Does a high dietary intake of resistant starch affect glycaemic control and alter the gut microbiome in women with gestational diabetes? A randomised control trial protocol.

BACKGROUND: Gestational Diabetes Mellitus (GDM) is prevalent with lasting health implications for the mother and offspring. Medical nutrition therapy is the foundation of GDM management yet achieving optimal glycaemic control often requires treatment with medications, like insulin. New dietary strategies to improve GDM management and outcomes are required. Gut dysbiosis is a feature of GDM pregnancies, therefore, dietary manipulation of the gut microbiota may offer a new avenue for management. Resistant starch is a fermentable dietary fibre known to alter the gut microbiota and enhance production of short-chain fatty acids. Evidence suggests that short-chain fatty acids improve glycaemia via multiple mechanisms, however, this has not been evaluated in GDM. METHODS: An open-label, parallel-group design study will investigate whether a high dietary resistant starch intake or resistant starch supplement improves glycaemic control and changes the gut microbiome compared with standard dietary advice in women with newly diagnosed GDM. Ninety women will be randomised to one of three groups - standard dietary treatment for GDM (Control), a high resistant starch diet or a high resistant starch diet plus a 16 g resistant starch supplement. Measurements taken at Baseline (24 to 30-weeks' gestation), Day 10 and Day 56 (approximately 36 weeks' gestation) will include fasting plasma glucose levels, microbial composition and short-chain fatty acid concentrations in stool, 3-day dietary intake records and bowel symptoms questionnaires. One-week post-natal data collection will include microbial composition and short-chain fatty acid concentrations of maternal and neonatal stools, microbial composition of breastmilk, birthweight, maternal and neonatal outcomes. Mixed model analysis of variance will assess change in glycaemia and permutation-based multivariate analysis of variance will assess changes in microbial composition within and between intervention groups. Distance-based linear modelling will identify correlation between change in stool microbiota, short-chain fatty acids and measures of glycaemia. DISCUSSION: To improve outcomes for GDM dyads, evaluation of a high dietary intake of resistant starch to improve glycaemia through the gut microbiome needs to be established. This will expand the dietary interventions available to manage GDM without medication. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry, ACTRN12620000968976p . Registered 28 September 2020.

The effect of bedtime snacks on fasting blood glucose levels in gestational diabetes mellitus.

AIM: To investigate the effect of different bedtime snacks (higher carbohydrate versus lower carbohydrate versus no snack) on first morning fasting blood glucose levels (BGLs) in women with diet-controlled gestational diabetes mellitus (GDM) and borderline fasting glucose levels. METHODS: This prospective randomised crossover trial enrolled women with diet controlled GDM between 24 and 34 weeks gestation who had two or more first morning fasting BGLs between 4.7 and 5.4 mmol/L in the week prior to recruitment. The women were randomly allocated to 6 different orders of 5 days each of a standardised higher carbohydrate bedtime snack, a lower carbohydrate bedtime snack and no bedtime snack. The primary outcome was fasting capillary BGL as measured with a home glucometer, and the secondary outcome was requirement for insulin as assessed by a physician. RESULTS: A total of 68 women with GDM were enrolled in and completed the study at a median gestation of 30.8 weeks. Compared with no bedtime snack, the higher carbohydrate snack (4.96 vs 4.87 mmol/L, mean difference: 0.09 mmol/L, 95% CI 0.05-0.13, p < 0.001) and the lower carbohydrate snack (5.01 vs 4.87 mmol/L, mean difference: 0.14 mmol/L, 95% CI 0.09-0.18, p < 0.001) were both associated with a slightly higher fasting BGL the following morning. CONCLUSIONS: Taking a bedtime snack was associated with slightly higher fasting BGLs in women with diet-controlled GDM compared with no bedtime snack (Clinical trial registration: ACTRN12617000659303).

An Update of Medical Nutrition Therapy in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a serious and frequent pregnancy complication that can lead to short and long-term risks for both mother and fetus. Different health organizations proposed different algorithms for the screening, diagnosis, and management of GDM. Medical Nutrition Therapy (MNT), together with physical exercise and frequent self-monitoring, represents the milestone for GDM treatment in order to reduce maternal and fetal complications. The pregnant woman should benefit from her family support and make changes in their lifestyles, changes that, in the end, will be beneficial for the whole family. The aim of this manuscript is to review the literature about the Medical Nutrition Therapy in GDM and its crucial role in GDM management.

A Glimpse at the Size of the Fetal Liver-Is It Connected with the Evolution of Gestational Diabetes?

Gestational diabetes mellitus (GDM) is defined as an impairment of glucose tolerance, manifested by hyperglycemia, which occurs at any stage of pregnancy. GDM is more common in the third trimester of pregnancy and usually disappears after birth. It was hypothesized that the glycemic status of the mother can modulate liver development and growth early during the pregnancy. The simplest modality to monitor the evolution of GDM employs noninvasive techniques. In this category, routinely obstetrical ultrasound (OUS) examinations (simple or 2D/3D) can be employed for specific fetal measurements, such as fetal liver length (FLL) or volume (FLV). FLL and FLV may emerge as possible predictors of GDM as they positively relate to the maternal glycated hemoglobin (HbA1c) levels and to the results of the oral glucose tolerance test. The aim of this review is to offer insight into the relationship between GDM and fetal nutritional status. Risk factors for GDM and the short- and long-term outcomes of GDM pregnancies are also discussed, as well as the significance of different dietary patterns. Moreover, the review aims to fill one gap in the literature, investigating whether fetal liver growth can be used as a predictor of GDM evolution. To conclude, although studies pointed out a connection between fetal indices and GDM as useful tools in the early detection of GDM (before 23 weeks of gestation), additional research is needed to properly manage GDM and offspring health.

Effect of an individualised nutritional intervention on gestational diabetes mellitus prevention in a high-risk population screened by a prediction model: study protocol for a multicentre randomised controlled trial.

BACKGROUND: The ability of a preventive nutritional intervention to reduce the morbidity of gestational diabetes mellitus (GDM) remains controversial. We aim to assess whether GDM can be prevented by an individualised nutritional intervention in pregnant women who are at high risk for the disease based on a prediction model. METHODS/DESIGN: A multicentre randomised controlled trial was designed to assess the efficacy of an individualised nutritional intervention for the prevention of GDM in a high-risk population screened by a novel prediction model in the first trimester. Pregnant women evaluated to be at high risk for GDM by the prediction model at less than 14 gestational weeks will be included. Women with pre-existing chronic diseases, including pregestational diabetes, or who are currently prescribed medicines that affect glucose values will be excluded. Allocation to intervention/control at a ratio of 1:1 will be conducted by a computerized randomisation system. The intervention group will complete 3-day food records and receive 3 individualised nutritional consultations with professional dieticians before the oral glucose tolerance test. The primary intention of the intervention is to promote a long-term healthy dietary pattern and prevent excessive gestational weight gain throughout pregnancy. The control group will complete 3-day food records at designated gestational weeks and receive standard antenatal care according to local health care provisions. The primary outcome is the incidence of GDM according to the criteria of the International Association of Diabetes and Pregnancy Study Group (IADPSG). A sample of 464 participants will provide 80% power to detect a 30% reduction in GDM incidence (α = 0.05 two tailed, 10% dropout). A total of 500 participants will be recruited. DISCUSSION: To date, this is the first randomised controlled trial aimed to evaluate the protective effect of an individualised nutritional intervention against GDM based on a logistic regression prediction model. Eligibility is not limited to obese women or singleton pregnancies, as in previous studies. This pragmatic trial is expected to provide valuable information on early screening and effective GDM prevention methods. TRIAL REGISTRATION NUMBER: ChiCTR, ChiCTR1900026963 . Registered 27 October 2019.

The effect of probiotic supplementation on the risk of gestational diabetes mellitus among high-risk pregnant women: A parallel double-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Based on a comprehensive search, we realized that the findings of the available literature are contradictory, and also limited data are available on Middle Eastern populations in terms of probiotic supplementation during the pregnancy. Therefore, the current double-blind, randomized, placebo-controlled clinical trial was carried out to investigate the effects of probiotic supplementation during pregnancy on the risk of gestational diabetes mellitus and also other maternal and neonatal outcomes. MATERIALS AND METHODS: The pregnant women were randomized to either received probiotic supplement (n = 271) or placebo (n = 271) from the first half of the second trimester (14 weeks of pregnancy) up to 24 weeks when pregnant women routinely evaluated regarding the GDM. During the 24-28 weeks of pregnancy, mothers were evaluated regarding the presence of GDM using a 75 g oral glucose tolerance test (OGTT). The fasting blood glucose (FBG) was also evaluated within OGTT processes. Each 500 mg probiotic capsule was a mixture of Lactobacillus acidophilus LA1 (>7.5 × 109 CFU), Bifidobacterium longum sp54 cs (>1.5 × 109 CFU), and Bifidobacterium bifidum sp9 cs (>6 × 109 CFU). RESULTS: Overall, 507 pregnant women make up our study population with a mean age of 32.03 years and a Body Mass Index (BMI) of 30.20 kg/m2. There was no significant difference between the intervention and the control group regarding FBG (88.68 vs. 89.61 mg/dL; P = 0.338), OGTT-1h (163.86 vs. 166.88; mg/dL; P = 0.116), and OGTT-2h (138.39 vs. 139.27; mg/dL; P = 0.599). The incidence of GDM in the intervention group was 41.9% which was not significantly different from the control group (40.2%) (P = 0.780). Likewise, no significant difference was detected in terms of other studied parameters. CONCLUSIONS: It seems that probiotics supplementation of pregnant women from the first half of the second trimester up to 24 weeks of pregnancy does not reduce the risk of GDM, or improve other neonatal and maternal outcomes.

Whey protein preloading can alleviate stress adaptation disorder and improve hyperglycemia in women with gestational diabetes mellitus.

AIMS: To investigate the change of stress hormones, oxidative stress and insulin resistance (IR) in women with gestational diabetes mellitus (GDM) after supplement whey protein, in an attempt to gain insights into the prevention and treatment of GDM. MATERIALS AND METHODS: 60 GDM women were recruited in this study, and 30 women received a preload drink containing 20 g whey protein as group GDM-W, and the other 30 women received control flavoring drink as group GDM, and the trial lasted for 14 days. Plasma epinephrine (E), noradrenaline (NE), and cortisol were detected; we also determined levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH). Homeostasis model assessment of insulin resistance (HOMA-IR) was used to assess IR. RESULTS: In the GDM-W group, postprandial blood glucose was decreased significantly on 3, 5, 7, and 14 days (all p < .05), plasma 2 h insulin was increased by 7.2, 8.6, and 20.5% on days 5, 7, and 14 (p < .05, .05, .01). HOMA-IR was decreased significantly on day 14 (p < .05). MDA was decreased by 20.7% on day 14 (p < .01), and anti-oxidative enzymes' SOD was decreased by 13.4% on day 14 (p < .05) and GSH was decreased by 16.7 and 29.1% on days 7 and 14 (both p < .05). Stress hormones E and cortisol were decreased by 10.8 and 19.8%, respectively, on day 14 (p < .05). There was no significant difference in NE between the two groups within 14 days. CONCLUSIONS: Whey protein supplementation may improve hyperglycemia by alleviating stress disorder and oxidative stress injury in GDM women. This trial was registered at chictr.org.cn/as ChiCTR1800020413.

The effects of vitamin and mineral supplementation on women with gestational diabetes mellitus.

BACKGROUND: The effects of vitamin and mineral supplementation on women with gestational diabetes mellitus (GDM) have not been well established. We conduct a meta-analysis to evaluate the effects of vitamin and mineral supplementation on glycemic control, inflammation and oxidative stress for women with GDM. METHODS: A systematic search of randomized controlled trials (RCTs) was conducted from PubMed, Embase, Web of Science and Cochrane Library up to July, 2020. Various results were pooled by using Review manager 5.3 and Stata 12.0. Mean difference (MD) with 95% confidence interval (CI) was estimated. Heterogeneity between studies was assessed by I-squared (I2) tests. RESULTS: Six hundred ninety-eight patients from 12 trials were included in our meta-analysis. Magnesium, zinc, selenium, calcium, vitamin D and E (alone or in combination) were found to significantly improve glycemic control in women with GDM compared to those receiving placebos: fasting plasma glucose (FPG) (MD = - 9.02; 95% CI: - 12.09, - 5.96; P < 0.00001), serum insulin (MD = - 4.33; 95% CI: - 5.35, - 3.32; P < 0.00001), homeostasis model assessment-insulin resistance (HOMA-IR) (MD = - 1.34; 95% CI: - 1.60, - 1.07; P < 0.00001), and homeostasis model of assessment for ß cell function (HOMA-B) (MD = - 15.58; 95% CI: - 23.70, - 7.46; P = 0.0002). Vitamin and mineral supplementation was found to attenuated inflammation and oxidative stress through decreasing high-sensitivity C-reactive protein (hs-CRP) (MD = - 1.29; 95% CI: - 1.82, - 0.76; P < 0.00001), malondialdehyde (MDA) (MD = - 0.71; 95% CI: - 0.97, - 0.45; P < 0.00001), and increasing total antioxidant capacity (TAC) (MD = 45.55; 95% CI: 22.02, 69.08; P = 0.0001). CONCLUSIONS: This meta-analysis shows that vitamin and mineral supplementation significantly improved glycemic control, attenuated inflammation and oxidative stress in women with GDM.

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.

Dietary recommendations for women with gestational diabetes mellitus: a systematic review of clinical practice guidelines.

CONTEXT: Dietary advice is the cornerstone of care for women with gestational diabetes mellitus (GDM) to improve maternal and infant health. OBJECTIVES: This study aimed to compare dietary recommendations made in clinical practice guidelines (CPGs) for the management of GDM, evaluate their evidence base, identify research gaps, and assess CPG quality. The PRISMA guidelines were used. DATA SOURCES: Six databases were searched for CPGs, published between 2000 and 2019, that included dietary advice for the management of GDM. DATA EXTRACTION: Two reviewers independently assessed CPG quality (using the AGREE II tool) with respect to dietary recommendations (their strength, evidence base, and research gaps). DATA ANALYSIS: Of the 31 CPGs, 68% were assessed as low quality, mainly due to lack of editorial independence. Dietary advice was recommended as the first-line treatment by all CPGs, although the dietary recommendations themselves varied and sometimes were contradictory. Most dietary recommendations were strongly made (70%), but they were often based on very low-quality (54%), or low-quality (15%) evidence. Research gaps were identified for all diet-related recommendations. CONCLUSION: High-quality research is needed to improve the evidence base and address the research gaps identified. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42019147848.

Supplemental Berberine in a High-Fat Diet Reduces Adiposity and Cardiac Dysfunction in Offspring of Mouse Dams with Gestational Diabetes Mellitus.

BACKGROUND: There are few evidence-based strategies to attenuate the risk of metabolic syndrome in offspring exposed to gestational diabetes mellitus (GDM). Berberine (BBR) is an isoquinoline alkaloid extracted from Chinese herbs and exhibits glucose lowering properties. OBJECTIVES: We hypothesized that dietary BBR would improve health outcomes in the mouse offspring of GDM dams. METHODS: Wild-type C57BL/6 female mice were fed either a Lean-inducing low-fat diet (L-LF,10% kcal fat, 35% kcal sucrose) or a GDM-inducing high-fat diet (GDM-HF, 45% kcal fat, 17.5% sucrose) for 6 wk prior to breeding with wild-type C57BL/6 male mice throughout pregnancy and the suckling period. The resulting Lean and GDM-exposed male and female offspring were randomly assigned an LF (10% kcal fat, 35% kcal sucrose), HF (45% kcal fat, 17.5% sucrose), or high-fat berberine (HFB) (45% kcal fat, 17.5% sucrose diet) containing BBR (160 mg/kg/d, HFB) at weaning for 12 wk. The main outcome was to evaluate the effects of BBR on obesity, pancreatic islet function, and cardiac contractility in GDM-exposed HF-fed offspring. Significance between measurements was determined using a 2 (gestational exposure) × 3 (diet) factorial design by a 2- way ANOVA using Tukey post-hoc analysis. RESULTS: In the GDM-HF group, body weights were significantly increased (16%) compared with those in baseline (L-LF) animals (P < 0.05). Compared with the L-LF animals, the GDM-HF group had a reduction in pancreatic insulin glucose-stimulated insulin secretion (74%) and increased cardiac isovolumetric contraction time (IVCT; ∼150%) (P < 0.05). Compared with GDM-HF animals, the GDM-HFB group with the dietary addition of BBR had significantly reduced body weight (16%), increased glucose-stimulated insulin secretion from pancreatic islets (254%), and reduced systolic heart function (46% IVCT) (P < 0.05). CONCLUSIONS: In a mouse model of GDM, dietary BBR treatment provided protection from obesity and the development of pancreatic islet and cardiac dysfunction.

Metagenomics analysis of gut microbiota in response to diet intervention and gestational diabetes in overweight and obese women: a randomised, double-blind, placebo-controlled clinical trial.

OBJECTIVE: Gut microbiota and diet are known to contribute to human metabolism. We investigated whether the metagenomic gut microbiota composition and function changes over pregnancy are related to gestational diabetes mellitus (GDM) and can be modified by dietary supplements, fish oil and/or probiotics. DESIGN: The gut microbiota of 270 overweight/obese women participating in a mother-infant clinical study were analysed with metagenomics approach in early (mean gestational weeks 13.9) and late (gestational weeks 35.2) pregnancy. GDM was diagnosed with a 2 hour 75 g oral glucose tolerance test. RESULTS: Unlike women with GDM, women without GDM manifested changes in relative abundance of bacterial species over the pregnancy, particularly those receiving the fish oil + probiotics combination. The specific bacterial species or function did not predict the onset of GDM nor did it differ according to GDM status, except for the higher abundance of Ruminococcus obeum in late pregnancy in the combination group in women with GDM compared with women without GDM. In the combination group, weak decreases over the pregnancy were observed in basic bacterial housekeeping functions. CONCLUSIONS: The specific gut microbiota species do not contribute to GDM in overweight/obese women. Nevertheless, the GDM status may disturb maternal gut microbiota flexibility and thus limit the capacity of women with GDM to respond to diet, as evidenced by alterations in gut microbiota observed only in women without GDM. These findings may be important when considering the metabolic complications during pregnancy, but further studies with larger populations are called for to verify the findings.

The Impacts of Fish Oil and/or Probiotic Intervention on Low-Grade Inflammation, IGFBP-1 and MMP-8 in Pregnancy: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial.

BACKGROUND: We investigated the impact of fish oil and/or probiotics on serum and vaginal inflammatory and metabolic proteins and their relation to the onset of gestational diabetes mellitus (GDM). METHODS: Overweight/obese pregnant women received fish oil + placebo, probiotics + placebo, fish oil + probiotics or placebo + placebo from early pregnancy until six months postpartum (fish oil: 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid; probiotics: Lactobacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 colony-forming units each). Serum high sensitivity C-reactive protein (hsCRP) and serum/vaginal (s/v) phosphorylated insulin-like growth factor binding-protein-1 (phIGFBP-1), IGFBP-1 and matrix metalloproteinase 8 (MMP-8) were analyzed. GDM was diagnosed according to 2 h 75 g OGTT. RESULTS: The intervention had no impact on the change in proteins during pregnancy. Nevertheless, s-MMP-8 decreased and s-IGFBP-1 increased more in obese than in overweight women in the fish oil + probiotics group, while a decrease in s-MMP-8 was seen in obese women and an increase was seen in overweight women in the probiotics + placebo group. The late pregnancy s-phIGFBP-1 was higher in women who developed GDM in fish oil + probiotics-group compared to fish oil + placebo-group. The concentrations of s-phIGFBP-1 (635.9 ± 315.3 ng/mL vs. 753.2 ± 335.1 ng/mL, p = 0.005) and s-IGFBP-1 (3.78 ± 0.72 ng/mL vs. 3.96 ± 0.69 ng/mL, p = 0.042) were lower in early pregnancy in women who developed GDM than in women remaining healthy. CONCLUSIONS: The intervention per se had no impact on the proteins, but obesity and GDM may modify the effect. IGFBPs may affect the development of GDM.

Effect of Probiotic Supplementation on Newborn Birth Weight for Mother with Gestational Diabetes Mellitus or Overweight/Obesity: A Systematic Review and Meta-Analysis.

High birth weight indicates the future risk of obesity and increased fat mass in childhood. Maternal gestational diabetes mellitus (GDM) or overweight are powerful predictors of high birth weight. Studies on probiotic supplementation during pregnancy have reported its benefits in modulating gut microbiota composition and improving glucose and lipid metabolism in pregnant women. Therefore, probiotic intervention during pregnancy was proposed to interrupt the transmission of obesity from mothers to newborns. Thus, we performed a meta-analysis to investigate the effect of probiotic intervention in pregnant women with GDM or overweight on newborn birth weight. We searched PubMed, EMBASE, Cochrane Library, and Web of Science databases up to 18 December 2019. Randomized controlled trials (RCTs) comparing pregnant women with GDM or overweight who received probiotic intervention during pregnancy with those receiving placebo were eligible for the analysis. Newborn birth weights were pooled to calculate the mean difference with a 95% confidence interval (CI). Two reviewers assessed the trial quality and extracted data independently. Seven RCTs involving 1093 participants were included in the analysis. Compared with the placebo, probiotics had little effect on newborn birth weight of pregnant women with GDM or overweight (mean difference = -10.27, 95% CI = -90.17 to 69.63, p = 0.801). The subgroup analysis revealed that probiotic intake by women with GDM decreased newborn birth weight, whereas probiotic intake by obese pregnant women increased newborn birth weight. Thus, no evidence indicates that probiotic intake by pregnant women with GDM or overweight can control newborn birth weight.

Improvement of glucose metabolism in pregnant women through probiotic supplementation depends on gestational diabetes status: meta-analysis.

The aim of this study was to assess the effects of probiotic and synbiotic supplementation on glucose metabolism in pregnant women using data from randomized controlled trials. Furthermore, this meta-analysis examines whether the observed effects depend on the presence or absence of gestational diabetes mellitus (GDM), and if the effect is dependent on the type of supplement used (probiotic or synbiotic). We performed a literature search of databases (Medline, Scopus, Web of Knowledge, and Cochrane Library) and identified all relevant randomized controlled trials (RCTs) published prior to May 2019. We compared the effects of probiotic supplementation with the administration of placebos in pregnant women with and without GDM. The systematic review and meta-analysis protocol were registered in the International Prospective Register of Systematic Reviews as number CRD 42019111467. 1119 study participants from 15 selected studies were included. The participants in four studies did not have GDM (being recruited to the study before week 20 of pregnancy) and the participants in the rest of the studies were diagnosed with GDM between weeks 24 and 28 of gestation. The meta-analysis showed that supplementation lowers serum glucose, insulin levels, and HOMA-IR index, but only in pregnant women with GDM. Moreover, both probiotics and synbiotics lower serum insulin level and HOMA-IR index, but the glucose lowering effect is specific only to probiotics and not synbiotics. Probiotic supplementation may improve glucose metabolism in pregnant women with GDM. There is a need for more RCT studies with larger groups to better estimate this effect.

Effect of dietary myo-inositol supplementation on the insulin resistance and the prevention of gestational diabetes mellitus: study protocol for a randomized controlled trial.

BACKGROUND: Gestational diabetes mellitus (GDM) is defined as impaired glucose tolerance with onset or first recognition during pregnancy, which is characterized by an increased insulin resistance. Gestational diabetes mellitus is associated with pregnancy-related maternal and fetal morbidity (both antenatal and perinatal). Myo-inositol has been suggested to improve insulin resistance in women with polycystic ovary syndrome. The aim of this study is to examine the impact of myo-inositol supplementation during pregnancy on the incidence of gestational diabetes mellitus. METHODS: We will conduct a single-center, open-label, randomized controlled trial. A total of 160 healthy pregnant women with singleton pregnancy at 11-13+6 weeks of gestation will be randomly allocated in two groups: intervention group (N = 80) and control group (N = 80). The intervention group will receive myo-inositol and folic acid (4000 mg myo-inositol and 400 mcg folic acid daily) from 11 to 13+6 weeks of gestation until 26-28 weeks of gestation, while the control group will receive folic acid alone (400 mcg folic acid daily) for the same period of time as intervention group. The primary outcome will be gestational diabetes incidence rate at 26-28 weeks of gestation, according to the results of a 75 g oral glucose tolerance test held at 26-28 weeks of gestation. The secondary outcomes will include fasting blood glucose levels, glycated hemoglobin levels, insulin resistance level (evaluated by homeostasis model assessment of insulin resistance and Matsuda Index), and incidence rate of diet-treated gestational diabetes and diabetes requiring insulin therapy at 26-28 weeks of gestation. DISCUSSION: This trial will provide evidence for the effectiveness of myo-inositol supplementation during pregnancy in reducing the incidence of gestational diabetes mellitus. TRIAL REGISTRATION: ISRCTN registry: ISRCTN16142533 . Registered on 9 March 2017.

Addition of olive oil to diet of rats with mild pre-gestational diabetes impacts offspring ß-cell development.

Maternal diabetes impairs fetal development and increases the risk of metabolic diseases in the offspring. Previously, we demonstrated that maternal dietary supplementation with 6% of olive oil prevents diabetes-induced embryo and fetal defects, in part, through the activation of peroxisome proliferator-activated receptors (PPARs). In this study, we examined the effects of this diet on neonatal and adult pancreatic development in male and female offspring of mothers affected with pre-gestational diabetes. A mild diabetic model was developed by injecting neonatal rats with streptozotocin (90 mg/kg). During pregnancy, these dams were fed a chow diet supplemented or not with 6% olive oil. Offspring pancreata was examined at day 2 and 5 months of age by immunohistochemistry followed by morphometric analysis to determine number of islets, α and ß cell clusters and ß-cell mass. At 5 months, male offspring of diabetic mothers had reduced ß-cell mass that was prevented by maternal supplementation with olive oil. PPARα and PPARγ were localized mainly in α cells and PPARß/δ in both α and ß cells. Although Pparß/δ and Pparγ RNA expression showed reduction in 5-month-old male offspring of diabetic rats, Pparß/δ expression returned to control levels after olive-oil supplementation. Interestingly, in vitro exposure to oleic acid (major component of olive oil) and natural PPAR agonists such as LTB4, CPC and 15dPGJ2 also significantly increased expression of all Ppars in αTC1-6 cells. However, only oleic acid and 15dPGJ2 increased insulin and Pdx-1 expression in INS-1E cells suggesting a protective role in ß-cells. Olive oil may be considered a dietary supplement to improve islet function in offspring of affected mothers with pre-gestational diabetes.

Association between plasma irisin and glucose metabolism in pregnant women is modified by dietary n-3 polyunsaturated fatty acid intake.

AIMS/INTRODUCTION: The role of irisin in maternal glucose metabolism and how it would respond to dietary n-3 polyunsaturated fatty acid (n-3 PUFA) intake remains unclear. This study aimed to explore whether maternal plasma irisin is associated with glucose metabolism and whether this association is modified by dietary n-3 PUFA. MATERIALS AND METHODS: A total of 932 pregnant women (20-28 weeks' gestation) aged 20-45 years were recruited. Dietary n-3 PUFA was estimated using a validated quantitative food frequency questionnaire. Plasma irisin and insulin were tested by enzyme-linked immunosorbent assay, and insulin resistance (IR) was estimated using the homeostatic model assessment (HOMA). Gestational diabetes mellitus was diagnosed with a 75-g oral glucose tolerance test. Adjusted multivariable linear regression and logistic regression were carried out to examine the associations between plasma irisin and glucose metabolism. The moderating effect of dietary n-3 PUFA intake was determined by fully multiplicative models by including the interaction term. RESULTS: Maternal plasma irisin was negatively associated with HOMA-IR and oral glucose tolerance test 0 h glucose level (ß -0.250, -0.067; corrected P-value for false discovery rate = 0.012, 0.018, respectively), positively associated with HOMA of insulin sensitivity (ß 0.028; corrected P-value for false discovery rate = 0.012), but not associated with postprandial glucose or the risk of gestational diabetes mellitus. Furthermore, we found a moderating effect of dietary n-3 PUFA on the relationships of plasma irisin with HOMA-IR and HOMA of insulin sensitivity; these associations were strengthened with increased n-3 PUFA intake (ß -0.037, 0.004; P = 0.014, 0.041, respectively). CONCLUSIONS: Plasma irisin was negatively associated with HOMA-IR and fasting glucose, whereas it was positively associated with HOMA of insulin sensitivity in pregnant women. We first showed that these associations were modified by dietary n-3 PUFA intake.

Effects of Nutritional Strategies on Glucose Homeostasis in Gestational Diabetes Mellitus: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, and nutritional therapy is the basis of GDM treatment. However, the effects of different forms of nutritional supplementation on improving gestational diabetes are uncertain. OBJECTIVE: We conducted a network meta-analysis to evaluate the effects of supplementation with different nutrients on glucose metabolism in women with GDM. METHODS: We conducted a literature search using PubMed, EMBASE, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing the differences between different nutritional strategies in women with GDM. The Cochrane tool was used to assess the risk of bias. Pairwise meta-analysis and network meta-analysis were used to compare and rank the effects of nutritional strategies for the improvement of fasting plasma glucose (FPG), serum insulin, and homeostasis model assessment-insulin resistance (HOMA-IR). RESULTS: We included thirteen RCTs with a total of 754 participants. Compared with placebo, omega-3, magnesium, vitamin D, zinc, and probiotics were more beneficial for improving FPG, serum insulin, and HOMA-IR. Network analysis showed that vitamin D supplementation was superior to omega-3 (-3.64 mg/dL, 95% CI: -5.77 to -1.51), zinc (-5.71 mg/dL, 95% CI: -10.19 to -1.23), probiotics (-6.76 mg/dL, 95% CI: -10.02 to -3.50), and placebo (-12.13 mg/dL, 95% CI: -14.55 to -9.70) for improving FPG. Magnesium supplementation was more beneficial for decreasing serum insulin compared with probiotics (-5.10 µIU/mL, 95% CI: -9.32 to -0.88) and placebo (-7.80 µIU/mL, 95% CI: -9.32 to -0.88) and placebo (-7.80 . CONCLUSION: Vitamin D supplementation significantly reduced FPG and regulated HOMA-IR. Magnesium supplementation was superior in decreasing serum insulin than supplementation with other nutrients. Nutrient supplementation seemed to have an effect on glucose homeostasis maintenance in patients with GDM and may be considered an adjunctive therapy.