Maria Lieta Interdonato

myo-Inositol Supplementation and Onset of Gestational Diabetes Mellitus in Pregnant Women With a Family History of Type 2 Diabetes: A prospective, randomized, placebo-controlled study

OBJECTIVE To check the hypothesis that myo-inositol supplementation may reduce gestational diabetes mellitus (GDM) onset in pregnant women with a family history of type 2 diabetes. RESEARCH DESIGN AND METHODS A 2-year, prospective, randomized, open-label, placebo-controlled study was carried out in pregnant outpatients with a parent with type 2 diabetes who were treated from the end of the first trimester with 2 g myo-inositol plus 200 µg folic acid twice a day (n = 110) and in the placebo group (n = 110), who were only treated with 200 µg folic acid twice a day. The main outcome measure was the incidence of GDM in both groups. Secondary outcome measures were as follows: the incidence of fetal macrosomia (>4,000 g), gestational hypertension, preterm delivery, caesarean section, shoulder dystocia, neonatal hypoglycemia, and neonatal distress respiratory syndrome. GDM diagnosis was performed according to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recommendations. RESULTS Incidence of GDM was significantly reduced in the myo-inositol group compared with the placebo group: 6 vs. 15.3%, respectively (P = 0.04). In the myo-inositol group, a reduction of GDM risk occurrence was highlighted (odds ratio 0.35). A statistically significant reduction of fetal macrosomia in the myo-inositol group was also highlighted together with a significant reduction in mean fetal weight at delivery. In the other secondary outcome measures, there were no differences between groups. CONCLUSIONS myo-Inositol supplementation in pregnant women with a family history of type 2 diabetes may reduce GDM incidence and the delivery of macrosomia fetuses.

Myo-inositol may prevent gestational diabetes in PCOS women

To evaluate retrospectively the prevalence of gestational diabetes (GD) in pregnancies obtained with myo-inositol administration in women with polycystic ovary syndrome. A total of 98 pregnancies in PCOS women obtained in a 3-year period, either with myo-inositol (n. 54), or with metformin (n. 44) were considered. While myo-inositol was assumed through the whole pregnancy, the group of women treated with metformin stopped the drug assumption after pregnancy diagnosis, and was considered as a control group. After having eliminated cases of miscarriages and twin pregnancies, a definitive number of 46 women in the myo-inositol group and 37 in the control group was taken in account to be retrospectively evaluated. The primary outcome measure was GD occurrence in both groups; whereas secondary outcome measures were pregnancy outcomes: hypertensive disorders, pre-term birth, macrosomia and caesarean section occurrence. Prevalence of GD in the myo-inositol group was 17.4% versus 54% in the control group, with a highly significant difference also after adjusting for covariates. Consequently, in the control group the risk of GD occurrence was more than double compared to the myo-inositol group, with an odds ratio 2.4 (confidence interval 95%, 1.3–4.4). There was no difference between the groups in relation to secondary outcome measures. This study suggests a possible effect of myo-inositol in the primary prevention of GD in PCOS women.

Myo-inositol Supplementation for Prevention of Gestational Diabetes in Obese Pregnant Women: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether myo-inositol supplementation, an insulin sensitizer, reduces the rate of gestational diabetes mellitus (GDM) and lowers insulin resistance in obese pregnant women. METHODS: In an open-label, randomized trial, myo-inositol (2 g plus 200 micrograms folic acid twice a day) or placebo (200 micrograms folic acid twice a day) was administered from the first trimester to delivery in pregnant obese women (prepregnancy body mass index 30 or greater. We calculated that 101 women in each arm would be required to demonstrate a 65% GDM reduction in the myo-inositol group with a statistical power of 80% (&agr;=0.05). The primary outcomes were the incidence of GDM and the change in insulin resistance from enrollment until the diagnostic oral glucose tolerance test. RESULTS: From January 2011 to April 2014, 220 pregnant women at 12–13 weeks of gestation were randomized at two Italian university hospitals, 110 to myo-inositol and 110 to placebo. Most characteristics were similar between groups. The GDM rate was significantly reduced in the myo-inositol group compared with the control group, 14.0% compared with 33.6%, respectively (P=.001; odds ratio 0.34, 95% confidence interval 0.17–0.68). Furthermore, women treated with myo-inositol showed a significantly greater reduction in the homeostasis model assessment of insulin resistance compared with the control group, −1.0±3.1 compared with 0.1±1.8 (P=.048). CONCLUSION: Myo-inositol supplementation, started in the first trimester, in obese pregnant women seems to reduce the incidence in GDM through a reduction of insulin resistance. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01047982.

One-year effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome.

ABSTRACT Objective To evaluate the 12-month effect of myo-inositol treatment on some biochemical parameters of women affected by metabolic syndrome. Methods Eighty outpatient postmenopausal women, affected by metabolic syndrome, were enrolled in a 12-month study. All women were treated with a low-energy diet, and then they were randomly assigned to myo-inositol 2 g b.i.d. (n = 40) or placebo (n = 40). All the women were evaluated for serum glucose, insulin, HOMA-IR (Homeostasis Model Assessment-Insulin Resistance), triglycerides, total and high density lipoprotein cholesterol, body mass index (BMI), waist circumference and blood pressure at baseline and after 12 months of treatment. Results With the exception of BMI and waist circumference, after 12 months of treatment, all the parameters studied showed a significant improvement in the myo-inositol group compared to the control group. At the end of the study, in the myo-inositol group, the number of women without metabolic syndrome was eight (20%) whereas, in the control group, only one woman no longer had the metabolic syndrome after 12 months of diet. Conclusions Myo-inositol might be considered one of the insulin-sensitizing substances in the treatment of metabolic syndrome.

Correspondence between first-trimester fasting glycaemia, and oral glucose tolerance test in gestational diabetes diagnosis.

AIM To evaluate the correspondence between first-trimester fasting glycaemia and the results of the OGTT in diagnosing gestational diabetes (GDM). METHODS The medical records of all consecutive women who had undergone a diagnostic OGTT, performed according to the IADPSG, during the past year were retrospectively reviewed. All first-trimester fasting glucose values greater or equal to 5.1 mmol/L (92 mg/dL), recommended as a diagnostic value, were also verified for each patient in this cohort. Moreover, a ROC curve and a multiple logistic-regression model were constructed to calculate the predictive capability of this cut-off value in diagnosing GDM. RESULTS In our population of 738 eligible pregnant women, an 11.9% prevalence of GDM was revealed by OGTT. However, when the first-trimester fasting glucose value for each patient was retrospectively considered, there were a further 29 patients who should have been diagnosed as GDM cases (glycaemia ≥ 5.1 mmol/L), although their OGTT was normal. Yet, when the value of fasting glucose was considered not diagnostic, but only predictive, an AUC of 0.614 (95% CI: 0.544-0.684) and an aOR of 7.1 (95% CI: 3.8-13.1) was obtained in these patients compared with the reference group (fasting glucose < 5.1 mmol/L). CONCLUSION There was no complete correspondence in diagnosing GDM between the first-trimester fasting glucose value and the results of a 2-h 75-g OGTT performed early in the third trimester. However, albeit not diagnostic, a fasting glucose value greater or equal to 5.1 mmol/L may be considered a highly predictive risk factor for GDM.

Effects of prepregnancy body mass index and weight gain during pregnancy on perinatal outcome in glucose-tolerant women

AIM The aim of this study was to determine the effects of maternal prepregnancy body mass index (BMI) and weight gain during pregnancy on perinatal outcome in non-diabetic women. METHODS The clinical records of consecutive women who had undergone a glucose challenge test (GCT) and then delivered in our university hospital between January 2004 and December 2009 were retrospectively reviewed. Prepregnancy BMI and pregnancy weight gain were classified according to the US Institute of Medicine guidelines (1990). RESULTS Of the eligible 2225 patients, obese and overweight women had a greater percentage of macrosomic babies (17.7% and 8.9%, respectively) compared with normal weight women (4.5%). However, when considered according to weight gain during pregnancy, the results were statistically significant only for excess weight gain in the obese (OR: 8.3, 95% CI: 2.4-28.4) and overweight (OR: 2.9, 95% CI: 1.2-6.8) groups. Also, the surgical delivery rate was significantly higher in the obese vs normal weight women (56% vs 36%, respectively) although, in this case, there was no difference according to normal and excess weight gain during pregnancy (OR: 1.4, 95% CI: 0.7-2.6). CONCLUSION Overweight and obese women have an increased risk rate of macrosomia that can be limited by well-controlled weight gain during pregnancy. There was also a significantly higher rate of surgical delivery in the obese compared with the normal weight group that was, however, independent of excessive weight gain during pregnancy.

Effects of a New Flavonoid and Myo-Inositol Supplement on Some Biomarkers of Cardiovascular Risk in Postmenopausal Women: A Randomized Trial

Background and Aim. Cardiovascular risk is increased in women with menopause and metabolic syndrome. Aim of this study was to test the effect of a new supplement formula, combining cocoa polyphenols, myo-inositol, and soy isoflavones, on some biomarkers of cardiovascular risk in postmenopausal women with metabolic syndrome. Methods and Results. A total of 60 women were enrolled and randomly assigned (n = 30 per group) to receive the supplement (NRT: 30 mg of cocoa polyphenols, 80 mg of soy isoflavones, and 2 gr of myo-inositol), or placebo for 6 months. The study protocol included three visits (baseline, 6, and 12 months) for the evaluation of glucose, triglycerides, and HDL-cholesterol (HDL-C), adiponectin, visfatin, resistin, and bone-specific alkaline phosphatase (bone-ALP). At 6 months, a significant difference between NRT and placebo was found for glucose (96 ± 7 versus 108 ± 10 mg/dL), triglycerides (145 ± 14 versus 165 ± 18 mg/dL), visfatin (2.8 ± 0.8 versus 3.7 ± 1.1 ng/mL), resistin (27 ± 7 versus 32 ± 8 µg/L), and b-ALP (19 ± 7 versus 15 ± 5 µg/mL). No difference in HDL-C concentrations nor in adiponectin levels between groups was reported at 6 months. Conclusions. The supplement used in this study improves most of the biomarkers linked to metabolic syndrome. This Trial is registered with NCT01400724.

Italian risk factor-based screening for gestational diabetes

Abstract There is a debate about whether universal or risk factors-based screening is most appropriate for gestational diabetes diagnosis. The aim of our retrospective study was to compare in our population the universal screening test recommended by the International Association of Diabetes in Pregnancy Study Group (IADPSG) panel and the American Diabetes Association (ADA) versus the selective screening proposed by the United Kingdom National Institute for Health and Clinical Excellence guidelines (NICE) but modified by the Italian National Institute of Health. From May 2010 to October 2011 all consecutive pregnant women were screened for gestational diabetes according to the IADPSG’s panel criteria, while all the risk factors for each patient were registered. Of the 1015 pregnant women included in the study, 113 (11%) were diagnosed with gestational diabetes and 26 (23%) of them would not have been identified by the selective screening proposed by the Italian National Institute of Health. However, all the risk factors considered by the selective screening revealed a good predictive role except for maternal age ≥35 years (OR: 0.98). In the group without the risk factors considered, it was reported the predictive role for gestational diabetes of prepregnancy BMI and nulliparity. The selective risk factors-based screening proposed by the Italian National Institute of Health has detected 77% of gestational diabetes cases in our population, sparing the oral glucose tolerance test for more than 40% of pregnant women at the same time. More information on the clinical impact of this choice could be obtained by a strict analysis of treatment, perinatal outcome and follow-up of an adequate sample size of “missed” gestational diabetes.

Myo-inositol in Down syndrome amniotic fluid. A case-control study.

Down syndrome (DS) is caused by the trisomy of chromosome 21. In DS, gene products of the extra chromosome 21 may cause abnormal levels of certain metabolites directly or by affecting gene expression of other chromosomes. Myo-inositol (MI) is one of these; it is a polyalcohol deriving from glucose, which is synthesized by a few organs in the body, such as the testes, kidneys, and brain. MI concentrations are significantly increased in DS cerebrospinal fluid, and its levels are directly correlated with the plasmatic ones. Thus, it is plausible to hypothesize that DS could be associated with MI accumulation not only in cerebrospinal fluid but also in other fluids, in which it might be detected very early in life. The aim of our study was to evaluate midtrimester amniotic fluid (AF) in DS pregnancies, compared with normal pregnancies. A retrospective study was carried out on 22 AF samples of DS pregnancies stored at 80 °C, collected over the last 6 years, after amniocentesis, performed between 15 and 18weeks gestation at our Prenatal Diagnosis Center. A group of 25 samples of normal pregnancy AF, matched for maternal age, body mass index (BMI) and gestational age, were used as a control group. The protocol was consistent with the principles of the Declaration of Helsinki, and all the participants gave their written informed consent for the utilization of 1mL of their AF for experimental purposes. MI quantification was performed by Chelab Pharma Division using gas chromatography–mass spectrometry analysis after extraction with organic solvents and derivation. Injection (1.0μL) was performed in a split-less mode at 270 °C and a capillary column Agilent 122-5532 DB-5 ms (0.25mm×30m×0.25 ×μm) was used. The total run-time was 15min: oven at 70 °C from 0 to 1min; 20 °C/min to 150 °C; 10 °C/min to 240 °C; 4 min at 320 °C post run. The flow rate was fixed at 1.2mL/min, and results were analyzed by an MS 5973 Network Series detector in sim mode. Statistical analysis was carried out with an SPSS statistical package version 17 (SPSS, Chicago, IL). Data are expressed as medians and interquartile range (IQR). The Mann–Whitney test was used to compare AF MI values between groups, and Spearman’s test was used to correlate normal pregnancy AF values with maternal age, BMI, and parity. The general characteristics of the two groups are reported in Table 1. There were no statistical differences between them in BMI, gestational age, parity, and maternal age. The indications for amniocentesis were maternal age in 17 and positive biochemical genetic screening test in four. In all DS pregnancies, an induced abortion was requested and then performed. A significant difference (p< 0.001) was found inMI concentrations between groups (Figure 1): DS 135.2μmol/L (IQR 119.2–147.8); control group 84.0μmol/L (IQR 63.1–112.8) (Figure 1). In the control group, there was no correlation between AF MI levels andmaternal age (r=0.15, p=0.46); BMI (r=0.11, p=0.57); parity (r=0.2, p=0.32); gestational age (r=0.21, p=0.3) or neonatal weight (r= 0.003, p=0.9). Inositol is found in the cellular membrane as inositol phosphoglycans (IPGs). The placenta plays a fundamental role in the complex metabolism of inositol. In fact, IPGs are released into microvilli caveolae by the action of the enzyme glycosylphosphatidylinositol phospholipase D (GPI-PLD) on their lipid precursors, the membrane-associated glycosylphosphatidylinositol (GPI). Placental GPI-PLD, necessary for the production of IPG, is not produced by the placenta but is taken up from maternal plasma. Placental microvilli have therefore a potential source for placenta-derived IPG molecules which can be released into the maternal blood stream, where they could act as systemic (paracrine) factors, in addition to their role as autocrine mediators of a large number of growth factors and hormones. The lack of correlation between AF MI concentrations and maternal parameters confirms a possible fetal origin of this substance. An increased production of MI AF in subjects affected by DS is in accordance with an accumulation of MI in other DS tissues. In particular, fibroblasts of non-DS patients with

Use of Diet and Myoinositol in Postmenopausal Women: A New Approach to the Metabolic Syndrome

The menopause transition or perimenopause begins several years before the menopause, when the ovaries gradually begin to produce less estrogen, and it ends on the first year after menopause, when a woman has gone 12 months without having her period. Decreasing endogenous estrogens after menopause may be the critical factor in removing the relative protection against cardiovascular diseases (CVDs) that women have in their premenopausal years. CVD risk in women until menopause is considerably less than in men, after menopause the risk is overlapped. So that CVD represents the leading causes of morbidity and mortality for both men and women in developed countries. Deep metabolic changes involving women in the menopause transition are responsible for the onset of metabolic syndrome. It is characterized by hyperinsulinemia with underlying insulin resistance, and a cluster of other CVD risk factors including impaired glucose regulation, elevated levels of triglycerides, decreased levels of HDL-cholesterol, raised blood pressure, and centrally distributed obesity. First-line intervention in the management of metabolic syndrome is to reduce the modifiable, underlying risk factors (obesity, physical inactivity, and atherogenic diet) through lifestyle changes, including low-caloric diet and physical activity. A new chance in pharmacological treatment may be myoinositol, which is a natural supplement, capable of reducing insulin resistance and all other features of metabolic syndrome.