Myo-Inositol Moderates Glucose-Induced Effects on Human Placental 13C-Arachidonic Acid Metabolism.

Maternal hyperglycemia is associated with disrupted transplacental arachidonic acid (AA) supply and eicosanoid synthesis, which contribute to adverse pregnancy outcomes. Since placental inositol is lowered with increasing glycemia, and since myo-inositol appears a promising intervention for gestational diabetes, we hypothesized that myo-inositol might rectify glucose-induced perturbations in placental AA metabolism. Term placental explants (n = 19) from women who underwent a mid-gestation oral glucose-tolerance-test were cultured with 13C-AA for 48 h in media containing glucose (5, 10 or 17 mM) and myo-inositol (0.3 or 60 µM). Newly synthesized 13C-AA-lipids were quantified by liquid-chromatography-mass-spectrometry. Increasing maternal fasting glycemia was associated with decreased proportions of 13C-AA-phosphatidyl-ethanolamines (PE, PE-P), but increased proportions of 13C-AA-triacylglycerides (TGs) relative to total placental 13C-AA lipids. This suggests altered placental AA compartmentalization towards storage and away from pools utilized for eicosanoid production and fetal AA supply. Compared to controls (5 mM glucose), 10 mM glucose treatment decreased the amount of four 13C-AA-phospholipids and eleven 13C-AA-TGs, whilst 17 mM glucose increased 13C-AA-PC-40:8 and 13C-AA-LPC. Glucose-induced alterations in all 13C-AA lipids (except PE-P-38:4) were attenuated by concurrent 60 µM myo-inositol treatment. Myo-inositol therefore rectifies some glucose-induced effects, but further studies are required to determine if maternal myo-inositol supplementation could reduce AA-associated pregnancy complications.

Associations between Maternal Iron Supplementation in Pregnancy and Changes in Offspring Size at Birth Reflect Those of Multiple Micronutrient Supplementation.

It was previously observed that in a population of a high-income country, dietary multiple micronutrient supplementation in pregnancy was associated with an increased risk of gestational diabetes (GDM) and increased offspring size at birth. In this follow-up study, we investigated whether similar changes are observed with dietary iron supplementation. For this we used the prospective Cambridge Baby Growth Study with records of maternal GDM status, nutrient supplementation, and extensive offspring birth size measurements. Maternal iron supplementation in pregnancy was associated with GDM development (risk ratio 1.67 (1.01-2.77), p = 0.048, n = 677) as well as offspring size and adiposity (n = 844-868) at birth in terms of weight (ß' = 0.078 (0.024-0.133); p = 0.005), head circumference (ß' = 0.060 (0.012-0.107); p = 0.02), body mass index (ß' = 0.067 (0.014-0.119); p = 0.01), and various skinfold thicknesses (ß' = 0.067-0.094; p = 0.03-0.003). In a subset of participants for whom GDM statuses were available, all these associations were attenuated by adjusting for GDM. Iron supplementation also attenuated the associations between multiple micronutrient supplementation and these same measures. These results suggest that iron supplementation may mediate the effects associated with multiple micronutrient supplementation in pregnancy in a high-income country, possibly through the increased risk of developing GDM.

The isoflavonoid calycosin inhibits inflammation and enhances beta cell function in gestational diabetes mellitus by suppressing RNF38 expression.

BACKGROUND: Gestational diabetes mellitus (GDM) is a medical complication and metabolic disorder associated with pregnancy. Calycosin is a traditional Chinese herbal medicine that is used for the treatment of multiple diseases. This study focused on exploring the effects and underlying mechanisms of Calycosin on GDM. METHODS: The db/+ diabetic mice model of GDM was used to evaluate the effects of calycosin administration on the symptoms of GDM mice. Blood glucose, cytokine production (interleukin 6, IL-6; tumor necrosis factor-α, TNF-α), and insulin levels were measured by ELISA assay. The expression level of signal transducer and activator of transcription 3 (STAT3), ring finger protein 38 (RNF38), and SH2-containing protein tyrosine phosphatase 1 (SHP-1) were determined by Western Blot assay. Beta cell proliferation was assessed by CCK-8 assay. RESULTS: Our data indicated that administration of calycosin significantly improved the GDM symptoms in pregnant db/+ mice as demonstrated by reduced blood glucose, TNF-a, and IL-6 levels as well as increased insulin level, and body weight. Furthermore, we revealed that RNF38/SHP-1/STAT3 signaling should play a critical role in calycosin-promoted beta cell function, and forced expression of RNF38 attenuated the positive effects of calycosin on beta cells. CONCLUSION: Our study implied that calycosin exerts favorable effects on GDM mice via rebalancing insulin sensitivity and inflammatory response.

Antidepressant continuation in pregnancy and risk of gestational diabetes.

PURPOSE: Previous studies observed modestly higher risk of gestational diabetes (GDM) associated with antidepressant use in pregnancy, potentially due to confounding by indication. We assessed the association of antidepressant continuation in pregnancy with GDM, as well as blood glucose levels, after accounting for confounding. METHODS: We conducted a retrospective cohort study of singleton live births from 2001 to 2014 to women enrolled in Kaiser Permanente Washington, an integrated health care delivery system, utilizing electronic health data and linked Washington State birth records. We required that women have ≥1 antidepressant prescription fills ≤6 months before pregnancy. Women with an antidepressant fill during pregnancy were categorized as "continuers" (n = 1634); those without a fill were "discontinuers" (n = 1211). We calculated relative risks (RRs) for GDM and mean differences in screening blood glucose levels using generalized estimating equations with inverse probability of treatment weighting to account for baseline characteristics, including mental health conditions and indicators of mental health severity. RESULTS: Compared with discontinuers, antidepressant continuers had comparable risk of GDM (RR: 1.10; 95% confidence interval [CI], 0.84-1.44) and blood glucose levels (mean difference: 2.3 mg/dL; 95% CI, -1.5 to 6.1 mg/dL). We observed generally similar results for specific antidepressants, with the potential exceptions of risk of GDM associated with sertraline (RR: 1.30; 95% CI, 0.90-1.88) and venlafaxine (RR: 1.52; 95% CI, 0.87-2.68), but neither association was statistically significant. CONCLUSIONS: Our study suggests that overall, women who continue antidepressants in pregnancy are not at increased risk for GDM or higher blood glucose, although further study may be warranted for sertraline and venlafaxine.

A retrospective study of supplemental iron intake in singleton pregnancy women with risk of developing gestational diabetes mellitus.

This study investigated the effect of supplemental iron intake (SII) in early singleton pregnancy women with the risk of developing gestational diabetes mellitus (GDM) among Chinese population.This study included 259 singleton pregnancy participants. Of those, 135 women underwent SII and were assigned to an intervention group, while 124 participants received no SII and were assigned to a control group. The outcome measurements consisted of the number of patients with GDM development, the levels of hemoglobin (Hb) and ferritin, and the outcomes of infant at delivery.No significant difference in the number of patients with GDM development was found between 2 groups at delivery. However, when compared with control group, subjects in the intervention group showed greater efficacy in delivery mode choice of vaginal delivery (P = .04), and cesarean section (P = .01), as well as the birthweight of infants (P < .01). Moreover, Hb and ferritin levels were also significantly higher in the intervention group than those in the control group (P < .01).The results of this retrospective study showed that SII may not increase risk of developing GDM in singleton pregnancy women; and also may benefit both pregnancy women and infants among Chinese population.

Protective effects of Morus alba leaves extract on ocular functions of pups from diabetic and hypercholesterolemic mother rats.

Phytotherapy is frequently considered to be less toxic and free from side effects than synthetic drugs. Hence, the present study was designed to investigate the protective use of crude water extract of Morus alba leaves on ocular functions including cataractogenesis, biochemical diabetic and hypercholesterolemic markers, retinal neurotransmitters and retinopathy of rat pups maternally subjected to either diabetes and/or hypercholesterolemia. Application of crude water extract of Morus alba resulted in amelioration of the alterations of maternal serum glucose, LDL, HDL, total cholesterol and creatine phosphokinase activity as well as retinal neurotransmitters including acetylcholine (ACE), adrenaline (AD), nor-adrenaline (NAD), serotonin (5-HT), histamine (HS), dopamine (DA) and gamma amino butyric acid (GABA). The retina of pups of either diabetic and/or hypercholesterolemia mothers exhibited massive alterations of retinal neurotransmitters. The alterations of retinal neurotransmitters were correlated with the observed pathological alterations of retinal pigmented epithelium, photoreceptor inner segment and ganglion cells and increased incidence of DNA fragmentation and apoptosis cell death. However, protection with Morus alba extract led to amelioration of the pathological alterations of retinal neurons and estimated neurotransmitters. Furthermore, a striking incidence of cataract was detected in pups of either diabetic and/or hypercholesterolemic mothers. Highest cataractogenesis was observed in pups of combined -treated groups. Our data indicate that experimental maternal diabetes alone or in combination with hypercholesterolemia led to alteration in the ocular structures of their pups, with an increasing incidence of cataract and retinopathy, and the effects of the extract might be attributed to the hypoglycaemic, antihypercholesterolemic and anti-oxidative potential of flavonoids, the major components of the plant extract.

High-saturated-fat diet induces gestational diabetes and placental vasculopathy in C57BL/6 mice.

Gestational diabetes mellitus (GDM) is a commonly encountered disorder of mid to late pregnancy that is characterized by hyperglycemia, hyperinsulinemia, and impaired glucose tolerance. Gestational diabetes mellitus is thought to be multifactorial in origin and derives from both genetic and environmental factors. However, the mechanisms underlying GDM are incompletely understood; and current GDM animal models do not appear to closely mimic the clinical situation in humans. The present study used environmental exposure to high-saturated-fat diet (HFD) in an effort to develop a GDM mouse model that closely simulates metabolic abnormalities seen in human GDM. This model was then used to determine the contributions of HFD-induced placental oxidative stress (OS) and vascular dysregulation, which are observed in GDM patients and are believed to contribute to the pathogenesis of the disease. Pathologic manifestations of the disease were quantified by evaluating the extent of placental lipid peroxidation and by determining protective effects of dietary antioxidant quercetin supplementation to reduce HFD-associated placental OS. In this study, female C57BL/6 mice were fed HFD for 1 month before conception and throughout gestation to mimic chronic maternal fast food consumption. Maternal body weight increased from gestation day (GD) 0 to GD19 by 41% with HFD, as compared with 23% in control dams; HFD dams also developed insulin resistance (66% increase in plasma insulin and 27% increase in plasma glucose levels by GD10) as compared with control dams. Placentas from HFD GD19 dams demonstrated loss of trophoblasts and OS-mediated labyrinthine endothelial cellular damage, the latter of which was prevented with quercetin supplementation. Our findings suggest that prenatal HFD alters glucose metabolism and elevates placental OS, which are believed to collectively relate to improper formation of the conceptus and impaired birth outcome.

Iron supplement in pregnancy and development of gestational diabetes--a randomised placebo-controlled trial.

OBJECTIVE: To test the hypothesis that iron supplement from early pregnancy would increase the risk of gestational diabetes mellitus (GDM). DESIGN: Randomised placebo-controlled trial. SETTING: A university teaching hospital in Hong Kong. POPULATION: One thousand one hundred sixty-four women with singleton pregnancy at less than 16 weeks of gestation with haemoglobin (Hb) level between 8 and 14 g/dl and no pre-existing diabetes or haemoglobinopathies. METHODS: Women were randomly allocated to receive 60 mg of iron supplement daily (n= 565) or placebo (n= 599). Oral glucose tolerance tests (OGTTs) were performed at 28 and 36 weeks. Women were followed up until delivery. OUTCOME MEASURES: The primary outcome was development of GDM at 28 weeks. The secondary outcomes were 2-hour post-OGTT glucose levels, development of GDM at 36 weeks and delivery and infant outcomes. RESULTS: There was no significant difference in the incidence of GDM in the iron supplement and placebo groups at 28 weeks (OR: 1.04, 95% confidence interval [CI]: 0.7-1.53 at 90% power) or 36 weeks. Maternal Hb and ferritin levels were higher in the iron supplement group at delivery (P < 0.001 and P= 0.003, respectively). Elective caesarean section rate was lower in the iron supplement group (OR: 0.58, 95% CI: 0.37-0.89). Infant birthweight was heavier (P= 0.001), and there were fewer small-for-gestational-age babies in the iron supplement group (OR: 0.46, 95% CI: 0.24-0.85). CONCLUSION: Iron supplement from early pregnancy does not increase the risk of GDM. It may have benefits in terms of pregnancy outcomes.