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Effects of probiotic supplementation during pregnancy on metabolic outcomes: A systematic review and meta-analysis of randomized controlled trials.
Masulli, M, Vitacolonna, E, Fraticelli, F, Della Pepa, G, Mannucci, E, Monami, M
Diabetes research and clinical practice. 2020;:108111
Abstract
AIM: To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of probiotics in pregnancy on the incidence of gestational diabetes (GDM) and fasting plasma glucose (FPG). METHODS A MEDLINE, EMBASE, Scopus and Cochrane search (up to May 30th, 2019) was performed to identify RCTs of comparison of probiotics with placebo/active comparators in pregnant women. Principal endpoints were the incidence of GDM and the change of FPG. Other maternal and fetal outcomes were secondary endpoints. Mantel-Haenszel Odds Ratio with 95% CI (MH-OR) was calculated for dichotomous outcomes, whereas standardized differences in means was calculated for continuous variables. (PROSPERO registration CRD42019139889). FINDINGS A total of 17 RCTs, all versus placebo, was identified. The overall quality of the trials was satisfactory. No effect of probiotics on incidence of GDM (MH-OR: 0.77[0.51,1.16], p = 0.21,I2:62%) was observed, with a small but significant reduction of FPG (mean difference -1.01 [-1.96, -0.06]mg/dl, p = 0.02, I2:46%). Among secondary endpoints, a significant reduction of maternal insulin (both in women with or without diabetes) was observed in the probiotics group. INTERPRETATION Probiotics during pregnancy do not reduce the incidence of GDM, with a very little (statistically but not clinically significant) reduction of fasting plasma glucose.
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Effects of gum chewing on glycaemic control in women with gestational diabetes mellitus: A randomized controlled trial. Impact of chewing on hyperglycaemia in women with GDM.
Yerlikaya-Schatten, G, Trimmal, L, Rosicky, I, Husslein, P, Schatten, C, Eppel, D, Eppel, W, Tura, A, Göbl, CS
European journal of obstetrics, gynecology, and reproductive biology. 2020;:61-65
Abstract
BACKGROUND The amount of chewing might be relevant in reducing hyperglycaemia in diabetic patients. The study assessed the impact of enhanced chewing on glycaemic control in women with gestational diabetes mellitus (GDM). METHODS As an open-label, mono-centre randomized controlled trial, 59 women with recent diagnosis of GDM were included. They received either routine care or additional chewing gum intervention. SMBG was performed for five days. RESULTS No significant impact on mean values of postprandial glucose levels were observed. The estimated mean differences (intervention vs. control group) were: 4.9 mg/dl, 98.4 %CI -7.2-17.1 (breakfast); -4.5 mg/dl, 98.4 %CI -15.1-6.0 (lunch); -3.8 mg/dl, 98.4 %CI -15.9 to 8.4 (dinner). OGTT levels at 60 and 120 min. were associated with glucose levels after breakfast. CONCLUSION In conclusion, no significant differences in blood glucose levels were observed between the groups and therefore major effects of chewing on hyperglycaemia in women with GDM could be excluded. TRIAL REGISTRATION ClinicalTrials.gov; NCT03961542, Date of registration: 20.01.2019. Retrospectively registered.
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Role of insulin, adenosine, and adipokine receptors in the foetoplacental vascular dysfunction in gestational diabetes mellitus.
Subiabre, M, Villalobos-Labra, R, Silva, L, Fuentes, G, Toledo, F, Sobrevia, L
Biochimica et biophysica acta. Molecular basis of disease. 2020;(2):165370
Abstract
Gestational diabetes mellitus (GDM) is a disease of pregnancy associated with maternal and foetal hyperglycaemia and altered foetoplacental vascular function. Human foetoplacental microvascular and macrovascular endothelium from GDM pregnancy show increased maximal l-arginine transport capacity via the human cationic amino acid transporter 1 (hCAT-1) isoform and nitric oxide (NO) synthesis by the endothelial NO synthase (eNOS). These alterations are paralleled by lower maximal transport activity of the endogenous nucleoside adenosine via the human equilibrative nucleoside transporter 1 (hENT1) and activation of adenosine receptors. A causal relationship has been described for adenosine-activation of A2A adenosine receptors, hCAT-1, and eNOS activity (i.e. the Adenosine/l-Arginine/Nitric Oxide, ALANO, signalling pathway). Insulin restores these alterations in GDM via activation of insulin receptor A (IR-A) form in the macrovascular but IR-A and IR-B forms in the microcirculation of the human placenta. Adipokines are secreted from adipocytes influencing the foetoplacental metabolic and vascular function. Various adipokines are dysregulated in GDM, with adiponectin and leptin playing major roles. Abnormal plasma concentration of these adipokines and the activation or their receptors are involved in the pathophysiology of GDM. However, involvement of adipokines, adenosine, and insulin receptors and membrane transporters in the aetiology of this disease of pregnancy is unknown. This review focuses on the pathophysiology of insulin and adenosine receptors and l-arginine and adenosine membranes transporters giving an overview of the key adipokines leptin and adiponectin in the foetoplacental vasculature in GDM. This article is part of a Special Issue entitled: Membrane Transporters and Receptors in Pregnancy Metabolic Complications edited by Luis Sobrevia.
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Probiotic treatment for women with gestational diabetes to improve maternal and infant health and well-being.
Okesene-Gafa, KA, Moore, AE, Jordan, V, McCowan, L, Crowther, CA
The Cochrane database of systematic reviews. 2020;(6):CD012970
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Abstract
BACKGROUND Gestational diabetes mellitus (GDM) is carbohydrate intolerance first recognised during pregnancy and associated with complications for mothers and babies. Probiotics are naturally occurring micro-organisms, which when ingested in adequate amounts, may confer health benefits. Evidence of the role of probiotics as treatment for GDM is limited. OBJECTIVES To evaluate the safety and effectiveness of probiotics in treating women with GDM on maternal and infant outcomes. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth's Trials Register ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (24 July 2019), and reference lists of retrieved studies. SELECTION CRITERIA Randomised controlled trials (RCTs) comparing the use of probiotics versus placebo/standard care for the treatment of GDM. DATA COLLECTION AND ANALYSIS Two review authors independently assessed study eligibility, extracted data, checked data accuracy, and assessed risk of bias of included trials. The certainty of evidence for selected maternal and infant/child outcomes was assessed using GRADE. MAIN RESULTS Nine RCTs (695 pregnant women with GDM) comparing probiotics versus placebo were identified. The overall risk of bias in the nine RCTs was low to unclear and the evidence was downgraded for imprecision due to the small numbers of women participating in the trials. The trials were carried out in hospitals and universities in Iran (seven trials), Thailand (one trial) and Ireland (one trial). All trials compared probiotics with placebo. Maternal outcomes We are uncertain if probiotics have any effect compared with placebo on hypertensive disorders of pregnancy, (risk ratio (RR) 1.50, 95% confidence interval (CI) 0.64 to 3.53; participants = 256; studies = 3; low-certainty evidence) and mode of birth as caesareans (average RR 0.64, 95% CI 0.30 to 1.35; participants = 267; studies = 3; low-certainty evidence) because the certainty of evidence is low and the 95% CIs span possible benefit and possible harm. No trials reported primary outcomes of: mode of birth as vaginal/assisted and subsequent development of type 2 diabetes. We are uncertain if probiotics have any effect compared with placebo on induction of labour (RR 1.33, 95% CI 0.74 to 2.37; participants = 127; studies = 1; very low-certainty evidence). For other secondary maternal outcomes, we are uncertain if there are differences between probiotics and placebo for: postpartum haemorrhage; weight gain during pregnancy intervention and total gestational weight gain; fasting plasma glucose and need for extra pharmacotherapy (insulin). Probiotics may be associated with a slight reduction in triglycerides and total cholesterol. In probiotics compared with placebo, there was evidence of reduction in markers for insulin resistance (HOMA-IR) and HOMA-B; and insulin secretion. There was also an increase in quantitative insulin sensitivity check index (QUICKI). Probiotics were associated with minor benefits in relevant bio-markers with evidence of a reduction in inflammatory markers high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and marker of oxidative stress malondialdehyde; and an increase in antioxidant total glutathione, but we are uncertain if there is any difference in total antioxidant capacity. No trials reported secondary outcomes: perineal trauma, postnatal weight retention or return to pre-pregnancy weight and postnatal depression. Infant/child/adult outcomes We are uncertain if probiotics have any effect, compared with placebo, on the risk of large-for-gestational-age babies (RR 0.73, 95% CI 0.35 to 1.52; participants = 174; studies = 2; low-certainty evidence) or infant hypoglycaemia (RR 0.85, 95% CI 0.39 to 1.84; participants = 177; studies = 3; low-certainty evidence) because the certainty of evidence is low and the 95% CIs span possible benefit and possible harm. No trials reported primary outcomes of: perinatal (fetal/neonatal) mortality; or neurosensory disability. For other secondary outcomes, we are uncertain if there is any difference between probiotics and placebo in gestational age at birth, preterm birth, macrosomia, birthweight, head circumference, length, infant hypoglycaemia, and neonatal intensive care unit (NICU) admissions. There was evidence of a reduction in infant hyperbilirubinaemia with probiotics compared with placebo. No trials reported secondary outcomes: infant adiposity, and later childhood adiposity. There were no adverse events reported by any of the trials. AUTHORS' CONCLUSIONS Low-certainty evidence means we are not certain if there is any difference between probiotic and placebo groups in maternal hypertensive disorders of pregnancy, caesareans; and large-for-gestational-age babies. There were no adverse events reported by the trials. Due to the variability of probiotics used and small sample sizes of trials, evidence from this review has limited ability to inform practice. Well-designed adequately-powered trials are needed to identify whether probiotics may improve maternal blood glucose levels and/or infant/child/adult outcomes; and whether they can be used to treat GDM.
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Intergenerational Metabolomic Analysis of Mothers with a History of Gestational Diabetes Mellitus and Their Offspring.
Ott, R, Pawlow, X, Weiß, A, Hofelich, A, Herbst, M, Hummel, N, Prehn, C, Adamski, J, Römisch-Margl, W, Kastenmüller, G, et al
International journal of molecular sciences. 2020;(24)
Abstract
Shared metabolomic patterns at delivery have been suggested to underlie the mother-to-child transmission of adverse metabolic health. This study aimed to investigate whether mothers with gestational diabetes mellitus (GDM) and their offspring show similar metabolomic patterns several years postpartum. Targeted metabolomics (including 137 metabolites) was performed in plasma samples obtained during an oral glucose tolerance test from 48 mothers with GDM and their offspring at a cross-sectional study visit 8 years after delivery. Partial Pearson's correlations between the area under the curve (AUC) of maternal and offspring metabolites were calculated, yielding so-called Gaussian graphical models. Spearman's correlations were applied to investigate correlations of body mass index (BMI), Matsuda insulin sensitivity index (ISI-M), dietary intake, and physical activity between generations, and correlations of metabolite AUCs with lifestyle variables. This study revealed that BMI, ISI-M, and the AUC of six metabolites (carnitine, taurine, proline, SM(-OH) C14:1, creatinine, and PC ae C34:3) were significantly correlated between mothers and offspring several years postpartum. Intergenerational metabolite correlations were independent of shared BMI, ISI-M, age, sex, and all other metabolites. Furthermore, creatinine was correlated with physical activity in mothers. This study suggests that there is long-term metabolic programming in the offspring of mothers with GDM and informs us about targets that could be addressed by future intervention studies.
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Systematic review of effectiveness and cost-effectiveness of lifestyle interventions to improve clinical diabetes outcome measures in women with a history of GDM.
Hewage, SS, Wu, S, Neelakantan, N, Yoong, J
Clinical nutrition ESPEN. 2020;:20-29
Abstract
OBJECTIVE Lifestyle interventions have been shown to be both effective and cost-effective in reducing diabetes and metabolic risk in high-risk populations. We systematically reviewed the effectiveness and cost-effectiveness of lifestyle interventions on anthropometric, glycemic and cardiovascular outcomes in women with previous gestational diabetes mellitus (GDM). METHOD Relevant randomized control trials (RCT) were identified by searching multiple electronic databases through 20th June 2018. Data were pooled using random-effects models. The review protocol was registered on the PROSPERO international prospective register of systematic reviews (PROSPERO 2016: CRD42018108870). RESULTS Twenty-one studies met the inclusion criteria and 16 studies with outcome data were analyzed in the meta-analysis. No RCT studies included cost-effectiveness data on lifestyle interventions. The pooled estimate for postpartum weight showed a significant mean reduction in the intervention arm (-1.8 kg [95% CI: -2.9, -0.6; p = 0.002; I2 = 92.2%; p < 0.05]). Further, the effect of lifestyle intervention on weight change was significantly greater in studies of longer duration. Most of the other endpoints had modest improvements but only anthropometric endpoints were statistically significant. However, there was high heterogeneity between the studies. CONCLUSIONS Lifestyle interventions showed statistically and clinically significant improvements in anthropometric outcomes. However, more research is needed to explore lifestyle effects on glycemic and cardiovascular risk factors and to establish cost-effectiveness. Methodologically sound, large scale studies on diverse ethnicities and with longer follow-up would establish the real effect of lifestyle interventions to reduce diabetes risk in women with previous GDM.
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The influence of different inositol stereoisomers supplementation in pregnancy on maternal gestational diabetes mellitus and fetal outcomes in high-risk patients: a randomized controlled trial.
Celentano, C, Matarrelli, B, Pavone, G, Vitacolonna, E, Mattei, PA, Berghella, V, Liberati, M
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2020;(5):743-751
Abstract
Objective: To identify the effects of different dietary inositol stereoisomers on insulin resistance and the development of gestational diabetes mellitus (GDM) in women at high risk for this disorder.Design: A preliminary, prospective, randomized, placebo controlled clinical trial.Participants: Nonobese singleton pregnant women with an elevated fasting glucose in the first or early second trimester were studied throughout pregnancy.Intervention: Supplementation with myo-inositol, d-chiro-inositol, combined myo- and d-chiro-inositol or placebo.Main outcome measure: Development of GDM on a 75 grams oral glucose tolerance test at 24-28 weeks' gestation. Secondary outcome measures were increase in BMI, need for maternal insulin therapy, macrosomia, polyhydramnios, neonatal birthweight and hypoglycemia.Results: The group of women allocated to receive myo-inositol alone had a lower incidence of abnormal oral glucose tolerance test (OGTT). Nine women in the control group (C), one of the myo-inositol (MI), five in d-chiro-inositol (DCI), three in the myo-inositol/D-chiro-inositol group (MI/DCI) required insulin (p = .134). Basal, 1-hour, and 2 hours glycemic controls were significantly lower in exposed groups (p < .001, .011, and .037, respectively). The relative risk reduction related to primary outcome was 0.083, 0.559, and 0.621 for MI, DCI, and MI/DCI groups.Conclusions: This study compared the different inositol stereoisomers in pregnancy to prevent GDM. Noninferiority analysis demonstrated the largest benefit in the myo-inositol group. The relevance of our findings is mainly related to the possibility of an effective approach in GDM. Our study confirmed the efficacy of inositol supplementation in pregnant women at risk for GDM.
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Do raised two-hour pre-pregnancy insulin levels confer the same risks of developing GDM, as raised fasting levels, in recurrent miscarriage patients?
McCormack, C, Leemaqz, S, Furness, D, Dekker, G, Roberts, CT
Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology. 2020;(6):803-807
Abstract
This study questioned whether raised pre-pregnancy two-hour (2 h) insulin levels, measured in recurrent embryonic miscarriage (RM) patients via a 75 g Oral Glucose Tolerance Test (OGTT), are associated with an increased risk of gestational diabetes mellitus (GDM) in a subsequent pregnancy. Patients had a 75 g OGTT and insulin levels evaluated (n = 170). 54.1% had normal glucose and insulin levels, 45.9% had levels indicating hyperinsulinism (HI). In the 98 patients who achieved a pregnancy, the prevalence of GDM was 3.7% in those without HI, and 35.7% in the patients who only had raised 2 h insulin levels. While HI has been described as a risk factor for miscarriages only in relation to raised fasting (basal) insulin levels, this study demonstrated that raised 2 h insulin levels predict an increased risk of GDM in a subsequent pregnancy. Thus raised 2 h insulin levels likely confer a similar risk to raised fasting insulin levels in RM patients.Impact statementWhat is already known on this subject? Fasting hyperinsulinism is known to be associated with an increased risk of gestational diabetes mellitus (GDM) in pregnancy. Hyperinsulinism, as reflected by the fasting (basal) insulin levels >20mU/L, has been recognized as a risk factor for recurrent miscarriages, particularly in patients with polycystic ovarian syndrome (PCOS), in the World literature. Raised two-hour insulin levels have not been considered as a risk factor in the literature before.What do the results of the study add? We have demonstrated a 10-fold increase in the development of GDM in patients with fasting insulin resistance, and/or raised 2h insulin levels, and an almost 10-fold increase in patients with only raised 2h levels. 58.8% of the patients who subsequently developed GDM only had raised 2h levels and would have been missed with routine testing.What are the implications of these findings for clinical practice and/or further research? Our study has demonstrated that GDM was three times more prevalent in the patients with only raised 2h levels, than in those only with raised fasting levels, reflecting insulin resistance/hyperinsulinism. Insulin studies including 2h insulin levels are therefore an important factor to consider when working up these patients. Insulin studies pre-pregnancy may be useful in identifying women at risk of suffering miscarriages or of developing GDM in a subsequent pregnancy.
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Effects of breastfeeding education based on the self-efficacy theory on women with gestational diabetes mellitus: A CONSORT-compliant randomized controlled trial.
You, H, Lei, A, Xiang, J, Wang, Y, Luo, B, Hu, J
Medicine. 2020;(16):e19643
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BACKGROUND Women with gestational diabetes mellitus (GDM) face big challenges of breastfeeding. In order to improve breastfeeding self-efficacy and breastfeeding rate of them, we formulated perinatal individualized interventions based on self-efficacy theory and conducted a randomized controlled trial to verify the effectiveness. METHODS We conducted a randomized controlled trial. The perinatal individualized interventions based on the self-efficacy theory including 4 phases were led by the International Board Certified Lactation Consultant (IBCLC). Women allocated to the control group received usual care for lactation support during the antenatal and postnatal period. Data collection occurred at admission, discharge, 6 weeks postpartum, 4 months postpartum, and 6 months postpartum. RESULTS We enrolled 226 women with GDM, 113 in the intervention group and 113 in the control group. The scores of breastfeeding self-efficacy in the intervention group were significantly higher than those in the control group at discharge, at 6 weeks, 4 months, and 6 months postpartum (P < .05). We found higher rates of exclusive and any breastfeeding in the intervention group at discharge (Exclusive: 25.2% vs 13.5%, P < .05; Any: 94.4% vs 89.4%, P > .05), at 6 weeks postpartum (Exclusive: 75.5% vs 62.5%, P < .05; Any: 100.0% vs 96.2%, P > .05), at 4 months postpartum (Exclusive: 68.9% vs 43.3%, P < .05; Any: 94.3% vs 83.7%, P < .05) and at 6 months postpartum (Exclusive: 55.8% vs 36.9%, P < .05; Any: 88.5% vs 64.1%, P < .05). CONCLUSION Perinatal individualized breastfeeding education based on the self-efficacy theory had positive effects on breastfeeding self-efficacy and breastfeeding rate of women with GDM.
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Gestational diabetes mellitus prediction? A unique fatty acid profile study.
Ogundipe, E, Samuelson, S, Crawford, MA
Nutrition & diabetes. 2020;(1):36
Abstract
OBJECTIVE To elucidate whether women at risk of gestational diabetes mellitus (GDM) have a unique fatty acid profile compared to women considered normal healthy controls (NHC). METHODS Three hundred pregnant women were randomized to a control group (NHC) (n = 50) and to one of three high risk groups (n = 250), one of which was GDM (n = 50). At recruitment participants' booking bloods were taken and analyzed for lipid profiles. The GDM group's fatty acid profile is reported here. RESULTS GDM women compared to NHC had elevated levels of omega 6 (n-6) fatty acids compared to omega 3 (n-3) fatty acids (p = 0.01), of linoleic acid (LA) to docosahexaenoic acid (DHA) p = 0.001, sequentially distorted levels of n-6 fatty acids LA and arachidonic acid (ArA) p = 0.035, as well as significantly depressed levels of n-3 DHA (p = 0.01). CONCLUSION This paper shows that GDM women have a unique fatty acid profile with elevated levels of n-6 fats, depressed levels of n-3 fats and an abnormal pattern of sequential n-6 metabolism. This profile probably results from a combination of factors including underexpression and or poor utilization of desaturase enzymes, suboptimal dietary fatty acids intake, poor micronutrient status or dysbiosis of the microbiome. These results help inform development of a clinical predictive tool.