The Efficacy and Safety of Myo-inositol Supplementation for the Prevention of Gestational Diabetes Mellitus in Overweight and Obese Pregnant Women: A Systematic Review and Meta-Analysis.

Background: Myo-inositol has emerged as one of the preventive therapies for the development of gestational diabetes mellitus in at-risk populations. This systematic review and meta-analysis was conducted to determine the efficacy and safety of myo-inositol in decreasing the incidence of gestational diabetes in overweight and obese pregnant women. Methodology: This meta-analysis was conducted using the standard Cochrane methodology and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines. Inclusion criteria were randomized controlled trials (RCTs) that enrolled overweight and obese pregnant women and used myo-inositol supplementation. The primary outcome was the incidence of gestational diabetes mellitus at 24-28 weeks. Secondary outcomes included cesarean section rate, the incidence of pregnancy-induced hypertension, macrosomia and preterm delivery. Risk ratios (RRs) and 95% confidence intervals (CIs) were used for dichotomous data. Results: Six RCTs were included. Compared to standard micronutrient supplementation, standard dose of myo-inositol (4 g) may reduce the incidence of GDM (RR 0.54; CI [0.30, 0.96]; n = 887 women), but the certainty of evidence is low to very low. With low-dose myo-inositol however, evidence is uncertain about its benefit on the incidence of gestational diabetes mellitus in overweight and obese women with RR 0.71; CI [0.14, 3.50]. No adverse effects were noted. For the secondary outcomes, standard dose myo-inositol appears to reduce the incidence of pregnancy-induced hypertension and preterm delivery, but the certainty of evidence is low to very low. Conclusion: Current evidence is uncertain on the potential benefit of myo-inositol supplementation in overweight and obese pregnant women. While studies show that 4 g myo-inositol per day may decrease the incidence of GDM, pregnancy-induced hypertension and pre-term birth with no associated risk of serious adverse events, the certainty of evidence is low to very low. Future high-quality trials may provide more compelling evidence to support practice recommendations.

The effect of myo-inositol supplementation on the prevention of gestational diabetes in overweight pregnant women: a randomized, double-blind, controlled trial.

BACKGROUND: This study strove to investigate the hypothesis that a low dosage of myo-inositol supplementation might decrease the likelihood of gestational diabetes in overweight, pregnant women. METHODS: A randomized, double-blind, controlled trial was performed on 60 eligible overweight, pregnant women, at 12-14 weeks of gestation, at two Iranian obstetric clinics. The participants were divided into two groups based on blocked randomization. The myo-inositol group received 2000 mg plus 400 µg folic acid daily and the control group received 400 µg of folic acid daily from 14-24 gestational weeks. The occurrence of gestational diabetes was determined based on 75-g 2-hour oral glucose tolerance test (OGTT) at 24-28 gestational weeks, which was the primary outcome of the study. The secondary outcomes were: the evaluation of insulin therapy, insulin resistance and lipid profile, gestational weight gain, and fetal and maternal outcomes. RESULTS: The incidence of gestational diabetes in myo-inositol group was noticeably minimized compared to that in the control group (RR=0.29, 95% CI: 0.09-0.94, P=0.037). There were no differences between the two groups in terms of fasting blood sugar, fasting insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR), insulin therapy, and triglyceride. There was no report of severe adverse drug reactions. CONCLUSIONS: The absolute risk reduction and the number-needed-to-treat for gestational diabetes were 26.8% (95% CI: 5.6-48) and 3.7 (95% CI: 2.1-18.0), respectively. Hence, it can be concluded that approximately one out of every four overweight pregnant women receiving myo-inositol benefitted from its daily intake.

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.

Differences in levothyroxine action on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity between metformin- and myo-inositol-treated women with autoimmune subclinical hypothyroidism.

WHAT IS KNOWN AND OBJECTIVE: Insulin resistance impairs the impact of levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity. Both metformin and myo-inositol were found to improve insulin sensitivity and to reduce thyrotropin levels in individuals with hypothyroidism. The aim of the present study was to compare the effect of levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity between women receiving metformin and myo-inositol. METHODS: The study included two groups of women with autoimmune hypothyroidism, treated for at least 6 months with either metformin (group A; n = 25) or myo-inositol (group B; n = 25). Both groups were matched for age, insulin sensitivity, hormone levels and antibody titers. For the following 6 months, all women received levothyroxine. Plasma levels of glucose, insulin, thyrotropin, free thyroid hormones, prolactin, 25-hydroxyvitamin D and high-sensitivity C-reactive protein (hsCRP), as well as titers of thyroid peroxidase and thyroglobulin antibodies were assessed at the beginning and at the end of the study. RESULTS AND DISCUSSION: At baseline there were not differences between the study groups. Although levothyroxine reduced thyrotropin levels, increased free thyroid hormone levels and decreased antibody titers in both study groups, these effects were more pronounced in group A than group B. Only in group A, levothyroxine increased 25-hydroxyvitamin D, decreased hsCRP and improved insulin sensitivity. The impact of levothyroxine on thyrotropin and free thyroid hormones correlated with treatment-induced changes in insulin sensitivity, antibody titers, 25-hydroxyvitamin D and hsCRP. WHAT IS NEW AND CONCLUSION: The present study suggests that the impact of levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity is stronger in women receiving metformin than in women treated with myo-inositol.

The effect of voglibose on metabolic profiles in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of clinical trials.

OBJECTIVE: The effect of voglibose on metabolic homeostasis is not well characterized. Therefore, we conducted a systematic review and meta-analysis of clinical trials assessing the effect of voglibose on metabolic profile in patients with type 2 diabetes mellitus (T2DM). METHODS: Systematic searches were conducted in PubMed, Scopus, Embase, Google Scholar, Web of Science and Cochrane Library to identify clinical trials assessing the effects of voglibose supplementation on cardio-metabolic profile from incept up to 29 July 2019. Data was pooled using fixed- or random-effect models and weighted mean difference (WMD) as the effect size. RESULTS: Eight clinical trials from 1094 reports, were eligible for inclusion. Pooled findings identified significant reductions in hemoglobin A1c (HbA1c) (WMD= -0.27; 95 %CI -0.49 to -0.05; P = 0.01; I2 = 64.8 %) and an increase in LDL-cholesterol levels (WMD=5.97 mg/dl, 95 % CI 0.88, 11.06, P = 0.02; I2 = 0.0 %). However, no evidence of effect for voglibose intake on T2DM patients was observed for: fasting blood sugar (FBS) (WMD -7.43 mg/dl; 95 %CI -16.56 to 1.71; P = 0.110; I2 = 69.3 %), serum insulin (WMD= -0.15 µU/mL; 95 %CI -0.89 to 0.60; P = 0.70; I2 = 0.0 %), total-cholesterol (WMD=2.82 mg/dl, 95 %CI -2.36 to 8.01, P = 0.70; I2 = 49.7 %), triglycerides (WMD= -7.07 mg/dl, 95 %CI -21.76 to 7.62, P = 0.34; I2 = 0.0 %), HDL-cholesterol levels (WMD= -2.10 mg/dl, 95 %CI -4.48 to 0.27, P = 0.08; I2 = 0.0 %,), body mass index (BMI) (WMD=0.09 kg/m2, 95 %CI -0.70 to 0.87; P = 0.87; I2 = 0.0 %), body weight (WMD= -0.42 kg, 95 %CI -0.84 to 0.00; P = 0.05; I2 = 0.0 %), and adiponectin levels (WMD = 0.32 µg/mL, 95 %CI -0.74 to 1.38; P = 0.55; I2 = 0.0 %). CONCLUSIONS: The current meta-analysis identified a decrease in HbA1c and an increase in LDL-cholesterol with administration of voglibose. However, no significant effect was observed on FBS, insulin, bodyweight, BMI, adiponectin, triglycerides, total- and HDL-cholesterol levels.

Myoinositol in the Prevention of Gestational Diabetes Mellitus: Is It Sensible?

Gestational diabetes mellitus (GDM) is a complication that increasingly affects pregnant women. Due to the risk of adverse outcomes in the mother as well as in the fetus which is caused by GDM, appropriate diagnosis and treatment is very essential. Nevertheless, it is important to find new, effective ways of prevention of GDM to avoid side effects. A promising example of such an action may be supplementation of myoinositol. As shown in studies, myoinositol may reduce the risk of developing gestational diabetes mellitus by improving insulin sensitivity.

A Prospective Study Evaluating the Effects of a Nutritional Supplement Intervention on Cognition, Mood States, and Mental Performance in Video Gamers.

Cognitive function is critical for successful prolonged performance in eSports. This double-blind placebo-controlled study examined the effect of an inositol-enhanced arginine silicate oral supplement on cognitive performance and energy in eSports athletes. Sixty healthy men and women who spent 5 or more hours a week playing video games were randomly assigned to take supplement or placebo for 7 days. On day 1 and 7, before and 15 min after dosing, subjects completed the Trail Making Test (TMT), Parts A and B; Stroop Test; and Profile of Mood States (POMS) questionnaire, and then played a video game for 60 min. Immediately after, cognitive tests were repeated. Self-reported energy levels increased, anger decreased, and TMT-B test errors decreased in the supplement group compared to placebo (p < 0.05). Fatigue, TMT-B time, and TMT B-A score improved in the supplement group compared to baseline (p < 0.05). After 60 min of gaming, supplementation decreased Stroop Test errors and TMT-A time (p < 0.05). Adverse events were minimal and not different between groups. These data appear to support the use of the studies product (nooLVL®) in eSports gamers looking to improve their accuracy, decision making, and reaction time during gaming.

Inositol and antioxidant supplementation: Safety and efficacy in pregnancy.

Pregnancies complicated by diabetes have largely increased in number over the last 50 years. Pregnancy is characterized by a physiologic increase in insulin resistance, which, associated with increased oxidative stress and inflammations, could induce alterations of glucose metabolism and diabetes. If not optimally controlled, these conditions have a negative impact on maternal and foetal outcomes. To date, one can resort only to diet and lifestyle to treat obesity and insulin resistance during pregnancy, and insulin remains the only therapeutic option to manage diabetes during pregnancy. However, in the last years, in a variety of experimental models, inositol and antioxidants supplementation have shown insulin-sensitizing, anti-inflammatory, and antioxidant properties, which could be mediated by some possible complementary mechanism of action. Different isomers and multiple combinations of these compounds are presently available: Aim of the present review article is to examine the existing evidence in order to clarify and/or define the effects of different inositol- and antioxidant-based supplements during pregnancy complicated by insulin resistance and/or by diabetes. This could help the clinician's evaluation and choice of the appropriate supplementation regimen.

Alpha-glucosidase inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus.

BACKGROUND: Alpha-glucosidase inhibitors (AGI) reduce blood glucose levels and may thus prevent or delay type 2 diabetes mellitus (T2DM) and its associated complications in people at risk of developing of T2DM. OBJECTIVES: To assess the effects of AGI in people with impaired glucose tolerance (IGT), impaired fasting blood glucose (IFG), moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and the reference lists of systematic reviews, articles and health technology assessment reports. The date of the last search of all databases was December 2017. SELECTION CRITERIA: We included randomised controlled trials (RCTs), with a duration of one year or more, comparing AGI with any pharmacological glucose-lowering intervention, behaviour-changing intervention, placebo or no intervention in people with IFG, IGT, moderately elevated HbA1c or combinations of these. DATA COLLECTION AND ANALYSIS: Two review authors read all abstracts and full-text articles or records, assessed quality and extracted outcome data independently. One review author extracted data, which were checked by a second review author. We resolved discrepancies by consensus or involvement of a third review author. For meta-analyses we used a random-effects model with assessment of risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the overall quality of the evidence by using the GRADE instrument. MAIN RESULTS: For this update of the Cochrane Review (first published 2006, Issue 4) we included 10 RCTs (11,814 participants), eight investigating acarbose and two investigating voglibose, that included people with IGT or people "at increased risk for diabetes". The trial duration ranged from one to six years. Most trials compared AGI with placebo (N = 4) or no intervention (N = 4).Acarbose reduced the incidence of T2DM compared to placebo: 670 out of 4014 people (16.7%) in the acarbose groups developed T2DM, compared to 812 out of 3994 people (20.3%) in the placebo groups (RR 0.82, 95% CI 0.75 to 0.89; P < 0.0001; 3 trials; 8008 participants; moderate-certainty evidence). One trial including participants with coronary heart disease and IGT contributed 64% of cases for this outcome. Acarbose reduced the risk of T2DM compared to no intervention: 7 out 75 people (9.3%) in the acarbose groups developed T2DM, compared to 18 out of 65 people (27.7%) in the no-intervention groups (RR 0.31, 95% CI 0.14 to 0.69; P = 0.004; 2 trials; 140 participants; very low-certainty evidence).Acarbose compared to placebo did not reduce or increase the risk of all-cause mortality (RR 0.98, 95% CI 0.82 to 1.18; P = 0.86; 3 trials; 8069 participants; very low-certainty evidence), cardiovascular mortality (RR 0.88; 95% CI 0.71 to 1.10; P = 0.26; 3 trials; 8069 participants; very low-certainty evidence), serious adverse events (RR 1.12, 95% CI 0.97 to 1.29; P = 0.13; 2 trials; 6625 participants; low-certainty evidence), non-fatal stroke (RR 0.50, 95% CI 0.09 to 2.74; P = 0.43; 1 trial; 1368 participants; very low-certainty evidence) or congestive heart failure (RR of 0.87; 95% CI 0.63 to 1.12; P = 0.40; 2 trials; 7890 participants; low-certainty evidence). Acarbose compared to placebo reduced non-fatal myocardial infarction: one out of 742 participants (0.1%) in the acarbose groups had a non-fatal myocardial infarction compared to 15 out of 744 participants (2%) in the placebo groups (RR 0.10, 95% CI 0.02 to 0.53; P = 0.007; 2 trials; 1486 participants; very low-certainty evidence). Acarbose treatment showed an increased risk of non-serious adverse events (mainly gastro-intestinal events), compared to placebo: 751 of 775 people (96.9%) in the acarbose groups experienced an event, compared to 723 of 775 people (93.3%) in the placebo groups (RR 1.04; 95% CI 1.01 to 1.06; P = 0.0008; 2 trials; 1550 participants). Acarbose compared to no intervention showed no advantage or disadvantage for any of these outcome measures (very low-certainty evidence).One trial each compared voglibose with placebo (1780 participants) or diet and exercise (870 participants). Voglibose compared to placebo reduced the incidence of T2DM: 50 out of 897 participants (5.6%) developed T2DM, compared to 106 out of 881 participants (12%) in the placebo group (RR 0.46, 95% CI 0.34 to 0.64; P < 0.0001; 1 trial; 1778 participants; low-certainty evidence). For all other reported outcome measures there were no clear differences between voglibose and comparator groups. One trial with 90 participants compared acarbose with diet and exercise and another trial with 98 participants reported data on acarbose versus metformin. There were no clear differences for any outcome measure between these two acarbose interventions and the associated comparator groups.None of the trials reported amputation of lower extremity, blindness or severe vision loss, end-stage renal disease, health-related quality of life, time to progression to T2DM, or socioeconomic effects. AUTHORS' CONCLUSIONS: AGI may prevent or delay the development of T2DM in people with IGT. There is no firm evidence that AGI have a beneficial effect on cardiovascular mortality or cardiovascular events.

A randomized controlled trial comparing lifestyle intervention to letrozole for ovulation in women with polycystic ovary syndrome: a study protocol.

BACKGROUND: Polycystic ovary syndrome (PCOS) affects between 8 and 18% of women and is the leading cause of female anovulatory infertility. Unfortunately, common treatments for women trying to conceive can be ineffective as well as disruptive or harmful to patients' quality of life. Despite evidence that women with PCOS have expressed the need for alternative fertility treatments, lifestyle interventions incorporating a nutritional plan with supplementation, increased physical activity, and techniques for stress management have not been combined as a program and studied in this population. Literature suggests that each of these individual components can positively influence reproductive hormones and metabolic health. METHODS/DESIGN: This is a randomized controlled trial which will include 240 women diagnosed with PCOS, according to the Rotterdam criteria, who are trying to conceive. Participants will be randomized to either a comprehensive lifestyle intervention program or prescribed an oral fertility medication, letrozole. These two groups will be further randomized to consume either myo-inositol or a placebo. Participants will be between the ages of 18 and 37 years. Exclusion criteria include women who have already begun fertility treatment, who are currently using myo-inositol or have taken it within the past 3 months, or who are being treated for, or have a history of, an eating disorder. The primary outcome will be the ovulation rate, the secondary outcome will be conception. Other outcomes include miscarriage rates, validated rating measures of overall quality of life (including social, relational, mind/body and emotional sub-categories) and mental health scores (depression, anxiety, and stress). DISCUSSION: This trial will determine the effectiveness of a structured lifestyle-based comprehensive intervention program for women with PCOS experiencing infertility. In addition, it will determine whether supplementing with myo-inositol provides any further benefit. The objective of this study is to assess a possible non-pharmacological solution to ovulatory dysfunction in these patients and perhaps improve other associated features of PCOS. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02630485 . Registered on 15 December 2015.

Effects of myo-inositol on glucose variability in women with gestational diabetes.

OBJECTIVE: Myo-inositol supplementation prevents gestational diabetes (GDM) in women at risk and reduces insulin resistance in women with GDM. No data are available about its effect on glucose variability. The aim of this study was to evaluate the effects of a supplementation of myo-inositol on glucose variability in women with GDM. PATIENTS AND METHODS: Myo-inositol effect on glucose variability was studied in a pilot case-control study involving 12 consecutive pregnant women (median age 34 years, 25.0% insulin-treated) with GDM. Six women received myo-inositol 2 g plus 200 mg folic acid twice a day, the others received only folic acid. Information on side effects was collected. A continuous glucose monitoring system was wore before and at the beginning of the supplementation. Mean amplitude of glucose excursion (MAGE), standard deviation (SD) and variability coefficient were the indexes of glucose variability. RESULTS: Myo-inositol lowered glucose levels in the first days after the treatment was started. However, pre-post supplementation overall mean glucose difference was similar between groups (-4.8 vs. 5.0 mg/dL for controls and treated, respectively; p = 0.79). Pre-post differences in SD (13.7 vs. 6.0; p < 0.001), MAGE (3.5 vs.-1.5; p < 0.001) and variability coefficient (0.14 vs. 0.02; p < 0.001) were improved in myo-inositol group. No side effects were recorded. CONCLUSIONS: Myo-inositol is effective in reducing glucose variability in women with GDM. It could be a useful strategy for treating GDM.

Effectiveness and acceptability of myo-inositol nutritional supplement in the prevention of gestational diabetes (EMmY): a protocol for a randomised, placebo-controlled, double-blind pilot trial.

INTRODUCTION: Gestational diabetes increases maternal and offspring complications in pregnancy and cardiovascular complications in the long term. The nutritional supplement myo-inositol may prevent gestational diabetes; however, further evaluation is required, especially in multiethnic high-risk mothers. Our pilot trial on myo-inositol to prevent gestational diabetes will evaluate trial processes, assess acceptability to mothers and obtain preliminary estimates of effect and cost data prior to a large full-scale trial. METHODS AND ANALYSIS: EMmY is a multicentre, placebo-controlled, double-blind, pilot, randomised trial, with qualitative evaluation. We will recruit pregnant women at 12-15+6 weeks' gestation, with gestational diabetes risk factors, from five maternity units in England between 2018 and 2019. We will randomise 200 women to take either 2 g of myo-inositol powder (intervention) or placebo, twice daily until delivery. We will assess rates of recruitment, randomisation, adherence to intervention and follow-up. Gestational diabetes will be diagnosed at 24-28 weeks as per the National Institute for Health and Care Excellence (NICE) criteria (fasting plasma glucose: ≥5.6 mmol/L and 2-hour plasma glucose: ≥7.8 mmol/L). We will assess the effects of myo-inositol on glycaemic indices at 28 weeks and on other maternal, fetal and neonatal outcomes at postnatal discharge. Qualitative evaluation will explore the acceptability of the trial and the intervention among women and healthcare professionals. Cost data and health-related quality of life measures will be captured. We will summarise feasibility outcomes using standard methods for proportions and other descriptive statistics, and where appropriate, report point estimates of effect sizes (eg, mean differences and relative risks) and associated 95% CIs. ETHICS AND DISSEMINATION: Ethical approval was obtained through the London Queen Square Research Ethics Committee (17/LO/1741). Study findings will be submitted for publication in peer-reviewed journals. Newsletters will be made available to participants, healthcare professionals and members of Katie's Team (a patient and public advisory group) to disseminate. TRIAL REGISTRATION NUMBER: ISRCTN48872100. PROTOCOL VERSION AND DATE: Version 4.0, 15 January 2018.

Effects of myo-inositol plus alpha-lactalbumin in myo-inositol-resistant PCOS women.

BACKGROUND: Myo-inositol (MI), successfully used in polycystic ovary syndrome (PCOS), was administered with α-LA to exploit its action of favouring the passage of other molecules through biological barriers, and also considering its anti-inflammatory effect. METHODS: PCOS patients, according to the Rotterdam ESHRE-ASRM criteria, with anovulation and infertility > 1 year, were included in this open and prospective study. The preliminary phase was aimed at determining a set of MI-resistant PCOS patients. This treatment involved 2 g MI, taken twice per day by oral route, for three months. The Homeostasis Model Assessment (HOMA) index and MI plasma levels were measured. In the main phase, previously selected MI-resistant patients received the same daily amount of MI plus 50 mg α-LA twice a day, for a further three months. Ovulation was assessed using ultrasound examination on days 12, 14 and 20 of the cycle. The HOMA index, lipid, hormone and MI plasma levels were detected at baseline and at the end of this phase. RESULTS: Thirty-seven anovulatory PCOS subjects were included in the study. Following MI treatment, 23 of the 37 women (62%) ovulated, while 14 (38%) were resistant and did not ovulate. In the latter group, MI plasma levels did not increase. These MI-resistant patients underwent treatment in the main phase of the study, receiving MI and α-LA. After this combined treatment, 12 (86%) of them ovulated. Their MI plasma levels were found to be significantly higher than at baseline; also, a hormone and lipid profile improvement was recorded. CONCLUSION: The combination of MI with α-LA allowed us to obtain significant progress in the treatment of PCOS MI-resistant patients. Therefore, this new formulation was able to re-establish ovulation, greatly increasing the chances of desired pregnancy. TRIAL REGISTRATION: Clinical trial registration number: NCT03422289 ( ClinicalTrials.gov registry).

Lack of effects of myo-inositol on metabolism of primary rat adipocytes.

Myo-inositol is a ubiquitous cyclitol, has an important regulatory role, and its intracellular depletion is associated with pathological changes. Effects of myo-inositol on adipose tissue are poorly elucidated. In this report, short-term influence of 20, 100, and 500 µM myo-inositol on metabolism of the isolated rat adipocytes was studied. Cells were incubated for 90 min with glucose and insulin with or without myo-inositol and glucose conversion to lipids and lactate release were measured. Moreover, effects of myo-inositol on lipolysis and on the antilipolytic action of insulin were also studied. It was demonstrated that lipogenesis and lactate release were unchanged by myo-inositol. Moreover, lipolytic response to epinephrine and dibutyryl-cAMP was also unchanged. Myo-inositol was also found to be without influence on the antilipolytic action of insulin. Results of this study show that metabolism of the isolated rat adipocytes is not affected by short-term exposure of these cells to myo-inositol.

Treatment of gestational diabetes mellitus with myo-inositol: analyzing the cutting edge starting from a peculiar case.

OBJECTIVE: The robust data about myo-inositol (Myo-Ins) safety profile and effectiveness opened a new scenario for the treatment and prevention of Gestational Diabetes Mellitus (GDM). We report our experience about a case of GDM successfully treated with Myo-Ins. PATIENTS AND METHODS: An overweight 29-year-old Caucasian pregnant woman, nulliparous, affected by GDM, according to the National Institute for Health and Care Excellence (NICE) Guideline. After diagnosis, the patient underwent regular glycemia checks: mean fasting blood glucose value was 103.63 ± 1.46 mg/dl, whereas 1-hour and 2-hours after-meal values were 122.74 ± 11.14 mg/dl and 110.74 ± 10.70 mg/dl, respectively. We decided to prescribe a low-calorie diet and oral treatment with 4 g of Myo-Ins, 3 times per day for 3 weeks. RESULTS: After the treatment, mean fasting value was 90.74 ± 5.30 mg/dl, whereas 1-hour after and 2-hours after-meal values were 108.11 ± 6.05 mg/dl and 101.21 ± 4.78 mg/dl, respectively. DISCUSSION: We reported a significant decrease of glycemia in a faster and steady way at fasting, 1-hour and 2-hours after-meal post oral treatment with 4 g of Myo-Ins 3 times per day, in a patient affected by GDM. CONCLUSIONS: On the one hand, we could confirm the safety profile of the molecule also at this high dosage, free from any side effects; on the other hand, our experience highlighted the faster glucose-lowering effect due to a higher dose of Myo-Ins. This outcome may open a new scenario in the treatment of GDM.

Inositol for the prevention of neural tube defects: a pilot randomised controlled trial.

Although peri-conceptional folic acid (FA) supplementation can prevent a proportion of neural tube defects (NTD), there is increasing evidence that many NTD are FA non-responsive. The vitamin-like molecule inositol may offer a novel approach to preventing FA-non-responsive NTD. Inositol prevented NTD in a genetic mouse model, and was well tolerated by women in a small study of NTD recurrence. In the present study, we report the Prevention of Neural Tube Defects by Inositol (PONTI) pilot study designed to gain further experience of inositol usage in human pregnancy as a preliminary trial to a future large-scale controlled trial to evaluate efficacy of inositol in NTD prevention. Study subjects were UK women with a previous NTD pregnancy who planned to become pregnant again. Of 117 women who made contact, ninety-nine proved eligible and forty-seven agreed to be randomised (double-blind) to peri-conceptional supplementation with inositol plus FA or placebo plus FA. In total, thirty-three randomised pregnancies produced one NTD recurrence in the placebo plus FA group (n 19) and no recurrences in the inositol plus FA group (n 14). Of fifty-two women who declined randomisation, the peri-conceptional supplementation regimen and outcomes of twenty-two further pregnancies were documented. Two NTD recurred, both in women who took only FA in their next pregnancy. No adverse pregnancy events were associated with inositol supplementation. The findings of the PONTI pilot study encourage a large-scale controlled trial of inositol for NTD prevention, but indicate the need for a careful study design in view of the unwillingness of many high-risk women to be randomised.

Retrospective comparison of voglibose or acarbose as an add-on therapy to sulfonylureas in Western Indian patients with uncontrolled overweight/obese type 2 diabetes.

AIM: The study was aimed to investigate the effect of voglibose or acarbose as an add-on treatment in overweight/obese type 2 diabetes (T2DM) patients who are uncontrolled with metformin and sulfonylureas (SUs) in Western part of India. PARTICIPANTS AND METHODS: A retrospective study included 77 participants (BMI≥25kg/m(2); HbA1c level>8% and<9.5%) with overweight/obese T2DM. These participants were treated with either voglibose or acarbose. Glycemic parameters (fasting blood glucose and glycated hemoglobin [HbA1c]), bodyweight, BMI and lipid parameters were evaluated at baseline, 3-month, 6-month and 9-month of treatment. Adverse events were also captured at respective time points. RESULTS: Voglibose showed significant reduction in HbA1c and bodyweight with short duration of treatment (6 months; P<0.05 and 9 months; P<0.01) whereas acarbose showed significant reduction with longer duration of treatment (9 months; P<0.05) when compared with baseline. Moreover, both treatment groups were reported with reduction in BMI. Further, significant improvement in lipid parameters except LDL and HDL were observed in both treatment groups when compared with baseline. None of participant was discontinued due to side effects of the treatment. In addition, the frequency of hypoglycemia was decreased in both treatment groups. CONCLUSION: Voglibose or acarbose as an add-on treatment with metformin and sulfonylureas in uncontrolled obese/overweight T2DM provides desired glycemic control, reduces bodyweight and improves lipid parameters with good tolerability profile.

Chronic consumption of an inositol-enriched carob extract improves postprandial glycaemia and insulin sensitivity in healthy subjects: A randomized controlled trial.

BACKGROUND & AIMS: Inositols are thought to be mediators of the insulin signalling pathway. We assessed the effects of inositols on glycaemic control in fasting and postprandial states and evaluated lipoprotein profile and LDL particle size in healthy population. METHODS: A 12-week double-blind clinical trial was performed with forty healthy subjects administered either an inositol-enriched beverage (IEB) -containing 2.23 g of inositols in 250 ml- or a sucrose-sweetened beverage (SB) twice a day. Anthropometric measurements, fasting glucose levels, insulin and HOMA-IR index, lipoprotein profile and postprandial glucose concentrations (measured using the continuous glucose monitoring system (CGMS)) were recorded throughout the intervention period. RESULTS: Following the 12-week trial subjects receiving the IEB exhibited a significant decrease in insulin, HOMA-IR and Apo B and an increase in LDL particle size, whereas the SB group showed increases in BMI and fasting glucose concentration. Analysis of postprandial glucose levels at breakfast, lunch and dinner revealed a mean reduction of glucose of ≈14% and a significant reduction in the area under the curve at 24 h after consumption of the IEB. CONCLUSIONS: Our results show that chronic IEB supplementation induces a significant improvement in carbohydrated metabolism parameters in healthy subjects.

Antenatal dietary supplementation with myo-inositol in women during pregnancy for preventing gestational diabetes.

BACKGROUND: Gestational diabetes, glucose intolerance with onset or first recognition during pregnancy, is a rising problem worldwide. Both non-pharmacological and pharmacological approaches to the prevention of gestational diabetes have been, and continue to be explored. Myo-inositol, an isomer of inositol, is a naturally occurring sugar commonly found in cereals, corn, legumes and meat. It is one of the intracellular mediators of the insulin signal and correlated with insulin sensitivity in type 2 diabetes. The potential beneficial effect on improving insulin sensitivity suggests that myo-inositol may be useful for women in preventing gestational diabetes. OBJECTIVES: To assess if antenatal dietary supplementation with myo-inositol is safe and effective, for the mother and fetus, in preventing gestational diabetes. SEARCH METHODS: We searched the Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, WHO ICTRP (2 November 2015) and reference lists of retrieved studies. SELECTION CRITERIA: We sought published and unpublished randomised controlled trials, including conference abstracts, assessing the effects of myo-inositol for the prevention of gestational diabetes mellitus (GDM). Quasi-randomised and cross-over trials were not eligible for inclusion, but cluster designs were eligible. Participants in the trials were pregnant women. Women with pre-existing type 1 or type 2 diabetes were excluded. Trials that compared the administration of any dose of myo-inositol, alone or in a combination preparation were eligible for inclusion. Trials that used no treatment, placebo or another intervention as the comparator were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, risk of bias and extracted the data. Data were checked for accuracy. MAIN RESULTS: We included four randomised controlled trials (all conducted in Italy) reporting on 567 women who were less than 11 weeks' to 24 weeks' pregnant at the start of the trials. The trials had small sample sizes and one trial only reported an interim analysis. Two trials were open-label. The overall risk of bias was unclear.For the mother, supplementation with myo-inositol was associated with a reduction in the incidence of gestational diabetes compared with control (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.29 to 0.64; three trials; n = 502 women). Using GRADE methods this evidence was assessed as low with downgrading due to unclear risk of bias for allocation concealment in two of the included trials and lack of generalisability of findings. For women who received myo-inositol supplementation, the incidence of GDM ranged from 8% to 18%; for women in the control group, the incidence of GDM was 28%, using International Association of Diabetes and Pregnancy Study Groups Consensus Panel 2010 criteria to diagnose GDM.Two trials reported on hypertensive disorders of pregnancy, a primary maternal outcome of this review. There was no clear difference in risk of hypertensive disorders of pregnancy between the myo-inositol and control groups (average RR 0.43, 95% CI 0.02 to 8.41; two trials; n = 398 women; Tau(2) = 3.23; I(2) = 69%). Using GRADE methods, this evidence was assessed as very low, with downgrading due to wide confidence intervals with very low event rates, a small sample size, and lack of blinding and unclear allocation concealment methods, and a lack of generalisability. For women who received myo-inositol the risk of hypertensive disorders of pregnancy ranged from 0% to 33%; for women in the control group the risk was 4%.For the infant, none of the included trials reported on the primary neonatal outcomes of this systematic review (large-for-gestational age, perinatal mortality, mortality or morbidity composite).In terms of this review's secondary outcomes, there was no clear difference in the risk of caesarean section between the myo-inositol and control groups (RR 0.95, 95% CI 0.76 to 1.19; two trials; n = 398 women). Using GRADE methods, this evidence was assessed as low, with downgrading due to unclear risk of bias in one trial and lack of generalisability. For women who received myo-inositol supplementation, the risk of having a caesarean section ranged from 34% to 54%; for women in the control group the was 45%. There were no maternal adverse effects of therapy in the two trials that reported on this outcome (the other two trials did not report this outcome).Two trials found no clear difference in the risk of macrosomia between infants whose mothers received myo-inositol supplementation compared with controls (average RR 0.35, 95% CI 0.02 to 6.37; two trials; n = 398 infants;Tau(2) = 3.33; I(2) = 73%). Similarly, there was no clear difference between groups in terms of neonatal hypoglycaemia (RR 0.36, 95% CI 0.01 to 8.66) or shoulder dystocia (average RR 2.33, 95% CI 0.12 to 44.30, Tau(2) = 3.24; I(2) = 72%).There was a lack of data available for a large number of maternal and neonatal secondary outcomes, and no data for any of the long-term childhood or adulthood outcomes, or for health service cost outcomes. AUTHORS' CONCLUSIONS: Evidence from four trials of antenatal dietary supplementation with myo-inositol during pregnancy shows a potential benefit for reducing the incidence of gestational diabetes. No data were reported for any of this review's primary neonatal outcomes. There were very little outcome data for the majority of this review's secondary outcomes. There is no clear evidence of a difference for macrosomia when compared with control.The current evidence is based on small trials that are not powered to detect differences in outcomes including perinatal mortality and serious infant morbidity. All of the included studies were conducted in Italy which raises concerns about the lack of generalisability of the evidence to other settings. There is evidence of inconsistency and indirectness and as a result, many of the judgements on the quality of the evidence were downgraded to low or very low quality (GRADEpro Guideline Development Tool).Further trials for this promising antenatal intervention for preventing gestational diabetes are encouraged and should include pregnant women of different ethnicities and varying risk factors and use of myo-inositol (different doses, frequency and timing of administration) in comparison with placebo, diet and exercise or pharmacological interventions. Outcomes should include potential harms including adverse effects.