Effects of vitamin and omega-3 fatty acid co-supplementation on blood glucose in women with gestational diabetes mellitus: A protocol for systematic review and meta analysis.

BACKGROUND: There is limited study that has conducted a review investigating the clinical effects of vitamin and omega-3 fatty acid co-supplementation on blood glucose in women with gestational diabetes mellitus (GDM). Therefore, in order to provide new evidence-based medical evidence for clinical treatment, we undertook a systematic review and meta-analysis to assess the effectiveness and safety of vitamin and omega-3 fatty acid co-supplementation on blood glucose in women with GDM. METHODS: This protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement guidelines. We will conduct systematic reviews and meta-analyses to identify relevant randomized controlled trials (RCTs) involving vitamin and omega-3 fatty acid co-supplementation on GDM in electronic databases including PubMed, Web of Science, Embase, and the Cochrane Library up to June 2021. Exclusion criteria include observational studies, non-RCTs, review articles, studies with a sample size <50, and studies with insufficient outcome data. The primary outcomes include fasting glucose and insulin. Secondary outcomes are evaluated in a homeostasis model of insulin resistance, total antioxidant capacity, triglycerides, total cholesterol, low-density lipoprotein cholesterol, preterm birth and macrosomia over 4 kg. RESULTS: The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings. REGISTRATION NUMBER: 10.17605/OSF.IO/NSW54.

Correlation between plasma ferritin level and gestational diabetes mellitus and its impact on fetal macrosomia.

AIMS/INTRODUCTION: To explore the relationship between plasma iron levels and gestational diabetes mellitus, as well as its impact on macrosomia. MATERIALS AND METHODS: We retrospectively compared ferritin level and other characteristics between pregnant women with gestational diabetes mellitus (GDM) and pregnant women without GDM. The correlation between the levels of plasma ferritin, glucose and hemoglobin was explored. Meanwhile, we assessed the risk factors of macrosomia. Furthermore, we explored the relationship between ferritin level and the incidence of macrosomia. RESULTS: A total of 793 pregnant women were enrolled in the present study, of which 92 pregnant women had GDM and 701 pregnant women were healthy. Meanwhile, 51 pregnant women gave birth to infants with macrosomia and another 742 women had normal infants. Compared with non-GDM women, pregnant women with GDM were older, with higher pre-pregnancy body mass index, plasma ferritin, fasting plasma glucose, 1-h postprandial glucose, 2-h plasma glucose and hemoglobin. In addition, our results showed a significant positive correlation between the levels of ferritin and fasting plasma glucose when ferritin levels were >70 ng/mL. Our results also showed that pre-pregnancy overweight or obesity, a high concentration of ferritin, as well as abnormal levels of fasting plasma glucose, 1-h plasma glucose and 2 h plasma glucose were risk factors for macrosomia. Furthermore, as the level of ferritin increased, so did the incidence of macrosomia. CONCLUSIONS: The current study provides evidence that pregnant women with high levels of ferritin might be prone to GDM. In addition, a high level of ferritin might be an independent risk factor for macrosomia. Therefore, the negative effect of iron supplementation in non-anemic pregnant women might be noteworthy.

Maternal and cord blood fatty acid patterns with excessive gestational weight gain and neonatal macrosomia.

BACKGROUND AND OBJECTIVES: This study evaluated the association of maternal excessive gestational weight gain with saturated and polyunsaturated fatty acid concentrations in maternal and cord serum. METHODS AND STUDY DESIGN: We included 77 pairs of women and their newborns and classified them into three groups as follows: mothers with normal gestational weight gain and their babies with normal birth weight in group I (30 pairs), mothers with excessive gestational weight gain and their babies with normal birth weight in group II (30 pairs), and mothers with excessive gestational weight gain and their macrosomic babies in group III (17 pairs). Serum fatty acid concentrations were determined through gas chromatography-mass spectrometry. RESULTS: No remarkable difference in maternal dietary intake was observed among the three groups. C16:0, C18:0, eicosapentaenoic acid, and docosahexaenoic acid concentrations were significantly higher in group III mothers than in group I mothers. Compared with group I neonates, total saturated and polyunsaturated fatty acid concentrations were significantly lower but total n-3 polyunsaturated fatty acid and docosahexaenoic acid concentrations were significantly higher in group II neonates (p<0.05). The n-6: n-3 ratio in maternal and cord serum was approximately 10:1 and 1.5:1, respectively. CONCLUSION: Women with excessive gestational weight gain who deliver a macrocosmic neonate tend to have higher total saturated fatty acid concentrations but lower docosahexaenoic acid concentrations in their neonate cord serum. Fatty acid concentrations in maternal and cord serum are not associated with maternal dietary pattern.

Calcium plus vitamin D supplementation affects pregnancy outcomes in gestational diabetes: randomized, double-blind, placebo-controlled trial.

OBJECTIVE: The present study was designed to assess the effects of Ca+vitamin D supplementation on pregnancy outcomes in women with gestational diabetes mellitus (GDM). DESIGN: A randomized, double-blind, placebo-controlled trial was conducted among sixty women with GDM. Participants were divided into two groups to receive Ca+vitamin D supplements or placebo. Individuals in the Ca+vitamin D group (n 30) received 1000 mg Ca/d and two pearls containing 1250 µg (50 000 IU) of cholecalciferol (vitamin D(3)) during the intervention (one at study baseline and another at day 21 of the intervention); those in the placebo group (n 30) received two placebos of vitamin D at the mentioned times and placebos of Ca every day for 6 weeks. Pregnancy outcomes were determined. SETTING: A urban community setting in Arak, Iran. SUBJECTS: Sixty women with GDM and their newborns, living in Arak, Iran were enrolled. RESULTS: Women treated with Ca+vitamin D had a significant decrease in caesarean section rate (23·3 % v. 63·3 %, P=0·002) and maternal hospitalization (0 v. 13·3 %, P=0·03) compared with those receiving placebo. In addition, newborns of GDM women randomized to Ca+vitamin D had no case of macrosomia, while the prevalence of macrosomia among those randomized to placebo was 13·3 % (P=0·03). Lower rates of hyperbilirubinaemia (20·0 % v. 56·7 %, P=0·03) and hospitalization (20·0 % v. 56·7 %, P=0·03) were also seen in the supplemented group of newborns than in the placebo group. CONCLUSIONS: Ca+vitamin D supplementation for 6 weeks among pregnant women with GDM led to decreased caesarean section rate and maternal hospitalization, and decreased macrosomia, hyperbilirubinaemia and hospitalization in newborns.

Low cord blood serum levels of vitamin D: cause or effect of fetal macrosomia?

UNLABELLED: Aim: The aim of the study was to compare cord blood vitamin D levels of macrosomic large for gestational age (LGA) and appropriate gestational age (AGA) newborns. MATERIALS AND METHODS: Seventy-nine healthy, normal term newborns were included in the study. They were divided by birth weight into two groups: 37 in the LGA group above 4,000 g, and 42 newborns in the AGA group birth weight between 3,000 g and 4,000 g. Cord blood samples from groups were collected. Circulating 25(OH)D was measured as 25 hydroxyvitamin D3 (25(OH)D3) by high-performance liquid chromatography (HPLC) in serum using a kit. RESULTS: Maternal characterstics (age, body mass index [BMI], and gestational age) did not differ between the AGA and LGA groups. Cord blood 25 OH vitamin D levels were significantly low in neonates with LGA (p = 0,02). CONCLUSIONS: The authors found that macrosomic infants had low levels of vitamin D. Providing vitamin D supplements to pregnant women may prevent macrosomia. Randomized controlled trials are needed to prove this assertion.

Beneficial effects of omega-3 polyunsaturated Fatty acids in gestational diabetes: consequences in macrosomia and adulthood obesity.

Omega-3 polyunsaturated fatty acids (PUFAs) are increasingly being used to prevent cardiovascular diseases, including diabetes and obesity. In this paper, we report data on the observed effects of omega-3 PUFA on major metabolic disorders and immune system disruption during gestational diabetes and their consequences on macrosomia. While controversies still exist about omega-3 PUFA effects on antioxidant status regarding the level of omega-3 PUFA in diet supplementation, their lipid-lowering effects are unanimously recognized by researchers. Animal studies have shown that omega-3 PUFA contributes to the maintenance of the immune defense system by promoting the differentiation of T helper (Th) cell to a Th2 phenotype in diabetic pregnancy and by shifting the Th1/Th2 ratio from a deleterious proinflammatory Th1 phenotype to a protective anti-inflammatory Th2 phenotype in macrosomia and in adulthood obesity that results from macrosomia at birth. Based on the available evidence, international nutritional and food agencies recommend administration of omega-3 PUFA as triglyceride-lowering agents, for the prevention of cardiovascular disease risk and during human pregnancy and lactation. Furthermore, studies targeting humans are still required to explore application of the fatty acids as supplement in the management of gestational diabetes and inflammatory and immune diseases.

Effect of dietary n - 3 polyunsaturated fatty acids on oxidant/antioxidant status in macrosomic offspring of diabetic rats.

The aim of this work was to determine the effect of dietary n - 3 PUFA on oxidant/antioxidant status, in vitro very low and low density lipoprotein (VLDL-LDL), and VLDL-LDL-fatty acid composition in macrosomic pups of diabetic mothers. We hypothesized that n - 3 PUFA would improve oxidative stress in macrosomia. Diabetes was induced in female Wistar rats fed with the ISIO diet (control) or with the EPAX diet (enriched in n - 3 PUFAs), by streptozotocin. The macrosomic pups were killed at birth (day 0) and at adulthood (day 90). Lipid parameters and VLDL-LDL-fatty acid composition were investigated. The oxidant/antioxidant status was determined by measuring plasma oxygen radical absorbance capacity (ORAC), hydroperoxides, carbonyl proteins, and VLDL-LDL oxidation. Macrosomic rats of ISIO fed diabetic mothers showed an increase in plasma and VLDL-LDL-triglycerides and VLDL-LDL-cholesterol levels and altered VLDL-LDL-fatty acid composition. Plasma ORAC was low with high hydroperoxide and carbonyl protein levels. The in vitro oxidizability of VLDL-LDL was enhanced in these macrosomic rats. The EPAX diet corrected lipid parameters and improved oxidant/antioxidant status but increased VLDL-LDL susceptibility to oxidation. Macrosomia is associated with lipid abnormalities and oxidative stress. n - 3 PUFA exerts favorable effects on lipid metabolism and on the oxidant/antioxidant status of macrosomic rats. However, there are no evident effects on VLDL-LDL oxidation.

The relationship between maternal and fetal vitamin D, insulin resistance, and fetal growth.

Evidence for a role of vitamin D in maintaining normal glucose homeostasis is inconclusive. We sought to clarify the relationship between maternal and fetal insulin resistance and vitamin D status. This is a prospective cohort study of 60 caucasian pregnant women. Concentrations of 25-hydroxyvitamin D (25-OHD), glucose, insulin, and leptin were measured in early pregnancy and at 28 weeks. Ultrasound at 34 weeks assessed fetal anthropometry including abdominal wall width, a marker of fetal adiposity. At delivery birth weight was recorded and fetal 25-OHD, glucose, C-peptide, and leptin measured in cord blood. Insulin resistance was calculated using the Homeostasis Model Assessment (HOMA) equation. We found that those with lower 25-OHD in early pregnancy had higher HOMA indices at 28 weeks, (r = -.32, P = .02). No significant relationship existed between maternal or fetal leptin and 25-OHD, or between maternal or fetal 25-OHD and fetal anthropometry or birth weight. The incidence of vitamin D deficiency was high at each time point (15%-45%). These findings lend support to routine antenatal supplementation with vitamin D in at risk populations.

[Impact of HAPO study findings on future diagnostics and therapy of gestational diabetes]. / Bedeutung der HAPO-Ergebnisse für die zukünftige Diagnostik und Therapie des Gestationsdiabetes.

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study is a trial on a high evidence level that included 25,000 women recruited in 15 centers all over the world who underwent a 75-gram oral glucose tolerance test (oGTT) at 24-32 weeks of gestation. Data remained blinded if the fasting plasma glucose level was below 105 mg/dl (5.8 mmol/l) and the 2-hour plasma glucose level was below 200 mg/dl (11.1 mmol/l). The aim of the study was to clarify whether maternal hyperglycemia less severe than that in diabetes mellitus is associated with increased risks of adverse pregnancy outcomes. The results indicate a continuous association of maternal glucose levels below those diagnostic of diabetes with an adverse outcome, with the strongest risk for increased birth weight and cord blood serum C peptide levels indicating fetal hyperinsulinism. Additionally an increased risk for maternal complications like preeclampsia was seen. Like in many biological processes, there were no obvious thresholds at which risks increased. An international expert committee proposed how to transfer the HAPO data into criteria for the oGTT in pregnancy for the future diagnosis of gestational diabetes mellitus (GDM) which will be based on acute pregnancy problems in contrast to the recent Carpenter and Coustan criteria. The availability of uniform, internationally accepted and applied GDM criteria will provide more clinical and legal security for the caregivers which will be a big advantage also in Germany where a wide diversity of GDM criteria is used. Beside the threshold discussion, the HAPO data are of enormous relevance for Germany. The HAPO data will significantly influence the decision of the German Health Authorities whether to finally establish a general screening for GDM as obligatory part of prenatal care. A report from the German Institute for Quality and Efficiency in Health Care (IQWiG) which was ordered from the German Health Authorities describes--mainly based on the HAPO Study--an indirect benefit of blood glucose screening for GDM for all pregnant women.

N-3 fatty acids modulate Th1 and Th2 dichotomy in diabetic pregnancy and macrosomia.

We assessed the implication of Th (helper)-cells and the modulation of the Th1/Th2 dichotomy by n-3 polyunsaturated fatty acids (PUFA) in type I diabetic pregnancy (DP) and macrosomia. Female gestant rats fed a standard diet or n-3 PUFA regimen were rendered diabetic by administration of five low doses of streptozotocin. The macrosomic (MAC) offspring were sacrificed at the age of 90 days. The mRNAs of IL-2 and IFN-gamma (Th1 cytokines) and IL-4 (Th2 cytokine) were downregulated in the pancreas and spleen of diabetic pregnant rats. The levels of IL-10 mRNA, another Th2 cytokine, were unchanged in the spleen or upregulated in the pancreas of these animals. Feeding an n-3 PUFA diet to rats with DP upregulated IL-10 mRNA in the pancreas and IL-4 and IL-10 mRNA in the spleen. In MAC offspring, high expression of IL-2 and IFN-gamma mRNA, but not of Th2 cytokines, was observed. The n-3 PUFA diet diminished Th1 mRNA quantities and increased the levels of IL-4, but not of IL-10, mRNA in MAC offspring. Our study shows that DP is associated with a decreased Th1 phenotype and IL-4 mRNA expression in the pancreas and spleen, and an n-3 PUFA diet upregulates Th2 profile. In MAC offspring, the Th1 phenotype is upregulated and an n-3 PUFA diet downregulates this phenomenon.

Thiamin status of gravidas treated for gestational diabetes mellitus compared to their neonates at parturition.

Since thiamin plays a role in glucose metabolism we wanted to know if blood thiamin influx from gravida to neonate was influenced by treatment of gravidas having gestational diabetes mellitus (GDM). In this study we found thiamin hypovitaminemia in 19% of the 77 pregnancies despite vitamin supplementation and treatment for GDM; neonates born to mothers with hypovitaminemia were also thiamin hypovitaminemic. All neonatal blood had significantly higher thiamin concentration than gravidas. Indeed, cord blood from neonates born to mothers treated with insulin for GDM had significantly higher thiamin concentration than other neonates in the study. A significant weight depression was noted in neonates born to treated GDM mothers. Healthy gravidas giving birth to macrosomia neonates, had significant thiamin hypovitaminosis, but only macrosomic neonates of treated diabetic mothers had significantly depressed blood thiamin concentrations. We noted that subclinical thiamin hypovitaminemia is prominent during pregnancy despite vitamin supplementation. Perhaps increased thiamin supplementation during pregnancy seems warranted to avoid metabolic stress in mother and fetus due to thiamin hypovitaminemia.