates on amniotic fluid obtained from 127 non-diabetic patients. At 35 to 40 weeks, significant differences were observed between the L/S ratio and palmitic acid concentration in diabetics and non-diabetics, whereas the P/S ratio was similar in the two groups. The amniotic fluid L/S ratio, palmitic acid concentration, and P/S ratio were estimated on amniotic fluid obtained from 20 diabetic patients within 48 hours of induction, and the clinical outcome of the newborn infant was used to assess the predictive value of the three parameters. In 19 out of 20 diabetics the P/S ratio correctly predicted fetal lung maturity, whereas the palmitic acid concentration was correct in 12 patients and the L/S ratio in only 10 patients.